Primary prevention

Vaccines

  • The World Health Organization (WHO) has authorised the use of the following vaccines for global use:

    • mRNA vaccines: Comirnaty® (Pfizer/BioNTech); Spikevax® (Moderna)

    • Adenovirus vector vaccines: Vaxzevria® (AstraZeneca); Jcovden® (Janssen); Convidecia® (Cansino)

    • Protein subunit vaccines: Nuvaxoid® (Novavax); Covovax® (Serum Institute of India)

    • Inactivated virus vaccines: Covilo® (Sinopharm); CoronaVac® (Sinovac)

    • WHO: COVID-19 vaccines technical documents Opens in new window

  • Vaccine availability and immunisation programmes differ between countries.

    • Other vaccines may be authorised in specific countries (e.g., Valneva inactivated virus vaccine).

    • Vaccines are generally available under emergency-use, provisional, or conditional marketing authorisations, but may be fully approved in some countries.

    • Consult your local COVID-19 vaccination schedule for more information.

  • Vaccine efficacy depends on the vaccine used, the predominant circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and time since vaccination.

    • Initial authorization of vaccines was based on interim analyses of ongoing phase 3 clinical trials with a median follow-up of 2 months. Overall initial vaccine efficacy for preventing symptomatic infection was reported as 95% (Pfizer/BioNTech), 94.1% (Moderna), 74% (AstraZeneca), and 66.9% (Janssen).[343][344][345][346]

    • Observational evidence from the initial global vaccine rollout suggested real-world efficacy in reducing the rate of symptomatic or asymptomatic infection, disease severity, hospitalisation, death, and possibly even reinfection. However, evidence indicates a minimal to modest reduction of vaccine protection against severe disease over the 6 months after the primary series, while waning efficacy against all clinical disease and infection is more pronounced. Vaccine efficacy against severe disease decreased by about 8% over a 6-month period in all age groups (10% in those aged >50 years), and vaccine efficacy against symptomatic disease decreased by 32% in those aged >50 years.[347]

    • Efficacy is highest for the Alpha variant, with lower efficacy reported for Beta, Gamma, and Delta variants.[348] See Classification under Aetiology for evolving information on vaccine efficacy against the Omicron variant.

  • Variant-updated vaccines based on the Omicron variant are currently being developed and will be assessed by regulatory authorities.[349][350][351]

    • While current vaccines continue to perform well in preventing severe disease and death due to the Omicron variant, particularly with the use of a booster dose(s), protection against infection and symptomatic illness due to the Omicron variant is lower than other variants and declines rapidly, even after a third (booster) dose.

Vaccines: dose schedules

  • Administer the primary vaccination series according to local public health authority recommendations.

    • One-, two-, or three-dose schedules may be recommended depending on the vaccine used and the patient’s age.

    • Some vaccines may only be authorised for use in adults ≥18 years of age, while others may be approved for use in children ≥6 months of age and adults. Authorisations may differ between countries.

    • Doses in children ≥12 years of age and adolescents are typically the same as doses for people ≥18 years of age. However, lower doses are recommended in children <12 years of age and depend on the vaccine brand used.

    • Vaccine vials may have different coloured caps to help identify the correct formulation and dose for a particular age group, and therefore help to reduce the risk of dose administration errors.

    • Intervals between doses depend on the vaccine used and may differ between countries. Some countries may recommend longer intervals between doses as it has been associated with higher vaccine efficacy and a lower risk of myocarditis (e.g., in young men).

  • Additional doses may be recommended as part of the primary vaccination series for moderately to severely immunocompromised people.

    • The WHO recommends that the primary vaccination series for all vaccines should be extended to include an additional dose in moderately to severely immunocompromised people.[352]

    • There are no vaccine efficacy studies following a third dose in immunocompromised people.[353] Although there is no direct evidence that the ability to produce antibodies in these patients offers protection, it is expected that the extra dose increases protection, at least in some patients.[354]

  • Administer booster doses according to local public health authority recommendations. The booster dose may differ from the dose used for the primary series for some vaccines.

