Rijkers 2020.

Study characteristics
Patient Sampling	Purpose: To compare the antibody response in patients with severe (hospitalised) and mild (non‐hospitalised) COVID‐19 and determine sensitivity for diagnosis of current acute infection and current convalescent infection Design: Single‐group study to estimate sensitivity only [1] Confirmed COVID patients (n = 62) [1a] Severe Covid‐19 group (n = 38) [1b] Mild Covid‐19 group (n = 24) Recruitment: [1a] Consecutive hospital Covid patients admitted to the Admiral de Ruyter Hospital in Goes, The Netherlands, in the period March 2020–May 2020 [1b] Not stated Prospective or retrospective: [1a] Prospective [1b] Not stated (possibly prospective) Sample size: 62 (62) patients, number of samples unclear (serial sampling from week 1 to week 4 post‐symptom onset) Further detail: Inclusion: [1a] Subjects who had positive RT‐PCR and were hospitalised, both ICU and non‐ICU (admitted to the Admiral de Ruyter Hospital in Goes, The Netherlands) [1b] Hospital personnel (both from clinical departments as well as laboratory departments) who developed fever, coughing, and/or dyspnoea and had positive RT‐PCR and were non‐hospitalised with mild disease Exclusion: [1] Test group ‐ PCR‐negative samples
Patient characteristics and setting	Setting: [1a] Hospital inpatients [1b] non‐hospitalised patients (home isolation, under control of GP) Location: [1] Admiral de Ruyter Hospital in Goes Country: The Netherlands Dates: [1a] March 2020–May 2020 [1b] Not stated Symptoms and severity: [1a] The criteria for hospital admission were severity and/or progression of clinical symptoms, as assessed by the referring general practitioner. The presenting clinical symptoms included fever (n = 17), cough (n = 18), dyspnoea (n = 11), dizziness and/or confusion (n = 4), and general malaise (n = 6). The clinical criteria for admission of hospitalised patients to the ICU primarily were respiratory insufficiency, haemodynamic instability, and/or multiorgan failure. ICU 15/38 non‐ICU 23/38 6/38 died [1b] Mild symptoms (fever, coughing, and/or dyspnoea), non‐hospitalised Demographics: [1a] Age (years) ‐ median 70 (range 38‐87) Male gender ‐ 26 (68%) Any comorbidities ‐ 26 (68%) Diabetes mellitus ‐ 4 (11%) Hypertension ‐ 13 (34%) Coronary heart disease ‐ 8 (21%) COPD ‐ 10 (26%) Body Mass Index ‐ median 27 (range 19‐41) [1b] Median age 42 years (range, 21–66 years) Exposure history: [1a] Not stated [1b] Hospital personnel
Index tests	Test name: The Wantai SARS‐CoV‐2 total antibody ELISA (catalog number WS1096) Manufacturer: Beijing Wantai Biological Pharmacy Enterprise, Beijing, China Antibody: Total antibodies Antigen target: receptor binding domain antigen of SARS‐CoV‐2 Evaluation setting: Hospital laboratory Test method: sandwich ELISA Timing of samples: Serial blood sampling (3 times per week) was started a median of 2 days (range, 1–7 days) after positive RT‐PCR 1‐7 days pso 8‐14 days pso 15‐21 days pso 22‐28 days pso Samples used: Serum Test operator: Lab personnel from hospital laboratories Definition of test positivity: [A] and [B] Optical density (OD) was measured at 450 nm and the antibody titer for each sample was calculated as the ratio of the reading of that sample to the reading of a calibrator (included in the kit):OD ratio. Threshold not stated Blinding reported: Not stated (no as only COVID cases included) Threshold predefined: yes (according to the manufacturer’s instructions)
Target condition and reference standard(s)	Reference standard: RT‐PCR, threshold not stated Samples used: [1a] Nasopharyngeal swabs [1b] Not stated Timing of reference standard: [1a] On the first hospital day [1b] Not stated Blinded to index test: Yes, prior to index test Incorporated index test: No
Flow and timing	Time interval between index and reference tests: [1a] Serial blood sampling (3 times per week) was started at a median of 2 days (range, 1–7 days) after positive RT‐PCR. [1b] Not stated All patients received same reference standard: Yes Missing data: yes (no sensitivity data for 24 non‐hospitalised patients [1b] for test [B], no sensitivity data for time points 1‐7 days, 8‐14 days and 15‐21 days pso reported for both groups) Uninterpretable results: Not stated Indeterminate results: Not stated Unit of analysis: Multiple samples per patient but only 1 sample per patient included per time split
Comparative
Notes	Funding: None stated Publication status: Published paper Source: Journal of Infectious Diseases Author COI: All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors considered relevant to the content of the manuscript have been disclosed.
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?	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?	Yes
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?			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?	Yes
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