Last reviewed: 22 May 2021
Last updated: 10 Jun 2021
09 Jun 2021

Guidelines recommend measures to manage acute and chronic conditions during the COVID-19 pandemic: updated

Further guidelines have been published to inform the management of patients with coexisting conditions during the COVID-19 pandemic.

New this update:

  • Considerations for perinatal care (updated)

  • Considerations for patients receiving systemic anticancer therapy (updated)

  • Considerations for mental health of adults (updated)

  • Potential impact of COVID-19 pandemic on diagnosis and management of other conditions (updated)

  • Giant cell arteritis (updated)

  • HIV infection (updated)

  • Obesity in adults (updated)

  • Renal transplant (updated)

  • Rheumatoid arthritis (updated)

  • Systemic lupus erythematosus (SLE) (updated)

Original source of updateexternal link opens in a new window

Introduction

Considerations for perinatal care

Considerations for newborn care

Considerations for patients with dermatologic conditions receiving drugs that affect the immune response

Considerations for patients with gastrointestinal or liver conditions treated with drugs that affect the immune response

Considerations for patients with lower gastrointestinal symptoms

Considerations for endoscopy

Considerations for patients receiving systemic anticancer therapy

Considerations for patients receiving radiation therapy

Considerations for patients with head and neck cancer

Considerations for patients with neuromuscular diseases

Use of ACE inhibitors and angiotensin-II receptor antagonists

Use of proton-pump inhibitors

Routine immunization

Considerations for patients who require anticoagulation

Considerations for management of patients in community psychiatry services

Considerations for mental health of adults

Mental health of children and adolescents

Considerations for the mental health of healthcare workers

Considerations for immunocompromised children and young people

Safeguarding children and young people

Use of valproate

Considerations for cardiac investigations

Considerations for patients with cardiac implantable electronic devices (CIEDs)

Considerations for laparoscopy

Considerations for gastrointestinal motility tests

Considerations for elective surgery

Considerations for emergency surgery

Considerations for patients with eating disorders

Considerations for patients with hyperthyroidism

Potential impact of COVID-19 pandemic on diagnosis and management of other conditions

Resources

Condition
Description

Our full topic on Coronavirus disease 2019 (COVID-19) includes information on diagnosis and management, as well as prevention, differential diagnosis, epidemiology, etiology, prognosis, and complications.

A Cochrane review has evaluated the effectiveness and safety of treatments for heavy menstrual bleeding that are commonly available during pandemics.[217] Treatments evaluated included nonsteroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics, combined hormonal contraceptives, and progestogens. The review found that there is moderate-certainty evidence that antifibrinolytics and combined hormonal contraceptives reduce heavy menstrual bleeding compared with placebo; there is low‐certainty evidence that NSAIDs reduce heavy menstrual bleeding compared with placebo; and there is low‐certainty evidence that antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with NSAIDs and short‐cycle progestogens. The authors were unable to draw conclusions about the effects of antifibrinolytics compared with long‐cycle progestogens and no conclusions could be made about quality of life, patient satisfaction with treatment, or serious adverse events. The review’s authors suggest that within the context of a pandemic when treatment is selected remotely, antifibrinolytics (e.g., tranexamic acid), NSAIDs, and combined hormonal contraceptives can be offered. They also emphasise the importance of providing a complete face-to-face assessment (physical exam, blood tests, ultrasound) when services are available.

A multisociety position statement advises that laparoscopic cholecystectomy remains the treatment of choice for acute cholecystitis during the COVID-19 pandemic. Early cholecystectomy (performed as soon as possible after the onset of symptoms) is preferred. Air exiting the peritoneum should be filtered through ultra-low particulate air filters to remove viral particles. If surgery needs to be postponed because of a COVID-19 outbreak, patients must be closely monitored for signs of sepsis and pain progression. If patients are not fit for surgery and have not improved with antibiotic therapy, percutaneous gallbladder drainage may be considered.[218]

Patients with COVID-19 may develop acute kidney injury (AKI). Age ≥60 years and severe COVID-19 are independent risk factors for mortality.[219] Patients who have severe COVID-19 are more likely to require continuous renal replacement therapy compared with patients who have nonsevere COVID-19. AKI significantly increases the risk of in-hospital death in patients with COVID-19.[220] One cohort study of patients with in-hospital AKI in the US found that COVID-19-associated AKI was associated with a greater rate of estimated glomerular filtration rate decrease after discharge compared with AKI in patients without COVID-19, and this was independent of underlying comorbidities or AKI severity.[221]

UK guidelines note that in people with COVID-19, AKI can develop at any time (before, during, or after hospital admission), and that maintaining euvolemia (optimal fluid status) is critical to reducing AKI incidence.[121]

The treatment of AKI in patients with COVID-19 appears to be the same as in other populations, including continuous renal replacement therapy if necessary.[222] Medications that can cause or worsen AKI should be stopped unless essential. Some treatments for COVID-19 may increase the risk of AKI.[121] Patients with elevated body temperature and increased respiratory rate will have greater insensible fluid losses.[223][121] Intravenous fluids are required in many cases, and choice should be guided by biochemistry. The goal of intravenous fluid therapy is to maintain a euvolemic state. Hypernatremia is common at presentation and can also develop later.[223] Potassium binders can be used as part of the emergency management of life-threatening hyperkalemia, alongside standard care.[121] These agents may have a role in preventing or delaying the need for renal replacement therapy if resources are limited.[223][224]

Analysis of US health-insurance claims data has shown that leukemia is a significant risk factor for fatal COVID-19.[75] An international expert panel and the American Society of Hematology have made recommendations for the treatment of adult acute lymphocytic leukemia.[225][226] Clinicians should consider minimizing corticosteroid exposure and reducing doses of daunorubicin and pegaspargase (pegylated asparaginase) during treatment induction in older people and people at high risk for complications of COVID-19.[225][226] Anti-CD20 monoclonal antibodies reduce immune globulin levels; treatment with these agents should be deferred if possible. Second-generation tyrosine kinase inhibitors with reduced-dose corticosteroids should be considered in Philadelphia chromosome-positive disease.[225][226]

Clinicians should consider blinatumomab if patients are positive for minimal residual disease after two cycles of chemotherapy. If patients are negative for minimal residual disease and have received most of their chemotherapy, they may be advanced to maintenance. During maintenance, clinicians should consider reducing corticosteroids and avoiding vincristine in patients >65 years. Recommendations are given for relapsed or refractory disease and transplantation. Growth factor support should be considered in patients without COVID-19 to facilitate neutrophil count recovery and maintain absolute neutrophil count above 1000 cells per microliter during all phases of treatment. Growth factors should probably be avoided in patients with moderate-to-severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection because there is a potential risk of exacerbating inflammatory pulmonary injury.[225]

Trials of SARS-CoV-2 vaccination in patients with hematological conditions are lacking. Such patients are likely to have an attenuated response to vaccination. Additional measures, such as early vaccination of household contacts, may be considered.[227]

Analysis of US health-insurance claims data has shown that leukemia is a significant risk factor for fatal COVID-19.[75] Acute myelogenous leukemia (AML) is associated with worse survival in patients with COVID-19.[228] Patients with AML should be screened for COVID-19 before starting induction or consolidation chemotherapy.[229] Patients receiving intensive therapy should, ideally, be barrier nursed in a COVID-19-negative ward with enhanced screening and protection measures. Chemotherapy should be delayed until the resolution of symptoms and the patient has a negative polymerase chain reaction test. Cytogenetics and nucleophosmin-1 (NPM1) and fsm-related tyrosine kinase-3 (FLT3) status will guide choice of chemotherapy. Venetoclax and gilteritinib have been granted emergency approval from NHS England for use in selected patient groups.[229]

Growth factors should probably be avoided in patients with moderate-to-severe COVID-19 because there is a potential risk of exacerbating inflammatory pulmonary injury.[225]

Trials of severe acute respiratory syndrome coronavirus 2 vaccination in patients with hematological conditions are lacking. Such patients are likely to have an attenuated response to vaccination. Additional measures, such as early vaccination of household contacts, may be considered.[230]

Patients with adrenal insufficiency are at an increased risk of infection, which may be complicated by developing an adrenal crisis. Guidance on prevention of adrenal crisis in patients with confirmed or suspected COVID-19 is available.[231] Patients should be given support to help them self-manage their condition safely and should be educated in the use of sick day rules. The guidelines recommend that patients with symptoms of COVID-19 should seek medical advice, and should take oral hydrocortisone or prednisone as directed. Patients are also advised to take acetaminophen for fever, and to drink regularly, monitoring how concentrated their urine appears. If there are signs of clinical deterioration (such as dizziness, intense thirst, shaking uncontrollably, drowsiness, confusion, lethargy, vomiting, severe diarrhea, increasing shortness of breath, respiratory rate >24/min, difficulty speaking) the patient or carer should inject hydrocortisone intramuscularly and call for emergency medical assistance.[231] Hospitalized patients should receive intravenous hydrocortisone and continuous intravenous fluid resuscitation with isotonic saline; fludrocortisone should be temporarily stopped. 

UK guidelines recommend that diagnosis of wet age-related macular degeneration should be confirmed with optical coherence tomography (OCT) and OCT angiography if available. Patients with newly diagnosed disease should be treated with a loading phase of 3 injections of a vascular endothelial growth factor (VEGF) inhibitor, followed by injections every 8 weeks with no clinic review. Patients already established on VEGF inhibitor treatment can continue to receive injections every 8 weeks without clinic review, unless there has been a significant drop in vision since their last injection visit. In this situation, repeat assessment of visual acuity and repeat OCT may be needed. As lockdown restrictions begin to be lifted, prepandemic protocols may be implemented.[232]

Statements from the British Society for Allergy and Clinical Immunology and the Italian Society of Pediatric Allergy and Immunology advise that patients with allergic rhinitis should continue usual treatment, including topical intranasal corticosteroids and antihistamines. Uncontrolled allergic rhinitis may lead to sneezing and increased hand-eye and hand-nose contact, facilitating severe acute respiratory syndrome coronavirus-2 transmission.[233][234] Skin testing for aeroallergens, sublingual immunotherapy, and subcutaneous immunotherapy should be deferred. Post-dose observation may be decreased and intervals between doses may be increased for patients already taking subcutaneous immunotherapy.[233]

UK screening for amblyopia has stopped during the pandemic. Clinical judgement should be used to determine the urgency of treating suspected amblyopia; delaying treatment until the pandemic has passed is justifiable given the risk of virus transmission and pressure on health resources. Atropine treatment requires follow-up visits to monitor for reversal of amblyopia. Therefore, atropine should be discontinued and changed to patching. Parents should be supported to reattempt occlusion if patching has previously failed. Follow up for children receiving patching should be with video or telephone call. Reduction or cessation of patching treatment may be appropriate for certain patients.[235]

A position statement from the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions provides recommendations for the triage of patients referred for transcatheter aortic valve replacement (TAVR) during the pandemic.[183] For patients with severe symptomatic aortic stenosis (AS), TAVR should be considered to decrease the risk for clinical deterioration, prolonged hospital stay, or repeat hospitalization. Data are not robust enough for clear recommendations for patients with minimally symptomatic severe to critical AS; however, urgent TAVR or close outpatient virtual monitoring may be considered. Particularly high peak or mean gradient, very small calculated aortic valve area and very low dimensionless index warrant consideration of TAVR. For asymptomatic patients, consideration of TAVR may be postponed for 3 months or until elective procedures are resumed. Close outpatient monitoring should continue for all patients with severe AS.

The British Heart Valve Society has published recommendations for the outpatient management of heart valve disease following the COVID-19 pandemic. They recommend that patients with severe symptomatic AS and advanced heart failure, impaired ventricular function (left ventricular (LV) ejection fraction of <50%) or syncope are the highest clinical priority and ideally require valve intervention within 2 weeks and no more than 4 weeks. Interventions for AS include surgical aortic valve replacement (sAVR) or transcatheter aortic valve implantation (TAVI), and currently the benefits of sAVR versus TAVI should be considered for each patient, taking into account the requirement for general anesthesia and intensive care unit admission, length of stay in hospital and risk of peri-procedural exposure to COVID-19.[236]

The definitive treatment options for severe aplastic anemia (AA) are stem cell transplant or immunosuppressive therapy. The American Society of Hematology advise that for patients with absolute neutrophil count (ANC) <200/microlitre (very severe AA) the risk of delaying transplant or immunosuppressive therapy outweighs the risks of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during hospitalisation or the impact of immunosuppression on the course of infection, but that optimal management may not currently be practical.[237]

Immunosuppressive treatment options are antithymocyte globulin (ATG), cyclosporine, and eltrombopag; administration of ATG requires hospitalization. The American Society of Hematology, the European Society for Blood and Marrow Transplantation, and NHS England have released statements recommending the use of eltrombopag, with or without cyclosporine, as bridging treatment to stem cell transplant or immunosuppressive therapy with ATG for patients with severe or very severe AA during the COVID-19 pandemic.[237][238][239]

Trials of SARS-CoV-2 vaccination in patients with hematological conditions are lacking. Such patients are likely to have an attenuated response to vaccination. Additional measures, such as early vaccination of household contacts, may be considered.[230] The American Society of Hematology advises that the benefits of COVID-19 vaccination outweigh the risks in patients with AA, particularly those with additional risk factors for severe COVID-19 disease, though some patients receiving immunosuppressive therapies may not mount an appropriate immune response to the vaccine.[237]

The Global Initiative for Asthma (GINA) reports that people with asthma do not appear to be at increased risk of acquiring COVID-19 and that people with well-controlled, mild-to-moderate asthma are not at increased risk of severe COVID-19.[240] GINA also reported that people with well-controlled asthma are not at increased risk of death from COVID-19 overall; however, people who recently needed oral corticosteroids for their asthma did have an increased risk of COVID-19-related death.[240] Additional studies have found that patients with severe asthma (treated with 3 different classes of medication) have an increased risk of hospitalization, intensive care admission, and death from COVID-19.[241][242] A rapid systematic review by the World Health Organization found that the current evidence on association between asthma and increased risk of COVID-19 infection or severe outcomes was unclear and that more studies are needed.[243] Among people with asthma and COVID-19, risk factors for worse outcomes were comorbid chronic obstructive pulmonary disease, nonallergic asthma, nonwhite ethnicity, and older age.[243]

Patients should continue taking their prescribed asthma medication as usual, including inhaled and oral corticosteroids and biologic therapy.[240][244][245][234][246][247] GINA advises that all patients should have a written action plan so they know how to recognize worsening asthma, how to increase reliever and controller medications, and when to seek medical help.[240] GINA advises that nebulizers should be avoided for acute attacks due to the risk of transmitting respiratory viral particles, and that a pressurized metered-dose inhaler and spacer with mouthpiece or tightly fitting facemask can be used to deliver a short-acting beta-2 agonist instead.[240] The US Centers for Disease Control and Prevention advises that nebulizer administration may generate infectious aerosols; however, it is unclear whether association between nebulizer administration and infection is due to the generation of infectious particles or the close contact between the patient and healthcare professional administering the nebulizer.[248] However, UK guidelines advise that nebulizers may continue to be used, as the aerosol comes from the fluid in the nebulizer chamber and will not carry virus particles from the patient.[240][244] GINA advises that where community transmission of SARS-CoV-2 is occurring, spirometry and peak-flow measurement within healthcare facilities are postponed unless there is an urgent need.[240] UK guidelines currently advise that bronchoscopy and most pulmonary function tests such as spirometry should only be done for urgent cases and if the results will have a direct impact on patient care.[244] Strict infection control precautions should be followed if spirometry is urgently required.[240]

Patients should ensure they have a sufficient supply of medication at home, but should not stockpile. Patients may be reminded that they should not share inhalers or spacers with others. Clinicians should encourage smoking cessation.[234]

Advise patients that COVID-19 may present with symptoms similar to an asthma attack (e.g., cough, shortness of breath); however, additional symptoms such as fever, fatigue, and change in taste or smell are more likely to suggest COVID-19 infection.[249] A large prospective cohort study reported that 1 in 7 patients aged 16-49 years with COVID-19 presented with wheeze.[250]

In studies of patients hospitalized with COVID-19, asthma does not appear to be an independent risk factor for intubation.[251] Patients with asthma who are aged 16 years and older have more severe disease on presentation to hospital, and are more likely to require critical care, noninvasive ventilation, and oxygen compared with patients without asthma. In patients aged 50 years and older with asthma, ICS use within 2 weeks of hospital admission was associated with decreased mortality compared with patients without an underlying respiratory condition.[241]

GINA reports that in 2020, there was a reduction in asthma exacerbations in many countries.[240] Emergency department attendances and hospital admissions for asthma decreased significantly in Scotland and Wales during the first 2020 lockdown. Prescriptions for inhaled and oral corticosteroids increased significantly before lockdown in Wales, suggesting that improved adherence to preventative treatment and self-management of exacerbations may have contributed to this change. Reduced circulation of other respiratory viruses, decreased air pollution, and changes in smoking habits during lockdown may also have contributed to the decrease.[252] In England, primary care attendances for asthma exacerbations decreased during the first 2020 lockdown, but there was no significant decrease in exacerbations requiring a hospital visit.[253]

GINA recommends COVID-19 vaccination for people with asthma, following the usual vaccine precautions.[240] For people with severe asthma receiving biologic therapy, the COVID-19 vaccine and the biologic therapy should not be given on the same day.[240]

The European ADHD guidelines group have published guidance for management of patients with ADHD during the COVID-19 pandemic. Service provision should continue using telehealth where possible. Parents or carers are encouraged to use behavioral parenting strategies and schools are advised to prioritize monitoring of students with ADHD. Patients should be offered the opportunity to start on medication, if indicated, following an initial assessment. Patients who are already established on medication should continue taking it as prescribed. Parents and patients should not increase medication doses above the dose prescribed to manage the stress of confinement. Routine cardiovascular examination and face-to-face monitoring can be deferred for individuals without any cardiovascular risk factors. Home blood pressure and heart rate monitoring is recommended.[254]

A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[44] UK, European, and US guidelines advise against making anticipatory adjustments to immunosuppressive drugs in patients without COVID-19.[57][58][59] Doing so may cause a flare of autoimmune hepatitis (AIH). Budesonide may be considered to induce remission in patients without cirrhosis who have a flare of AIH, to minimise systemic corticosteroid exposure.[59]

The American Association for the Study of Liver Disease (AASLD) advises that immunosuppressive therapy should be commenced in patients with AIH, with or without COVID-19.[58] The risks and benefits of starting a new drug (including need to start treatment during the COVID-19 pandemic, risk profile, feasibility of monitoring and review, and route of administration) should be considered.[57]

If a patient develops COVID-19, the AASLD advises that clinicians consider reducing doses of immunosuppressants, particularly azathioprine and mycophenolate, based on general principles for managing infections in immunosuppressed patients and to decrease the risk of superinfection.[58] Adjustment should be individualized and will depend on the severity of COVID-19. If a patient is taking corticosteroids and develops COVID-19, corticosteroid dosing must be sufficient to prevent adrenal insufficiency.[59] Corticosteroids should not be stopped suddenly.

COVID-19 may cause abnormal liver function tests in patients with AIH; these should not be attributed to a disease flare without biopsy confirmation.[58]

A joint statement from the British Society of Gastroenterology, British Association for the Study of the Liver, NHS Blood & Transplant, and British Liver Trust advises that patients with autoimmune hepatitis should consider SARS-CoV-2 vaccination with any of the available vaccines.[255]

A European observational study reported an unadjusted mortality rate of 15.2% for patients with breast cancer and COVID-19. Overall mortality in patients with cancer and COVID-19 was higher in male patients, patients ≥ 65 years and patients with ≥2 comorbidities.[71] Among newly diagnosed patients, African-American patients are more likely to develop COVID-19 than white patients.[74]

The American Society of Breast Surgeons has released recommendations for the prioritization, treatment, and triage of patients with breast cancer during the COVID-19 pandemic.[256] The highest-priority conditions for treatment during the pandemic are:

- Potentially unstable breast disease (e.g., hematoma, infection): assessment and surgery

- New diagnosis of invasive breast cancer (may be suitable for telemedicine)

- Surgery: revision of ischemic mastectomy flap; revascularization/revision of autologous tissue flap

- Chemotherapy: neoadjuvant/adjuvant chemotherapy for triple-negative and HER2-positive breast cancer; early chemotherapy likely to improve outcomes in metastatic disease; completion of adjuvant/neoadjuvant chemotherapy that has already started; adjuvant or metastatic endocrine therapy

- Radiation therapy for painful, inoperable breast masses; continuation of radiation therapy that has started; treatment for critical metastatic lesions (e.g., brain metastasis, spinal cord compression).

