Xiao 2020b [A].

Study characteristics
Patient Sampling	Purpose: screening and diagnosing asymptomatic carriers; comparing asymptomatic, pre‐symptomatic and symptomatic cases Diagnosis of current or prior infection Design: Three‐group study to estimate sensitivity according to symptomatic status: (1) 23 asymptomatic cases, (2) 33 pre‐symptomatic cases, (3) 19 age‐matched symptomatic cases Recruitment: unclear Participants selected from consecutive series of 449 COVID‐19 patients observed at single hospital: a. 77 asymptomatic on admission. Excluded: 21 due to severe disease (n = 2), inpatients (n = 5) or having undetectable RNA and IgM (n = 14), leaving 56 discharged patients for inclusion: 1) 23 who remained asymptomatic and 2) 33 who became symptomatic after admission (pre‐symptomatic group) b. 372 symptomatic on admission; random sample of 19 age‐matched cases selected (group 3) Prospective or retrospective: retrospective analysis Sample size: 75 (75)
Patient characteristics and setting	Setting: hospital inpatients Location: Shenzhen Third People's Hospital Country: China Dates: January 23, 2020‐April 1, 2020 Symptoms and severity: Pre‐symptomatic* ‐ fever 11 (13%), cough 22 (67%), chest tightness 2 (6%); Symptomatic ‐ fever 13 (68%), cough 13 (68%), chest tightness 1 (5%) *2/77 asymptomatic on admission were excluded due to disease severity and 5/77 excluded as remained as inpatients Demographics: Asymptomatic: Age: median (IQR): 30 (41.8), gender, n (%): male 5 (21.7), female 18 (78.3); pre‐symptomatic: Age: median (IQR): 45 (30.5), gender, n (%): male 18 (54.6), female 15 (45.5); symptomatic: Age: median (IQR): 25 (36.0), gender, n (%): male 9 (47.4), female 10 (52.6) Exposure history: not clearly reported; asymptomatic on admission (n = 77) identified through active surveillance and contact tracing Non‐Covid group 1: NA
Index tests	Test name: [A] Wantai Biological Pharmacy Enterprise CLIA Total‐Ab assay [B] Wantai Biological Pharmacy Enterprise SARS‐CoV‐2 IgG ELISA [C] Wantai Biological Pharmacy Enterprise SARS‐CoV‐2 IgM ELISA [D] Wantai Biological Pharmacy Enterprise ELISA IgA assay Manufacturer: [A] Wantai Biological Pharmacy Enterprise [B] Wantai Biological Pharmacy Enterprise [C] Wantai Biological Pharmacy Enterprise [D] Wantai Biological Pharmacy Enterprise Antibody: [A] total antibody (Ab), [B] IgG, [C] IgM, and [D] IgA Antigen target: [A] RBD [B] [C] [D] S based Evaluation setting: laboratory test Test method: [A] CLIA [B] [C] [D] ELISA Timing of samples: day 0 to 65 post‐symptom onset (or post‐admission for asymptomatic group). Number of patients with samples obtained per week varied (total (asymptomatic/pre‐symptomatic/symptomatic)): day 1‐7 48/75 (17/23/8); day 8‐14 38/75 (9/17/22); day 15‐30 48/75 (10/21/19); day 31‐65 64/75 (17/28/19) Samples used: plasma Test operator: not reported Definition of test positivity: The relative fluorescence of sample to control (COI) was used to estimate the result. Positive: COI > 1 Blinding reported: Not stated Threshold predefined: not reported; presumably as per manufacturer instructions
Target condition and reference standard(s)	Reference standard: RT‐PCR (GeneoDX Co., Ltd., Shanghai, China on an ABI 7500 thermo cycler) or antibody tests for SARS‐CoV‐2 (not described), as per Chinese NHC guidelines (version 6) RT‐PCR‐positive if Ct < 40.0, and negative if the viral load was undetectable. Samples with Ct > 37 were retested. Samples used: respiratory specimens for COVID‐19 confirmation; anal swabs also obtained (appeared from Figure that fewer anal swabs obtained compared to respiratory) Timing of reference standard: not reported; appeared to be on admission for majority (64/75) and repeated over time. Tabl 1 reported no obvious difference in the calculated initial Ct value of NP samples between groups: mean (SD) 29.9 (4.8) (n = 19 asymptomatic; 29.1 (6.8) (n = 30 pre‐symptomatic); 29.2 (5.7) (n = 15 symptomatic) Blinded to index test: yes, as only confirmed cases were included Incorporated index test: No Definition of non‐COVID cases: NA Samples used: Timing of reference standard: Blinded to index test: Incorporated index test:
Flow and timing	Time interval between index and reference tests: not reported, but ref standard was performed before index test as only COVID‐19 confirmed cases were included All patients received same reference standard: not reported, but unlikely, as it was reported that RT‐PCR tests or antibody tests for SARS‐CoV‐2 used to confirm diagnosis Missing data: Unclear; data were not reported for all participants per week since onset and only 32/33 pre‐symptomatic were reported in supplementary tables Uninterpretable results: none reported Indeterminate results: none reported Unit of analysis: Patients; multiple samples obtained per participant (total 324; 77 asymptomatic, 142 pre‐symptomatic, 105 symptomatic), however data per week and overall were reported on a per patient basis (not every patient contributed samples to each week of data post‐onset)
Comparative
Notes	Funding: This work was supported by Shenzhen Bay Laboratory Open Fund (SZBL202002271001). Publication status: Pre‐print Source: medRxiv Author COI: Authors declared no competing interests.
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Unclear
Did the study avoid inappropriate inclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
DOMAIN 2: Index Test (Antibody tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	No
If a threshold was used, was it pre‐specified?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
The reference standard does not incorporate the index test	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Unclear
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Unclear
Were all patients included in the analysis?	Unclear
Did all participants receive a reference standard?	Yes
Were results presented per patient?	No
Could the patient flow have introduced bias?		High risk