Renard 2021 [A].

Study characteristics
Patient Sampling	Purpose: Diagnosis of current acute or convalescent SARS‐CoV‐2 infection Design: Multi‐group study estimating sensitivity and specificity: [1] Covid‐positive, N = 405 samples, n = 142 patients [2] Covid‐negative controls, N = 989 patients, pre‐pandemic healthy donors [3] Serum cross‐reactivity pre‐pandemic samples, n = 276 Recruitment: [1] RT‐PCR‐positive, symptomatic patients from three hospitals: Centre Hospitalier Saint Joseph Saint Luc, Lyon, France; Centre de Ressources Biologiques (CRB) des Hospices Civils de Lyon, CRB Nord and CRB Sud, Lyon, France [2] Pre‐pandemic adult donors, before September 2019. Healthy donors. Collected at Etablissement Francais du Sang (EFS), France and Clinilabs, Inc., United States [3] Frozen pre‐pandemic sera from patients with other potentially interfering infections or medical conditions (bioMerieux, Centre Hospitalier Grenoble‐Alpes and Saint Joseph Saint Luc Lyon collections) Prospective or retrospective: [1] Unclear [2] [3] Retrospective Sample size: 1670 (405) Further detail: [1] Inclusion: Symptomatic patients from three hospitals (inpatient and outpatients). Exclusion: Asymptomatic patients. [2] Inclusion: Healthy adult blood donors. Exclusion: Not stated [3] Inclusion: Patients with potentially interfering infections or medical conditions, including 5 pregnant women. Exclusion: Not stated.
Patient characteristics and setting	Setting: Hospital inpatients and hospital outpatients Location: Centre Hospitalier Saint Joseph Saint Luc, Lyon, France; Centre de Resources Biologiques (CRB) des Hospices Civils de Lyon, CRB Nord and CRB Sud, Lyon, France Country: France Dates: March 31 to June 2, 2020 Symptoms and severity: Symptomatic, severity not stated. Data for 130 patients (time post‐PCR+ analyses) Hospitalised (n = 54) and non‐hospitalised (n = 61), 15 missing data Data for 63 patients (time pso analyses) 48 (76.2%) hospitalised 15 (23.8%) missing Demographics: Data for 130 patients (time post‐PCR+ analyses) 61 non‐hospitalised: missing data on age, 69 other patients: median 70 (range 27–96) years; 47 male, 22 female, 61 missing Data for 63 patients (time pso analyses) Age: median 70 (range 27–96) years; 45 (71.4%) male Exposure history: Not stated. Non‐Covid group 1: [2] pre‐pandemic healthy donors Source: Etablissement Francais du Sang (EFS), France and Clinilabs, Inc., United States. Collected before September 2019 Characteristics: Healthy donors Non‐Covid group 2: [3] Cross‐reactivity sera, pre‐pandemic Source: Cross‐reactivity sera from bioMerieux, Centre Hospitalier Grenoble‐Alpes and Saint Joseph Saint Luc Lyon collections Time not stated Characteristics: Patients with potentially interfering infections or medical conditions: Pregnant women 5 Antinuclear antibody (ANA)a 47 Rheumatoid factor 19 Human anti‐mouse antibody (HAMA) 5 Borrelia burgdorferib 10 Haemophilus influenzae B 5 Plasmodium falciparum 3 Toxoplasma gondiib 10 Treponema pallidum 3 Trypanosoma cruzi 5 Hepatitis A virus (HAV) 3 Hepatitis B virus (HBV) 5 Hepatitis C virus (HCV) 5 Hepatitis E virus (HEV)b 7 Herpes simplex virus (HSV)b 6 Human immunodeficiency virus (HIV) 5 Cytomegalovirus (CMV) 4 Measles virus (MV) 4 Mumps virus (MuV) 1 Rubella virus (RuV)b 10 Dengue virus (DENV) 3 West Nile virus (WNV) 4 Yellow fever virus (YFV) 4 Zika virus (ZIKV)b 5 Adenovirus (AdV) 2 Metapneumovirus (MPV) 4 Rhinovirus/enterovirus (RV/EnteroV)c 20 Influenza A and B virus (IAV/IBV) 30 Parainfluenza viruses 1/2/3 (PIV‐1/2/3) 11 Respiratory syncytial virus A or B (RSV A or B) 13 Coronavirus NL63/HKU1 (CoV‐NL63/HKU1)d 9 Coronavirus 229E (CoV‐229E) 7 Coronavirus OC43 (CoV‐OC43) 2
Index tests	Test name: [A] Vidas SARS‐CoV‐2 IgM (423833) [B] Vidas SARS‐CoV‐2 IgG (423834) Manufacturer: [A] [B] bioMerieux, France Antibody: [A] IgM [B] IgG Antigen target: [A] [B] RBD of spike‐protein Evaluation setting: [A] [B] Laboratory Test method: [A] [B] two‐step enzyme immunoassay combined with an enzyme‐linked fluorescent assay (ELFA) detection technique Timing of samples: 0 to 32+ 1‐65 days pso (n = 105), 0‐7 days: n = 22 8‐15 days: n = 29 16‐23 days: n = 26 24‐31 days: n = 18 >= 32 days: n = 10 0‐65 days post‐PCR +ve (n = 232) 0‐7 days: n = 110 8‐15 days: n = 60 16‐23 days: n = 38 24‐31 days: n = 13 >= 32 days: n = 11 Samples used: Serum or plasma Test operator: Laboratory staff Definition of test positivity: [A] [B] Positive COI >= 1.00, negative < 1.00 Blinding reported: Unclear Threshold predefined: Yes
Target condition and reference standard(s)	Reference standard: RT‐PCR, threshold not stated Samples used: Not stated Timing of reference standard: Not stated. Blinded to index test: Yes Incorporated index test: No Definition of non‐COVID cases: [2] Pre‐pandemic (before September 2019) [3] Pre‐pandemic (timing unclear) Samples used: [2] [3] Pre‐pandemic Timing of reference standard: [2] [3] Pre‐pandemic Blinded to index test: yes, prior Incorporated index test: no
Flow and timing	Time interval between index and reference tests: Index tests conducted 0‐65 days post‐reference test 0‐7 days: n = 110 8‐15 days: n = 60 16‐23 days: n = 38 24‐31 days: n = 13 >= 32 days: n = 11 All patients received same reference standard: No Missing data: [1] 173 samples excluded from time split post‐PCR+ analyses: 2 missing date of positive PCR, 171 as IgM test or IgG test not done, multiple measurements per patient in one time frame, or missing paired test 300 samples excluded from time split post‐symptom onset analyses: 194 Missing date of symptom onset, 106 as IgM test or IgG test not done, multiple measurements per patient in one time frame, or missing paired test [2] [3] Not all samples tested with IgG test [B] Uninterpretable results: Not stated. Indeterminate results: No borderline range Unit of analysis: Samples. To avoid a statistical bias, only one patient’s measurement per time period was included in the analysis.
Comparative
Notes	Funding: Work was supported by bioMerieux. J.L received research funding from bioMerieux for this study. Publication status: Published paper. Source: Journal of Clinical Microbiology. Author COI: M.P declared a consulting contract with bioMerieux.
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?			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	Yes
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?			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?	No
Were results presented per patient?	Yes
Could the patient flow have introduced bias?		High risk