UK guidelines recommend giving highest priority to patients receiving:[76]

Curative systemic anticancer treatment with a high (more than 50%) chance of success

- Adjuvant or neoadjuvant systemic anticancer treatment that adds at least 50% chance of cure to surgery or radiation therapy alone or treatment given at relapse.

- The UK Association of Breast Surgery has published recommendations for delivering breast services during the pandemic. New referrals should be triaged and patients should be contacted before clinic attendance. Patients with COVID-19 symptoms should self isolate for 7 days and their appointment deferred until after self isolation. Patients should be seen in person where there is a strong suspicion of cancer; patients with low suspicion of cancer (e.g., breast pain, or bilateral nipple discharge in a woman <30 years) may be contacted by telephone and considered for deferred imaging. Frail, older patients with comorbidities or who require residential care are at highest risk from COVID-19. Therefore, these patients should not be seen in person. Empiric letrozole treatment may be considered. Follow-up for existing patients should be performed by telephone where possible.[257]

Capacity for surgery is limited in many hospitals. The Association of Breast Surgery suggests prioritising patients in the following order:[257]

1. Estrogen receptor (ER) negative

2. Human epidermal growth factor receptor 2 (HER2) positive

3. Premenopausal patients

4. Postmenopausal, ER positive patients with high risk disease (grade 3 or node positive)

5. Large areas of high grade ductal carcinoma in situ (DCIS)

6. Postmenopausal, ER positive patients with lower risk disease

7. Remaining patients with DCIS

Neoadjuvant chemotherapy should only be given where it is clear that chemotherapy is indicated, and would be given in the adjuvant setting. Neoadjuvant chemotherapy should be routinely supported with granulocyte-colony stimulating factor during the pandemic. Multidisciplinary team discussion is recommended for all cases.[258][81]

COVID-19 vaccination is associated with a higher incidence of axillary lymphadenopathy on breast MRI. Guidelines have been published to help avoid biopsies of reactive nodes. MRI-detected, unilateral, axillary lymphadenopathy ipsilateral to the vaccination arm is most likely to be COVID-19 vaccination-related if within 4 weeks of either dose. A follow-up ultrasound 6 to 8 weeks after the second vaccine dose is recommended.[259]

Further oncology resources are available at:

NCCN: COVID-19 resources for the cancer care community external link opens in a new window

ASCO: coronavirus resources external link opens in a new window

ESMO: COVID-19 and cancer external link opens in a new window

Royal College of Radiologists (UK): Coronavirus (COVID-19) cancer treatment documents external link opens in a new window

UK guidance recommends optimizing preventive treatment, including influenza vaccination and palivizumab for eligible children.[260] Key features of assessment are oxygenation, hydration, and nutrition, irrespective of the child’s potential COVID-19 status. High-flow nasal cannula oxygen is an aerosol-generating procedure; a senior clinician should be consulted if its use is being considered. Children who require admission to hospital should be tested for respiratory viruses, including severe acute respiratory syndrome coronavirus (SARS-Cov-2), influenza, and respiratory syncytial virus. Children who require intensive/high-dependency care or surgery should be prioritized for rapid SARS-CoV-2 testing.

In the UK, the criteria for passive immunization against respiratory syncytial virus will be temporarily widened to include a larger population of at-risk pre-term infants, with the aim of decreasing hospitalization and intensive care admission rates.[117]

Interim guidance for the management of patients with neuroendocrine tumors is available from the UK and Ireland Neuroendocrine Tumour Society.[261] Patients already receiving somatostatin analog therapy should continue on their treatment, but delivery of medication and dose intervals may change in order to minimize hospital visits; this is highly individual and decided on a patient-by-patient basis. Patients with highly functional tumors due to start treatment will need initiation of therapy to control their condition. Initiation of therapy in patients with nonfunctioning tumors may be delayed depending on patient fitness and tumor characteristics; again, this is decided on a patient-by-patient basis. Use of chemotherapy and peptide receptor radiotherapy should also be individualized, with the risks and benefits of starting or continuing considered for eligible patients. Surgery may be considered where it is life-saving or potentially curative.

Giving CPR poses a high risk to healthcare workers in the context of COVID-19 due to the aerosol-generating procedures, close proximity of multiple healthcare workers and the patient, and the need to work quickly.

If cardiac arrest is recognized (patient is unresponsive and breathing abnormally) look for breathing, but do not open the airway or listen/feel for breathing by placing the face close to the patient's mouth.[262][263][264]

In acute hospital settings, full Aerosol Generating Procedure (AGP) Personal Protective Equipment (PPE) must be worn by all members of the resuscitation team before entering the room; no chest compressions or airway procedures should be started without full AGP PPE. The number of staff in the room should be restricted, and airway interventions should be done by experienced staff, minimizing aerosolization risk.[262][263][264][265]

In first aid and community settings, lay-rescuers should perform compression-only resuscitation and defibrillation (where there is access); a cloth may be placed over the patient's mouth and nose if there is a perceived risk of infection. Pediatric cardiac arrest is more likely to be caused by a respiratory problem, and ventilation is vital; lay-rescuers may consider that the risk of not giving rescue breaths could be greater than the risk of transmission of COVID-19.[262][263][264][265]

In-water mouth-to-mouth resuscitation should not be performed on drowned patients. Rescuers should prioritize removal from water where PPE and first aid equipment can be used. Rescuers should wear gloves, facemask and eye protection for all resuscitations. Two-person bag-filter-mask ventilation using a high-efficiency particulate arrestance (HEPA) filter is preferred. If this is not possible, mouth-to-mask ventilation with HEPA filter is the second line technique and passive oxygenation is third line. If rescuers cannot follow this guidance, they should provide compression only CPR and cover the patient’s nose and mouth with a cloth.[266]

Brazilian guidelines recommend beginning continuous chest compressions to deliver CPR to adults. The patient’s oral cavity should be sealed with a cloth or a mask providing low flow (6-10 liters/minute) oxygen before starting chest compressions; the seal should be kept in place until an invasive airway is secured. Bag-valve-mask or bag-valve tube ventilation should be avoided if possible; if it is needed, two rescuers should provide ventilation (to allow a two-handed seal around the mask) and an oropharyngeal airway should be used. A HEPA filter should be placed between the mask and bag. If the patient is prone at the time of cardiac arrest and does not have an invasive airway, they should be repositioned supine. If the patient is intubated, chest compressions should be delivered while prone. Resuscitation of children should ideally be with chest compressions and use of a bag-valve-mask apparatus with a HEPA filter until a definitive airway is established.[267]

International Liaison Committee on Resuscitation: COVID-19 Practical Guidance for Resuscitation. external link opens in a new window

European Resuscitation Council: COVID-19 and resuscitation. external link opens in a new window

The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) advises that a biopsy-sparing approach to diagnosis can be used in more children with suspected celiac disease during the pandemic, to mitigate potential delays in diagnosis and treatment caused by reduced access to endoscopy. A biopsy-sparing approach can be used for children who have positive endomysial antibodies and a tissue transglutaminase IgA titer between 5 and 10 times the upper limit of normal.[268]

Patients with cerebellar ataxia (CA) may be at higher risk from serious COVID-19 infection as they are likely to be older, and also because of the neurologic complexities of their underlying disorder and comorbid medical illnesses.[269] Recommendations suggest that patients with immune ataxias continue their therapies (including intravenous immune globulin, corticosteroids, plasma exchange), but they are considered high risk and should follow local advice on physical distancing.[269] Patients with symptoms of infection may be instructed to stop immunosuppressive therapies until they have fully recovered. Starting patients on immunotherapies may also be delayed, but balanced against the risk of not starting, particularly in patients with rapidly progressive immune-mediated ataxias.[269] Decisions for patients with CA who are hospitalized with COVID-19 should involve the ataxiologist.

Patients with heart failure have a significantly increased risk of death if they develop COVID-19.[75] One cohort study investigated outcomes for patients with a history of heart failure (≥1 hospitalization or ≥2 outpatient visits for heart failure) who were admitted to hospital with COVID-19. In-hospital mortality was 24.2%. Male sex, class III obesity, and increasing age were associated with increased risk of in-hospital mortality.[270]

Patients with chronic heart failure are prone to developing acute heart failure after a diagnosis of COVID-19.[271] European guidelines recommend using the same treatment strategy for acute heart failure in patients with COVID-19 as for patients without COVID-19.[272] One observational study reported that discontinuation of medical therapy for chronic heart failure (ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists) in patients with COVID-19 was associated with increased mortality. The authors recommend that even if these medications are reduced or discontinued during the acute illness, they should be reintroduced at discharge whenever possible.[271]

People of any age with chronic kidney disease (CKD) are at increased risk of severe illness and death from COVID-19.[273][274][275][276] One meta-analysis reported a hazard ratio of 3.6 for COVID-19-related mortality in patients with chronic kidney disease.[70] The UK National Institute for Health and Care Excellence has published guidelines for managing patients with CKD during the COVID-19 pandemic. Patients should be advised to continue taking their usual medications, even if they have symptoms of COVID-19, unless directed otherwise by a healthcare professional. This includes ACE inhibitors, angiotensin-II receptor antagonists, immunosuppressants, and diuretics. Patients should be advised to keep a list of their medications, other medical conditions, and allergies and a copy of a recent clinic letter to give to healthcare staff if they need treatment for COVID-19. Clinicians should review the medication of any patients diagnosed with COVID-19, taking into account whether any have the potential to adversely affect renal function. When deciding whether to admit a patient who has CKD and COVID-19 to the hospital, clinicians should consider the patient's wishes, the severity of CKD, any comorbidities, whether the patient is taking any immunosuppression, the risks and benefits of admission, and how the care that can be offered in hospital compares with care that can be offered at home. All patients with advanced CKD should have the opportunity to participate in advance care planning.[277]

After recovery from COVID-19, renal function should be reassessed. The urgency of assessment should be based on the patient's glomerular filtration rate (eGFR) category, comorbidities, and clinical circumstances.[277]

Urgent outpatient appointments are needed for: patients with accelerated progression of CKD (a sustained decrease in GFR of 25% or more and a change in GFR category in the preceding 12 months, or a sustained decrease in GFR of 15 mL/min/1.73 m² per year); nephrotic syndrome or very severe proteinuria (urinary albumin:creatinine ratio >300 mg/mmol; or a new diagnosis of GFR category G5 (GFR <15 mL/min/1.73 m²). Clinicians should seek specialist advice if the urgency of referral is unclear. Renal ultrasound should be performed if the result might change immediate management, for example, in patients with accelerated progression of CKD, visible or persistent invisible hematuria, symptoms of urinary tract obstruction or a nephrologist has identified an urgent need for renal biopsy. Patients who will be starting dialysis should have procedures to establish vascular or peritoneal access.[224][277]

Patients who have stable renal function may be able to increase the interval between blood and urine testing, depending on comorbidities and whether their CKD is progressive. Clinicians should encourage self-monitoring and self-management where patients are able to do so, for example, patients may monitor their blood pressure at home and access parts of their medical record online. If patients are self-monitoring or self-management, they should receive clear instructions on when to seek help and who to contact. Non-urgent referrals, for example, patients with mild to moderate proteinuria and a stable GFR, may be delayed to reduce risk from COVID-19. Renal ultrasound may be deferred if the result is unlikely to change management immediately, for example, exclusion of polycystic kidney disease in patients with a family history of the condition, if a nephrologist has identified a possible need for non-urgent renal biopsy or the patient has a GFR of <30 mL/min/1.73m² that has been stable for at least 6 months.[277]

US and international guidelines recommend that patients with fever or respiratory symptoms should be asked to contact the unit before arrival and should be isolated and tested for COVID-19 on arrival.[278][279] Patients should also report any close contact with persons with severe acute respiratory syndrome coronavirus 2 infection in the past 14 days.[279] Each patient should have their temperature monitored on arrival and confirm the absence of symptoms of COVID-19. Patients should wear their own mask while in the facility. If they are not wearing their own on arrival, they should be offered a medical facemask as supplies allow.[279]

UK guidelines recommend that patients should be screened before each episode of dialysis to assess whether they are known or suspected to have COVID-19, or have been in contact with someone who has confirmed COVID-19. Patients who might have COVID-19 should be tested, ideally using a rapid turnaround test. They should be assessed for alternative causes for their symptoms and whether dialysis could be delayed until their test results are known.[224]

US guidelines advise that a distance of 6 feet should be maintained between patients in the waiting area and during dialysis, especially in areas of moderate to substantial community transmission. Patients may prefer to wait in their vehicle and receive a message when it is their turn to enter the dialysis unit.[224][279]

Patients with fever should receive dialysis in the last shift of the day until COVID-19 infection is excluded.[278] Consideration should be given to cohorting patients with suspected or confirmed COVID-19 with the same healthcare professional, in the same section of the unit, at the same time.[279] UK guidelines recommend that patients should receive dialysis in cohorts, according to their COVID-19 status. If a patient tests positive for COVID-19, they should remain in that cohort for 10 days or until their symptoms resolve, whichever is the longer.[224]

Healthcare professionals should follow recommended infection control precautions.[224][279]

UK guidelines advise clinicians to consider the use of potassium binders, such as patiromer or sodium zirconium cyclosilicate, to treat hyperkalemia or support delaying the start of dialysis.[224] Patients who receive home dialysis and their caregivers and assistants should be tested if they develop symptoms.[224]

Kidney transplant recipients are at higher risk of severe illness.[273] They are advised to take particularly strict infection prevention and social distancing precautions.

UK guidelines advise clinicians to refer patients for renal transplant where indicated, but explain that some of the tests and assessments may be delayed during the COVID-19 pandemic.[277]

Experts in China have published consensus recommendations for management of children receiving chronic dialysis during the COVID-19 pandemic. Caregivers should promptly report any sign of illness in a patient or family member to the dialysis unit. If a family member has a history of exposure to COVID-19, they should be isolated from the patient. If the patient has fever and/or respiratory symptoms with COVID-19 exposure, evaluation at a hospital or fever clinic should be arranged. Only one caregiver should accompany the patient to hemodialysis. The patient and accompanying person should be screened for symptoms of COVID-19 and have their body temperature checked outside the dialysis centre. The patient should wear a general disposable surgical mask while undergoing dialysis; respirator or filtering facepiece masks are not recommended. Patients with suspected or confirmed COVID-19 should be quarantined and receive dialysis in an isolation room or area if possible. If isolation is not possible, the patient should receive dialysis during the last session of the day. The patient should be isolated until they are symptom free, apyrexial and 14 days have elapsed since symptom onset. Recommendations are also given for managing the home environment for peritoneal dialysis.[280]

Analysis of US health-insurance claims data has shown that leukemia is a significant risk factor for fatal COVID-19.[75] Older age is associated with increased severity of COVID-19 in patients with chronic lymphocytic leukemia (CLL).[281] The American Society of Hematology recommends postponing treatment initiation for CLL in areas where COVID-19 is active. If immediate therapy is needed, treatments that can be provided in an outpatient setting with fewer clinic visits are preferred. Treatment with monoclonal antibodies should be avoided, especially in combination with targeted agents, and initiation of venetoclax should be avoided if possible.[282] Immune globulin replacement may be continued in highly selected patients where the potential benefits are outweighed by the risks of visiting a clinic for the infusion. Intravenous immune globulin can be continued in those who have COVID-19, but requires close monitoring for thromboembolic events. Patients who are already receiving treatment for CLL and have COVID-19 with mild symptoms should generally not have their treatment modified. Treatment may be modified in patients with more severe symptoms depending on the aggressiveness of CLL, history of infections, and the risk of more severe COVID complications; decisions are made on a case-by-case basis, but generally monoclonal antibodies are withheld in patients with COVID-19. Treatment with ibrutinib and acalabrutinib should be continued in patients diagnosed with CLL and COVID-19.[282]

Recommendations from Australia and New Zealand also advise delaying therapy where possible during the pandemic.[283] If therapy is considered essential, then oral therapies should be considered where available.

There are limited data on trials of severe acute respiratory syndrome coronavirus 2 vaccination in patients with hematological conditions. Such patients are likely to have an attenuated response to vaccination. One study of the BNT162b2 mRNA COVID-19 vaccine in patients with CLL found the antibody response was reduced compared with healthy controls and affected by disease activity and treatment.[284] Relatively low antibody responses were seen in patients treated with Bruton's tyrosine kinase inhibitors or venetoclax alone or in combination with antiCD20 antibody. Additional measures, such as early vaccination of household contacts, may be considered.[230]

Analysis of US health-insurance claims data has shown that leukemia is a significant risk factor for fatal COVID-19.[75] The American Society of Hematology has published recommendations on the management of chronic myelogenous leukemia (CML) during the COVID-19 pandemic.[285] Treatment with tyrosine kinase inhibitors (TKI) is not immunosuppressive and should not be interrupted in patients without COVID-19 infection receiving treatment, or delayed in those with newly diagnosed CML. Some TKIs may have pulmonary side effects and stopping therapy may be considered in affected patients who have COVID-19. Patients in remission should be monitored as normal where possible. Remote monitoring or less-frequent monitoring may be considered where local conditions change. Patients in the chronic phase of CML are not at higher risk of COVID-19 infection, and those that do have COVID-19 infection may not be at higher risk of more severe disease. Possible drug-drug interactions should be reviewed in patients being treated for COVID-19.

Trials of severe acute respiratory syndrome coronavirus 2 vaccination in patients with hematological conditions are lacking. Such patients are likely to have an attenuated response to vaccination. Additional measures, such as early vaccination of household contacts, may be considered.[230]

Patients with COPD are at higher risk for severe COVID-19 illness and death, and should carefully follow public health advice.[274][286][241][287] The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends that patients with COPD who have new or worsening respiratory symptoms, fever, and/or any other possible COVID-19-related symptoms should be tested for severe acute respiratory disease coronavirus 2 (SARS-CoV-2), even if the symptoms are mild.[288] A large prospective cohort study found that patients aged 50 years and older with COPD, with or without asthma, were more likely to require supplemental oxygen and noninvasive ventilation, but less likely to receive invasive mechanical ventilation or critical care compared with patients without a respiratory condition. Mortality in this group exceeded 40%.[241]

National and international respiratory organizations advise that patients should maintain their regular treatment and that there is currently no evidence to recommend avoiding corticosteroids (inhaled or oral) in patients with COPD during the COVID-19 pandemic.[246][289]

UK guidelines also advise that patients established on inhaled corticosteroids should delay any planned withdrawal.[290]

Exacerbations of COPD should be managed by the patient following their individualized plan, and there should be no change to advance prescribing of rescue antibiotics and corticosteroids. Patients should not start rescue antibiotics and corticosteroids to treat symptoms of COVID-19, and should not start prophylactic antibiotics to reduce risk.[290][291] Canadian guidelines recommend that patients with COPD who develop COVID-19 should continue their usual inhaled maintenance therapy and that acute exacerbations of COPD should be treated with prednisone if needed, irrespective of whether the exacerbation is triggered by SARS-CoV-2.[245] Patients already taking prophylactic antibiotics should continue to take them as prescribed (unless there is a new reason to stop, such as side effects).[290] 

To reduce the risk of acute exacerbations, and a poorer outcome from COVID-19 infection, strongly encourage patients who are still smoking to stop.[290][291]

Patients receiving oxygen therapy should continue as advised, and those using airway clearance techniques should also continue but should take additional precautions to protect family members, as inducing sputum may generate infectious aerosols.[290] Precautions are also advised for those receiving noninvasive ventilation at home, as this is also a potentially infectious aerosol-generating procedure.[290] UK guidelines advise that nebulization is not considered a viral aerosol-generating procedure and may continue to be used, as the aerosol comes from the fluid in the nebulizer chamber and will not carry virus particles from the patient.[290] However, GOLD does consider nebulization to have an increased risk of droplet generation and disease transmission.[289] The US Centers for Disease Control and Prevention advises that nebulizer administration may generate infectious aerosols, however it is unclear whether association between nebulizer administration and infection is due to the generation of infectious particles or the close contact between the patient and healthcare professional administering the nebulizer.[248]

GOLD recommends that during periods of high COVID-19 prevalence, spirometry is restricted to patients requiring urgent diagnosis of COPD, and/or to assess lung function prior to interventional procedures or surgery.[289]

The British Thoracic Society has developed online pulmonary rehabilitation resources for patients to use while face-to-face meetings are not possible and a resource pack for patients who survive COVID-19.[292]

One study in Singapore reported a significant and sustained decrease in hospital admissions for acute exacerbations of COPD, including respiratory virus infection-associated acute exacerbations, during the pandemic, which coincided with the introduction of public health measures such as social distancing and universal mask-wearing.[293]

A panel of experts from North America and Europe has developed recommendations to guide management of chronic pain during the pandemic.[294] The panel recommend the use of telemedicine as the first approach and exclusively in most cases. Opioids may continue to be prescribed or initiated and patients should be informed of the potential risks and impact of long-term opioid use on the immune system. Patients who regularly use nonsteroidal anti-inflammatory drugs (NSAIDs) should continue, while being monitored for adverse effects, and patients should promptly report any mild fever or new myalgia. Use of corticosteroids increases the potential for adrenal insufficiency and altered immune response; clinicians should consider the risks and benefits of corticosteroid injections and use a decreased dose.[294] Insertion of new intrathecal pumps should be avoided, except for highly selected cancer patients where the benefit outweighs the risk. New neurostimulator trials or implants should also be avoided.