    • The WHO recommends an initial booster dose for the highest priority-use groups 4 to 6 months after the completion of the primary vaccination series. Once high booster dose coverage has been achieved in these groups, a booster may be considered for other lower priority-use groups. Data on the usefulness of additional booster doses are limited, especially in relation to the duration of further protection, and only exist for mRNA vaccines. Data suggest that there is a benefit in administering an additional booster dose only in the highest risk groups, and there is minimal benefit for healthy younger populations.[355]

    • Evidence for the benefit of an initial booster dose is inferred through immunogenicity, and the overall level of certainty is very low for prevention of symptomatic disease, hospitalisation, and death, as well as serious adverse events and reactogenicity.[356] Observational data to support the safety and efficacy of an initial booster dose are available, but their follow-up periods are generally too short to assess long-term effectiveness, the number of trial participants is small, and studies focus on plasma neutralising antibodies and don’t take into account the protection provided by cellular immunity.[357][358][359][360][361][362][363][364] Evidence for the benefit of a second booster dose is limited and largely comes from Israel.[365][366][367]

  • Heterologous vaccination schedules may be recommended in some countries.

    • The WHO recommends that homologous schedules should be considered standard practice. However, a flexible approach is supported, and two heterologous doses of any authorised vaccine may be used to complete a primary series.[368]

    • A systematic review and network meta-analysis found that different heterologous and homologous three-dose regimens worked comparably well in preventing infection, even against different variants. However, the effectiveness against death remains uncertain.[369]

  • COVID-19 and influenza vaccines may be administered together.

    • The WHO recommends that coadministration of any dose of a COVID-19 vaccine with an inactivated seasonal influenza vaccine is acceptable and may be considered during the same visit (in contralateral limbs). Only limited evidence exists to support this recommendation, but available evidence does not show increased adverse events. No coadministration data are available for other live or inactivated vaccines.[370]

    • A multicentre randomised controlled phase 4 trial found that concomitant COVID-19 and influenza vaccine administration raised no safety concerns, most systemic reactions were mild or moderate, and the immune response was not adversely affected.[371]

  • Consult your local COVID-19 vaccination schedule for detailed information on choice of vaccine, dose schedule, contraindications, warnings, and cautions.

Vaccines: special patient populations

  • Pregnancy

    • The WHO recommends offering vaccination to all pregnant women. Pregnancy testing prior to vaccination is not recommended. Delaying pregnancy or terminating a pregnancy because of vaccination is not recommended.[372]

    • There are limited safety and efficacy data available in pregnant women. A systematic review and meta-analysis found that there was no evidence of a higher risk of adverse outcomes in pregnant women including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postnatal haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission with mRNA vaccines.[373] However, these data have limitations, and continued monitoring is needed to further assess the risk.

    • Emerging observational evidence suggests that vaccination during pregnancy may protect the infant against infection during the first 4 months of life, and reduce the risk of hospitalisation among infants <6 months of age.[374][375]

  • Breastfeeding

    • The WHO recommends offering vaccination to all breastfeeding women. Discontinuing breastfeeding because of vaccination is not recommended.[376]

    • There are limited safety and efficacy data available in breastfeeding women. Studies have found robust secretion of SARS-CoV-2 specific immunoglobulin A (IgA) and IgG antibodies in breast milk after vaccination.[377] However, it is unclear how long antibodies persist in the breast milk after vaccination, and their impact on the prevention of infection in infants is also unclear. Vaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals.[378] Further research is required.

  • Children and adolescents

    • Vaccines are authorised for infants from 6 months of age in some countries. Available evidence suggests that the safety and efficacy of vaccines are acceptable in children and adolescents. Older children and adolescents were at significantly increased risk of adverse reactions after vaccination compared with younger children. There is a need for additional multicentre, large-sample studies and long-term follow-up data.[379]

    • Due to the limited number of children included in the original clinical trials, studies could not have detected rare adverse effects such as myocarditis. However, safety monitoring of the Vaccine Adverse Event Reporting System (VAERS) noted over 9000 reports of adverse events post-vaccination in adolescents aged 12 to 17 years (as of 16 July 2021), 9.3% of which were for serious adverse events including myocarditis (4.3%).[380] Preliminary real world data has not picked up an increased risk of myocarditis in children aged 5 to 11 years as yet.[381] No data is available for children <5 years of age as yet.

