Investigations

1st investigations to order

Test
Result
Test

Order an RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with suspected infection whenever possible (see the Criteria section).[536]

Commonly used assays are expected to be able to detect SARS-CoV-2 variants.[168] However, some tests may be impacted by variants.[577] The US Food and Drug Administration has warned that false-negative results may occur with any molecular test for the detection of SARS-CoV-2 if a mutation occurs in the part of the virus’ genome assessed by that test. Multiple genetic targets to determine a final result are less likely to be impacted by increased prevalence of genetic variants. Consider negative results in combination with clinical observations, patient history, and epidemiologic information.[694]

Molecular testing is an aid to diagnosis only. The World Health Organization recommends that healthcare providers consider a positive or negative result in combination with specimen type, clinical observations, patient history, and epidemiologic information. Where a test result does not correspond with the clinical presentation, a new specimen should be taken and retested using the same or a different molecular test.[576]

Base decisions about who to test on clinical and epidemiologic factors.[536] Consult local health authorities for guidance as testing priorities depend on local recommendations and available resources.

The World Health Organization recommends testing all people who meet the suspected case definition of COVID-19, regardless of vaccination status or disease history. When resources are constrained, people who are at risk of developing severe disease, healthcare workers, inpatients, and the first symptomatic individuals in the setting of a suspected outbreak should be prioritized. Testing of asymptomatic individuals is currently recommended only for specific groups including contacts of confirmed or probable cases and frequently exposed groups such as healthcare workers and long-term care facility workers.[578]

In the UK, testing is recommended in: (1) people with symptoms of new continuous cough, high temperature, or altered sense of smell/taste; (2) people with acute respiratory infection, influenza-like illness, clinical or radiologic evidence of pneumonia, or acute worsening of underlying respiratory illness, or fever without another cause (whether presenting in primary or secondary care).[579]

In the US, testing is recommended in: (1) anyone with signs or symptoms consistent with COVID-19; (2) asymptomatic unvaccinated people identified through contact tracing efforts; (3) asymptomatic unvaccinated people with recent known or suspected exposure to SARS-CoV-2, including those who have been in close contact (less than 6 feet [2 meters] for a total of 15 minutes or more over a 24-hour period) with a person with documented infection; (4) asymptomatic unvaccinated people without recent known or suspected exposure to SARS-CoV-2 for early identification, isolation, and disease prevention (only when screening testing is recommended by public health officials).[580] 

The American Academy of Pediatrics recommends testing children with symptoms consistent with COVID-19, children in close contact with an individual with probable or confirmed infection, and children who require screening based on recommendations from public health authorities or other situations (e.g., prior to a medical procedure such as elective surgery or as a school or workplace requirement). The decision to test does not differ by the age of the child. Testing is not recommended for other illnesses that lack shared symptoms (e.g., urinary tract infection, cellulitis), or for children exposed to close contacts of infected individuals unless those contacts are symptomatic or other criteria are met.[581]

The optimal specimen for testing depends on the clinical presentation and the time since symptom onset. The World Health Organization recommends upper respiratory specimens (nasopharyngeal and/or oropharyngeal swabs) for early-stage infections, especially asymptomatic or mild cases, and lower respiratory specimens (sputum and/or endotracheal aspirate or bronchoalveolar lavage in patients with more severe respiratory disease) for later-stage infections or patients in whom there is a strong suspicion for infection and their upper respiratory tract specimen test was negative. Other specimens (e.g., nasal mid-turbinate swab, anterior nares swab, nasopharyngeal/nasal wash/aspirate, saliva, fecal) may be recommended in some circumstances; consult local guidance.[536][591][589] Meta-analyses of paired saliva samples and nasopharyngeal swabs found no statistically significant difference in sensitivity or specificity between these specimens for SARS-CoV-2 detection, especially in the ambulatory setting. Sensitivity was not significantly different among asymptomatic people and outpatients. Methods of saliva collection may affect sensitivity. Meta-analyses demonstrate that saliva is as valid as nasopharyngeal sampling for the detection of SARS-CoV-2 infections in symptomatic and asymptomatic patients. Saliva sampling is simple, fast, noninvasive, inexpensive, and painless.[583][584][585][586][587][588]