Studies have found no association between use of NSAIDs and worse outcomes in patients with COVID-19; one prospective multicentre study in the UK in patients hospitalized with COVID-19 found that those taking NSAIDs before admission had the same outcomes as those who did not.[295]

The European Academy of Allergy and Clinical Immunology advise that patients with chronic rhinosinusitis should continue to take intranasal corticosteroids at their individually prescribed dose and should not modify or stop treatment without consulting their physician.[296] There is no evidence that the use of intranasal corticosteroids in the approved dose and indications leads to increased risk of COVID-19 infection or a more severe disease course. Discontinuation of intranasal corticosteroids can lead to worsening of chronic sinusitis. Systemic corticosteroids should be used with caution during the pandemic and in patients with severe symptoms and no therapeutic alternative. Patients with severe chronic rhinosinusitis with nasal polyps should be considered for systemic corticosteroids if surgery is not possible; patients should quarantine themselves during the course of treatment, and for one week afterwards.[296]

Physicians should assess the risks and benefits of initiating biologics in low-risk patients; biologic therapy may be deferred in high-risk patients during the pandemic. Patients who do not have COVID-19 and are already receiving biologic therapy may continue following a risk/benefit assessment; there is insufficient evidence to recommend discontinuation. Physicians should discontinue or postpone biologic therapy in patients who test positive for COVID-19.[296][297]

Patients with chronic liver disease have a higher mortality rate from COVID-19 infection, and mortality is associated with liver disease severity.[58][59] European guidelines advise that patients who have cirrhosis and COVID-19 should be admitted to the hospital for inpatient care. Such patients are at high risk of new or worsening hepatic decompensation, severe COVID-19, and death.[59] Patients with cirrhosis and portal hypertension should avoid nonsteroidal anti-inflammatory drugs. Care should be taken to avoid acetaminophen overdosing in patients with cirrhosis.[298] Guidelines to prevent complications should be followed closely for patients with decompensated cirrhosis. Vaccination against Streptococcus pneumoniae and influenza is recommended. Treatment for complications (e.g., spontaneous bacterial peritonitis, hepatic encephalopathy, ascites) should be continued.[59] Organ donations and transplants are likely to be reduced in many countries. Liver transplant services should be restored following the peak of the pandemic, wherever possible. Where resources remain limited, listing for transplantation should be restricted to patients with poor short-term prognosis, including those with acute liver failure, acute-on-chronic liver failure, a high model for end-stage liver disease (MELD) score, and hepatocellular carcinoma at the upper limits of the Milan criteria.[59]

Transient elastography may reduce the need for endoscopic screening for varices in some patients with cirrhosis. Non-invasive assessments including the Baveno VI criteria, platelet-to-liver stiffness measurement ratio, liver stiffness measurement and spleen stiffness measurement have good predictive value for clinically significant varices and to identify patients at risk of bleeding. Screening for varices should balance the risks of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) transmission from endoscopy against the risk of bleeding. Testing for SARS-CoV-2 is recommended before endoscopy. Endoscopy should not be delayed if the patient is negative for SARS-CoV-2 and the burden of COVID-19 in the local area is low.[59] Endoscopic eradication of esophageal varices should be performed following a variceal bleed.[68] Patients with cirrhosis are likely to have an attenuated response to SARS-CoV-2 vaccination; nevertheless, experts recommend priority vaccination for these patients because of the high COVID-19-related mortality in patients with decompensated cirrhosis.[299] A joint statement from the British Society of Gastroenterology, British Association for the Study of the Liver, NHS Blood & Transplant, and British Liver Trust advises that patients with chronic liver disease should consider SARS-CoV-2 vaccination with any of the available vaccines.[300]

As there is a potential risk of transmission of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) via fecal microbiota transplantation (FMT), the US Food and Drug Administration (FDA) has made the following new recommendations for stool donated after 1 December 2019:[301]

- Screen donors to identify those who may be currently or recently infected with SARS-CoV-2.

- Test donors and/or donor stool for SARS-CoV-2, if possible.

- Patients should give informed consent after being advised about the potential risk of transmission of SARS-CoV-2 via FMT.

Stool used for FMT should have been donated before 1 December 2019 if these criteria are not met.

Fever, cough and shortness of breath may be symptoms of fungal pneumonias, including coccidioidomycosis, histoplasmosis and blastomycosis. Fungal pneumonias may be indistinguishable from COVID-19 and bacterial pneumonias. The diagnosis should be considered if SARS-CoV-2 testing is negative, although coinfection with fungi and SARS-CoV-2 may occur.[302]

The National Health Service in England has approved use of the immunotherapies nivolumab and pembrolizumab as alternatives to chemotherapy during the pandemic. Nivolumab and pembrolizumab may be used in patients with metastatic colorectal cancer with high levels of microsatellite instability or deficient mismatch repair in order to reduce number of hospital visits and the risk of neutropenia.[79] Intermittent treatment with chemotherapy regimens containing cetuximab or panitumumab may be used to reduce the need for immunosuppressive treatment.[79]

Antibiotics should be started as soon as possible for patients in the community with suspected or confirmed secondary bacterial pneumonia. Patients should be advised to seek urgent medical help if their symptoms do not improve as expected, or rapidly or significantly worsen, regardless of whether they are taking an antibiotic. Antibiotics should not be used to prevent secondary bacterial pneumonia.[121]

There are no validated tests for assessing dyspnea by telephone or video consultation.[303] UK guidelines recommend that you should assess the need for hospital admission based on the patient's symptoms and signs. Indicators of more severe illness include: severe shortness of breath at rest or difficulty breathing; hemoptysis; cyanosis; cold, clammy, pale, or mottled skin; syncope; new confusion or difficult to rouse; and little or no urine output.[121]

Tests including respiratory and blood cultures, severe acute respiratory disease coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR), throat samples for respiratory viral and atypical pathogen PCR, chest imaging, full blood count, and urinary legionella and pneumococcal antigen tests are recommended for patients admitted to hospital, to help identify secondary bacterial pneumonia and guide decisions about antibiotic use.[121] High C-reactive protein (CRP) levels do not distinguish between bacterial and COVID-19 pneumonia, but low CRP levels make secondary bacterial pneumonia less likely.[121]

Empiric antibiotics should be started if there is clinical suspicion of secondary bacterial infection in patients with COVID-19 in hospital.[121] Antibiotic treatment should be started within 4 hours of diagnosis and within 1 hour if the patient has suspected sepsis.[121] Choice of antibiotic will depend on local resistance data and availability. Specialist advice on antibiotic choice is recommended for patients who are immunocompromised, pregnant, in critical care, or who have a history of infection with resistant organisms or repeated infective exacerbations of lung disease.

Use of antibiotics should be reviewed at 24-48 hours, or as soon as test results are available. A narrower spectrum antibiotic should be used, if appropriate. Antibiotic treatment should stop after five days, unless there is an indication to continue.[121] Patients should be reassessed if they do not improve as expected, or if symptoms become significantly or rapidly worse. Specialist advice should be sought if there is clinical or microbiological evidence of infection and the person’s condition does not improve after 48-72 hours antibiotic treatment, or if an infection with multidrug-resistant bacteria is suspected.[121]

Where possible, clinicians should discuss the benefits, risks, and likely outcomes of any treatment with the patients, their relatives, and caregivers. The patient's preference about treatment and escalation plans should be sought, and clinicians should enquire about any advance care plans, advance decisions to refuse treatment, or "do not attempt resuscitation" decisions.[121]

World Health Organization guidelines advise that antibiotics should not be prescribed for patients with mild COVID-19 and should only be prescribed for patients moderate COVID-19 if there is clinical suspicion of a bacterial infection.[33]

Fever, cough, and shortness of breath may be symptoms of fungal pneumonias, including coccidioidomycosis, histoplasmosis, and blastomycosis. Fungal pneumonias may be indistinguishable from COVID-19 and bacterial pneumonias. The diagnosis should be considered if SARS-CoV-2 testing is negative, although coinfection with fungi and SARS-CoV-2 may occur.[304]

People with congenital heart disease (CHD) may be at increased risk for more severe COVID-19 infection, particularly those with more severe anatomic and physiologic features of CHD.[305][306] Additional considerations for management have been recommended during the current pandemic with strategies for prevention and management of COVID-19 in adults with CHD based on risk stratification.[307][306] For example, patients in the low risk category (e.g., those with normal ventricular function, normal exercise capacity, no relevant arrhythmia, no pulmonary hypertension) can be advised to take general prevention measures against COVID-19. Low risk patients with mild COVID-19 infection may be cared for at home with remote follow-up, but there should still be a low threshold for hospital admission if there is deterioration/progression or dyspnea. Adults with CHD in the high risk category (e.g., those with cyanotic conditions, univentricular palliated conditions, severe stenosis or regurgitation, severe ventricular dysfunction, or pulmonary arterial hypertension) are advised to follow stricter prevention measures, such as physical distancing. High risk patients with COVID-19 infection generally require hospital admission and involvement of a CHD specialist.

It is recommended that cardiac medications, including aspirin, ACE inhibitors, angiotensin-II receptor antagonists, beta-blockers, diuretics, and antiarrhythmic medications are continued during COVID-19 illness, unless there is a clear contraindication.[305] Clinicians should be aware of the QT-prolonging effects of some COVID-19 medications (e.g., chloroquine or hydroxychloroquine, azithromycin, lopinavir/ritonavir).

Adults with CHD at high risk are advised to follow meticulous physical distancing.[306]

The American College of Obstetrics and Gynecology recommends giving prescription refills for as long as possible to reduce the need for pharmacy visits.[308] UK guidelines advise that a 6- to 12-month course of combined hormonal contraception can be provided without rechecking body mass index and blood pressure.

A 12-month course of a progestogen-only pill can be issued without a face-to-face review.[309] 

Users of depot medroxyprogesterone may be offered ongoing contraception with desogestrel (if it is available as a progestogen-only pill).

Routine removals of long-acting contraception should be postponed and users counseled on contraceptive efficacy past the duration of licensed use.[309][308]

Many new patients can be safely screened and offered a prescription for contraception remotely.[308]

UK guidance recommends that patients who wish to start contraception may be assessed remotely and offered a 6- to 12-month course of desogestrel (as a progestogen-only pill). If desogestrel is not suitable, complete remote assessment of medical eligibility and accurate self-reported blood pressure and body mass index is needed to prescribe combined hormonal contraception.[309]

Self-administered contraception may be offered as a bridge when insertion of long-acting reversible contraception is delayed due to the COVID-19 outbreak.[308]

Provision of long-acting reversible contraception for women who cannot tolerate oral contraception or who take teratogenic drugs should adhere to local infection control protocols.[309]

The American College of Obstetricians and Gynecologists recommends that women should be counseled on the use of emergency contraception, including over-the-counter and prescription options. Clinicians may consider providing advanced prescriptions for emergency contraception, particularly ulipristal.[308]

The Faculty of Sexual and Reproductive Healthcare in the UK recommends that a copper intrauterine device (Cu-IUD) should continue to be offered as first-line emergency contraception, where possible, to eligible patients. If Cu-IUD provision is delayed, additional oral emergency contraception should be offered. If a Cu-IUD is unsuitable or declined, clinicians should perform a remote assessment to determine the most suitable oral emergency contraception. In addition to this, clinicians should prescribe 3 months' supply of desogestrel (as a progestogen-only pill) and provide clear instructions about starting contraception and taking a pregnancy test.[309]

US and UK guidelines emphasize that timely access to abortion should not be compromised during the COVID-19 outbreak. The American College of Obstetricians and Gynecologists (ACOG) advises that gestational age can be assessed remotely for women who have regular periods, a known last menstrual period, and no risk factors for ectopic pregnancy.[308] Assessment, consent, and follow-up can be performed remotely, and medication for medical abortion can be self-administered at home.[308][310] ACOG advises that there is a low risk of rhesus isoimmunization during a medical abortion; rhesus testing and administration of Rho(D) immune globulin should not be a barrier to provision.[308]

A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[44] Patients should be advised to continue their current medications. Medication should only be stopped or reduced in discussion with a specialist. Preventing disease flares is a priority to reduce the risk of corticosteroid use and hospitalization.[311] UK guidelines recommend reviewing the dose, route of administration, and mode of delivery for drugs that affect the immune response to minimise face-to-face contact.[57]

Patients may continue taking aminosalicylates; these drugs do not affect the immune response.[57] Patients receiving immunosuppressive medication may develop atypical symptoms of COVID-19 (e.g., patients who take an oral corticosteroid may not develop fever). Patients who take an oral or rectal corticosteroid should not stop suddenly if they develop COVID-19, due to the risk of adrenal crisis.[57] Patients taking at least 20 mg/day of prednisone should observe shielding precautions.[311] Urgent specialist advice should be sought before stopping or changing medications that affect the immune response in patients with COVID-19.[57]

Testing for COVID-19 is recommended before starting medication for a presumptive inflammatory bowel disease (IBD) flare, because COVID-19 can present with gastrointestinal symptoms and administration of higher-dose corticosteroids to these patients could be detrimental.[312] Testing for COVID-19 is also recommended before initiating biologics, although where possible, initiation should be postponed.[313]

Blood tests to monitor response to therapy should be performed at the minimum safe frequency.[57][311]

International guidelines recommend that patients should stop taking methotrexate, thiopurines, or tofacitinib if they develop COVID-19. Detailed recommendations are given depending on the level of inflammatory bowel disease activity and severity of COVID-19 infection.[314]

If a patient has stopped taking their IBD medication because they have COVID-19, medication can be restarted when at least 10 days have elapsed since symptom onset and at least 3 days have elapsed since recovery. Recovery is defined as the resolution of fever, without use of antipyretics, and an improvement in respiratory symptoms. In patients with severe or critical COVID-19, restarting medication 7-14 days after recovery may be appropriate, depending on the severity of their IBD. If a patient has laboratory confirmed severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection but has not had symptoms, IBD medication can be restarted 10 days after the first test, providing that no symptoms have developed in the interim.[315] Viral shedding may persist after recovery, particularly in immunocompromised patients, therefore experts recommend making decisions to restart medication based on symptoms rather than repeat testing.[315]

Infliximab use is associated with impaired serological response to SARS-CoV-2 infection in patients with inflammatory bowel disease. Concomitant use of methotrexate or a thiopurine further attenuated the serological response.[316]

Elective endoscopic procedures should be deferred, but urgent or emergent endoscopy should continue. This includes cases of IBD where endoscopy would urgently change management: for example, establishing the diagnosis in a patient with signs of moderate to severe inflammation, investigating subacute obstruction if imaging suggests a fibrotic or neoplastic stricture, and therapeutic endoscopic retrograde cholangiopancreatography in patients with primary sclerosing cholangitis who have worsening cholangitis and jaundice.[317][318] International guidelines recommend that surgical management of IBD should be considered in some patients, as delay may result in significant downstream morbidity and mortality; decisions on surgery should be individualized for each patient with a multidisciplinary team.[319]

The British Society of Gastroenterology has published a position statement strongly supporting SARS-CoV-2 vaccination for patients with IBD.[320]

Management of Cushing syndrome is complex and recommendations for clinical practice during the COVID-19 pandemic have been developed by an international group of experts.[321] They advise that patients with active Cushing syndrome are immunosuppressed, and should follow public health advice to minimize their risk of infection.[321] Patients with active Cushing syndrome who develop COVID-19 may not develop fever, and symptoms of dyspnea may be more severe.[322] Cushing syndrome is a hypercoagulable state and anticoagulation with low molecular weight heparin is recommended for hospitalized patients with COVID-19 and Cushing syndrome.[323] Patients with active Cushing syndrome are at risk of prolonged viral infection and secondary bacterial and fungal infection. Prolonged antiviral treatment and empirical antibiotic prophylaxis should be considered for hospitalized patients.[323]

Diagnosis of Cushing syndrome is considered to be challenging at all times, and during the pandemic the guidance recommends prioritizing those with key clinical features, investigating those for whom diagnosis is more likely. Patients with moderate and severe clinical disease require urgent investigation and management as they are prone to developing comorbidities that require hospitalization and have immunosuppression that may make them vulnerable to infection. Investigation should be deferred if clinical features are mild or in doubt; however, treatment of comorbidities such as diabetes and hypertension should be optimized.[321] The guidelines recommend avoiding salivary cortisol/cortisone tests due to potential for viral contamination, until it is known how long severe acute respiratory disease coronavirus 2 (SARS-CoV-2) remains infectious in salivary samples. The usual approach to investigating the cause of Cushing syndrome is significantly modified: immediate computed tomography (CT) scan of thorax, abdomen, and pelvis should be done once Cushing syndrome is confirmed or highly likely to identify cancer, the source of ectopic adrenocorticotropic hormone syndrome, and any major comorbidities; the presence of Cushing disease can be predicted using a combination of clinical factors, such as age, onset of symptoms, and increases in urinary free cortisol and adrenocorticotropic hormone; pituitary imaging by magnetic resonance imaging or CT should be done if there is visual field compromise or severe headaches; all other investigations should usually be avoided during periods of high SARS-CoV-2 viral prevalence as they will not affect specific management.[321] The guidelines recommend that surgery for Cushing syndrome is avoided or altered during periods of high SARS-CoV-2 viral prevalence. Comorbidities should be treated with medical therapy as standard. The guidelines recommend avoiding initiating ACE inhibitors or angiotensin-II receptor antagonists for treatment of hypertension until their influence on susceptibility to SARS-CoV-2 infection is clarified; however, patients established on these should continue. Most patients will have steroidogenesis inhibitors. Patients with severe Cushing syndrome should receive prophylaxis for Pneumocystis jirovecii; symptoms of COVID-19 may be similar to infections such as Pneumocystis jirovecii pneumonia, and differentiation is needed to ensure appropriate treatment.[321]

The European Organisation for Research and Treatment of Cancer has published guidelines on the management of patients with primary cutaneous lymphoma.[324] Patients with indolent or low-risk lymphomas who are on topical or systemic treatment should be consulted remotely to avoid trips to hospital. In some centers, phototherapy may be postponed.[324]

Patients with aggressive or late-stage lymphoma should be treated, because patients with controlled disease have fewer infections. Systemic therapy and radiation should be started if indicated. Treatment with medications including brentuximab vedotin, rituximab, gemcitabine, and extracorporeal photopheresis should be continued. Treatment should not be stopped prophylactically and risk/benefit discussion should take place for each patient. Patients in partial remission, particularly older patients or those with comorbidities, may consider stopping treatment or reducing its frequency.[324]

Patients with cystic fibrosis (CF) are at higher risk for severe COVID-19 illness and should carefully follow public health advice.