  • Immunocompromised

    • Seroconversion rates were significantly lower in immunocompromised people, especially solid organ transplant recipients, but increased after the second dose. However, seroconversion remained severely reduced in solid organ transplant recipients even after second and third doses compared with the general population.[382][383] Approximately 20% to 40% of solid organ transplant recipients did not mount an antibody response despite receiving multiple doses of mRNA vaccines.[384]

    • Immunosuppressive medication was the most prominent risk factor associated with seroconversion failure in transplant patients, although this was dependent on the specific drug regimen used. Calcineurin inhibitors, corticosteroids, and mycophenolate were associated with an increased risk of seroconversion failure, while azathioprine and mTOR inhibitors were not.[383] Other risk factors include older age, short interval from receiving the vaccine to the time of transplantation, or comorbidities (e.g., diabetes, kidney disease).[383][385]

    • Interrupting methotrexate treatment for 2 weeks after a vaccine booster dose has been shown to double the antibody response in people with immune-mediated inflammatory diseases after 4 weeks, and this improvement in antibody response was maintained for 12 weeks. However, there was a temporary deterioration in self-reported disease activity and control at 4 weeks that resolved by 12 weeks.[386]

    • Further research is needed to understand vaccine efficacy among this group.

  • Autoimmune disease

    • Data suggests that vaccine efficacy may be lower in patients with autoimmune disease.[387][388][389][390] It is uncertain whether vaccines may cause an exacerbation of pre-existing autoimmune diseases; however, there are case reports of new autoimmune conditions or flares of existing autoimmune conditions post vaccination.[391][392][393][394] Further research is needed to understand vaccine efficacy among this group.

  • Malignancy

    • Data suggests that vaccine efficacy may be lower in cancer patients compared with the general population. Antibody response was lower in haematological malignancies compared with solid tumours. Antibody response was also lower for allogeneic and autologous haematopoietic stem cell transplant recipients, and those receiving active treatment. The response varied depending on the treatment; lower responses were reported for anti-CD20 therapies, Bruton kinase inhibitors, venetoclax, ruxolitinib, and chimeric antigen receptor T-cell therapy.[395] Further research is needed to understand vaccine efficacy among this group.

Vaccines: breakthrough infections

  • Breakthrough infections are possible after vaccination.

    • Breakthrough infections that have resulted in hospitalisation or death, as well as mild or asymptomatic infections, have been reported in fully vaccinated people.[396][397]

    • One observational study found that 46% of fully vaccinated people with breakthrough infection were asymptomatic, while 26% had severe or critical disease, 20% had moderate disease, and 7% had mild disease.[398] In another study, the rate of severe disease or death per 1000 person-days was 4.08 among those with breakthrough infections and 3.6 among unvaccinated matched controls with infection.[399]

    • One systematic review and meta-analysis of 18 studies found that there were no statistically significant differences in the risk of hospitalisation, invasive mechanical ventilation, or mortality between unvaccinated people and fully vaccinated people with breakthrough infections (during the Delta variant-dominant period). However, unvaccinated people showed an increased need for oxygen supplementation. There was a limited number of studies included in the meta-analysis and a high level of heterogeneity across studies; therefore, these results should be interpreted with caution. Further prospective studies that adjust for the baseline characteristics of patients are necessary to evaluate vaccine efficacy more precisely.[400]

  • Vaccinated people should be considered a possible source of transmission and continue to follow local public health recommendations.

    • Limited evidence suggests that fully vaccinated people with breakthrough infections have similar viral loads compared with unvaccinated people, and therefore may be equally likely to transmit the infection, including to fully vaccinated contacts.[401][402][403]

    • Secondary attack rates among household contacts exposed to fully vaccinated index cases were similar to household contacts exposed to unvaccinated index cases (25% for vaccinated versus 23% for unvaccinated).[404]

  • Risk factors for breakthrough infections and progression to severe disease are similar to those for unvaccinated people.

    • Risk factors for breakthrough infection include frailty in older adults aged ≥60 years, dementia, living in deprived areas, immune dysfunction (including HIV infection), cancer (especially haematological malignancies and those undergoing active cancer care), and obesity.[405][406][407][408][409]

    • Older age, male sex, increasing number of comorbidities, hospitalisation in the previous 4 weeks, high-risk occupation, care home residence, socioeconomic deprivation, and smoking history were all associated with an increased risk of hospitalisation or death in patients with breakthrough infections.[410]

    • Prior SARS-CoV-2 infection may be associated with a lower risk for breakthrough infection.[411]

  • Breakthrough infections have been reported with the Omicron variant, including people who have received a booster dose.

