QUADAS‐2
Index test(s):	Imaging studies of the chest (computed tomography (CT), chest X‐ray and ultrasound) for diagnosis of COVID‐19
Participants (setting, intended use of index test, presentation, prior testing):	People with suspected COVID‐19 All settings, in particular secondary care, emergency care and intensive care units (ICUs) In people presenting with suspected COVID‐19; suspicion may be based on prior testing, such as general lab testing Signs and symptoms often used for triage or referral
Reference standard and target condition:	A positive diagnosis for COVID‐19 by the following. A positive reverse transcriptase polymerase chain reaction (RT‐PCR) test for SARS‐CoV‐2 infection, from any manufacturer in any country, from any source, including nasopharyngeal swabs or aspirates, oropharyngeal swabs, bronchoalveolar lavage fluid (BALF), sputum, saliva, serum, urine, rectal or faecal samples Positive on WHO criteria for COVID‐19, which includes some testing RT‐PCR‐negative Positive on China CDC criteria for COVID‐19, which includes some testing RT‐PCR‐negative Positive serology in addition to consistent symptomatology Positive on study‐specific list of criteria for COVID‐19, which includes some testing RT‐PCR‐negative Other criteria (symptoms, imaging findings, other tests) A negative diagnosis for COVID‐19 by the following. People with suspected COVID‐19 with negative RT‐PCR test results, whether tested once or more than once Current healthy or with another disease (no RT‐PCR test) This list is not exhaustive, as we anticipate that studies will use a variety of reference standards and we plan to include all of them, at least for the earlier versions of the review. Although RT‐PCR is considered the best available test, it is suspected of missing a substantial proportion of cases, and thus may not be the ideal reference standard if used as a standalone test (Li 2020b; Loeffelholz 2020). Therefore, we are likely to use alternative reference standards, such as a combination of RT‐PCR, and symptoms or imaging findings, or both. We will judge how likely each reference standard definition is to correctly classify individuals in the assessment of methodological quality. All reference standards are likely to be imperfect in some way; details of reference standard evaluation are provided in the 'Risk of bias' tool below. We will use a consensus process to agree the classification of the reference standard as to what we regard as good, moderate and poor. 'Good' reference standards need to have very little change of misclassification, 'moderate', a small but acceptable risk, 'poor', a larger and probably unacceptable risk.
Participant selection
Was a consecutive or random sample of patients enrolled?	YES: if a study explicitly states that all participants within a certain time frame were included; that this was done consecutively; or that a random selection was done. NO: if it is clear that a different selection procedure was employed; e.g. selection based on clinician’s preference, or based on institutions (i.e. ‘convenience’ series) UNCLEAR: if the selection procedure is not clear or not reported at all.
Was a case‐control design avoided?	YES: if a study explicitly states that all participants came from the same group of (suspected) patients. NO: if it is clear that a different selection procedure was employed for the participants depending on their COVID‐19 status (e.g. proven infected patients in one group and proven non‐infected patients in the other group). UNCLEAR: if the selection procedure is not clear or not reported at all.
Did the study avoid inappropriate in‐ or exclusions?	This needs to be addressed on a case‐to‐case basis. YES: If all eligible patients were ore or less equally suspected of having COVID‐19 and were included and if the numbers in the flow chart show not too many excluded participants (a maximum of 20% of eligible patients excluded without reasons). NO: If over 20% of eligible patients were excluded without providing a reason; if only proven patients were included, or only proven non‐patients were included; if in a retrospective study participants without index test or reference standard result were excluded; if exclusion was based on severity assessment post‐factum or comorbidities (cardiovascular disease, diabetes, immunosuppression). If the study oversampled patients with particular characteristics likely to affect estimates of accuracy. UNCLEAR: if the exclusion criteria are not reported.
Could the selection of patients have introduced bias?	HIGH: if one or more signalling questions were answered with NO, as any deviation from the selection process may lead to bias. LOW: if all signalling questions were answered with YES. UNCLEAR: all other instances
Is there concern that the included patients do not match the review question?	This needs to be addressed on a case‐to‐case basis, based on the objective the included study answers to. HIGH: if accuracy was assessed in a case‐control design, or the study was able to only estimate sensitivity or specificity. LOW: any situation where imaging is generally available. UNCLEAR: if a description about the participants is lacking.
Index tests
Were the index test results interpreted without knowledge of the results of the reference standard?	YES: if blinding was explicitly stated or index test was recorded before the results from the reference standard were available NO: if it was explicitly stated that the index test results were interpreted with knowledge of the results of the reference standard UNCLEAR: if blinding was unclearly reported.
If a threshold was used, was it prespecified?	YES: for any of these index tests it is highly unlikely that any numerical threshold is used. Still we expect studies to report their criteria for test‐positivity (e.g. the constellation of imaging findings used). If these criteria are reported in the methods section, we will score ‘YES’ for this question. NO: if the optimal criterion for test‐positivity was based on the reported data (for example, different scores on a quantitative scoring system) we will score ‘NO’. UNCLEAR: if the criteria for test positivity were not or unclearly reported.