UK guidance advises that patients and their families and caregivers should continue with all usual self-care, including airway clearance, regular medication, and home exercise. Exacerbations should be managed as previously advised, including taking rescue medication and contacting their CF team.[325] Patients should be advised to contact their CF team if they have symptoms of COVID-19. It may be difficult to differentiate COVID-19 from pulmonary disease exacerbations at initial presentation.[325]

If the patient is known or suspected to have COVID-19, airway clearance should be done in a well-ventilated room, separate from other people if possible, as it is a potentially infectious aerosol-generating procedure.[325]

UK guidelines advise that nebulizers will not generate infectious aerosols, as the aerosol comes from fluid in the nebulizer chamber, not the patient, so may be used as normal; however, caregivers should use appropriate hand hygiene when helping patients with masks.[325] However, the Global Initiative for Asthma (GINA) does consider nebulization to have aerosol-generating potential - see Asthma, above.[240] The US Centers for Disease Control and Prevention advises that nebulizer administration may generate infectious aerosols; however, it is unclear whether association between nebulizer administration and infection is due to the generation of infectious particles or the close contact between the patient and healthcare professional administering the nebulizer.[248]

Patients are managed remotely where possible. Lung function tests should only be done in the hospital if the results will have a direct impact on management; home spirometry should be used where possible.[325]

Patients with dementia, especially vascular dementia, have increased odds of developing COVID-19 compared with patients without dementia. Black patients with dementia are more likely to develop COVID-19 than white patients with dementia.[326] A US case control study reported that, for patients with COVID-19 and dementia, the risk of hospitalization is almost 60% and 6-month mortality is almost 21%.[326] 

The European Academy of Neurology has published advice for healthcare professionals who look after patients with dementia.[327] Infection with COVID-19 may cause worsening confusion and precipitate delirium or acute cognitive decline.[327][135] A significant change in daily routine during the pandemic may trigger behavioral disturbances, and patients with dementia may be less able to comply with infection prevention measures such as washing hands or wearing a face covering. The following measures may be helpful: looking at old photographs, objects, or newspaper clippings, singing old songs, keeping to a regular schedule, simple exercise such as climbing a flight of stairs, using lighting appropriate to the time of day, going outside to orient a person to the time of day, assisting with hand hygiene, facilitating telephone and video calls from relatives, asking directly about symptoms of infection, and accounting for an individual's cognitive impairment when explaining the pandemic.[327]

Further resources are available at:

Alzheimer's Association: coronavirus (COVID-19) - tips for dementia caregivers external link opens in a new window

Alzheimer Europe: COVID-19 external link opens in a new window

Alzheimer's Society (UK): coronavirus - information for people affected by dementia external link opens in a new window

Alzheimer’s Disease International. ADI offers advice and support during COVID-19 external link opens in a new window

NHS: Dementia wellbeing in the COVID-19 pandemic external link opens in a new window

Patients with type 1 diabetes are at higher risk for severe illness.[273][328] They are more likely to need hospitalization, intensive care, and mechanical ventilation if they develop COVID-19, compared with patients who do not have diabetes, and have a higher case fatality rate and increased odds of in-hospital death with COVID-19.[329][330][331][332][333][276][70][334] Poor glycemic control, hypertension, recent diabetic ketoacidosis, previous stroke, previous heart failure, renal impairment, body mass index <20 kg/m² or ≥40 kg/m², male sex, older age, nonwhite ethnicity, and socioeconomic deprivation are associated with increased mortality from COVID-19.[335][336][337] Although prevalence of diabetes is lower in patients <50 years, one study found that younger patients with diabetes have an increased relative risk of fatal outcomes compared with older patients.[338] Patients with COVID-19 infection are at greater risk of hyperglycemia with ketones, including patients with newly diagnosed diabetes. COVID-19 disease can precipitate atypical presentations of diabetes emergencies (e.g., mixed diabetic ketoacidosis and hyperosmolar states).[339] At admission hyperglycemia may also be an independent factor associated with poor prognosis for those hospitalized with COVID-19.[340][341]

UK guidance advises checking blood glucose and ketones in all patients with diabetes who are admitted to the hospital.[339] Out of the hospital, patients should follow their usual sick day rules, taking care to continue insulin, remain hydrated, and monitor blood glucose and ketones as appropriate.[342][343] Clinicians may need to prescribe additional blood glucose and ketone testing equipment to support increased monitoring. Patients admitted to intensive care may have insulin resistance and increased insulin requirements. There is a risk of hypoglycemia if feeding is interrupted (e.g., if the patient is nursed prone).[339] Specialist advice may be needed, particularly for patients who have severe illness on admission or if infusion pumps for insulin are not available.[339]

A panel of international experts has published practical recommendations for the management of diabetes in patients with and without COVID-19.[344] They advise that those with diabetes who have not been infected with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) should intensify their metabolic control as a measure to prevent COVID-19 infection, including blood pressure and lipid control, and patients should reduce their risk of exposure by having remote healthcare consultations where possible and following public health advice on hand hygiene and physical distancing. The panel recommends that patients with diabetes and COVID-19 require continuous and reliable glycemic control and that they continue antihypertensive and lipid-lowering treatments. The panel also advises that patients without diabetes are monitored for new-onset diabetes triggered by SARS-CoV-2 infection, particularly those at high risk for metabolic disease. People with type 1 diabetes are more susceptible to infection and require more intensive monitoring and supportive therapy to reduce the risk of metabolic decompensation, including diabetic ketoacidosis; the panel advised that patients are made aware of this and reminded about typical symptoms, home-measurement of urine or blood ketones, sick day rules, and seeking medical advice early if concerned.[344] Guidelines for the management of dexamethasone-related hyperglycemia in patients with diabetes and COVID-19 have also been published.[345]

Further diabetes resources are available at:

American Diabetes Association: COVID-19 professional resources external link opens in a new window

Association of British Clinical Diabetologists: COVID-19 (coronavirus) information for healthcare professionals external link opens in a new window

Patients with type 2 diabetes are at higher risk for severe illness.[273][328] They are more likely to need intensive care and mechanical ventilation if they develop COVID-19, compared with patients who do not have diabetes, and have a higher case fatality rate and increased odds of in-hospital death with COVID-19.[329][330][331][332][346][275][276][70][334] Poor glycemic control, hypertension, previous stroke, previous heart failure, renal impairment, cancer, body mass index <20 kg/m² or ≥40 kg/m², male sex, older age, nonwhite ethnicity, socioeconomic deprivation, and elevated C-reactive protein are associated with increased mortality from COVID-19.[335][347][348][337] Although prevalence of diabetes is lower in patients <50 years, one study found that younger patients with diabetes have an increased relative risk of fatal outcomes compared with older patients. Use of insulin is associated with poor prognosis (progression to severe or critical illness, and in-hospital death).[349][348] Use of beta-blockers is associated with increased mortality, and use of dipeptidyl peptidase-4 inhibitors is associated with decreased mortality.[348] Patients with COVID-19 infection appear to have a greater risk of hyperglycemia with ketones, including patients with type 2 diabetes and those with newly diagnosed diabetes. COVID-19 disease can precipitate atypical presentations of diabetes emergencies (e.g., mixed diabetic ketoacidosis and hyperosmolar states).[339] At admission hyperglycemia may also be an independent factor associated with poor prognosis for those hospitalized with and without COVID-19.[340]

Patients taking sodium-glucose co-transporter-2 (SGLT2) inhibitors should be advised to stop these if they become unwell, to reduce their risk of developing diabetic ketoacidosis.[344] Metformin may need to be temporarily stopped if patients are at risk of dehydration.[343][344] UK guidance advises temporarily stopping SGLT2 inhibitors and metformin in all patients admitted to the hospital.[339]  Blood glucose and ketones should be checked in all patients with diabetes who are admitted to the hospital.[339]

Patients should follow their usual sick day rules, taking care to continue insulin, remain hydrated, and monitor blood glucose and ketones as appropriate.[342][343] Clinicians may need to prescribe additional blood glucose and ketone testing equipment to support increased monitoring. Patients admitted to intensive care may have insulin resistance and increased insulin requirements. There is a risk of hypoglycemia if feeding is interrupted (e.g., if the patient is nursed prone).[339] Specialist advice may be needed, particularly for patients who have severe illness on admission or if infusion pumps for insulin are not available.[339]

A panel of international experts has published practical recommendations for the management of diabetes in patients with or without COVID-19.[344] They advise that those with diabetes who have not been infected with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) should intensify their metabolic control as a measure to prevent COVID-19 infection, including blood pressure and lipid control, and patients should reduce their risk of exposure by having remote healthcare consultations where possible and following public health advice on hand hygiene and physical distancing. The panel recommends that patients with diabetes and COVID-19 require continuous and reliable glycemic control and that they continue antihypertensive and lipid-lowering treatments. The panel also advises that patients without diabetes are monitored for new-onset diabetes triggered by SARS-CoV-2 infection, particularly those at high risk for metabolic disease. People with type 2 diabetes and comorbid conditions such as obesity and fatty liver disease may be at increased risk for more severe COVID-19 disease, and those with fatty liver disease may be screened for hyperinflammation using trends in laboratory tests to determine where immunosuppression might improve the outcome.[344] Guidelines for the management of dexamethasone-related hyperglycemia in patients with diabetes and COVID-19 have also been published.[350]

One study in the UK looking at the indirect effects of the COVID-19 pandemic on type 2 diabetes between March and December 2020 found reductions in diagnosis and monitoring of type 2 diabetes. Those aged 65 years and older, men, and people from deprived areas had the greatest reductions in diagnosis rates.[207]

Further diabetes resources are available at:

American Diabetes Association: COVID-19 professional resources external link opens in a new window

Association of British Clinical Diabetologists: COVID-19 (coronavirus) information for healthcare professionals external link opens in a new window

The British Association of Dermatologists has issued advice to patients with eczema affecting the hands. Patients should adhere to national advice to wash hands with soap and water. Patients should be advised to pat the skin dry and apply emollient generously after handwashing and when the skin feels dry. Patients should be advised that applying emollient before sleep and covering the hands with cotton gloves may help their condition. Patients should protect their hands using gloves if they need to handle detergent for purposes other than handwashing (e.g., washing a child's hair, washing dishes, or cleaning). [351] Patients with facial dermatitis are advised to apply a barrier cream before wearing a face mask and to avoid masks containing metal wires in case of nickel allergy.[234]

For information on managing patients with eczema who take drugs that affect the immune response, please see the section "considerations for patients with dermatologic conditions receiving drugs that affect the immune response" in the introduction to this topic.

The World Endometriosis Society has provided advice for the management of endometriosis during the pandemic.[352] Appointments should be offered by telephone or video call, and in person when considered safe. Medical management should be optimized in the absence of surgical interventions. Complementary and alternative treatment options may also be considered. In addition, healthcare providers are encouraged to consult with other specialists, such as those who manage chronic pain. When surgical and fertility treatments can be restarted, patients should be triaged based on disease severity and treatment response.

The European Academy of Neurology has published advice on the management of epilepsy during the COVID-19 pandemic.[353] Patients with epilepsy should be advised to continue taking their medication, and regular follow-up should continue using telephone or video consultations. Face-to-face appointments should be arranged if required. Fever can trigger seizures in some people with epilepsy, and experts recommend using antipyretics if people with epilepsy develop COVID-19. Coronavirus infection per se is not known to trigger seizures. Patients should be advised to avoid stockpiling medication.[354]

ENT UK has published guidance on the management of epistaxis, aiming to reduce the number of patients admitted to the hospital while ensuring safety of patients and staff. Personal protective equipment should be worn, including a level 2 gown, gloves, filtering face-piece (FFP)-3 mask, visor, and hat. Nasal pressure should be applied for 15 minutes and tranexamic acid given. Factors that could promote bleeding, for example elevated blood pressure or use of antiplatelet agents or anticoagulants, should be sought and controlled. A unilateral bioresorbable dressing should be inserted. If the bleeding stops, patients may be discharged from the emergency department with instructions to take 48 hours' bed rest and use a suitable topical antibiotic preparation; if the bleeding does not stop, the patient should be reviewed by an ear, nose, and throat specialist. Silver nitrate cautery and nonabsorbable packing should be attempted by a specialist before admitting the patient to the hospital.[355]

Hypertension is associated with an increased risk of severe COVID-19 and death; this association is stronger in younger populations.[275][276][70]

There is no evidence that patients with hypertension should discontinue ACE inhibitors or angiotensin-II receptor antagonists.[93][94][95][96][97][98][356] Cohort studies have reported that ACE inhibitor or angiotensin-II receptor antagonist use does not alter risk of intensive care admission or mortality.[99][100] Randomized controlled trials of patients admitted to hospital with COVID-19 found that continuation of renin-angiotensin system inhibitors had no overall effect on survival, progression of COVID-19, need for intensive care, need for invasive mechanical ventilation, shock, cardiovascular events, or length of hospitalization compared with discontinuation.[101][357] British, European, American, and Asian heart groups advise that patients should continue to take ACE inhibitors and angiotensin-II receptor antagonists as prescribed.[103][104][105][106] Any change in medication should be based on individual patient risk assessment.

The British Society for Allergy and Clinical Immunology has recommended modifications to pediatric allergy services during the pandemic. Most new patient and follow-up visits can be performed using telehealth. Allergy testing, and most food challenges, can be deferred. Priority for hospital testing should be given to food challenges where there is a critical nutritional need and it would be unsafe for the parent or caregiver to perform the food challenges: for example, in infants with milk/soya/hydrolysate food protein enterocolitis syndrome. Where possible, dietitians should contact patients on multiple food exclusions to establish whether food shortages are a concern; additional vitamins, supplements, or formulas may be needed. Initiation and updosing of food immunotherapy should be deferred.[358] Sublingual and subcutaneous immunotherapy should be continued as usual in patients who have no symptoms of COVID-19 and have not been exposed to infected individuals within the last 14 days, in patients who have had a negative reverse-transcriptase polymerase chain reaction (RT-PCR) test and in patients who have serum IgG antibodies to severe acute respiratory disease coronavirus 2 (SARS-CoV-2) without virus-specific IgM. Patients who develop COVID-19, have been exposed to infected individuals, or have a positive RT-PCR test should discontinue allergen immunotherapy, independent of disease severity, until symptoms have resolved or adequate quarantine has been performed.[359]

A consensus statement from the Italian Society of Pediatric Allergy and Immunology advises that it may be more difficult for children to access specialty allergy foods during the pandemic, and the potential requirement to try new products increases the risk of an allergic reaction. The society recommends that children have a written action plan with emergency drug doses and have two available epinephrine autoinjectors.[234]

A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[44] Experts recommend that patients taking long-term glucocorticoids for giant cell arteritis (GCA) should titrate the dose down to the lowest possible dose that achieves symptom control. Patients at risk of adrenal insufficiency who develop COVID-19 may require additional doses of glucocorticoid to prevent an adrenal crisis. Adjuvant immunosuppression should be considered at an early stage, since major relapse of GCA might require in-person consultation and/or significant glucocorticoid dose increases.[360] The UK criteria for use of tocilizumab have been temporarily altered to permit treatment beyond 12 months in order to reduce the risk of relapse.[361]

Clinicians are advised to engage patients with rheumatic disease in a shared decision-making process to discuss receiving a severe acute respiratory disease coronavirus 2 (SARS-CoV-2) vaccine. The response to vaccination is likely to be blunted in patients receiving systemic immunomodulatory therapies compared with the general population. The American College of Rheumatology advises that, beyond known allergies to vaccine components, there are no additional contraindications to SARS-CoV-2 vaccination for patients with autoimmune and inflammatory rheumatic diseases. Vaccination should ideally occur when rheumatologic disease is well controlled.[362]

Hematopoietic stem cell transplantation

UK guidelines advise that for at least 2 weeks before receiving hematopoietic stem cell transplantation (HSCT), patients should follow professional advice on how to minimize their risk of respiratory infection, including COVID-19.[363] All patients receiving HSCT should be tested for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) and have a negative test before starting conditioning.[363][364] Polymerase chain reaction testing is preferred.[364] Patients should also be tested if they have any symptoms of COVID-19.

If COVID-19 is confirmed, HSCT should be deferred. The length of deferral is guided by the patient’s risk of disease progression, morbidity and mortality, and their symptom burden from COVID-19.[363][364] Patients with confirmed or suspected COVID-19 should have repeat echocardiography, pulmonary function tests, and chest x-ray before starting treatment.[363]

UK guidelines advise that for at least 2 weeks before HSCT, donors should follow government advice on social distancing.[363] Donors should be tested at the initial assessment, before stem cells or donor lymphocytes are harvested, and 72 hours before starting conditioning if fresh cell donations are needed. Donors who test positive should defer donations for 2 weeks after their symptoms resolve; however, if less than 2 weeks has passed and donation is urgent, this should be referred for risk assessment.[363] If the donor tests positive for COVID-19 on the day of donation after cryopreservation of cells, a shared decision should be made over use of the cells. Donors with known or suspected COVID-19 should not donate other blood products (including lymphocytes) for at least 2 weeks after symptom resolution.[363]

HSCT should be deferred if possible, particularly for myeloma, low-grade lymphoproliferative conditions, chronic hematologic conditions, and nonmalignant indications.[365]

Following transplantation, patients are at high risk of severe sickness and should follow the national recommendations for protecting themselves.[273][363][364][366]

Clinicians in Italy have reported assessing patients within 3 months of transplantation and without symptoms of COVID-19 in-person. Patients who are 3 to 24 months post-transplantation may be screened for symptoms of infection or graft-versus-host disease and triaged to in-person or telehealth consultations as appropriate.[367]

Patients who are profoundly immunosuppressed following HSCT may shed viable SARS-CoV-2 virus for up to 78 days after the onset of symptoms.[368]

Further hematology resources are available at:

ASH: COVID-19 resources external link opens in a new window

BSH: COVID-19 updates external link opens in a new window

Patients with non-alcoholic fatty liver disease (NAFLD) are at higher risk of disease progression if they contract COVID-19, compared with people without NAFLD.[369] European guidelines recommend that early hospital admission should be considered for patients with NAFLD.[59] It is unclear whether NAFLD is an independent risk factor for poor COVID-19 prognosis or whether observations are confounded by the presence of obesity, hypertension, or type 2 diabetes. Treatment for arterial hypertension should be continued.[59] Clinicians should also optimize diabetes management, promote weight loss, and give nutritional guidance, which may prevent a severe disease course in future severe acute respiratory syndrome coronavirus 2 infection. People with type 2 diabetes and fatty liver disease may be screened for hyperinflammation using trends in laboratory tests to determine where immunosuppression might improve the outcome.[344]

Usual treatment should be continued for patients with chronic hepatitis B (HBV) infection who are established on treatment. In patients without COVID-19, treatment should be initiated according to local or national guidelines.[59] The impact of interferon alfa on systemic inflammation in patients with COVID-19 is not known. European Association for the Study of the Liver (EASL) guidelines recommend that alternative agents should be considered when starting treatment for HBV during the pandemic.[59]

Patients who have chronic, occult, or resolved HBV infection and COVID-19 should be considered for antiviral therapy to avoid HBV reactivation and hepatitis flare if they receive immunosuppressive agents for treatment of COVID-19.[68][59] EASL guidelines advise that initiation of antiviral therapy is usually not warranted in patients with HBV and COVID-19 and may be deferred until recovery. In patients with suspected severe acute HBV hepatitis or a flare of disease activity, a specialist should be consulted to decide whether to initiate antiviral therapy.[59] Asia-Pacific guidelines recommend that patients who are newly diagnosed with HBV infection at the time of presentation with COVID-19 should be started on antiviral therapy.[68] Use of tenofovir with lopinavir/ritonavir is relatively contraindicated as the concentration of tenofovir might be increased when these drugs are used together.[68] 

European and Asia-Pacific position papers recognize that screening for hepatocellular carcinoma (HCC) using ultrasound may need to be deferred during the COVID-19 pandemic, depending on local resources (including availability of treatment options) and individual patient risk assessment. Patients at highest risk should be prioritized for screening, including patients with: elevated alfa-fetoprotein levels, chronic hepatitis B, advanced cirrhosis, and nonalcoholic steatohepatosis/diabetes.[68][59] HCC surveillance can be deferred until after recovery in patients who develop COVID-19.[59] The European Association for the Study of the Liver recommends that guidelines for treatment of patients with HCC should be followed, including multidisciplinary board review to make treatment recommendations, systemic treatments, and evaluation for liver transplant.[59] The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic recommends that patients with HCC who have COVID-19 should have treatment for HCC deferred until after recovery from COVID-19. For those who have had surgical resection deferred, bridging transarterial chemoembolization, radiofrequency ablation, or systemic chemotherapy might be considered in selected patients.[68]

Organ donations and transplants are likely to be reduced in many countries. Listing for transplantation should be restricted to patients at the upper limit of the Milan criteria.[59] Guidelines emphasize the importance of vaccination against Streptococcus pneumoniae and influenza.[59]

Recommendations for the management of patients with primary hepatic malignancies during the COVID-19 pandemic have also been developed by an international group of experts.[370] They propose treatment recommendations for different stages of HCC (according to the Barcelona Clinic Liver Cancer classification system), specifically surgery, locoregional, and systemic therapy, and suggest strategies to modify risk and assist with multidisciplinary treatment decision-making.