    • While breakthrough infections with the Omicron variant are more frequent compared with the Delta variant, hospital admissions were less frequent with Omicron.[412][413]

Vaccines: significant adverse events

  • Myocarditis and pericarditis

    • Myocarditis or pericarditis may occur following vaccination with mRNA vaccines.[414] It has been postulated that mRNA vaccines may increase inflammation on the endothelium and T-cell infiltration of cardiac muscle, but further research is required.[415] Cases have also been reported with adenovirus vector vaccines and protein subunit vaccines, albeit more rarely.[416][417]

    • Estimates of incidence vary. In the UK, monitoring by the Yellow Card reporting system detected approximately 48 cases of myocarditis and pericarditis per million vaccinees who had received at least one dose of the Pfizer/BioNTech vaccine, and 203 cases of myocarditis and pericarditis per million vaccinees who had received at least one dose of the Moderna vaccine (as of 16 March 2022).[418] In the US, monitoring by VAERS detected 70.7 cases of myocarditis per million doses in males aged 12 to 15 years after the second dose of the Pfizer/BioNTech vaccine, 105.9 cases per million doses in males aged 16 to 17 years after the second dose of the Pfizer/BioNTech vaccine, and 52.4 to 56.3 cases per million doses in males aged 18 to 24 years after the second dose of the Pfizer/BioNTech and Moderna vaccines, respectively (as of 30 September 2021).[419] Estimates are based on data from passive surveillance systems so the true number of cases may be higher.

    • Cases occur predominantly in adolescents and young adults (median age of onset 21 years), more often in males than in females, more often following the second dose, and typically within 3 days after vaccination (up to 25 days).[420][421] In a cohort study of 23.1 million residents aged ≥12 years across four Nordic countries, the risk of myocarditis was higher within 28 days of vaccination with both mRNA vaccines compared with being unvaccinated. The risk was highest within the first 7 days of being vaccinated, was increased for all combinations of mRNA vaccines, and was more pronounced after the second dose (with young males aged 16-24 years having the highest risk).[422] There appears to be an increased risk after the third dose (booster), but data are still emerging and the risk may be lower than after the second dose.[423] Reported rates in immunocompromised people were similar to the general population.[424]

    • Consider the diagnosis in children, adolescents, or adults with new-onset and unexplained significant chest pain, tachycardia or tachypnoea, dyspnoea, palpitations, dizziness or syncope, or general clinical concern, within 10 days of vaccination. Order a 12-lead electrocardiogram, inflammatory blood markers, and troponin. If any of these investigations are abnormal, discuss the management plan with the cardiology team.[425]

    • UK Health Security Agency: myocarditis and pericarditis after COVID-19 vaccination - clinical management guidance for healthcare professionals Opens in new window

    • The short-term clinical course appears to be mild in most patients, but the long-term risks remain unknown.[426] Consult your local public health authority for guidance on administering further doses of a COVID-19 vaccine in these patients.

    • Some countries have implemented age-related prescribing restrictions for mRNA vaccines due to the risk of myocarditis/pericarditis. Modifying mRNA vaccine programmes to incorporate age-based product considerations and longer interdose intervals may reduce the risk of myocarditis/pericarditis.[427]

  • Guillain-Barre syndrome

    • Guillain-Barre syndrome may occur following vaccination with adenovirus vector vaccines. Cases have also been reported with mRNA vaccines, albeit more rarely.[428][429]

    • Estimates of incidence vary. In the US, monitoring by VAERS detected 1 case of Guillain-Barre syndrome per 100,000 doses of the Janssen vaccine (as of 24 July 2021). The median time to onset following vaccination was 13 days (range 10-42 days), and 93% of cases were serious.[430]

  • Vaccine-induced immune thrombocytopenia and thrombosis (VITT)

    • VITT may occur following vaccination with adenovirus vector vaccines. Cases have also been reported with mRNA vaccines, albeit more rarely.[431][432][433]

    • Estimates of incidence vary. In the UK, observational data suggests the risk for a thrombotic event was highest in people aged <40 years, at 16.1 and 36.3 per million doses, respectively, for cerebral venous thrombosis or another thrombosis event, with the greatest elevated risk within 4 to 13 days after vaccination.[434] In the US, the overall risk with the Janssen vaccine has currently been estimated to be 3.83 cases per million people who receive the vaccine, with the reporting rate highest among women aged 30 to 39 years (10.6 cases per million doses) and 40 to 49 years (9.02 cases per million doses), with a case fatality rate of 15%.[435]

    • Some countries have implemented age-related prescribing restrictions for adenovirus vector vaccines due to the risk of VITT. Also, some public health authorities may recommend that people who have had VITT following the first dose of an adenovirus-vector vaccine should not receive a second dose of the same vaccine. Consult your public health authority for local guidance.