Could the conduct or interpretation of the index test have introduced bias?	HIGH: if one or more signalling questions were answered with NO. LOW: if all signalling questions were answered with YES. UNCLEAR: all other instances Note: For studies that use formal scoring systems with clearly defined thresholds, even if the signalling question about using a ‘prespecified threshold’ is 'unclear' or ‘no’, this domain should not be considered as having a ‘unclear’ or ‘high’ risk of bias based on the aforementioned question.
Is there concern that the index test, its conduct, or interpretation differ from the review question?	There is not a huge amount of variability from a technical perspective. Therefore, this question will probably be answered ‘LOW’ in all cases except when assessments are made using personnel not available in practice, or personnel not trained for the job, or using modalities that are uncommon in practice. We will consult expert clinicians on a case‐to‐case basis to judge this question.
Reference standard
Is the reference standard likely to correctly classify the target condition?	YES: for COVID‐19: RT‐PCR, done by trained personnel, and repeated after a first negative RT‐PCR, following guidelines for confirmed cases and done with an assay targeting minimum 2 targets in the genes N, E, S or RdRP (one target even acceptable in zone with known transmission). To clarify, a low risk of bias reference standard for true negative would require 2 (or more) negative RT‐PCR results. NO: any other test UNCLEAR: if no reference standard was reported, or if it was just reported that RT‐PCR was done.
Were the reference standard results interpreted without knowledge of the results of the index test?	YES: if it was explicitly stated that the reference standard results were interpreted without knowledge of the results of the index test, or if the result of the index test was obtained after the reference standard. NO: if it was explicitly stated that the reference standard results were interpreted with knowledge of the results of the index test or if the index test was used to make the final diagnosis (incorporation bias). UNCLEAR: if blinding was unclearly reported.
Could the conduct or interpretation of the reference standard have introduced bias?	HIGH: if one or more signalling questions were answered with NO. LOW: if all signalling questions were answered with YES. UNCLEAR: all other instances Note: For studies that use RT‐PCR testing as the reference standard, even if this signalling question about 'blinding' is 'unclear' or ‘no’, this domain should not be considered as having a ‘unclear’ or ‘high’ risk of bias based on the aforementioned question.
Is there concern that the target condition as defined by the reference standard does not match the review question?	HIGH: there is a high concern regarding applicability of the reference standard if the reference standard actually measures a different target condition than the one we are interested in for the review. For example, if the diagnosis is only based on clinical picture, without excluding other possible causes of this clinical picture (e.g. other respiratory pathogens), then there is considerable concern that the reference standard is actually measuring something else than COVID‐19. In addition, a positive RT‐PCR only measures SARS‐CoV‐2 infection and not COVID‐19 and therefore the reference standard for COVID‐19 is a combination of positive RT PCR and symptoms and/or imaging findings. LOW: if above situations not present UNCLEAR: if intention for testing is not reported in the study
Flow and timing
Was there an appropriate interval between index test(s) and reference standard?	YES: as the situation of a patient, including clinical presentation and disease progress, evolves rapidly and new/ongoing exposure can result in case status change. On the other hand, negative PCR results need to be repeated for several days. Therefore, an appropriate time interval will be within 7 days. NO: if there is more than 7 days between the index test and the reference standard or if patients are otherwise reported to be assessed with the index versus reference standard test at moments of different severity. UNCLEAR: if the time interval is not reported
Did all participants receive a reference standard?	YES: if all patients received a reference standard (clearly no partial verification) NO: if only (part of) the index test positives or index test negatives received the complete reference standard UNCLEAR: if it is not reported.
Did all participants receive the same reference standard?	YES: if all patients received the same reference standard (clearly no differential verification). Verification of negative PCR result with a second PCR measurement is considered to be one reference standard. NO: if (part of) the index test positives or index test negatives received a different reference standard UNCLEAR: If it is not reported.
Were all participants included in the analysis?	YES: if all included participants were included in the analyses as well NO: if after the inclusion/exclusion process, participants were removed from the analyses for different reasons: no reference standard done, no index test done, intermediate results of both index test or reference standard, indeterminate results of both index test or reference standard, samples unusable. UNCLEAR: If this is not clear from the reported numbers.
Could the patient flow have introduced bias?	HIGH: if one or more signalling questions were answered with NO, or if one question answered with NO was judged to have little impact on the methodological quality of the study (this should be justified in the scoring). LOW: if all signalling questions were answered with YES. UNCLEAR: all other instances
CT: computed tomography; CXR: chest X‐ray; ICU: intensive care unit; RT‐PCR: reverse transcriptase polymerase chain reaction; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; US: ultrasound