Concomitant COVID-19 infection is associated with a threefold increase in 30-day mortality in patients with hip fractures.[371] Nevertheless, surgical management remains the preferred treatment because nonoperative management is also associated with higher 30-day mortality.[372] Measures should be taken to shield patients from potential COVID-19 infection in the perioperative period.

There is currently little evidence that the COVID-19 infection rate is different in people living with HIV compared with those without HIV infection in European and North American populations, after accounting for demographic factors.[373][374][375][376][377] One cohort study conducted in the US reported lower prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) amongst people living with HIV compared with people without HIV (3.7% and 7.4% respectively), which may reflect increased shielding precautions taken by people living with HIV. SARS-CoV-2 IgG titers were lower in people living with HIV with a history of PCR-confirmed SARS-CoV-2 infection compared with people without HIV with previous SARS-CoV-2 infection.[378]

People living with HIV who are diagnosed with COVID-19 have an increased risk of hospitalization, compared with people without HIV, and hospitalization is associated with progression of HIV disease stage.[379] A UK cohort study reported that patients with HIV who had COVID-19 had a higher mortality than the general population (hazard ratio 2.59), even after adjusting for deprivation, ethnicity, smoking, and obesity.[380] A US cohort study reported higher 30-day mortality in patients with HIV who developed COVID-19 compared with patients without HIV, but found that this was attributable to the comorbidity burden in this population rather than HIV per se.[381] The clinical course of COVID-19 in the African population is under investigation; one study reports that patients with HIV in South Africa had a higher risk of death compared with people without HIV, irrespective of viral suppression.[382] A study conducted in Zambia reported that HIV status alone was not associated with COVID-19 infection severity or mortality. However, patients with severe HIV disease (hemoglobin <8.0 g/dL, CD2 <200 cells/microliter, active TB, or body mass index <18.5 kg/m²) were more likely to develop severe COVID-19 and were at increased risk of death from COVID-19.[383]

Guidance from the US, UK, and Europe recognizes that many people living with HIV are older and have comorbid chronic medical conditions such as cardiovascular disease or lung disease, which increase the risk for severe COVID-19 infection. The guidelines recommend that until more is known, additional caution is advised for all people with HIV, especially if advanced (i.e., CD4 cell count <200/microliter) or poorly controlled. Influenza and pneumococcal vaccinations should be kept up to date.[384][385] US guidelines also recommend that patients maintain an adequate supply of antiretroviral therapy (ideally a 90-day supply).[384] Advice from the Infectious Diseases Society of America and HIV Medicine Association states that people with HIV have a normal life expectancy and a readily treatable infection, therefore HIV status and current HIV control should not be factors in decision-making regarding potentially life-saving interventions or enrollment into clinical trials. Antiretroviral therapy should be continued in the hospital without interruption. Changes in antiretroviral therapy are generally not recommended. Routine viral load monitoring in patients with suppressed HIV and no adherence concerns can be delayed for up to 6 months to reduce the burden on testing laboratories. Viral load testing should be prioritized for patients with adherence concerns, patients whose HIV is not fully suppressed, patients starting a new drug regimen, and pregnant patients.[386] Pre-exposure prophylaxis to prevent HIV infection should be taken as directed; there is no evidence that it is effective against COVID-19.[387] The Centers for Disease Control and Prevention recommends that people with HIV can receive the Pfizer-BioNTech and Moderna vaccines if they have no contraindications. It is not yet known whether the level of protection is as strong for people with HIV as people without HIV.[386]

Further resources are available at:

WHO: Q&A - HIV, antiretrovirals and COVID-19 external link opens in a new window

European AIDS Clinical Society: EACS and BHIVA statement on risk of COVID-19 for people living with HIV (PLWH) external link opens in a new window

Analysis of US health-insurance claims data has shown that lymphoma is a significant risk factor for fatal COVID-19.[75] Interim treatment guidelines for the management of adult patients during the pandemic have been provided by experts from the UK and also from Australia and New Zealand.[388][283] Hodgkin lymphoma is curable in most patients and delivery of dose- and time-intensive treatment remains a high priority; recommendations are given for patients with early-stage and advanced-stage disease, elderly Hodgkin, relapsed Hodgkin, and nodular lymphocyte-predominant Hodgkin.

The American Society of Hematology has also published advice on the treatment of Hodgkin lymphoma.[389] Chemotherapy followed by interim staging positron emission tomography/computed tomography (PET/CT) is usually preferred to chemotherapy plus radiation therapy for early and advanced-stage disease because fewer hospital visits are needed. The International Lymphoma Radiation Oncology Group has published emergency guidelines for radiation therapy in hematologic malignancies, should radiation therapy be necessary. Alternative dose fractionations may be given.[88] Bleomycin should be omitted following a negative PET/CT to reduce the risk of bleomycin pneumonitis. Many experts recommend increased use of granulocyte-colony stimulating factor to reduce neutropenia and use of prophylactic antibiotics when neutropenia is expected. Recommendations are also given for older adult and pediatric patients and those with relapsed or refractory disease.[389] In general, it is considered safe and appropriate for people with Hodgkin lymphoma to be vaccinated against severe acute respiratory syndrome coronavirus 2.[389]

Hospital-acquired bacterial pneumonia (defined as developing at least 48 hours after hospital admission and not incubating at admission) can be difficult to distinguish from COVID-19 pneumonia. UK guidelines state that bacterial coinfection occurs in less than 8% of people with COVID-19, and infection rates may be lower in people in hospital with COVID-19.[121] The risk of hospital-acquired pneumonia increases with length of hospital stay and with immunosuppression.[121]

Where possible, clinicians should discuss the benefits, risks, and likely outcomes of any treatment with the patients, their relatives, and caregivers. The patient's preference about treatment and escalation plans should be sought, and clinicians should enquire about any advance care plans, advance decisions to refuse treatment, or "do not attempt resuscitation" decisions.[121]

Tests including respiratory and blood cultures, severe acute respiratory disease coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR), throat samples for respiratory viral and atypical pathogen PCR, chest imaging, full blood count, and urinary legionella and pneumococcal antigen tests are recommended to help diagnosis and guide decisions about antibiotic use.[121] High levels of C-reactive protein (CRP) do not distinguish between bacterial and COVID-19 pneumonia, but low CRP levels make secondary bacterial pneumonia less likely.[121]

Empiric antibiotics should be started if there is a strong clinical suspicion of bacterial infection. Antibiotic treatment should be started within 4 hours of diagnosis and within 1 hour if the patient has suspected sepsis. Antibiotics should not be used to prevent secondary bacterial pneumonia.[121]

World Health Organization guidelines advise that antibiotics should not be prescribed for patients with mild COVID-19 and should only be prescribed for patients with moderate COVID-19 if there is clinical suspicion of a bacterial infection.[33] 

Choice of antibiotic will depend on local resistance data and availability. Specialist advice on antibiotic choice is recommended for patients who are immunocompromised, pregnant, in critical care, or who have a history of infection with resistant organisms or repeated infective exacerbations of lung disease. Use of antibiotics should be reviewed at 24-48 hours, or as soon as test results are available, and treatment switched to a narrower spectrum antibiotic if appropriate.[121] Antibiotic treatment should stop after 5 days, unless there is an indication to continue. Seek specialist advice if patients do not improve as expected after 48-72 hours of antibiotic treatment, if there is a suspicion of infection with multidrug-resistant bacteria, or if symptoms become significantly or rapidly worse.[121]

COVID-19-associated pulmonary aspergillosis may occur in patients with severe COVID-19 who are receiving mechanical ventilation. Symptoms may be nonspecific. The diagnosis should be considered when patients with severe COVID-19 have sepsis or worsening respiratory function, even in the absence of typical risk factors. Lower respiratory tract specimens should be obtained for fungal culture and Aspergillusgalactomannan antigen testing.[302]

Patients with idiopathic pulmonary fibrosis are at increased risk of hospitalization and death due to COVID-19.[287] The UK National Institute of Health and Care Excellence and the Canadian Thoracic Society have published guidelines for the management of patients with interstitial lung disease, including idiopathic pulmonary fibrosis, during the pandemic.[390][391] Clinicians should discuss with patients whether the benefits of attending medical appointments outweigh the potential risks. Patients should be advised to keep a list of their medications, other medical conditions, and allergies and a copy of a recent clinic letter to give to healthcare staff if they need treatment for COVID-19. Clinicians should determine whether patients have advance care plans or advance decisions to refuse treatment, including "do not attempt resuscitation" decisions, and take these into account when planning care.[390]

Patients who take drugs that affect the immune response may have atypical presentations of COVID-19; for example, patients taking corticosteroids may not develop fever. Assessment can also be challenging because the symptoms of interstitial lung disease and side effects of medication used to manage the condition may be similar to the symptoms of COVID-19.[390] Decisions about stopping, adjusting, and restarting treatment in patients who develop COVID-19 should be made in conjunction with the patient's specialist team. [390][391] The half-life of some medicines means that the immunosuppressive effect will continue for some time after stopping treatment. Patients who are taking maintenance prednisone should not stop if they develop COVID-19; they may be at risk of adrenal crisis and require a temporary dose increase if they develop COVID-19. Initiation of immunotherapy should be deferred in patients with newly diagnosed or suspected COVID-19.[390][391] Antifibrotic drugs may be continued if the patient's blood parameters are in the acceptable range and there is no other reason to stop (e.g., significant adverse effects).[390][391] If patients with COVID-19 develop acute kidney injury or deranged liver function tests, medicines should be stopped and adjusted as recommended by your local drug formulary or prescribing information.[390]

In patients without COVID-19, UK guidelines advise that clinicians should consider, and discuss with patients, temporarily stopping treatment with immunosuppressants unless the benefits outweigh the risk of aggravating the patient's lung condition. [390] Canadian guidance advises that clinicians use the lowest effective dose of immunomodulatory therapy.[391]

When deciding whether to start or continue an immunosuppressant in patients who do not have COVID-19, clinicians should take into account whether the patient's condition is stable, which treatment has the best risk profile, the likely consequences of delaying the start of treatment, feasibility of monitoring and dose adjustments, frequency and route of treatment, and whether treatment could be reduced or stopped. Patients who are established on immunosuppressive therapy should continue their treatment as prescribed to minimise the risk of their condition worsening. It may be safe to increase the interval between monitoring blood tests if a patient's condition is stable and they have been advised to shield. If the patient's condition is responsive to immunosuppressants and they cannot attend for blood tests, prednisone alone may be used at the lowest possible dose. Antifibrotic therapy does not increase the risk of getting COVID-19 or make severe disease more likely. Patients who are already taking antifibrotic therapy should continue. Patients with a new diagnosis of idiopathic pulmonary fibrosis may start antifibrotic therapy if a multidisciplinary team confirms the diagnosis, usual eligibility criteria are satisfied, and the appropriate blood monitoring can be performed.[391]

New outpatient appointments should be telephone or video appointments if suitable. Unless the patient's condition has altered considerably, blood tests from the past 6 weeks, lung function tests from the past 6 months, and computed tomography scans from the last 12 months can be used to guide diagnosis and treatment. New tests should be performed if these test results are not available but are needed urgently to inform care. In particular, bronchoscopy and lung function testing have the potential to spread COVID-19, so these should only be performed if they are urgent and will directly influence patient care. Patients who require face-to-face appointments should be screened before arrival (by telephone) for symptoms of COVID-19. On arrival, they should be screened for symptoms again and have their temperature checked.[390] Canadian guidance advises testing for severe acute respiratory coronavirus-2 (SARS-CoV-2) 1 to 2 days before bronchoscopy or lung biopsy, if resources are available. Elective bronchoscopy or lung biopsy should be deferred in patients with SARS-CoV-2 infection.[391]

Long-term oxygen assessments should take place in the patient’s home, if possible. Assessments may be deferred, according to clinical need, and reassessments may be deferred if the patient's symptoms are stable. Patients should be referred for lung transplantation according to usual protocols. Patients should be referred for pulmonary rehabilitation or directed to the British Thoracic Society's online pulmonary rehabilitation resources if there are no local services available.[390]

Patients with persistent respiratory symptoms following recovery from COVID-19 should be evaluated for post-COVID pulmonary fibrosis and/or exacerbation of pre-existing interstitial lung disease.[391]

Further resources are available at:

British Thoracic Society. COVID-19: information for the respiratory community. external link opens in a new window

The American Society for Hematology has published advice on management of immune thrombocytopenia (immune thrombocytopenic purpura [ITP]) during the pandemic. Hospital visits should be minimized and treatment guided by symptom management rather than frequent platelet counts. Viral infections can trigger acute ITP or trigger exacerbations in patients with stable disease, so testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is recommended in these patients.[392]

Treatment of new patients should be individualized depending on: urgency of need to increase the platelet count, amount of bleeding, comorbidities, minimizing exposure to SARS-CoV-2, and usual practice. Most patients with immune thrombocytopenia do not experience severe bleeding with platelet counts above 20,000/microliter, in the absence of comorbidities. Intravenous immune globulin (IVIG) or oral thrombopoietic agents (e.g., eltrombopag or avatrombopag) are first line because they are not immunosuppressive. No change to treatment is recommended for patients who are stable on low doses of immunosuppressive drugs. Treatment change may be considered for patients taking higher doses of immunosuppressive drugs or corticosteroids; however, this must be balanced against the increased monitoring requirements and risk of relapse. If indicated, IVIG or oral thrombopoietic agents may allow dose reduction or cessation of immunosuppressive medication or corticosteroids. Rituximab should be avoided if possible.[392]

If a patient with immune thrombocytopenia develops COVID-19, IVIG should be given to maintain the platelet count above 10,000-20,000/microliter; platelet transfusion should be reserved to treat bleeding or cover procedures with a high bleeding risk. If the patient already takes a thrombopoietic agent, the dose can be increased or a second agent may be started. Treatments for COVID-19 illness should be given as appropriate. If the patient has had a splenectomy, intravenous antibiotics should be administered until bacterial cultures are documented negative, even if COVID-19 is strongly suspected as the cause.[392]

The guidance advises that vaccine administration in general can occasionally result in a drop in the platelet count in stable ITP patients; however, current knowledge suggests that the expected benefits of receiving the SARS-CoV-2 vaccine likely outweigh the risks.[392] Taking baseline and postvaccination platelet counts may be considered, particularly in those with ongoing thrombocytopenia or a history of unstable platelet counts.

The 2020-2021 influenza season is expected to coincide with continued or recurrent circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Signs and symptoms of influenza infection and COVID-19 infection are similar and can be difficult to distinguish clinically; only testing can distinguish between them. The US National Institutes of Health (NIH) COVID-19 Treatment Guidelines recommend testing for both SARS-CoV-2 and influenza viruses in all hospitalized patients with acute respiratory illness when both viruses are co-circulating.[83] The guidelines advise that treatment of influenza is the same in all patients, regardless of SARS-CoV-2 coinfection, and that hospitalized patients should be started on empiric treatment for influenza as soon as possible without waiting for influenza testing results (antiviral treatment for influenza can be stopped when influenza has been ruled out by nucleic acid detection assay in upper respiratory tract specimens for nonintubated patients, and in both upper and lower respiratory tract specimens for intubated patients).[83]

Vaccination against influenza is recommended to reduce prevalence of influenza infection, thus reducing symptoms that might be confused with those of COVID-19 and reducing the burden on the healthcare system.[113] The US Centers for Disease Control and Prevention recommend influenza vaccination of persons aged ≥6 months.[113][393] On the basis of practice for other acute respiratory infections, the NIH COVID-19 Treatment Guidelines recommend that people with COVID-19 should receive an inactivated influenza vaccine.[83] There is no data on the optimal timing of influenza vaccination in people with COVID-19 or recovering from COVID-19. Timing of vaccination should be guided by the individual's risk of medical complications due to influenza, and the degree of influenza circulating in their community.[393] The UK 2020-2021 influenza immunization programme has been expanded to include household contacts of shielding patients, children in school year 7, and health and social care workers who deliver domiciliary care.[115] Depending on availability following immunization of currently eligible groups, the influenza vaccine will also then be offered to all 50-64 year olds in the UK.[115] Clinicians are encouraged to achieve maximum uptake of influenza vaccination in existing eligible groups.

One study found that influenza infection was associated with a lower risk of SARS-CoV-2 infection, indicating that there may be pathogenic competition between them. Coinfection with influenza and SARS-CoV-2 was associated with an increased risk of death or severe disease.[394]

People with learning disabilities (LDs) are at higher risk of death from COVID-19 than the general population. Analysis of US health-insurance claims data found that intellectual disability was associated with a 2.75-fold increase in the odds of death from COVID-19.[75] In the UK, people with learning disabilities were over-represented threefold amongst people who died from COVID-19, with a larger disparity in younger age groups.[395] In the US, a study of nearly 65,000,000 patients across 547 healthcare organizations found that having an intellectual disability was the strongest independent risk factor for a COVID-19 diagnosis and the strongest independent risk factor for COVID-19 mortality other than age.[396]

Guidance recommends ensuring that patients with LDs have a handheld summary of their medical information, activities, and preferences to support staff in caring for them if admitted to hospital. Community LD teams are encouraged to work with people in their care and their families to develop COVID-19 care plans, which should include any issues associated with diagnostic overshadowing, views of parents, carers and family members, any reasonable adjustments required, communication needs, specialist mental health support, anticipatory care plans, and any end-of-life or do not attempt cardiopulmonary resuscitation discussions.[397] Stringent social distancing should be followed and community services should use tele- and video conferencing to contact patients and carers where appropriate.[398]

Patients with COVID-19 may have abnormal liver function tests, including elevated aminotransferases and mildly elevated bilirubin. Low serum albumin on admission to the hospital is a marker of COVID-19 severity. Recommendations from the American Association for Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), and the Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic all advise regular monitoring of liver biochemistries in all hospitalized patients with COVID-19, particularly those treated with remdesivir or tocilizumab, regardless of baseline values.[58][68][399] The Asia-Pacific Working Group advises that while the optimal interval for liver tests is uncertain, it would be reasonable to monitor liver tests twice weekly in patients on potentially hepatotoxic medication and patients with pre-existing liver disease, and more frequently in any patients with abnormal liver function.[68] The AASLD also advises that abnormal liver biochemistries should not be a contraindication to using investigational or off-label therapeutics for COVID-19, although aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >5 times the upper limit of normal (ULN) may exclude patients from consideration of some investigational agents.[58] The Asia-Pacific Working Group recommends that off-label COVID-19 therapies may be used with caution and close monitoring in those with abnormal liver function; the treatment should be stopped in those with moderate-to-severe liver injury (ie, ALT >5 times ULN or alkaline phosphatase >2 times ULN, and total bilirubin >2 times ULN or presence of coagulopathy or clinical decompensation).[68] Other causes of abnormal liver function tests, including viral hepatitides, should be considered in patients with COVID-19 and abnormal liver biochemistries.[68][399] In patients with autoimmune hepatitis or liver transplant recipients who develop COVID-19, suspected disease flare or acute cellular rejection should be confirmed on biopsy.[58] The Asia-Pacific Working Group recommends screening for hepatitis B surface antigen (HBsAg) in patients who are receiving systemic corticosteroids or other potent immunosuppressants for 7 days or longer as COVID-19 therapy. Tocilizumab has been associated with HBV reactivation. European guidelines recommend screening with HBV serology before initiating treatment with tocilizumab.[59] In patients with hepatitis C virus (HCV) infection, concomitant use of a protease inhibitor-containing direct-acting antiviral regimen with lopinavir/ritonavir is contraindicated, as protease inhibitor concentrations may increase when these drugs are used together, risking ALT elevations.[68]

A joint statement from the British Society of Gastroenterology, British Association for the Study of the Liver, NHS Blood & Transplant, and British Liver Trust advises that patients with chronic liver disease, autoimmune hepatitis, and those post-liver transplant should consider SARS-CoV-2 vaccination with any of the available vaccines.[300]

The European Academy of Neurology has published advice on the management of migraine during the COVID-19 pandemic.[400] Patients with migraine should be encouraged to continue managing lifestyle and dietary triggers: for example, stress, diet, alcohol consumption, and sleep. Social isolation, anxiety, and depression may negatively affect medication overuse, and medications for treatment of acute migraine should be limited to less than two times per week. Nonsteroidal anti-inflammatory drugs should be used as needed: they have established efficacy in the treatment of acute migraine, and there is no evidence that they can exacerbate symptoms of COVID-19. Acetaminophen and triptans may also be used as required for acute attacks. Ongoing care should be delivered using telemedicine where possible.