    • Thromboembolic events that are distinct from VITT may occur after vaccination with any COVID-19 vaccine, but most commonly occur after vaccination with the AstraZeneca vaccine. Venous thrombosis was more common than arterial thrombosis. Cerebral venous thrombosis was the most common manifestation in patients with venous thrombosis, followed by deep vein thrombosis. Myocardial infarction was common in patients with arterial thrombosis, followed by ischaemic stroke.[436]

    • See the Complications section for more information on VITT, including diagnosis and management.

  • Anaphylaxis

    • Severe allergic reactions, including anaphylaxis, may occur after vaccination. Reactions may be due to the presence of lipid pegylated ethylene glycol (PEG), or PEG derivatives such as polysorbates.[437]

    • Globally, the pooled incidence of post-vaccination anaphylaxis has been estimated to be between 5.58 to 7.91 cases per million doses based on available data, and depends on the vaccine used.[438][439] However, rates as high as 32 per million doses (Moderna) and 38 per million doses (Pfizer/BioNTech) have been reported.[440] A systematic review and meta-analysis of case studies and case reports found that the risk of immediate allergic reactions, including anaphylaxis, associated with a second dose of an mRNA vaccine was low among people who experienced an immediate allergic reaction to the first dose.[441]

    • A history of anaphylaxis to any component of the vaccine is a contraindication to vaccination. People who have an anaphylactic reaction following the first dose of the vaccine should not receive a second dose of the same vaccine. Observe people for 15 to 30 minutes after vaccination in healthcare settings where anaphylaxis can be immediately treated. Some countries have removed the requirement for the observation period following vaccination in certain people. Consult local guidelines for recommendations on vaccinating people with a history of allergies or anaphylaxis.

  • Immune thrombocytopenia

    • Immune thrombocytopenia may occur following vaccination with adenovirus vector vaccines. Use caution in people with a history of a thrombocytopenic disorder. People with a history of a thrombocytopenic disorder should have their platelets monitored for the first 4 weeks following vaccination.[442]

  • Transverse myelitis

    • Transverse myelitis may occur rarely following vaccination with adenovirus-vector vaccines.[443] Signs and symptoms include muscle weakness, localised or radiating back pain, bladder and bowel symptoms, and changes in sensation. Cases have also been reported with mRNA vaccines, albeit more rarely.[444]

  • Other adverse events and safety signals

    • Consult the manufacturer’s prescribing information for a complete list of adverse effects.

    • Other reported adverse events (e.g., case reports) and safety signals are listed below; however, a causal link may not have been confirmed, and this list is not exhaustive.

    • Cardiovascular/pulmonary: myocardial infarction, Takotsubo cardiomyopathy, isolated tachycardia, hypertension.[445][446] An epidemiological study suggests a slightly increased risk for myocardial infarction and pulmonary embolism after adenovirus vector vaccines, and the European Medicines Agency is currently assessing this risk.[447][448]

    • Dermatological: Stevens-Johnson syndrome, cutaneous vasculitis, erythematous and indurated skin reactions, alopecia areata.[449][450][451][452]

    • Endocrine: Graves' disease, subacute thyroiditis, menstrual disorders.[453][454][455]

    • Gastrointestinal: acute necrotising pancreatitis, appendicitis, autoimmune hepatitis (although the European Medicines Agency has ruled out a causal link at this stage).[456][457][458][459][460][461]

    • Haematological: acquired haemophilia A.[462]

    • Neurological: varicella zoster virus reactivation, demyelinating diseases, neuropathy, haemorrhagic stroke, myasthenic disorders, encephalopathy/encephalitis, acute disseminated encephalomyelitis, acute demyelinating polyneuropathy, new-onset multiple sclerosis, neuromyelitis optica spectrum disorder, sensorineural hearing loss, seizures.[428][463][464][465][466][467][468][469][470]