A positive RT-PCR result confirms SARS-CoV-2 infection (in the context of the limitations associated with RT-PCR testing). If the result is negative, and there is still a clinical suspicion of infection (e.g., an epidemiologic link, typical x-ray findings, absence of another etiology), resample the patient and repeat the test. A positive result confirms infection. If the second test is negative, consider serologic testing (see below).[536]

The pooled sensitivity has been estimated to be 87.8%, with the specificity estimated to be in the range of 87.7% to 100%.[597]

Interpret test results with caution. Evidence for the use of RT-PCR in the diagnosis of COVID-19 is still emerging, and uncertainties about its efficacy and accuracy remain.[597] It is not fully understood whether a positive result always represents infectious virus, especially at high cycle thresholds.[598][601][602][603] Interpreting the result depends on the accuracy of the test itself, and the pre- and post-test probabilities of disease.[600] When the pretest probability is low, positive results should be interpreted with caution, and ideally a second specimen tested for confirmation.[604] The lower the prevalence of disease in a given population, the lower the post-test probability.[605] False-positive results can be caused by a laboratory error or a cross-reaction with antibodies formed by current and past exposure to seasonal human coronavirus infections (e.g., common cold), and are more likely when the prevalence of disease is moderate to low.[607][608] Preliminary estimates of the false-positive rate in the UK are in the range of 0.8% to 4%.[609] False-negative rates of between 2% and 29% have been reported.[600] A systematic review found that the false-negative rate varied across studies from 1.8% to 58% (median 11%); however, there was substantial and largely unexplained heterogeneity across studies.[610]

Rapid molecular tests are available. They may be suitable for some testing scenarios (e.g., where obtaining test results within 2 hours will enable appropriate decision-making); however, evidence is limited.[624]

Also collect nasopharyngeal swabs to rule out influenza and other respiratory infections according to local guidance. It is important to note that coinfections can occur, and a positive test for a non-COVID-19 pathogen does not rule out COVID-19.[2][596] When SARS-CoV-2 and influenza viruses are cocirculating, test for both viruses in all hospitalized patients with acute respiratory illness, and only test for influenza virus in outpatients with acute respiratory illness if the results will change clinical management of the patient.[533] Single-test multiplex assays to diagnose infection caused by influenza A, influenza B, and SARS-CoV-2 are available in some countries.

Result

positive for SARS-CoV-2 viral RNA; may be positive for influenza A and B viruses and other respiratory pathogens

Test
Result
Test

Clinicians should be aware that patients with COVID-19 can develop "silent hypoxia": their oxygen saturations can drop to low levels and precipitate acute respiratory failure without the presence of obvious symptoms of respiratory distress.[563]

Pulse oximetry may be available as part of remote monitoring in the community. Evidence suggests that patients who may benefit most from monitoring are those who are symptomatic and are either over 65 years of age, or are under 65 years years of age and are extremely clinically vulnerable to COVID-19. NHS England: pulse oximetry to detect early deterioration of patients with COVID-19 in primary and community care settings external link opens in a new window

The UK National Institute for Health and Care Excellence recommends using oxygen saturation levels below 94% for adults (or below 88% for adults with known type 2 respiratory failure) and below 91% for children in room air at rest to identify people who are seriously ill.[564]

Pulse oximeters may exhibit suboptimal accuracy in certain populations. Limited data from studies with small numbers of participants suggest that skin pigmentation can affect pulse oximeter accuracy. In one study, occult hypoxemia (defined in the study as arterial oxygen saturation <88% by arterial blood gas despite oxygen saturation of 92% to 96% on pulse oximetry) was not detected by pulse oximetry nearly three times more frequently in Black patients compared with White patients.[565] The US Food and Drug Administration (FDA) has warned that multiple factors can affect the accuracy of a pulse oximeter reading (e.g., poor circulation, skin pigmentation, skin thickness, skin temperature, current tobacco use, use of fingernail polish). The FDA recommends considering accuracy limitations when using a pulse oximeter to assist in diagnosis and treatment decisions, and to use trends in readings over time rather than absolute cut-offs if possible.[566]