A position statement from the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions provides recommendations for the triage of patients referred for structural heart disease interventions during the pandemic.[183] The recommendations suggest that percutaneous mitral valve repair (edge-to-edge repair) can be safely deferred in the majority of patients with mitral regurgitation (MR), but some high risk patients should be considered for edge-to-edge repair during the pandemic. Patients who are deferred should be contacted on a weekly basis to monitor for decompensation.Valve-in-valve transcatheter mitral valve replacement (TMVR) is resource-intensive and should be deferred if the patient can be sufficiently managed on medical therapy in the interim. Valve-in-valve TMVR should be considered for patients with severe bioprosthetic mitral stenosis or mitral regurgitation who are inpatients with congestive heart failure or outpatients who have had hospitalizations for congestive heart failure within 30 days despite optimized guideline-directed medical therapy.

The British Heart Valve Society has published recommendations for the outpatient management of heart valve disease following the COVID-19 pandemic. They recommend that patients with severe symptomatic MR should be considered for urgent surgical repair; transcatheter mitral valve therapies may be considered in decompensated MR when timely access to surgical repair/replacement is not possible.[236]

The American Society of Hematology (ASH) and European Myeloma Network (EMN) advise that patients who have multiple myeloma with active disease need treatment during the COVID-19 pandemic, but this can be adapted for each patient to reduce additional COVID-19 exposure.[365][401] For patients who require treatment, ASH advises giving 6-12 cycles of bortezomib, lenalidomide, and dexamethasone (RVD), followed by lenalidomide maintenance (with the addition of bortezomib every 2 weeks for high-risk patients). Older myeloma patients may start treatment with RVD or daratumumab, lenalidomide, and dexamethasone (DRd) depending on cytogenetic risk and other comorbidities, and if necessary can continue on lenalidomide and dexamethasone (Rd) only after achieving best response.[365]

Patients should continue on maintenance therapy to reduce the risk of relapse. Lenalidomide can be provided for up to 2 months, with telemedicine visits and home phlebotomy as needed. Higher-risk patients on RVD should continue taking RVD, although if appropriate this could be changed to Rd. If a patient develops COVID-19, maintenance therapy should be interrupted until the infection resolves. Hematopoietic stem cell transplantation may be delayed if resources are limited; otherwise eligible patients should proceed to stem cell based transplant, particularly if they have high-risk myeloma.[365]

The EMN provides recommendations for transplant-eligible and transplant ineligible patients. Autologous stem cell transplantation should be postponed in patients with standard-risk disease and may be considered in patients with high-risk disease after 6-8 cycles of induction treatment. Either RVD, bortezomib with thalidomide and dexamethasone, (VTD), or daratumumab with VTD are the preferred induction therapies.[401] Patients not eligible for transplant should be given all-oral regimens (e.g., Rd), with the addition of bortezomib or daratumumab considered for patients with high-risk disease or for those without sufficient response to Rd.[401]

Guidelines from Australia and New Zealand advise that treatment during the pandemic may depend on available resources, but that management should be guided by the need for disease control in high-risk patients and avoiding unnecessary immune suppression in low-risk patients.[283] Treatment decisions should be individualized, taking into account factors such as newly diagnosed versus relapsed disease, stage, disease burden and rate of progression, and patient factors such as age, frailty, and comorbidities.[283]

The UK Myeloma Forum has released guidance to assist clinical decision making during the COVID-19 pandemic. Newly diagnosed patients with hypercalcemia, renal impairment, or bone disease should be offered primary treatment. If the patient is eligible for a stem cell transplant, treatment should include bortezomib and dexamethasone with either thalidomide (VTD) or cyclophosphamide (VCD). For patients who are ineligible for a transplant, lenalidomide and dexamethasone should be given for 9 cycles followed by single agent lenalidomide. Patients with clinical relapse should be offered second- and third-line therapy if the expected benefit outweighs the risk. Autologous hematopoietic stem cell transplant should be deferred unless the patient has clinically high-risk disease, in which case clinicians should judge the likelihood of progression without transplant. Allogeneic hematopoietic stem cell transplant should be deferred.[402]

The UK Medicines and Healthcare products Regulatory Agency has agreed temporary modifications to the pregnancy prevention programmes for patients taking thalidomide, lenalidomide, and pomalidomide. A home pregnancy test is sufficient, provided the patient has adequate support and instruction, the test meets the minimum sensitivity requirements and the result is verified by the prescriber. If the clinician deems it appropriate, these medications can be initiated during a remote consultation.[403]

There are limited data on trials of severe acute respiratory syndrome coronavirus 2 vaccination in patients with hematological conditions. Such patients are likely to have an attenuated response to vaccination. One study of the BNT162b2 mRNA COVID-19 vaccine in elderly patients with multiple myeloma found the antibody response was reduced compared with healthy controls after the first dose.[404] Additional measures, such as early vaccination of household contacts, may be considered.[230]

The Association of British Neurologists (ABN) has produced guidance on the use of disease-modifying therapies in patients with multiple sclerosis (MS) during the pandemic.[405] The ABN advises that the effect of disease-modifying therapies on the risk of COVID-19 remains uncertain. Disease-modifying treatments should be offered to patients, provided that the benefits of treatment outweigh the risks. The local rate of COVID-19 infection, the patient’s general health, and their exposure to the virus all influence this risk/benefit decision. Patients should be advised if their disease-modifying therapy might affect the efficacy of a future vaccine or the severity of COVID-19. Patients should also be informed if use of their treatment means they should be shielding. Self-isolation may be appropriate following use of high-dose corticosteroids for a relapse of MS. The guidance provides information on considered level of risk for specific disease-modifying therapies.[405] The US National MS Society also recommends that decisions on the use of disease-modifying therapies are individualized and should consider disease factors, risks and benefits of therapies, and risks associated with COVID-19.[406] The National MS Society recommends that people currently taking disease-modifying therapies should continue, and if they develop symptoms of COVID-19 or test positive, their therapies should be reviewed with someone familiar with their care.

Observational studies of patients with MS have found that risk factors for severe forms of COVID-19 are older age, increased levels of disability (Expanded Disability Severity Scale [EDSS] score ≥6, requiring assistance to walk, or being unable to walk), black race, cardiovascular disease, diabetes, obesity, and corticosteroid treatment within the previous 2 months.[407][408] One study found no association between use of disease-modifying therapies and severity of COVID-19.[407] Another study found that patients taking rituximab had an increased risk of hospitalization compared with patients who did not take any disease-modifying therapy, but there was no significantly increased risk of intensive care unit admission, need for mechanical ventilation, or death among the patients taking rituximab.[409]

Analysis of US health-insurance claims data has shown that lymphoma is a significant risk factor for fatal COVID-19.[75] Indolent and aggressive non-Hodgkin lymphomas are associated with worse survival in patients with COVID-19.[228][74] Interim treatment guidelines for the management of adult patients during the pandemic have been provided by experts from the UK and also from Australia and New Zealand.[388][283] For most patients with aggressive non-Hodgkin lymphoma subtypes, treatment is delivered with curative intent and this remains the clinical priority. Recommendations are given for patients with Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), primary mediastinal B cell lymphoma, central nervous system (CNS) lymphoma, peripheral T cell lymphoma, and relapsed/refractory aggressive lymphoma. For patients with low-grade non-Hodgkin lymphoma and not requiring immediate treatment, watchful waiting may be considered; initiation of treatment should be based on a risk–benefit discussion between the patient and physician.

The American Society for Hematology has published advice for the management of aggressive lymphomas. R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard of care for diffuse large B cell lymphoma. For older patients, R-mini-CHOP (a reduced dose regimen) with growth factor support is recommended. Subcutaneous rituximab may be considered for patients who have tolerated a first intravenous dose. Recommendations are also given for double-hit and primary mediastinal B cell lymphomas, patients at higher risk of CNS involvement, and patients with relapsed or refractory disease.[410] The International Lymphoma Radiation Oncology Group has published emergency guidelines for radiation therapy in hematologic malignancies, should radiation therapy be necessary. Alternative dose fractionations may be given.[88]

Trials of severe acute respiratory syndrome coronavirus 2 vaccination in patients with hematological conditions are lacking. Such patients are likely to have an attenuated response to vaccination. Additional measures, such as early vaccination of household contacts, may be considered.[230]

The European Society of Cardiology has published guidance on the diagnosis and management of cardiovascular disease during the COVID-19 pandemic, and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) has issued a position statement on invasive management of acute coronary syndromes.[272][411]

Patients presenting with non-ST-elevation acute coronary syndrome should be risk stratified into four groups: very high, high, intermediate, and low risk. Very high-risk patients include patients with cardiogenic shock, hemodynamic instability, recurrent or persistent chest pain refractory to medical therapy, life-threatening arrhythmias, cardiac arrest, mechanical complications of myocardial infarction, acute heart failure, and recurrent intermittent ST-elevation. High-risk patients are those with an established diagnosis of NSTEMI based on cardiac troponins and at least one of: dynamic ST/T changes, or recurrent symptoms.

Testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) should be performed as soon as possible after first medical contact. However, patients who are very high risk require immediate invasive management as per ST-elevation myocardial infarction (STEMI) protocols. High-risk patients should have early intervention (ideally within 24 hours) after their SARS-CoV-2 test results are known. Intermediate- and low-risk patients should initially be managed with noninvasive testing once their SARS-CoV-2 test results are known. Coronary computed tomography angiography (CCTA) is the favored investigation for intermediate-risk patients where equipment and expertise are available. Noninvasive imaging using CCTA may speed up risk stratification, avoid an invasive approach, and allow early discharge.[272][411]

UK guidance advises using ECG and measuring high-sensitivity troponin and N-terminal pro B-type natriuretic peptide in patients hospitalized with COVID-19 who have signs or symptoms of acute myocardial injury. In patients with severe COVID-19, elevated troponin levels may result from cardiac inflammatory response rather than acute coronary syndrome. Patients with suspected or confirmed acute myocardial injury should receive continuous ECG monitoring, as well as blood pressure, heart rate, and fluid monitoring, in a setting where deterioration can be quickly identified. Where diagnosis is not clear, ECG should be monitored daily and high-sensitivity troponin measurements should be repeated.[121]

Guidelines from Australia and New Zealand state that reliance on troponin measurements to diagnose acute coronary syndrome in patients with COVID-19 can be misleading, and greater emphasis should be given to high risk clinical features: recurrent chest pain, dynamic ECG changes, heart failure, hemodynamic instability, major arrhythmias, and the presence of regional wall motion abnormalities on echocardiography. Invasive investigations should be deferred in stable patients, particularly if they are COVID-19 positive.[172]

A cohort study from the UK reported that black and minority ethnic (BAME) patients had higher rates of hospitalization for acute myocardial infarction and longer time to coronary angiography for NSTEMI than white patients during the pandemic, compared with the same pre-pandemic period. BAME patients were more likely than white patients to present with out-of-hospital cardiac arrest and cardiogenic shock during the COVID-19 pandemic compared with the period before the pandemic. In-hospital and 7-day mortality was higher in BAME patients (relative to white patients) during the COVID-19 pandemic compared with the pre-pandemic period.[412]

Obesity (body mass index [BMI] ≥30kg/m²) is associated with increased risk of a positive COVID-19 test, hospitalization, severe COVID-19 requiring admission to intensive care, mechanical ventilation, and death.[273][275][413][414][415][416][334] The association is strongest in patients <65 years.[275][417] Patients with obesity who develop COVID-19 are also at higher risk for venous thromboembolism and dialysis.[414]

Being overweight (BMI >25kg/m² and <30kg/m²) might increase the risk of severe illness from COVID-19, and is associated with increased risk of mechanical ventilation.[273][417][334][418]

A study in the US found a nonlinear (J-shaped) relationship between BMI and risk of hospitalization, intensive care admission, and death.[417] A study in the UK also found nonlinear associations between BMI and hospital admission and death due to COVID-19, and a linear association between BMI and intensive care admission due to COVID-19.[418] In the UK study, the relative risk due to increasing BMI was particularly notable in people younger than 40 years and of black ethnicity.

There is currently no high-quality research on the effects of weight loss on COVID-19, but that the role of excess weight as a risk factor for serious COVID-19 complications warrants further consideration.[413] For those living with obesity, weight loss has been shown to bring general long-term health benefits.

Patients with obesity who recover from COVID-19 may be at increased risk of postacute sequelae. One study found that patients with obesity who did not require ICU admission and survived the acute phase of COVID-19 had an increased risk of hospital admission and needing diagnostic tests over the subsequent 8 months compared with patients with normal BMI.[419]

The American Academy of Pediatrics advises that children and adolescents with obesity are at increased risk for COVID-19 and worsening of their obesity during the pandemic. Disruption to routine, sleep dysregulation, decreased physical activity, food insecurity, and increased screen time may all contribute. Clinicians should continue to provide obesity treatment and should identify and treat obesity-related comorbidities during the pandemic. Clinicians should counsel patients and their families about the risk of COVID-19, screen for disordered eating (e.g., binge eating, purging, and restrictive eating), and connect families to resources to address social determinants of health. [187]

Obstructive sleep apnea (OSA) may increase the risk of developing COVID-19 infection, and may also increase the risk of having more severe COVID-19 infection.[420] In a study of people with diabetes who were hospitalized for COVID-19, treated OSA was independently associated with an increased risk of death.[421] One systematic review noted that many of the risk factors for OSA (such as age, hypertension, cardiovascular disease, lung disease, diabetes, and obesity) are associated with worse outcomes for COVID-19 infection.[422] The review also found that the COVID-19 pandemic has had a large effect on the diagnosis and treatment of OSA, and that new diagnosis and treatment pathways may be necessary (e.g., using disposable sleep study kits).

Olfactory loss (anosmia) may be a presenting symptom of COVID-19. The European Rhinologic Society advises against prescribing intranasal or systemic corticosteroids for patients with sudden olfactory loss. Patients should be advised to continue their usual medications, including intranasal corticosteroids prescribed for other indications.[423]

Many patients with open-angle glaucoma will be vulnerable to severe COVID-19. UK guidelines advise that clinicians should weigh the risks of visual loss from glaucoma against the population spread of COVID-19 by clinic attendance and the risk of death from COVID-19. Priority for surgery should be given to those on maximum tolerated medication whose intraocular pressure (IOP) remains high and is likely to cause significant vision loss in the short term. If possible, additional medication, diode laser or selective laser trabeculoplasty can be used to postpone the need for surgery. Where possible, procedures should be performed as day cases under local anaesthetic. Procedures requiring intensive postoperative follow up, antimetabolite injections or suture adjustment should be avoided if possible.[424]

Empirical treatment can be started for patients referred to the glaucoma clinic following an assessment of their symptoms, referral information, medical and drug history. Telephone or video consultation should be used to explain the diagnosis, explain how to use medication and assess side effects.[424]

Patients with mild glaucoma and well-controlled IOP, patients with ocular hypertension and patients with suspected glaucoma are considered low risk. Review appointments may be deferred but patients should be advised whom to contact if their symptoms deteriorate. Patients with moderate to advanced glaucoma and controlled IOP are considered medium risk and should be offered a telephone appointment; medication changes may be initiated remotely and face-to-face review arranged if needed. High risk patients include: children, people with advanced glaucoma or secondary glaucoma who have a significant risk of avoidable vision loss in the short term, and patients with uncontrolled IOP (>30mmHg, or 20-30 mmHg with advanced disc changes). Patients should be offered face-to-face or telephone/video appointments depending on their comorbidities and severity of glaucoma.[424]

Guidelines from an international group of experts suggest altering the approach to management of osteoporosis during the current pandemic:[425]

- Zoledronic acid can be delayed for 6 to 9 months during the pandemic.

- Patients established on 6-monthly denosumab should continue without any delay and self-administration can be considered where appropriate. Pre-treatment checking of serum vitamin D and calcium levels can be waived and empiric treatment with cholecalciferol (vitamin D3) can be considered for all patients.

- Patients established on teriparatide, abaloparatide, or romosozumab should continue; however, periods of discontinuation for many weeks are unlikely to affect the long-term beneficial effects on fracture risk reduction.

- No new patients should be started on zoledronic acid, teriparatide, abaloparatide, or romosozumab due to the risk of confusion from potential adverse effects of the therapies and symptoms of COVID-19.

- If not contraindicated, alternative treatment, such as continuing with an oral bisphosphonate, should be considered.

The American Society of Bone and Mineral Research (ASBMR) has also published recommendations for the management of osteoporosis during the pandemic.[426]

The American College of Rheumatology advises that the denosumab dosing interval can be extended if necessary to minimize healthcare encounters, but should not exceed 8 months.[427]

Patients should be educated on the importance of continuing with calcium and vitamin D through supplements or diet, and lifestyle measures such as regular exercise and healthy diet.

The National Institute for Health and Care Excellence in the UK has published guidelines for managing symptoms at the end of life during the COVID-19 pandemic. Where possible, clinicians should discuss the benefits, risks, and likely outcomes of any treatment with the patients, their relatives, and caregivers. The patient's preference about treatment and escalation plans should be sought, and clinicians should enquire about any advance care plans, advance decisions to refuse treatment, or "do not attempt resuscitation" decisions. Patients with COVID-19 can deteriorate rapidly; treatment escalation plans should be put in place as soon as possible.[121]

Cough should initially be managed with nonpharmacologic measures if possible. Patients should be discouraged from lying on their back because this makes coughing ineffective. Simple measures, such as honey, may be used. Persistent, distressing cough can be managed with opioids.[121][428]

If patients have fever and other symptoms, acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) may be used as antipyretics. They should only be taken while both the fever and other symptoms are present.[121]

Reversible causes, such as pulmonary embolism, pulmonary edema, or exacerbation of airway disease, should be sought and treated.[121] Relaxation and breathing techniques, changing body positioning, maintaining a cool environment, and opening a window or door may help ease symptoms of breathlessness.[121] A trial of oxygen may given if hypoxia is the likely cause of the breathlessness.[121]

A combination of opioids and benzodiazepines may be considered for patients who have moderate or severe breathlessness, are distressed, and are in the last days or hours of life.[121][428] An antiemetic and regular stimulant laxative should be considered concomitantly.