    • Renal: minimal change disease, IgA nephropathy, vasculitis, membranous nephropathy, scleroderma renal crisis.[471]

    • Rheumatological: rheumatoid arthritis, systemic lupus erythematosus, inflammatory myositis, dermatomyositis, autoimmune sclerosis diseases, adult-onset Still's disease.[457][472][473][474]

    • Fatal adverse events have been reported rarely post vaccination, and have been confirmed in postmortem studies.[475]

  • Report all suspected adverse events after vaccination via your local reporting system. This is mandatory in some countries. Surveillance of adverse events is extremely important, and may reveal additional, less frequent serious adverse events not detected in clinical trials. The mRNA vaccines have not been authorised for use in humans previously, so there is no long-term safety and efficacy data available for these types of vaccines.

Monoclonal antibodies: pre-exposure prophylaxis

  • Tixagevimab/cilgavimab is authorised in some countries for pre-exposure prophylaxis.

    • Tixagevimab/cilgavimab is a long-acting, neutralising monoclonal antibody combination with activity against SARS-CoV-2. It is designed to attach to the spike protein of the virus at two different sites.

    • It is authorised for use in the US, the UK, and Europe.[476][477][478]

  • Guideline recommendations for the use of tixagevimab/cilgavimab vary. Consult your local guidance.

    • In the US, the National Institutes of Health guidelines panel recommends tixagevimab/cilgavimab for pre-exposure prophylaxis in children aged ≥12 years (weighing ≥40 kg) and adults who do not have SARS-CoV-2 infection, who have not been recently exposed to an individual with SARS-CoV-2 infection, AND who are moderately to severely immunocompromised and may have an inadequate immune response to vaccination, or are not able to be fully vaccinated with any available COVID-19 vaccines due to a documented history of severe reactions. This included people with advanced or untreated HIV infection.[479]

    • The Infectious Diseases Society of America supports the use of tixagevimab/cilgavimab for pre-exposure prophylaxis when predominant regional variants are susceptible. It suggests against the use of tixagevimab/cilgavimab for post-exposure prophylaxis, unless predominal regional variants are susceptible.[480]

  • Consult your local drug formulary for information about contraindications, cautions, adverse effects, and drug interactions before prescribing this treatment.

    • Tixagevimab/cilgavimab is given as a single dose administered as two separate consecutive intramuscular injections.

    • Serious hypersensitivity reactions including anaphylaxis have been reported. Monitor and observe patients for at least 1 hour after administration.

    • There is a risk of cross-hypersensitivity with COVID-19 vaccines, and people with a history of a severe hypersensitivity reaction to a COVID-19 vaccine should consider consultation with an allergist/immunologist prior to administration of tixagevimab/cilgavimab.

    • Serious cardiac adverse events were reported infrequently in the clinical trial; however, it is unknown whether these events were caused by the drug.

  • Circulating SARS-CoV-2 variants may be associated with resistance to monoclonal antibodies.

    • In vitro data show that the Omicron BA.1 and BA.1.1 subvariants have decreased susceptibility to tixagevimab/cilgavimab.[479] However, according to the manufacturer, in vivo data suggests that tixagevimab/cilgavimab retains neutralising activity against Omicron variants (including the BA.2 subvariant).[481]

    • Dose recommendations may depend on the local circulating variant and whether the patient has had the treatment previously.

    • Consult local guidance for details regarding specific variants and resistance.

  • Evidence is limited.

    • In an ongoing multicentre, double-blind, parallel-group, randomised, placebo-controlled trial, tixagevimab/cilgavimab reduced the risk of developing symptomatic disease by 76.7% (relative risk reduction) compared with placebo at the primary analysis (median 83 days after administration), with an 82.8% relative risk reduction reported at the median 6-month follow-up. All cases of severe or critical disease were reported in the placebo group. The most common adverse event was injection-site reactions.[482]

    • A small cohort study found that pre-exposure administration of tixagevimab/cilgavimab was associated with a lower risk of infection in severely immunocompromised patients with immune-mediated inflammatory diseases who were fully vaccinated. However, due to the limitations of the study, these results should be interpreted with caution.[483]

Infection prevention and control for healthcare professionals

  • Consult local infection prevention and control protocols; only basic principles from the World Health Organization (WHO) guidelines are detailed here.[484][485]

  • Screen all people, including patients, visitors, and others entering the facility, for COVID-19 at the first point of contact with the health facility to allow for early recognition.

