Chen 2020 [A].

Study characteristics
Patient Sampling	Purpose: Diagnosis of current acute‐phase infection or current convalescent‐phase infection Design: Two‐group study to estimate sensitivity and specificity [1] Confirmed COVID patients (74 patients, n = 346 samples) [2] Non‐COVID samples (n = 194) [2a] Current patients with acute respiratory infection (n = 120) [2b] Current patients with presence of auto‐antibodies (n = 36) [2c] Pre‐pandemic samples with presence of antigens/antibodies (n = 38) Recruitment: [1] Consecutively qRT‐PCR‐confirmed COVID‐19 patients who were treated at six participating hospitals between 23 January 2020 and 31 May 2020 [2] Not stated [Hospitalised patients with an acute respiratory infection (ARI) who tested negative at least 2 times using qRT‐PCR with or without confirmed aetiology for ARI, treated between January 31 and May 31, 2020; patients with auto‐antibodies (1‐31 May 2020) or patients showing presence of specific microbiological antigens or antibodies, treated between 1 August and 31 December 2019] Prospective or retrospective: Retrospective Sample size: 540 (346) Further detail: [1] qRT‐PCR‐confirmed COVID‐19 patients who were treated at six participating hospitals between 23 January 2020 and 31 May 2020 [2] Not stated [Hospitalised patients with an acute respiratory infection (ARI) who tested negative at least 2 times using qRT‐PCR with or without confirmed aetiology for ARI, treated between January 31 and May 31, 2020; patients with auto‐antibodies (1‐31 May 2020) or patients showing presence of specific microbiological antigens or antibodies, treated between 1 August and 31 December 2019]
Patient characteristics and setting	Setting: Hospital inpatients (in Taiwan, all qRT‐PCR confirmed patients are mandatorily hospitalised) Location: 6 hospitals: National Taiwan University Hospital, National Cheng Kung University Hospital, Tao Yuan General Hospital, