Approach

Early recognition and rapid diagnosis are essential to prevent transmission and provide supportive care in a timely manner. Have a high index of clinical suspicion for COVID-19 in all patients who present with fever and/or acute respiratory illness and who report a travel history to an affected area or close contact with a suspected or confirmed case in the 14 days prior to symptom onset. Evaluation should be performed according to pneumonia severity indexes and sepsis guidelines (if sepsis is suspected) in all patients with severe illness.

It is important that general practitioners avoid in-person assessment of patients with suspected COVID-19 in primary care when possible.[102] Most patients can be managed remotely by telephone or video consultations.[103] Algorithms for dealing with these patients are available:

Infection prevention and control

Triage all patients on admission and immediately isolate all suspected and confirmed cases in an area separate from other patients. Suspected patients should be given a mask and kept at least 1 metre (3 feet) from other suspected patients. Implement appropriate infection prevention and control procedures. Screening questionnaires may be helpful. COVID-19 is a notifiable disease; report all suspected and confirmed cases to your local health authorities.

The World Health Organization (WHO) recommends the following basic principles:[104]

  • Immediately isolate all suspected cases in an area that is separate from other patients

  • Implement standard precautions at all times:

    • Practice hand and respiratory hygiene

    • Offer a medical mask to patients who can tolerate one

    • Wear personal protective equipment

    • Practice safe waste management, environmental cleaning, and sterilisation of patient care equipment and linen

  • Implement additional contact and droplet precautions until the patient is asymptomatic:

    • Place patients in adequately ventilated single rooms; when single rooms are not available, place all suspected cases together in the same ward

    • Wear a medical mask, gloves, an appropriate gown, and eye/facial protection (e.g., goggles or a face shield)

    • Use single-use or disposable equipment

    • Consider limiting the number of healthcare workers, family members, and visitors in contact with the patient, ensuring optimal patient care and psychosocial support for the patient

    • Consider placing patients in negative pressure rooms, if available

  • Implement airborne precautions when performing aerosol-generating procedures

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

Some countries and organisations recommend airborne precautions for any situation involving the care of a COVID-19 patient.[105][106]

It is important to disinfect inanimate surfaces in the surgery or hospital as patients may touch and contaminate surfaces such as door handles and desktops.[107] 

Detailed guidance on infection prevention and control procedures are available from the WHO and the Centers for Disease Control and Prevention (CDC):

History

Take a detailed history to ascertain the level of risk for COVID-19 and assess the possibility of other causes. Travel history may be key; it is crucial for timely diagnosis and to prevent further transmission.

Diagnosis should be suspected in:[75]

  • Patients with acute respiratory illness (i.e., fever and at least one sign/symptom of respiratory disease such as cough or shortness of breath) and a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset.

  • Patients with any acute respiratory illness if they have been in contact with a confirmed or probable COVID-19 case in the last 14 days prior to symptom onset.

See our Diagnostic criteria section for full case definitions.

Clinical presentation

The clinical presentation resembles viral pneumonia, and the severity of illness ranges from mild to severe. Approximately 80% of patients present with mild illness, 14% present with severe illness, and 5% present with critical illness.[9] Atypical presentations may occur, especially in older patients or patients who are immunocompromised. 

Severe illness is associated with older age and the presence of underlying health conditions.[9][76] Older patients and/or those with comorbidities may present with mild symptoms, but have a high risk of deterioration.[5] 

The most common symptoms are:[20][21][37][108][109][110]

  • Fever

  • Cough

  • Dyspnoea

  • Myalgia

  • Fatigue.

Less common symptoms include:

  • Anorexia

  • Sputum production

  • Sore throat

  • Confusion

  • Dizziness

  • Headache

  • Rhinorrhoea

  • Chest pain

  • Haemoptysis

  • Diarrhoea

  • Nausea/vomiting

  • Abdominal pain

  • Anosmia/dysgeusia

  • Conjunctival congestion

  • Cutaneous manifestations.