  • Immediately isolate all suspected or confirmed cases in a well-ventilated area that is separate from other patients. Place patients in adequately ventilated single rooms if possible. When single rooms are not available, place all cases together in the same adequately ventilated room and ensure there is at least 1 metre (3 feet) between patients.

  • Implement standard precautions at all times:

    • Practice hand and respiratory hygiene

    • Give patients a medical mask to wear

    • Wear appropriate personal protective equipment

    • Practice safe waste management and environmental cleaning.

  • Implement additional contact and droplet precautions before entering a room where suspected or confirmed cases are admitted.

    • A respirator or medical mask should be worn along with other personal protective equipment (i.e., gown, gloves, eye protection) before entering a room with a suspected or confirmed case.

    • A respirator should be worn in the following situations: in care settings where ventilation is known to be poor or cannot be assessed, or the ventilation system is not properly maintained; based on the worker’s values and preferences and on their perception of what offers the highest protection possible to prevent infection.

    • Appropriate mask fitting should always be ensured, as should compliance with appropriate use of personal protective equipment and other precautions.

    • Universal masking is strongly recommended in health facilities in areas of known or suspected community or cluster transmission.

  • Implement airborne precautions when performing aerosol-generating procedures, including placing patients in a negative pressure room and wearing a particulate respirator.

    • A respirator should always be worn along with other personal protective equipment while performing aerosol-generating procedures, and in settings where these procedures are regularly performed on patients with suspected or confirmed disease (e.g., intensive care units, emergency departments).

    • Some countries and organisations recommend airborne precautions for any situation involving the care of a COVID-19 patient.

  • All specimens collected for laboratory investigations should be regarded as potentially infectious.

  • Appropriate personal protective equipment gives healthcare workers a high level of protection.

    • A rapid review and meta-analysis found that wearing personal protective equipment conferred significant protection against infection compared with not wearing it. High-certainty evidence indicates that using N95 masks significantly reduces the risk of infection. No effect was found for wearing gloves and gowns. There is a lack of evidence for different combinations of personal protective equipment.[486]

  • Avoid in-person assessment of patients with suspected COVID-19 in primary care when possible to avoid infection. Most patients can be managed remotely by telephone or video consultations.[487]

  • Detailed infection prevention and control guidance is available:

Infection prevention and control for the general public

  • Public health recommendations vary between countries and you should consult your local guidance.

    • It is generally recommended that people stay at least 1 to 2 metres (3-6 feet) away from others (recommendations vary between countries), wash their hands often with soap and water (or hand sanitiser that contains at least 60% alcohol), cover coughs and sneezes, avoid crowds and poorly ventilated spaces, clean and disinfect high touch surfaces, monitor their health and self-isolate or seek medical attention if necessary, and get vaccinated.[488][489]

    • WHO: advice for the public – coronavirus disease (COVID-19) Opens in new window

  • Countries may sometimes implement non-pharmaceutical interventions in order to reduce and delay viral transmission (e.g., social distancing, city lockdowns, stay-at-home orders, curfews, non-essential business closures, bans on gatherings, school and university closures, remote working, quarantine of exposed people).

    • Implementing any non-pharmaceutical interventions was associated with a significant reduction in case growth when comparing countries with more restrictive non-pharmaceutical interventions to countries with less restrictive non-pharmaceutical interventions. However, there was no clear, significant beneficial effect of more restrictive non-pharmaceutical interventions compared with less restrictive non-pharmaceutical interventions in any of the countries studied.[490]

    • Negative consequences of community-based mass quarantine include psychological distress, food insecurity, economic challenges, diminished healthcare access, heightened communication inequalities, alternative delivery of education, and gender-based violence.[491]

  • Some countries have published guidance to support the next stage of the pandemic, living with COVID-19. This new phase focuses on protecting those who are most at risk from the virus. Consult your local guidance.

  • The following guidance has been published in the UK:

Face masks

  • Public health recommendations on wearing face masks vary between countries and you should consult your local guidance. Many countries have ended mask mandates, except in certain high-risk situations.