Only a small proportion of patients have other organ dysfunction, meaning that after the initial phase of acute deterioration, traditional methods of recognizing further deterioration (e.g., National Early Warning Score 2 [NEWS2] scores) may not help predict those patients who go on to develop respiratory failure.[563]

Pulse oximeters can be used at home to detect hypoxia. Home pulse oximetry requires clinical support (e.g., regular phone contact from a health professional in a virtual ward setting).

BMJ Practice Pointer: remote management of covid-19 using home pulse oximetry and virtual ward support external link opens in a new window

Result

may show low oxygen saturation (cut-off depends on local guidelines)

Test
Result
Test

Order in patients with severe illness as indicated to detect hypercarbia or acidosis.

Recommended in patients with respiratory distress and cyanosis who have low oxygen saturation (SpO₂ <90%).

Result

may show low partial oxygen pressure

Test
Result
Test

Order in patients with severe illness.

Lymphopenia, leukocytosis, thrombocytopenia, decreased eosinophils, decreased hemoglobin, and high neutrophil-to-lymphocyte ratio are significantly associated with severe disease, and may be useful for predicting disease progression. Severe cases are more likely to present with lymphopenia and thrombocytopenia, but not leukopenia.[695]

Elevated red blood cell distribution width (at admission and increasing during hospitalization) has been associated with a significantly increased risk of mortality in hospitalized patients.[696]

Absolute counts of major lymphocyte subsets, particularly CD4+ and CD8+ T-cell counts, are significantly decreased in patients with severe disease.[697]

Late-phase thrombocytopenia (i.e., occurring 3 weeks or more after symptom onset) has been reported but is uncommon.[698]

Result

lymphopenia; leukocytosis; leukopenia; thrombocytopenia; decreased eosinophils; decreased hemoglobin

Test
Result
Test

Order in patients with severe illness.

Elevated liver enzymes, total bilirubin, creatinine, and blood urea nitrogen, and hypoalbuminemia are significantly associated with severe disease, and may be useful for predicting disease progression.[695]

Hypokalemia has been reported in 54% of patients.[699] Hypocalcemia has been reported in 63% of patients, and is associated with poor outcomes.[700][701] Hyponatremia has been reported in 24% of patients, and is associated with poor outcomes.[702] Other electrolyte derangements may be present.

Result

elevated liver enzymes; elevated total bilirubin; renal impairment; hypoalbuminemia; electrolyte derangements

Test
Result
Test

Order in patients with severe illness.

Fasting hyperglycemia independently predicts poor prognosis and is associated with an increased risk of mortality, regardless of whether or not the patient has diabetes.[703][704]

Hypoglycemia has also been associated with increased mortality in a retrospective cohort study.[705]

Result

variable

Test
Result
Test

Order in patients with severe illness.

Elevated D-dimer, elevated fibrinogen (and fibrin degradation product), and prolonged prothrombin time are significantly associated with severe disease, and may be useful for predicting disease progression.[695][706]

The risk of severe disease and mortality is 2-fold and 4-fold higher, respectively, in patients with elevated D-dimer levels.[707] Patients with very high D-dimer levels have an increased risk of thrombosis.[708][709]

Result

elevated D-dimer; prolonged prothrombin time; elevated fibrinogen

Test
Result
Test

Order in patients with severe illness.

