Velay 2020 [A].

Study characteristics
Patient Sampling	Purpose: Diagnosis of current acute and convalescent‐phase infection of COVID‐19 Design: Multi‐group analysis to estimate sensitivity and specificity (n = 325) [1a] PCR‐confirmed hospital patients (n = 55) [1b] PCR‐confirmed healthcare workers (n =143) [2a] Pre‐pandemic controls (n = 100) [2b] Cross‐reactivity negative controls (n = 27) Recruitment: Unclear Prospective or retrospective: Retrospective Sample size: 325 (198) Further detail: Inclusion: [1a] Hospitalised PCR‐positive Covid patients (n = 55) [1b] PCR‐positive healthcare workers (n = 143) [2a] Pre‐pandemic healthy blood donors [2b] Pre‐pandemic non‐SARS‐CoV‐2 infection: (n = 20) anti‐hCoV positive, (n = 2) anti‐influenza A virus positive, (n = 1) anti‐rhinovirus positive, (n = 2) rheumatoid factor positive, (n = 2) antinuclear antibodies positive Exclusion: Not stated
Patient characteristics and setting	Setting: [1a] Hospital inpatients (n = 55) [1b] Outpatients Location: Strasbourg University Hospital (Strasbourg, France) Country: France Dates: 2020 April Symptoms and severity: [1a] 23 were admitted to ICU [1b] Not stated Demographics: Patient group ‐ median age 68, male/female = 17/38. Healthcare workers ‐ median age ‐ 32, male/female ‐ 96/47. Total ‐ median age ‐ 43, male/female ‐ 113/85 Exposure history: Not stated Non‐Covid group 1: [2a] Pre‐pandemic controls Source: March to November 2019 Characteristics: Serum samples from 40 patients and plasma samples from 60 healthy blood donors collected before the COVID‐19 pandemic onset Non‐Covid group 2: [2b] Controls for cross‐reactivity Source: 27 serum samples collected before the COVID‐19 pandemic onset were used to study cross‐reactivity. Characteristics: Previous human coronavirus infections ‐ HCoV‐229E, HCoV‐HKU1, HCoV‐NL63, and HCoV‐OC43), 2 from patients previously infected with influenza A virus, 1 from a patient previously infected with human rhinovirus, 2 containing rheumatoid factor, and 2 positive for antinuclear antibodies
Index tests	Test name: [A] Biosynex COVID‐19 BSS [B] COVID‐19 Sign IgM/IgG [C] ELISA anti–SARS‐CoV‐2 IgA and IgG [D] EDI™ novel coronavirus COVID‐19 IgM and IgG Manufacturer: [A] Biosynex, Switzerland, Fribourg [B] Servibio/VEDALAB, France, Alençon [C] Euroimmun, Lübeck, Germany [D] Epitope Diagnostics, San Diego, California Antibody: [A] IgM and IgG [B] IgM and IgG [C] IgA and IgG [D] IgM and IgG Antigen target: [A] N‐protein [B] S1‐protein Evaluation setting: [A][B] POC [C][D] Laboratory All performed in laboratory Test method: [A] [B] Lateral flow assay [C] [D] ELISA Timing of samples: [1a] Serum samples were collected at a median of 7 days pso (range, 0–31 days pso). [1b] 24 days pso (range, 15–39 days pso) Samples used: Serum and plasma Test operator: Unclear Definition of test positivity: [A] [B] Visible line [C] >= 1.1 positive [D] Values greater than the cut‐off positive Blinding reported: Unclear Threshold predefined: Yes
Target condition and reference standard(s)	Reference standard: RT‐PCR testing of nasopharyngeal swab specimens according to current guidelines (Institut Pasteur, Paris, France; WHO technical guidance). This assay targets 2 regions of the viral RNA‐dependent RNA polymerase (RdRp) gene, with a threshold limit of detection of 10 copies per reaction. Samples used: Nasopharyngeal Timing of reference standard: Total median time since symptom onset ‐ 2 days Blinded to index test: Yes, prior Incorporated index test: No Definition of non‐COVID cases: Pre‐pandemic Samples used: NA Timing of reference standard: NA Blinded to index test: Yes Incorporated index test: No
Flow and timing	Time interval between index and reference tests: Median time difference 20 days ‐ median time to PCR 2 days and median time to serum collection ‐ 22 days All patients received same reference standard: Yes Missing data: Not stated Uninterpretable results: Not stated Indeterminate results: Not stated Unit of analysis: Samples
Comparative
Notes	Funding: Study was supported by the Strasbourg University Hospital (COVID‐HUS study) Publication status: Published paper Source: Diagnostic Microbiology and Infectious Disease Author COI: None declared
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Unclear
Did the study avoid inappropriate inclusions?	No
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?	Unclear
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
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	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			High
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?	No
Were all patients included in the analysis?	Yes
Did all participants receive a reference standard?	Unclear
Were results presented per patient?	No
Could the patient flow have introduced bias?		High risk