Approximately 90% of patients present with more than one symptom, and 15% of patients present with fever, cough, and dyspnoea.[21] Some patients may be minimally symptomatic or asymptomatic. Mild illness is defined as patients with an uncomplicated upper respiratory tract infection with non-specific symptoms such as fever, cough (with or without sputum production), fatigue, anorexia, malaise, myalgia, sore throat, dyspnoea, nasal congestion, or headache. Patients may have gastrointestinal symptoms. The most common diagnosis in patients with severe COVID-19 is severe pneumonia.[5]

A retrospective case series of 62 patients in Zhejiang province found that the clinical features were less severe than those of the primary infected patients from Wuhan City, indicating that second-generation infection may result in milder infection. This phenomenon was also reported with Middle East respiratory syndrome.[111]

Co-infections (e.g., influenza, human metapneumovirus) have been reported. Patients with influenza co-infection showed similar characteristics to those patients with COVID-19 only.[74][112][113]

Perform a physical examination. Patients may be febrile (with or without chills/rigors) and have obvious cough and/or difficulty breathing. Auscultation of the chest may reveal inspiratory crackles, rales, and/or bronchial breathing in patients with pneumonia or respiratory distress. Patients with respiratory distress may have tachycardia, tachypnoea, or cyanosis accompanying hypoxia.

Children

Signs and symptoms may be similar to other common viral respiratory infections and other childhood illnesses, so a high index of suspicion for COVID-19 is required in children.

Children are typically asymptomatic or present with mild symptoms (e.g., brief and rapidly resolving fever, mild cough, sore throat, congestion, rhinorrhoea).[12][13][114][115][116] However, moderate to severe illness has also been reported in children.[117] Polypnoea has been reported in children with severe illness.[118] There are case reports of neonates and infants presenting with predominantly gastrointestinal symptoms.[119][120] 

In a case series of 2143 paediatric patients in China, over 90% of children were asymptomatic or had a mild or moderate illness; 16% were asymptomatic and had no radiological evidence of pneumonia.[15] However, it is important to note that children may have signs of pneumonia on chest imaging despite having minimal or no symptoms.[121]

Co-infections may be more common in children.[121] It is unknown whether children with underlying health conditions are more at risk of severe illness. Complications in children appear to be milder and more rare.

Pregnant women

Retrospective reviews of pregnant women with COVID-19 found that the clinical characteristics in pregnant women were similar to those reported for non-pregnant adults.[54][57] It is important to note that symptoms such as fever, dyspnoea, and fatigue may overlap with symptoms due to physiological adaptations of pregnancy or adverse pregnancy events.[5]

Initial investigations

Order the following investigations in all patients with severe illness:

  • Pulse oximetry

  • ABG (as indicated to detect hypercarbia or acidosis)

  • FBC

  • Comprehensive metabolic panel

  • Coagulation screen

  • Inflammatory markers (serum procalcitonin and C-reactive protein)

  • Serum troponin

  • Serum lactate dehydrogenase

  • Serum creatine kinase.

The most common laboratory abnormalities in patients hospitalised with pneumonia include leukopenia, lymphopenia, leukocytosis, elevated liver transaminases, elevated lactate dehydrogenase, and elevated C-reactive protein. Other abnormalities include neutrophilia, thrombocytopenia, decreased haemoglobin, decreased albumin, and renal impairment.[20][21][37][110][122]

Pulse oximetry may reveal low oxygen saturation (SpO₂ <90%).


Radial artery puncture animated demonstrationRadial artery puncture animated demonstration

Blood and sputum cultures

Collect blood and sputum specimens for culture in all patients to rule out other causes of lower respiratory tract infection and sepsis, especially patients with an atypical epidemiological history. Specimens should be collected prior to starting empirical antimicrobials if possible.[5]

Molecular testing

Molecular testing is required to confirm the diagnosis. Diagnostic tests should be performed according to guidance issued by local health authorities and should adhere to appropriate biosafety practices. If testing is not available nationally, specimens should be shipped to an appropriate reference laboratory. Specimens for testing should be collected under appropriate infection prevention and control procedures.

Decisions about who to test should be based on clinical and epidemiological factors. The WHO recommends prioritising people with a likelihood of infection. Consider testing asymptomatic or mildly symptomatic contacts of confirmed COVID-19 cases. Symptomatic pregnant women should also be prioritised in order to enable access to specialised care.[5] Consult local health authorities for guidance as testing priorities will depend on local guidelines and available resources. See our Criteria section for CDC and Infectious Diseases Society of America recommendations on testing priorities.