Elevated creatine kinase-myocardial band (CK-MB), B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and troponin are associated with severe disease and mortality, and may be useful for predicting disease progression or survival.[710]

CK-MB has been found to be elevated in mild disease in children. The significance of this is unknown.[572]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Elevated C-reactive protein is significantly associated with severe disease, and may be useful for predicting disease progression.[695]

Patients with elevated C-reactive protein at the time of initial presentation were more likely to have acute kidney injury, venous thromboembolism, critical illness, and in-hospital mortality during their hospital stay compared with patients with lower levels.[711]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Commonly elevated in patients with COVID-19.[570]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Elevated serum lactate dehydrogenase is significantly associated with severe disease, and may be useful for predicting disease progression.[695]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Elevated interleukin-6 level is significantly associated with severe disease, and may be useful for predicting disease progression.[695]

Less likely to be elevated in children.[712]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Elevated serum procalcitonin is significantly associated with severe disease, and may be useful for predicting disease progression.[695]

Elevated serum procalcitonin may be more common in children.[560]

May be elevated in patients with secondary bacterial infection.[50][51] 

There is insufficient evidence to recommend routine procalcitonin testing to guide decisions about the use of antibiotics. However, it may be helpful in identifying whether there is a bacterial infection, although the most appropriate procalcitonin threshold is uncertain.[564]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Elevated ferritin is significantly associated with severe disease, and may be useful for predicting disease progression.[713]

May indicate development of cytokine release syndrome.[714]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Levels increase in severe disease; therefore, it may be useful as a biomarker for predicting disease progression.[715]

Result

may be elevated

Test
Result
Test

Order in patients with severe illness.

Elevated serum creatine kinase and myoglobin are significantly associated with severe disease, and may be useful for predicting disease progression.[695]

Result

may be elevated

Test
Result
Test

Collect blood and sputum specimens for culture in patients with severe or critical disease to rule out other causes of lower respiratory tract infection and sepsis, especially patients with an atypical epidemiologic history.[2]

Specimens should be collected prior to starting empiric antimicrobials if possible.

Result

negative for bacterial infection

Test
Result
Test

Order 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.[50][51][628]

Chest x‐ray is moderately sensitive and moderately specific for the diagnosis of COVID‐19. Pooled results found that chest x‐ray correctly diagnosed COVID‐19 in 80.6% of people who had the disease. However, it incorrectly identified COVID‐19 in 28.5% of people who did not have the disease.[629]

Although chest x-ray appears to have a lower sensitivity compared with chest CT, it has the advantages of being less resource-intensive, associated with lower radiation doses, easier to repeat sequentially, and portable.[630]

Result

unilateral or bilateral lung infiltrates

Investigations to consider

Test
Result
Test

Consider a CT scan of the chest. Consult local guidance on whether to perform a CT scan. The British Society of Thoracic Imaging (BSTI) recommends CT imaging in patients with clinically suspected COVID-19 who are seriously ill if chest x-ray is uncertain or normal. BSTI: radiology decision tool for suspected COVID-19 external link opens in a new window Some institutions in the UK recommend a more pragmatic approach for patients with high clinical suspicion of COVID-19, with chest CT recommended only after two indeterminate or normal chest x-rays in combination with a negative RT-PCR test.[632] The American College of Radiology recommends reserving CT for hospitalized, symptomatic patients with specific clinical indications for CT, and emphasizes that a normal chest CT does not mean that a patient does not have COVID-19 and that an abnormal chest CT is not specific for COVID-19 diagnosis.[633]

Chest CT is sensitive and moderately specific for the diagnosis of COVID‐19. Pooled results found that chest CT correctly diagnosed COVID‐19 in 87.9% of people who had the disease. However, it incorrectly identified COVID‐19 in 20% of people who did not have the disease. Therefore, chest CT may have more utility for excluding COVID‐19 than for differentiating it from other causes of respiratory illness.[629] Accuracy appears to be lower among children; however, there are limited data in this population.[631]

Evidence of pneumonia on CT may precede a positive RT-PCR result for SARS-CoV-2 in some patients.[634] Some patients may present with a normal chest finding despite a positive RT-PCR.[635] Results of RT-PCR testing may be false-negative, so patients with typical CT findings should have repeat RT-PCR testing to confirm the diagnosis.[636] CT imaging abnormalities may be present in asymptomatic patients. The pooled estimate of the rate of positive chest CT findings in asymptomatic cases was 47.6% (mainly ground-glass opacity).[637]