  • The WHO recommends wearing a mask, regardless of vaccination status or history of prior infection, in settings where there is community or cluster transmission when interacting with non-household members in the following circumstances:[485]

    • Indoor settings where ventilation is poor or cannot be assessed, regardless of whether physical distancing of at least 1 metre (3 feet) can be maintained

    • Indoor settings with adequate ventilation if physical distancing cannot be maintained

    • Outdoor settings if physical distancing cannot be maintained

    • For people who are at higher risk of severe complications from infection, if physical distancing cannot be maintained in any setting.

  • Masks are not recommended:

    • During vigorous-intensity physical activity

    • In children aged <5 years for source control (a risk-based approach should be applied to children aged 6-11 years)

    • In children with severe cognitive or respiratory impairments, developmental disorders, disabilities, or other specific health conditions who experience difficulties wearing a mask or have health conditions that interfere with mask-wearing.

  • There is no high-quality or direct scientific evidence to support the widespread use of masks by healthy people in the community setting. Data on effectiveness is based on limited and inconsistent observational and epidemiological studies.

    • The only randomised controlled trial to investigate the efficacy of masks in the community found that the recommendation to wear surgical masks when outside the home did not reduce infection compared with a no mask recommendation. However, the study did not assess whether masks could decrease disease transmission from mask wearers to others (source control).[492] Evidence from randomised controlled trials for other respiratory viral illnesses shows no significant benefit of masks in limiting transmission but is of poor-quality and not SARS-CoV-2-specific.[493]

    • A Cochrane review found that wearing a mask may make little to no difference in how many people caught influenza-like illnesses. However, this was based on low-certainty evidence, and does not include results of studies from the current pandemic.[494]

    • A living rapid review found that the evidence for mask effectiveness for respiratory tract infection prevention is stronger in healthcare settings compared with community settings; however, direct evidence on comparative effectiveness in SARS-CoV-2 infection is insufficient. The strength of evidence for any mask use versus non-use in community settings is low-moderate.[495][496]

    • Cloth masks have limited efficacy in preventing viral transmission compared with medical-grade masks and the efficacy is dependent on numerous factors (e.g., material type, number of layers, fitting, moisture level), and may result in increased risk of infection.[497][498]

  • There are harms and disadvantages of wearing masks including headache, breathing difficulties, facial skin lesions, irritant dermatitis, worsening acne, difficulty wearing masks by certain members of the population (e.g., children, people with learning disabilities, mental illness or cognitive impairment, asthma, chronic respiratory or breathing problems, facial trauma or recent oral maxillofacial surgery, living in hot and humid environments), psychological issues, difficulty communicating, poor compliance, waste disposal issues, and increased viral load. There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks.[485][499][500]

Travel-related control measures

  • Many countries implemented measures including complete or partial closure of borders, entry or exit screening, and/or quarantine of travellers; however, these measures are no longer in place in most countries. Consult your local guidance.

    • Low- to very low-certainty evidence suggests that travel-related control measures may help to limit the spread of infection across national borders. Cross-border travel restrictions are likely to be more effective than entry and exit screening, and screening is likely to be more effective in combination with other measures (e.g., quarantine, observation).[501]

    • Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases; however, the evidence base comes from two mathematical model studies and is limited by their assumptions. Evidence suggests that one-time screening in apparently healthy people may miss between 40% and 100% of people who are infected, although the certainty of this ranges from very low to moderate. In very low‐prevalence settings, screening for symptoms or temperature may result in few false negatives and many true negatives, despite low overall accuracy. Repeated screenings may result in more cases being identified eventually and reduced harm from false reassurance.[502]

    • A Cochrane review found quarantine to be important in reducing the number of people infected and deaths, especially when started earlier and when used in combination with other prevention and control measures. However, the current evidence is limited because most studies are based on mathematical modelling studies that make assumptions on important model parameters.[503]

  • The psychosocial effects of enforced quarantine may have long-lasting repercussions.[504][505]

Lifestyle modifications

  • Lifestyle modifications (e.g., smoking cessation, weight loss) may help to reduce the risk of infection, and may be a useful adjunct to other interventions.[506]

  • The WHO recommends that tobacco users stop using tobacco given the well-established harms associated with tobacco use and second-hand smoke exposure.[214]

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