Benzodiazepines may also be considered to manage symptoms of anxiety and agitation.[428][121] Oral haloperidol may be considered if a patient has delirium.[121]

Consider whether the sublingual, rectal, or subcutaneous route is appropriate for administration for medication; this may be easier for relatives or caregivers to administer if there are fewer healthcare staff.[121] In the UK, hospices and care homes may run a medicines reuse scheme during the COVID-19 pandemic, following a strict standard operating procedure to ensure safety.[429]

Implantable cardiac defibrillators (ICDs) cannot be deactivated remotely. If a patient with an ICD is receiving end of life care, the treating clinical team should secure a magnet to the skin over the ICD where possible, rather than using the programmer.[173]

Further resources are available at:

The World Hospice and Palliative Care Alliance: COVID-19 resources external link opens in a new window

A UK consensus statement recommends that endoscopic therapy for malignant biliary obstruction, with biopsy or cytology specimen collection if indicated, should continue during the COVID-19 pandemic. Urgent (2 week wait) cancer referrals and endoscopic ultrasound requests should be considered on a case-by-case basis.[430]

Surgery for resectable pancreatic cancer remains the standard of care and should be performed whenever possible. If surgery is not available, systemic anticancer therapy (SACT) or hypofractionated chemoradiotherapy should be offered. Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the preferred SACT regimen. Radiation therapy may be given as 35-45 Gy in 5 fractions, depending on center expertise, or 36 Gy in 15 fractions with concurrent capecitabine.[430] FOLFIRINOX is most appropriate in patients with a good performance status without significant comorbidities. Dose modification, use of prophylactic antibiotics and growth factors and physical distancing measures should be used to reduce the risk of severe COVID-19 infection.

Patients with locally advanced pancreatic cancer are usually treated with upfront SACT, with or without radiation therapy. Hypofractionated radiation therapy or chemoradiotherapy may reduce risk of severe COVID-19 infection and allow a deferral or break from SACT; this should be balanced against the risk of metastasis without upfront chemotherapy. The risks of treatment in patients aged over 80 years are likely to outweigh the benefits. For fit patients with no significant comorbidities, treatment options include four cycles of modified FOLFIRINOX with or without hypofractionated radiation therapy or five cycles of radiation therapy alone.[430]

The median improvement in survival with palliative chemotherapy for metastatic disease is <6 months so the risks of treatment are likely to outweigh the benefits for many patients. The decision to treat should be taken on a case-by-case basis. Early response assessment should be considered, depending on radiology capacity, because this may allow a shorter duration of chemotherapy. A break from chemotherapy may be appropriate for patients with low volume disease or good disease control. Second-line palliative chemotherapy should not be offered.[430]

Patients with Parkinson disease who are treated with deep brain stimulation (DBS) require ongoing outpatient visits and surgical care and may not tolerate interruption or cessation of therapy, with some experiencing life-threatening DBS-withdrawal syndrome.[431] In the current pandemic, many elective procedures are being deferred; however, practical recommendations are available to guide management of DBS device complications or battery replacement. Patients who are at high risk for severe or life-threatening symptoms or hospitalization with DBS cessation would be considered the highest priority for DBS replacement; patients at lower risk may be able to have replacement postponed.[431]

Pediatric rheumatic diseases

The American College of Rheumatology (ACR) has published guidance for the management of pediatric rheumatic disease (PRD) during the pandemic.[432] Currently, the evidence does not suggest that children with PRD and children receiving immunomodulatory therapies for PRD have a higher risk of severe COVID-19 infection, and general preventative measures are advised. The ACR guidance provides recommendations for ongoing treatment of patients during the pandemic, including for those who have been exposed to severe acute respiratory syndrome coronavirus (SARS-CoV-2), and for those with probable or confirmed infection. 

Radiation oncologists from the US and the UK have agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. Visits should be conducted as video consultations whenever possible. In most cases, routine measurement of prostate-specific antigen (PSA) following treatment can be safely deferred for ≥3 months. Radiation therapy for very low-, low-, and favorable-intermediate-risk disease may be deferred until pandemic restrictions are lifted (assuming the pandemic wanes over the next 12 months).[433]

Remote telehealth visits should continue for patients with unfavorable-intermediate, high-risk, very high-risk, postprostatectomy, clinical node-positive, oligometastatic, and low-volume metastatic disease. Androgen deprivation therapy may allow radiation therapy to be deferred. If androgen deprivation therapy cannot be delivered, the benefits of radiation therapy should be weighed against the risk of COVID-19, taking into account the patient's age, comorbidities, and immunosuppression.[433]

If treatment is deemed necessary and the benefits outweigh the risks, the shortest fractionation schedule that has evidence of efficacy and safety should be followed. If treatment needs to be performed during the peak of the pandemic, brachytherapy is not recommended given its reliance on anesthesia staff and personal protective equipment. Brachytherapy performed with use of local anesthesia may be a suitable option for those experienced with this method and if resources are available.[433]

A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[44] The National Psoriasis Foundation has published guidance for the management of psoriatic disease during the COVID-19 pandemic. Patients with psoriasis seem to have similar rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 outcomes as the general population. However, patients with psoriasis, particularly those with severe disease, are more prone to comorbidities associated with poor COVID-19 outcomes. [53]

Patients and clinicians should make shared decisions regarding use of systemic therapies during the pandemic. The risks and benefits of starting or continuing a drug that affects the immune system need to be carefully considered, including considering whether the required monitoring is possible, whether the patient has had COVID-19 vaccination, and whether there are changes that could make hospital attendance or admission less likely.[46] In most cases, it is recommended that patients who do not have SARS-CoV-2 infection should continue biological or oral therapies.[53] Chronic systemic corticosteroids should be avoided if possible. If used, the dose should be tapered to the lowest therapeutic dose.[53] Patients who are already taking systemic corticosteroids should not stop them suddenly.[46] Initiation of systemic therapies should be discussed with patients who are newly diagnosed with psoriasis, because untreated psoriatic disease may lead to permanent joint damage and disability. Newly diagnosed patients, patients with unstable disease or flares, patients requiring a thorough skin and/or joint examination, and patients at risk for skin cancer should receive in-person care where pandemic conditions allow.[53] 

The International Psoriasis Council recommends discontinuing or postponing the use of immunosuppressive medications in patients diagnosed with COVID-19.[49] Patients with psoriasis who become infected with SARS-CoV-2 should receive evidence-based therapies and supportive care. Systemic corticosteroids should not be withheld due to concern about a psoriasis flare following withdrawal. Dermatology and/or rheumatology consultation may be needed for hospitalized patients. Decisions about restarting treatments for psoriasis and psoriatic arthritis after recovery form COVID-19 should be made on a case-by-case basis.[53]

The National Psoriasis Foundation recommends that in most cases, patients should take the first vaccine for which they are eligible and they are offered. Systemic medication for psoriasis or psoriatic arthritis is not a contraindication to any of the available SARS-CoV-2 vaccines.[53]

The American Society of Hematology advises that normal D-dimer can be used to effectively rule out pulmonary embolism (PE) in patients with COVID-19. Radiologic imaging is not necessary if the D-dimer is normal in the context of low pretest probability. Elevated D-dimer may have many causes, including COVID-19, myocardial infarction, coagulopathy, and renal failure; new symptoms or signs of PE should be sought, and if possible patients should be investigated for PE with computed tomography pulmonary angiogram and/or bilateral compression ultrasonography of the legs. Clinical features that increase the likelihood of PE include symptoms or signs of deep vein thrombosis, unexplained hypotension or tachycardia, unexplained worsening respiratory status, and risk factors for thrombosis. If pulmonary imaging is not feasible to confirm or refute the diagnosis of PE, bilateral compression ultrasonography of the legs, echocardiography, or point-of-care ultrasonography may be considered. These tests may identify thrombus in situ or in transit, but cannot exclude PE if no clot is detected.[434]

Empiric anticoagulation is discouraged, but may be given in the following circumstances if there is a very high clinical suspicion of thrombosis, no possibility of performing diagnostic imaging studies, and there are no contraindications:[434]

- Intubated patients who suddenly develop clinical and laboratory findings highly consistent with PE. These may include desaturation, tachycardia, increased central venous or pulmonary wedge pressure, or evidence of right heart strain on echocardiogram, particularly if their inflammatory markers and chest radiograph findings are improving.

- Patients with physical findings consistent with thrombosis, such as superficial thrombophlebitis, peripheral ischemia or cyanosis, thrombosis of dialysis tubing, or retiform purpura.

- Patients with respiratory failure in whom PE is highly suspected and other causes are not identified, particularly when D-dimer and/or fibrinogen levels are very high.

Patients who have documented or presumed PE should continue therapeutic anticoagulation for 3 months. Anticoagulation may then cease if the patient has fully recovered from COVID-19 and there are no other risk factors for thrombosis or indications for anticoagulation.[434]

Renal transplant

UK guidelines advise that renal transplant recipients are clinically extremely vulnerable to COVID-19 and should follow current government guidance on shielding. Clinicians should consider whether less frequent blood monitoring is appropriate for patients who are stable on immunosuppressive treatment. Patients who take immunosuppressive treatment may present with atypical symptoms and signs of COVID-19; for example, patients taking prednisone may not develop a fever. Other infectious and noninfectious causes should also be considered in patients who present with respiratory symptoms or fever. If a patient develops COVID-19, clinicians should consider modifying their immunosuppressive treatment.[435] Guidelines from the British Transplantation Society and Renal Association recommend stopping mycophenolate and azathioprine until the patient has fully recovered. If the patient has severe or progressive disease, clinicians should consider stopping or reducing calcineurin inhibitors.[436]

People who have been exposed to suspected or confirmed COVID-19 in the past 14 days, who have died from unexplained respiratory failure, or who test positive on a polymerase chain reaction test for COVID-19 are not suitable deceased donors.[437]

Live kidney donors and their household should follow comprehensive social distancing and hand-hygiene measures for 14 days before the transplant; clinicians should discuss with donors whether they should self-isolate for 14 days before the transplant, taking into account their individual risk of contracting COVID-19, the current local prevalence of COVID-19, and the delay to transplant if they contract COVID-19. Intended transplant recipients should self-isolate for 14 days before the transplant if possible, and dialysis should take place in a COVID-secure area.[435] Donors and recipients should have a nasopharyngeal swab for SARS-CoV-2 no more than three days before admission and should both self-isolate from the day of the test until admission. SARS-CoV-2 testing should be interpreted in the context of other assessments; a negative test does not definitely rule out infection. Donors should be assessed for symptoms and risk of COVID-19 when scheduling the transplant, on the day before the transplant, and on admission; recipients should be assessed the day before a scheduled live donor transplant and on admission for transplant. Assessment should include symptoms of COVID-19, history of social distancing, any contact with people who might have COVID-19, a respiratory assessment, review of SARS-CoV-2 test results, and completion of a rapid turnaround test if needed.[435] Donor surgery should not begin until both donor and recipient are confirmed swab-negative for SARS-CoV-2.[438]

If patients on the kidney transplant waiting list develop COVID-19, they should be suspended from the waiting list until they have recovered, been symptom-free for 28 days, and have a negative swab for SARS-CoV-2.[435]

In prospective cohort studies, 33% to 54% of kidney transplant recipients developed antibodies against SARS-CoV-2 after two doses of mRNA vaccine.[439][440] Antibody titers were lower amongst patients who did develop antibodies compared with immunocompetent people.[439]

A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[44] A cohort study conducted in the US found that systemic autoimmune rheumatic disease was associated with increased risk of hospitalization, intensive care admission, acute kidney injury, and venous thromboembolism. The risk was largely due to comorbidities, except for the risk of venous thromboembolism. Risk of mechanical ventilation and death was not increased in the patients with systemic autoimmune rheumatic disease.[441] Patients should continue their usual medication and observe recommended infection prevention and control precautions.[442][443] If it is possible and clinically safe, corticosteroid dose may be tapered. Clinicians should consider alternatives to corticosteroids where possible, and if corticosteroids are needed, prescribe the lowest effective dose for the shortest possible time. Corticosteroid injections should only be given when a patient has significant disease activity and/or intrusive and persistent symptoms, and there are no suitable alternatives.[444][445] UK guidelines recommend assessing whether patients receiving intravenous treatment can be switched to the same treatment in subcutaneous form, or, if this is not possible, to consider an alternative subcutaneous treatment option.[444]

Conventional synthetic disease-modifying antirheumatic drugs (DMARDS) may be started or switched in patients with newly diagnosed or active inflammatory arthritis.[427]

Patients receiving immunosuppressive medication may develop atypical symptoms of COVID-19 (e.g., patients who take an oral corticosteroid may not develop fever). Patients who take an oral corticosteroid should not stop suddenly if they develop COVID-19.[444][427] Patients who are taking long-term corticosteroids may be at risk of adrenal crisis and may require a higher dose if they are diagnosed with COVID-19.[444] American College of Rheumatology guidance recommends that patients should stop hydroxychloroquine and chloroquine if they become infected with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) because of the potential for cardiotoxicity, which could be heightened by COVID-19 infection and receipt of other drugs in hospital.[427] UK guidelines advise that patients may continue hydroxychloroquine and sulfasalazine if they are infected with SARS-CoV-2.[444] Interleukin-6 receptor inhibitors may be continued in select circumstances as part of a shared decision-making process.[427] The half-life of some drugs means that immunosuppression will continue for some time after stopping treatment.[444]

Patients may continue taking nonsteroidal anti-inflammatory drugs (NSAIDs). The Commission of Human Medicines in the UK reviewed the safety of ibuprofen in patients with COVID-19 and concluded that there is currently insufficient evidence to establish a link between use of ibuprofen, or other NSAIDs, and contracting or worsening of COVID-19.[446] The UK National Institute for Health and Care Excellence has also reviewed the evidence to determine if long-term use of NSAIDs is associated with an increased risk of developing COVID-19, or an increased risk of developing more severe COVID-19, and found no evidence to recommend that people taking NSAIDs for a long-term condition should stop, and that stopping or switching NSAID treatment could have a negative impact in some people.[447] The American College of Rheumatology advises stopping NSAIDs in patients who develop severe manifestations of COVID-19, such as kidney, cardiac, or gastrointestinal injury.[427]

The Food and Drug Administration (FDA) is investigating and states: "At this time, FDA is not aware of scientific evidence connecting the use of NSAIDs, like ibuprofen, with worsening COVID-19 symptoms."[448] The European Medicines Agency advises that patients and clinicians can continue using NSAIDs as per the approved product indication, and has highlighted the need for timely epidemiologic studies to provide adequate evidence for any effect of NSAIDs on the disease prognosis of COVID-19.[449] One prospective multicentre study in the UK in patients hospitalized with COVID-19 found that those taking NSAIDs before admission had the same outcomes as those who did not.[295]

A prospective study of patients with inflammatory arthritis who had confirmed or highly suspected COVID-19 infection found that older age, comorbid hypertension, comorbid COPD, and glucocorticoid use were associated with an increased risk of hospitalization. Maintenance anticytokine biologic therapies were not associated with an increased risk of hospitalization.[450]

Following recovery from COVID-19, US guidelines recommend that rheumatic disease treatments can be restarted within 7-14 days of symptom resolution in patients with mild or no pneumonia who were treated in the ambulatory setting or with self quarantine. Decisions regarding restarting rheumatic disease therapies in patients who had more severe COVID-19 should be taken on an individual basis. If a patient had a positive polymerase chain reaction test for SARS-CoV-2 but has remained asymptomatic, rheumatic disease treatments may be restarted 10-17 days after the positive test result.[427]

Clinicians should take measures to reduce hospital visits for patients, which may include longer duration of prescriptions, home delivery of medication, utilizing telephone or video appointments, and increasing drug monitoring to the maximum safe interval.[444]

UK guidelines recommend that patients urgently referred for suspected inflammatory arthritis, autoimmune connective tissue disease, and vasculitis are offered a face-to-face appointment. [444] Patients are advised to have influenza, whooping cough, and pertussis vaccinations.[451]

One study in the US found that, similar to findings in the general US population, black, Asian, and Latin American patients with rheumatic disease and COVID-19 had an increased risk of hospitalization and ventilatory support compared with white patients, even after adjustment for demographic, rheumatic disease activity, and comorbidities.[452]

Clinicians are advised to engage patients with rheumatic disease in a shared decision-making process to discuss receiving a SARS-CoV-2 vaccine.[453][362] The response to vaccination is likely to be blunted in patients receiving systemic immunomodulatory therapies compared with the general population.[453][362] The American College of Rheumatology advises that, beyond known allergies to vaccine components, there are no additional contraindications to SARS-CoV-2 vaccination for patients with autoimmune and inflammatory rheumatic diseases. Vaccination should ideally occur when rheumatologic disease is well controlled.[362]

Patients with sickle cell disease are at higher risk of severe disease and death if they become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A registry of patients with sickle cell disease and COVID-19 in the US reported that the rate of hospitalization amongst adults with sickle cell disease was 69%, the intensive care admission rate was 11% and mortality was 7%.[454] The Sickle Cell Disease Association of America has published advice on reducing sickle cell disease morbidity during the COVID-19 pandemic. Routine consultations should take place via telephone or video wherever possible and should not be canceled. Patients should be advised to adhere carefully to their usual medication, to use a thermometer at home, and to seek prompt medical advice if they develop fever. Clinicians should ensure that patients have an adequate supply of medication to manage acute and chronic pain, and consider starting or optimizing therapies known to reduce acute sickle cell pain frequency to reduce the need for hospital attendance.[455]

Patients who have acute sickle cell pain without fever or signs of infection should be encouraged to manage pain with oral medication at home. Patients should be closely monitored, with a low threshold for arranging a face-to-face evaluation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing.[455]

Patients with fever, cough, or shortness of breath require immediate evaluation for COVID-19. Care should include an assessment for other sources of infection with culture of blood (and other specimens as indicated), testing for typical viral infections, administering broad-spectrum antibiotics to cover encapsulated organisms, and assessing for acute chest syndrome. If the patient tests negative for SARS-CoV-2, home treatment with oral antibiotics and close monitoring may be appropriate. If possible, patients should be given an incentive spirometer to use at home.[455]

Patients with confirmed COVID-19 should be monitored closely for signs of rapidly progressive acute chest syndrome (thrombocytopenia, acute kidney injury, hepatic dysfunction, altered mental status, and multiorgan failure). The symptoms of acute chest syndrome may overlap significantly with symptoms of COVID-19. Standard care for acute chest syndrome should be given, including supplemental oxygen, empiric antibiotics, oseltamivir until influenza is excluded, incentive spirometry, and good pain control. Patients with worsening anemia, evidence of hypoxia, and chest x-ray changes should receive a transfusion of red blood cells. Clinicians should consider the possibility of undiagnosed pulmonary hypertension in acutely ill patients and be alert for signs of fat emboli syndrome. Signs of fat emboli syndrome include worsening anemia and mental status, hemolysis, thrombocytopenia, hypoalbuminemia, respiratory distress, and petechial rash; it may progress quickly and carries a high mortality. Patients who have COVID-19 and are discharged from the hospital remain at high risk of secondary bacterial infection and acute chest syndrome; they should be monitored daily.[455]

If availability of blood products is limited, the highest priority indications for chronic transfusion are: stroke prevention, progressive or critical neurovascular disease, recurrent acute chest syndrome unresponsive to hydroxyurea, and cardiovascular or respiratory comorbidity. Clinicians should assess whether patients can switch to hydroxyurea or whether transfusion strategy can be temporarily altered.[455]

In patients with COVID-19, evidence suggests that smoking is associated with an increased risk of symptomatic COVID-19 infection, more severe disease, and death.[456][457][457] People who smoke tobacco may also have an increased risk of contracting COVID-19. It is well-established that smoking damages the lungs and airways, and weakens the immune response; people exposed to second-hand smoke are also at increased risk.