Abnormal chest CT findings have been reported in up to 97% of hospitalized patients.[639] The most common findings are ground-glass opacity, either in isolation or coexisting with other findings such as consolidation, interlobular septal thickening, or crazy-paving pattern. The most common distribution pattern is bilateral, peripheral/subpleural, posterior distribution of the opacities, with a lower lobe predominance. Extensive/multilobar involvement with consolidations is more common in older patients and those with severe disease. Pulmonary vascular enlargement, interlobular or intralobular septal thickening, adjacent pleural thickening, air bronchograms, subpleural lines, crazy-paving pattern, bronchus distortion, bronchiectasis, vacuolar retraction sign, and halo sign are atypical features. Pleural effusion, pericardial effusion, cavitation, pneumothorax, and mediastinal lymphadenopathy have also been reported rarely.[640] Ground-glass opacity has the highest diagnostic performance for COVID-19 pneumonia, followed by ground-glass opacity plus consolidation, and consolidation only.[641]

Children frequently have normal or mild CT chest findings. The most common signs in children are patchy ground-glass opacity and, less frequently, nonspecific patchy shadows, areas of consolidation, and a halo sign. Abnormalities are more common in the lower lobes and are predominantly unilateral. Pleural effusion is rare.[644] Ground-glass opacity and peribronchial thickening were the most prevalent findings in infants younger than 1 year of age.[645]

CT scan generally shows an increase in the size, number, and density of ground-glass opacities in the early follow-up period, with a progression to mixed areas of ground-glass opacities, consolidations, and crazy paving peaking at day 10 to 11, before gradually resolving or persisting as patchy fibrosis.[640]

The positive predictive value was low (1.5% to 30.7%) in low-prevalence regions, and the negative predictive value ranged from 95.4% to 99.8% in one meta-analysis. Pooled sensitivity and specificity were 94% to 96% and 37%, respectively.[716][717] The simultaneous presence of ground-glass opacity and other features of viral pneumonia had optimum performance in the detection of COVID-19 (sensitivity 90% and specificity 89%).[642]

CT is more sensitive than RT-PCR in detecting COVID-19, but has a very low specificity.[718] 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.[719]com.bmj.content.model.Caption@62696cd6[Figure caption and citation for the preceding image starts]: Transverse CT scans from a 32-year-old man, showing ground-glass opacity and consolidation of lower lobe of right lung near the pleura on day 1 after symptom onset (top panel), and bilateral ground-glass opacity and consolidation on day 7 after symptom onsetXu XW et al. BMJ. 2020;368:m606 [Citation ends].

Result

ground-glass opacity in isolation or coexisting with other findings (e.g., consolidation, interlobular septal thickening, crazy-paving pattern); bilateral, peripheral/subpleural, posterior distribution with a lower lobe predominance

Test
Result
Test

Important: a positive test for spike protein IgM or IgG could indicate either prior infection or prior vaccination with a COVID-19 vaccine. To evaluate for evidence of prior infection in an individual who has received a vaccine, a test that specifically evaluates IgM or IgG to the nucleocapsid protein should be used. A positive nucleocapsid protein-based assay indicates prior infection. Antibody testing is not currently recommended to assess immunity following vaccination.[356][720][721][359]

Cannot be used as a standalone diagnostic for acute infections; however, may be useful in various settings (e.g, negative molecular testing, diagnosing patients with late presentation or prolonged symptoms, serosurveillance studies).[536][612]

BMJ practice pointer: testing for SARS-CoV-2 antibodies external link opens in a new window

The World Health Organization (WHO) recommends collecting a paired serum sample, one specimen in the acute phase and one in the convalescent phase 2 to 4 weeks later, in patients where infection is strongly suspected and the RT-PCR result is negative. Seroconversion or a rise in antibody titers in paired sera help to confirm whether the infection is recent and/or acute. If the initial sample tests positive, this could be due to a past infection that is not related to the current illness. Seroconversion may be faster and more robust in patients with severe disease compared with those with mild disease or asymptomatic infection.[536]