Perform a nucleic acid amplification test, such as real-time reverse-transcription polymerase chain reaction (RT-PCR), for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in appropriate patients with suspected infection, with confirmation by nucleic acid sequencing when necessary.[123]

  • Collect upper respiratory specimens (nasopharyngeal and oropharyngeal swab or wash) in ambulatory patients and/or lower respiratory specimens (sputum and/or endotracheal aspirate or bronchoalveolar lavage) in patients with more severe respiratory disease. Consider the high risk of aerolisation when collecting lower respiratory specimens. 

  • Also consider collecting additional clinical specimens (e.g., blood, stool, urine).

One or more negative results do not rule out the possibility of infection. If a negative result is obtained from a patient with a high index of suspicion for COVID-19, additional specimens should be collected and tested, especially if only upper respiratory tract specimens were collected initially.[123] Guidelines recommend that two consecutive negative tests (at least one day apart) are required to exclude COVID-19; however, there is a case report of a patient who returned two consecutive negative results and didn’t test positive until 11 days after symptom onset and confirmation of typical chest computed tomography (CT) findings.[124]

Collect nasopharyngeal swabs for testing to rule out infection with other respiratory pathogens (e.g., influenza, atypical pathogens) according to local guidance. It is important to note that co-infections can occur, and a positive test for a non-COVID-19 pathogen does not rule out COVID-19.[5][125]

Serological testing is not available as yet, but assays are in development.[126] Serum samples can be stored to retrospectively define cases when validated serology tests become available. Early data indicate continuous high levels of immunoglobulin M (IgM) during the acute phase of infection, with IgM lasting more than 1 month (indicating prolonged virus replication in infected patients). IgG responded later than IgM.[127]

Imaging

All imaging procedures should be performed according to local infection prevention and control procedures to prevent transmission.

Chest x-ray

  • Order a chest x-ray in all patients with suspected pneumonia. Unilateral lung infiltrates are found in 25% of patients, and bilateral lung infiltrates are found in 75% of patients.[20][21][128]

CT chest

  • Consider ordering a CT scan of the chest. Abnormal chest CT findings have been reported in up to 97% of patients in one meta-analysis of 50,466 hospitalised patients.[109] CT is the primary imaging modality in China.[129]

  • CT imaging generally shows bilateral multiple lobular and subsegmental areas of ground-glass opacity or consolidation in most patients, usually with a peripheral or posterior distribution, mainly in the lower lobes and less frequently in the right lower lobe. Consolidative opacities superimposed on ground-glass opacity may be found in a smaller number of cases, usually older patients. Other atypical features include interlobular or septal thickening (smooth or irregular), thickening of the adjacent pleura, subpleural involvement, crazy paving pattern, and air bronchograms. Some patients may rarely present with pleural effusion, pericardial effusion, bronchiectasis, cavitation, pneumothorax, lymphadenopathy, and round cystic changes. Atypical features appear to be more common in the later stages of disease, or on disease progression. None of these findings appear to be specific or diagnostic for COVID-19.[20][111][130] Abnormalities can rapidly evolve from focal unilateral to diffuse bilateral ground-glass opacities that progress to, or co-exist with, consolidations within 1 to 3 weeks.[131] The greatest severity of CT findings is usually visible around day 10 after symptom onset, and imaging signs associated with clinical improvement (e.g., resolution of consolidative opacities, reduction in number of lesions and involved lobes) usually occur after week 2 of the disease.[130] A small comparative study found that patients with COVID-19 are more likely to have bilateral involvement with multiple mottling and ground-glass opacity compared with other types of pneumonia.[132]

  • Small nodular ground-glass opacities are the most common finding in children.[133] Consolidation with surrounding halo signs is a typical finding in children.[121]

  • Evidence of viral pneumonia on CT may precede a positive RT-PCR result for SARS-CoV-2 in some patients.[126] However, CT imaging abnormalities may be present in minimally symptomatic or asymptomatic patients.[47][131] Some patients may present with a normal chest finding despite a positive RT-PCR.[134]

  • In a cohort of over 1000 patients in a hyperendemic area in China, chest CT had a higher sensitivity for diagnosis of COVID-19 compared with initial RT-PCR from swab samples (88% versus 59%). Improvement of abnormal CT findings also preceded change from RT-PCR positivity to negativity in this cohort during recovery. The sensitivity of chest CT was 97% in patients who ultimately had positive RT-PCR results. However, in this setting, 75% of patients with negative RT-PCR results also had positive chest CT findings. Of these patients, 48% were considered highly likely cases, while 33% were considered probable cases.[135]

Use of this content is subject to our disclaimer