Vaping/use of e-cigarettes is often used as nicotine-replacement therapy; however, the evidence on benefits and harms is still developing. People should not share vaping devices or cigarettes. Smoking cessation is strongly encouraged.[456][458]

The European Society of Cardiology has published guidance on the diagnosis and management of cardiovascular disease during the COVID-19 pandemic, and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) has issued a position statement on invasive management of acute coronary syndromes.[272][411]

The guidance emphasizes that the pandemic should not compromise the timely reperfusion of patients with STEMI, therefore in the absence of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing all patients should be managed as if they are COVID-19 positive. Primary percutaneous coronary intervention (PCI) is the reperfusion treatment of choice if it can be performed within 120 minutes in appropriate facilities while ensuring the safety of healthcare professionals and other patients. Experience suggests that a delay of up to 60 minutes may occur due to implementing protective measures, and clinicians should take this into account when assessing whether timely primary PCI is possible. If primary PCI cannot be performed within the target time, fibrinolysis is the intervention of choice provided there are no contraindications. All patients should undergo testing for SARS-CoV-2 as soon as possible following first medical contact irrespective of reperfusion strategy, at the latest upon admission to the intensive care unit after primary PCI. Clinicians should consider immediate complete revascularization, if indicated and appropriate, in order to avoid staged procedures and reduce hospital stay.[272][411]

UK guidance advises using ECG and measuring high-sensitivity troponin and N-terminal pro B-type natriuretic peptide in patients hospitalized with COVID-19 who have signs or symptoms of acute myocardial injury. The same ECG diagnostic criteria for cardiac conditions apply in patients with COVID-19 and the general population.[272] Patients with ST-elevation should be referred immediately to a cardiologist for consideration of percutaneous coronary intervention. In patients with severe COVID-19, elevated troponin levels may result from cardiac inflammatory response rather than acute coronary syndrome. Patients with suspected or confirmed acute myocardial injury should receive continuous ECG monitoring, as well as blood pressure, heart rate, and fluid monitoring, in a setting where deterioration can be quickly identified. Where diagnosis is not clear, ECG should be monitored daily and high-sensitivity troponin measurements should be repeated.[121]

A cohort study from the UK reported that black and minority ethnic (BAME) patients had higher rates of hospitalization for acute myocardial infarction and longer time to reperfusion therapy for STEMI than white patients during the pandemic, compared with the same pre-pandemic period. BAME patients were more likely than white patients to present with STEMI, out-of-hospital cardiac arrest, and cardiogenic shock during the COVID-19 pandemic compared with the period before the pandemic. In-hospital and 7-day mortality was higher in BAME patients (relative to white patients) during the COVID-19 pandemic compared with the pre-pandemic period.[459]

Guidance from the American Heart Association/American Stroke Association advises that patients with COVID-19 may present with neurologic symptoms (such as dizziness, headache, or encephalopathy) at the same time as, or even preceding, the development of respiratory symptoms and fever. Patients affected by stroke may be unable to give a history of COVID-19 symptoms or exposure owing to confusion or aphasia. Patients with stroke frequently develop a fever from stroke complications, including aspiration pneumonia and urinary tract infection; these patients require rapid evaluation for COVID-19.[460]

Evaluation using telemedicine can allow a timely assessment, reduce inter-provider transfers, and protect healthcare professionals. Ideally, full personal protective equipment should be worn by the assessing healthcare professional, but this may not be possible where there are shortages.[460]

All stroke teams should endeavor to adhere to guidelines for patient selection for therapy, treatment timeframes, and post-recanalization monitoring. Teams should use their judgment, guided by local circumstances, to treat as many patients with acute stroke as possible. Patients with large intracerebral bleeds, subarachnoid hemorrhage, or large ischemic strokes at risk of herniation should be monitored in an intensive care setting, with appropriately trained personnel, where possible. Stable patients may be moved out of intensive care to step-down facilities during the 24-hour post-thrombolysis or thrombectomy follow-up period, if an intensive care bed is needed. Stroke physicians should provide guidance to staff if patients with acute stroke have suspected or confirmed COVID-19 and require admission to a COVID-19 unit.[460]

Cerebrovascular disease is associated with increased mortality from COVID-19.[276]

Experts have made recommendations to reduce the risk of Strongyloides hyperinfection or dissemination in people at moderate to high risk of Strongyloides infection. There is a risk of hyperinfection following exposure to immunosuppressive drugs. Chronic strongyloidiasis is often asymptomatic; suspicion should be based on risk factors including residence in an endemic area, rural residence, and exposure to soil during labour. A screen-and-treat strategy is recommended for patients at moderate to high risk of Strongyloides infection without confirmed COVID-19, asymptomatic patients with a positive polymerase chain reaction test, and patients with mild COVID-19 who are not candidates for dexamethasone. Serologic testing is preferred. Patients in the hospital setting who are at moderate to high risk of Strongyloides infection, are SARS-CoV-2 positive, and are initiating or are likely candidates for dexamethasone should be treated presumptively with ivermectin. Patients at moderate to high risk of Strongyloides infection who have unexplained gram-negative rod infections after receiving dexamethasone or other immunosuppressive agents should have diagnostic testing for Strongyloides infection. Ivermectin should be given while awaiting results.[461]

Positive urine drug tests for cocaine, fentanyl, heroin, and methamphetamine in patients diagnosed with, or at risk of, substance abuse disorders increased significantly during the COVID-19 pandemic, compared with the preceding 4 months.[462]A survey comparing self-reported alcohol consumption in 2019 and 2020 found that frequency of alcohol consumption increased overall, and particularly in women, adults age 30 to 59 years, and non-Hispanic white individuals.[463] An urban emergency department in the US has reported a large increase in visits for nonfatal, unintentional opioid overdoses in March to June 2020, compared with the same period in 2019.[464] Fatal opioid overdoses also reportedly increased in some areas during lockdown periods.[465]

A retrospective analysis of US emergency medical services registry data observed a sharp rise in overdose-related cardiac arrests during April 2020, with peak rates in May 2020, more than double than in the same period in 2018 and 2019.[466] The increase in overdose-related deaths in the US during the pandemic was primarily driven by synthetic opioids.[467] The Substance Abuse and Mental Health Services Administration in the US has introduced flexibility in the Opioid Treatment Program, depending on stability of the patient,[125] and in the UK, most services transferred patients from supervised opioid substitution therapies to take-home doses. As the number of COVID-19 cases falls, UK clinicians are advised to consider whether supervised opioid substitution therapy can resume.[126]

Chloroquine and hydroxychloroquine should be started at full dose (when available) for patients with newly diagnosed SLE. Chloroquine and hydroxychloroquine should be continued at the same dose during pregnancy.[427] 

Belimumab, ACE inhibitors, angiotensin-II receptor antagonists, and glucocorticoids may be initiated if indicated. High-dose glucocorticoids or immunosuppressants may be initiated for patients with lupus nephritis. Glucocorticoids should not be stopped abruptly and should be used at the lowest possible dose to control disease.[427]

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be continued following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, but should be stopped if the patient develops severe COVID-19.[427] Chloroquine and hydroxychloroquine should be stopped temporarily if the patient develops COVID-19.[427]

Following recovery from COVID-19, US guidelines recommend that rheumatic disease treatments can be restarted within 7-14 days of symptom resolution in patients with mild or no pneumonia who were treated in the ambulatory setting or with self quarantine. Decisions regarding restarting rheumatic disease therapies in patients who had more severe COVID-19 should be taken on an individual basis. If a patient had a positive polymerase chain reaction test for SARS-CoV-2 but has remained asymptomatic, rheumatic disease treatments may be restarted 10-17 days after the positive test result.[427]

Race, presence of at least one comorbidity, and body mass index have been identified as predictors of hospitalization in patients with SLE and COVID-19.[468]One study in the US found that, similar to findings in the general US population, black, Asian, and Latin American patients with rheumatic disease and COVID-19 had an increased risk of hospitalization and ventilatory support compared with white patients, even after adjustment for demographic, rheumatic disease activity, and comorbidities.[452] Another cohort study conducted in the US found that systemic autoimmune rheumatic disease was associated with increased risk of hospitalization, intensive care admission, acute kidney injury, and venous thromboembolism. The risk was largely due to comorbidities, except for the risk of venous thromboembolism. Risk of mechanical ventilation and death was not increased in the patients with systemic autoimmune rheumatic disease.[441]

Clinicians are advised to engage patients with rheumatic disease in a shared decision-making process to discuss receiving a SARS-CoV-2 vaccine. The response to vaccination is likely to be blunted in patients receiving systemic immunomodulatory therapies compared with the general population. The American College of Rheumatology advises that, beyond known allergies to vaccine components, there are no additional contraindications to SARS-CoV-2 vaccination for patients with autoimmune and inflammatory rheumatic diseases. Vaccination should ideally occur when rheumatologic disease is well controlled.[362]

The American Society of Hematology has published recommendations for the treatment of thalassemia during the pandemic.[469] They advise that blood transfusion and luspatercept should be continued as usual. Iron chelation should be continued in well patients. If a patient develops COVID-19 then interruption of iron chelation is usually advisable; the case should be discussed with the patient's hematologist. Febrile, splenectomized patients should be investigated for bacterial infection and receive empiric antibiotics to cover secondary bacterial infections.[469]

The Thalassaemia International Federation (TIF) has published a position statement suggesting management strategies during the pandemic, covering patients’ risk level, adaptation of hemoglobinopathy care, safety of blood transfusions, blood supply challenges, and lifestyle and nutritional considerations.[470]

Plasma exchange remains the recommended initial treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP). Corticosteroids and rituximab should still be used in treatment of acute iTTP. Patients with severely deficient ADAMTS13 activity may still receive rituximab to prevent relapse; the potential increased risk of COVID-19 complications should be balanced against the benefit of delaying or preventing relapses of iTTP. If access to plasma exchange is limited, the patient should ideally be transferred to a facility that can offer plasma exchange; otherwise, caplacizumab and immunosuppressive therapy alone may be considered.[471]

If a patient develops COVID-19, plasma exchange should be used in the same way as for other patients; the risks and benefits of corticosteroids and rituximab should be carefully considered. Caplacizumab may be used in conjunction with plasma exchange as a temporizing measure to protect from exacerbations and relapses until recovery from COVID-19; after recovery, corticosteroids and/or rituximab may be used to increase ADAMTS13 activity.[471]

Trials of severe acute respiratory syndrome coronavirus 2 vaccination in patients with hematological conditions are lacking. Such patients are likely to have an attenuated response to vaccination. Additional measures, such as early vaccination of household contacts, may be considered.[230]

UK guidelines have been published for the management of adult patients with tonsillitis and quinsy during the pandemic. Personal protective equipment, including respirator mask, is recommended for all ear, nose, and throat examinations and aerosol-generating procedures. Patients without signs of airway compromise or sepsis may be suitable for treatment based on history alone. Intravenous antibiotics and dexamethasone are recommended to help expedite discharge. If signs of airway compromise or sepsis are present, follow sepsis guidelines and seek urgent expert help. Epinephrine should be administered via nebulizer and dexamethasone given intravenously.[472]

The Centers for Disease Control and Prevention advise that administration of mRNA COVID-19 vaccines should not be delayed because of testing for tuberculosis (TB) infection. Immune-based testing (tuberculin skin testing or interferon-release assay) may be done before or at the same time as COVID-19 vaccination. If this is not possible, immune-based testing should be delayed for at least 4 weeks after completion of COVID-19 vaccination, but generally should not be cancelled. Patients who have active TB, or an illness that is being evaluated as active TB, may receive COVID-19 vaccination. Severe or acute illness is a precaution to administration of all vaccines. Patients who have symptoms or other diagnostic findings consistent with active TB should receive further evaluation, regardless of immune based testing results.[473]

The UK National Health Service advises that an interferon-release assay blood test may be used instead of tuberculin skin testing for contact tracing to reduce person-to-person contact during the pandemic. Testing for latent tuberculosis and neonatal Bacillus Calmette-Guérin vaccination should continue.[474]

Evidence on COVID-19 infection in patients with TB is limited, but the World Health Organization (WHO) anticipates that people with coinfection may have poorer treatment outcomes, especially if TB treatment is interrupted.[475] WHO had advised that TB diagnosis and treatment services are maintained during the pandemic; however, in March 2021, WHO estimated that 1.4 million fewer people received care for TB in 2020 than in 2019, with low- and middle-income countries most affected.[476]

A cohort study of 500,000 people in the UK found that autoimmune disease and history of oral corticosteroid were associated with increased risk of fatal COVID-19.[44] Patients with ulcerative colitis (UC) should be advised to continue their current medications. Medication should only be stopped, reduced, or changed in discussion with a specialist.[57] Preventing disease flares is a priority to reduce the risk of corticosteroid use and hospitalization.[311] UK guidelines recommend assessing whether the dose, route of administration, or mode of treatment can be altered to reduce face-to-face contact during the pandemic.[57] Patients may continue taking aminosalicylates; these drugs do not affect the immune response.[57]

Patients receiving immunosuppressive medication may develop atypical symptoms of COVID-19 (e.g., patients who take an oral corticosteroid may not develop fever). Patients who take an oral or rectal corticosteroid should not stop suddenly if they develop COVID-19, due to the risk of adrenal crisis.[57] Patients taking at least 20 mg/day of prednisone should observe shielding precautions.[311]

A case-control study conducted in the UK found that more patients with acute, severe ulcerative colitis received rescue therapy or surgery during the pandemic period in 2020 compared with historical controls from 2019. More patients received ambulatory intravenous corticosteroids, biologicals, cyclosporine, and tofacitinib during the pandemic; fewer patients received thiopurines and aminosalicylates. Incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was low during hospitalization and during the 3-month follow-up period, and treatment for UC was not associated with adverse COVID-19 outcomes.[477]

Testing for COVID-19 is recommended before starting medication for a presumptive UC flare, because COVID-19 can present with gastrointestinal symptoms and administration of higher-dose corticosteroids to these patients could be detrimental.[312] Testing for COVID-19 is also recommended before initiating biologics, although where possible, initiation should be postponed.[313]

Blood tests to monitor response to therapy should be performed at the minimum safe frequency.[57][311][316]

International guidelines recommend that patients stop taking methotrexate, thiopurines, or tofacitinib if they develop COVID-19. Detailed recommendations are given depending on the level of inflammatory bowel disease activity and severity of COVID-19 infection.[314] If a patient has stopped taking their UC medication because they have COVID-19, medication can be restarted when at least 10 days have elapsed since symptom onset and at least 3 days have elapsed since recovery. Recovery is defined as the resolution of fever, without use of antipyretics, and an improvement in respiratory symptoms. In patients with severe or critical COVID-19, restarting medication 7-14 days after recovery may be appropriate, depending on the severity of their IBD. If a patient has laboratory-confirmed SARS-CoV-2 infection but has not had symptoms, medication can be restarted 10 days after the first test, providing that no symptoms have developed in the interim.[315] Viral shedding may persist after recovery, particularly in immunocompromised patients, therefore experts recommend making decisions to restart medication based on symptoms rather than repeat testing.[315]

Infliximab use is associated with impaired serological response to SARS-CoV-2 infection in patients with inflammatory bowel disease. Concomitant use of methotrexate or a thiopurine further attenuated the serological response.[316]

Elective endoscopic procedures should be deferred, but urgent or emergent endoscopy should continue. This includes cases of IBD where endoscopy would urgently change management: for example, establishing the diagnosis in a patient with signs of moderate to severe inflammation, diagnosing a severe acute flare of UC, investigating subacute obstruction if imaging suggests a fibrotic or neoplastic stricture, and therapeutic endoscopic retrograde cholangiopancreatography in patients with primary sclerosing cholangitis who have worsening cholangitis and jaundice.[317][318] International guidelines recommend that surgical management of UC should be considered in some patients, as delay may result in significant downstream morbidity and mortality; decisions on surgery should be individualized for each patient with a multidisciplinary team.[319]

The British Society of Gastroenterology has published a position statement strongly supporting SARS-CoV-2 vaccination for patients with UC.[478]

The International Uveitis Study Group has published consensus recommendations on the management of patients with uveitis during the COVID-19 pandemic. Patients without symptoms of COVID-19 should continue on their usual immunosuppressive treatment. If a face-to-face review for ophthalmic symptoms is necessary, patients with risk factors for severe COVID-19 should be seen separately from lower risk patients and ideally at the beginning of the day. Patients with symptoms or signs of COVID-19 should be tested as soon as possible to confirm the diagnosis. Immunosuppressive treatment, except tocilizumab or interferon, should be stopped. Slow reduction of systemic corticosteroids should be discussed with the treating medical team. Patients who are asymptomatic and test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should continue immunosuppressive therapy. The dose should be reduced if their white blood cell count falls below 4000 cells/microlitre.[479]

Patients who are due to start immunosuppressive treatment should be tested for SARS-CoV-2 in addition to the usual screen for infectious diseases. Consideration may be given to using local or regional corticosteroids as bridging therapy to delay the start of systemic immunosuppression. Patients with Behcet’s disease may require first-line systemic therapy; if so, self administered injections to reduce hospital outpatient visits could be considered.[480]

COVID-19 may present with gastrointestinal (GI) symptoms that mimic viral gastroenteritis. The estimated pooled prevalence of GI symptoms in patients with COVID-19 varies from less than 10% to 15%.[399][481] Nausea or vomiting, anorexia, and diarrhea are the most common manifestations.[481] Patients with severe COVID-19 had higher rates of GI symptoms than those with less severe disease. Most patients with GI symptoms and COVID-19 have concomitant respiratory symptoms or fever; 3% of patients reported GI symptoms only.[482] Patients may present with nausea or diarrhea 1 to 2 days prior to onset of fever and breathing difficulties.[329] A retrospective cohort study found that median duration of viral shedding in stool samples was 22 days, compared with 18 days in respiratory samples and 16 days in serum samples. The median duration of shedding was lower in mild illness (14 days) compared to severe illness (21 days).[483]

Guidelines from the American Gastroenterological Association (AGA) recommend that outpatients with new-onset diarrhea are asked about high risk contact exposure, whether they have a history of COVID-19-associated symptoms, and whether they have other GI symptoms (nausea, vomiting, abdominal pain).[399] Patients with new-onset GI symptoms should be monitored for symptoms of COVID-19, as GI symptoms may precede other COVID-related symptoms by a few days. Currently, there is not enough evidence to support stool testing for diagnosis or monitoring of COVID-19 as part of routine clinical practice.[399] In hospitalized patients with known or suspected COVID-19, the AGA recommends obtaining a thorough history of GI symptoms, including onset, characteristics, duration, and severity. 

The British Society for Haematology has published guidance on vitamin B12 (cyanocobalamin) supplementation during the COVID-19 pandemic.

Patients who have B12 deficiency that is not related to diet (e.g., pernicious anemia, gastrectomy, inflammatory bowel disease, achlorhydria) should be screened for symptoms of COVID-19 before injections. The ongoing need for B12 injections should be assessed for each patient; oral vitamin B12 may be offered until intramuscular injections can be resumed, aiming to have the shortest possible break between injections.[484]

Patients who have B12 deficiency related to diet should be offered advice on dietary sources of B12. Patients may suspend B12 supplementation during the pandemic because they are B12 replete; patients may also be offered oral B12 supplementation.[484]

Further hematology resources are available at:

ASH: COVID-19 resources external link opens in a new window

BSH: COVID-19 updates external link opens in a new window

In the UK, people are advised to consider taking a daily vitamin D supplement to maintain bone and muscle health during the COVID‑19 pandemic as people may have been indoors more than usual and not making enough vitamin D from sunlight.[485] There is little evidence that use of vitamin D supplements are effective in preventing or treating COVID-19, and they should not be offered solely for this purpose. The guidance advises:[485]

- Adults (including women who are pregnant or breastfeeding), young people, and children over 4 years should consider taking a daily supplement of vitamin D between October and early March

- Adults, young people, and children over 4 years should consider taking a daily supplement of vitamin D throughout the year if they have little or no sunshine exposure, or if they have dark skin

- Babies from birth to 1 year should have a daily supplement of vitamin D throughout the year if they are breastfed or formula-fed and are having less than 500 ml of infant formula a day

- Children aged 1-4 years should have a daily supplement of vitamin D throughout the year.

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