The Centers for Disease Control and Prevention recommends serologic testing as a method to support the diagnosis of illness or complications in the following situations: a positive antibody test at least 7 days following acute illness onset in people with a previous negative antibody test (i.e., seroconversion) and who did not receive a positive viral test may indicate SARS-CoV-2 infection between the dates of the negative and positive antibody tests; a positive antibody test can help support a diagnosis when patients present with complications of COVID-19 illness, such as multisystem inflammatory syndrome and other post-acute sequelae of COVID-19.[613]

The Infectious Diseases Society of America recommends serologic testing in the following circumstances: evaluation of patients with a high clinical suspicion for infection when molecular diagnostic testing is negative and at least 2 weeks have passed since symptom onset; evaluation of pediatric inflammatory multisystem syndrome in children; and serosurveillance studies.[614]

Antibody responses to SARS-CoV-2 typically occur during the first 1 to 3 weeks of illness, with the seroconversion time of IgG antibodies often being earlier than that of IgM antibodies.[615][616]

The estimated sensitivity of antibody tests ranged from 18.4% to 96.1% (the lowest reported sensitivity was from a point-of-care test, although a sensitivity <50% was reported for one laboratory test), and specificity ranged from 88.9% to 100%. Estimates of diagnostic accuracy need to be interpreted with caution in the absence of a definitive reference standard to diagnose or rule out COVID-19.[597]

Limitations of testing: serologic testing cannot be used to determine acute infection; results do not indicate the presence or absence of current or previous infection with certainty; reliable diagnosis is often only possible in the recovery phase when opportunities for management or interruption of transmission have passed; cross-reactivity with other coronaviruses, which can result in false-positive results.[536][613]

While rapid antibody detection kits have been approved for the qualitative detection of SARS-CoV-2 IgG/IgM antibodies in serum, plasma, or whole blood, the WHO does not recommend the use of these tests outside of research settings as they have not been validated as yet.[618]

Result

positive for SARS-CoV-2 virus antibodies; seroconversion or a rise in antibody titers in paired sera

Test
Result
Test

Rapid diagnostic test. Relies on direct detection of SARS-CoV-2 viral proteins in nasal swabs and other respiratory specimens using a lateral flow immunoassay. Results are usually available in less than 30 minutes. While antigen tests are substantially less sensitive than RT-PCR, they offer the possibility of rapid, inexpensive, and early detection of the most infectious cases in appropriate settings. If used, testing should occur within the first 5 to 7 days following the onset of symptoms. The World Health Organization recommends antigen testing only in certain scenarios where RT-PCR is unavailable or where prolonged turnaround times preclude clinical utility, provided that the test meets the minimum performance requirements of ≥80% sensitivity and ≥97% specificity compared with an RT-PCR reference assay.[620]

The Infectious Diseases Society of America recommends antigen testing in some individuals only when molecular testing is not readily available or is logistically infeasible, noting that the overall quality of available evidence supporting its use was graded as very low to moderate.[621]

The Centers for Disease Control and Prevention recommends antigen tests may be used in congregate and community settings; however, confirmatory molecular testing may be needed.[622]

The US Food and Drug Administration has warned that false-positive results can occur with antigen tests, including when users do not follow the instructions for use, and that the number of false-positive tests increases as disease prevalence decreases.[623] The agency has also recommended not using certain tests due to performance issues.[722]

A Cochrane review found that rapid antigen tests vary in sensitivity. Sensitivity was higher in the first week after symptom onset in symptomatic people (78.3%), compared with the second week of symptoms (51%). Sensitivity was higher in those with RT-PCR cycle threshold values ≤25 (94.5%), compared with those with cycle threshold values >25 (40.7%). Sensitivity was higher in symptomatic people (72%), compared with asymptomatic people (58.1%). Sensitivity also varied between brands of tests. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Evidence for testing in asymptomatic cohorts was limited, and no studies assessed the accuracy of repeated lateral flow testing or self‐testing.[624]

An observational cohort study that assessed the performance of rapid antigen lateral flow testing against RT-PCR in an asymptomatic general population in the UK found that the lateral flow test can be useful for detecting infections among asymptomatic adults, particularly those with a high viral load who are likely to be infectious. Lateral flow tests showed a sensitivity of 40%, specificity of 99.9%, positive predictive value of 90.3%, and negative predictive value of 99.2% in this population. Approximately 10% of people with a higher viral load detected by RT-PCR were missed by lateral flow tests.[625]

Rapid antigen testing appears to be a reliable diagnostic tool to quickly detect persons with a high viral load, and can help to detect and isolate potential superspreaders before RT-PCR results are available. However, testing is unsuccessful in detecting persons with lower viral load and asymptomatic patients.[626]

Rapid, lateral flow antigen tests for home use are available over-the-counter in some countries.[723]

Laboratory-based (nonrapid) antigen tests are also available in some countries.

Recommendations for the use of lateral flow tests differ between countries. For example, in the UK, lateral flow tests are only currently recommended for patients without symptoms.[724] Consult local guidance for more information.

BMJ: interpreting a lateral flow SARS-CoV-2 antigen test external link opens in a new window

Result

positive for SARS-CoV-2 virus antigen

Emerging tests

Test
Result
Test

A similar process to RT-PCR, but uses constant temperatures and produces more viral DNA compared with RT-PCR. While simple and quick, it is a newer technology and there is less evidence for its use. Assays for SARS-CoV-2 have been developed and are being evaluated.[646][647][648] A sensitivity of 95.5% and specificity of 99.5% has been reported.[649]

An at-home test kit that provides rapid results within 30 minutes has been approved in the US under an emergency-use authorization for self-testing at home that provides rapid results.[725]

Result

positive for SARS-CoV-2 viral RNA

Test
Result
Test

Lung ultrasound is used as a diagnostic tool in some centers as an alternative to chest x-ray and chest CT. Although there is only very low-certainty evidence supporting its diagnostic accuracy, it might be helpful as a supplemental or alternate imaging modality.[630]

Ultrasound is sensitive but not specific for the diagnosis of COVID‐19. Pooled results found that lung ultrasound correctly diagnosed COVID‐19 in 86.4% of people with the disease. However, it incorrectly diagnosed COVID‐19 in 45% of people who did not have the disease. Therefore, ultrasound may have more utility for excluding COVID‐19 than for differentiating it from other causes of respiratory illness.[629]

B-lines are the prominent pattern in patients with COVID-19, occurring with a pooled frequency of 97%. Pleural line abnormalities are also common with a pooled frequency of 70%. While these findings are not specific for COVID-19, they increase the likelihood of disease in the context of a characteristic clinical presentation. Other findings include consolidations, pleural thickening, and pleural effusion.[650]

Has the advantages of portability, bedside evaluation, reduced healthcare worker exposure, easier sterilization process, absence of ionizing radiation exposure, and repeatability during follow-up. It may also be more readily available in resource-limited settings. However, it also has some limitations (e.g., it is unable to discern chronicity of a lesion) and other imaging modalities may be required.[650]

May be used in pregnant women and children.[651][652]

Possible roles include: reducing nosocomial transmission; monitoring progress of patients; and a possible role in subpopulations who are vulnerable but are not suitable for CT (e.g., pregnant women).[653] Lung ultrasound score may play a role in prognosis.[654]

BSTI: lung ultrasound (LUS) for COVID-19 patients in critical care areas external link opens in a new window

Result

B-lines; pleural line abnormalities

Test
Result
Test

Calprotectin is an emerging biomarker of interest. Calprotectin levels often increase following infection or trauma, and in inflammatory disease. Serum/fecal calprotectin levels have been demonstrated to be significantly elevated in COVID-19 patients with severe disease, and it may have prognostic significance.[655]

Result

elevated

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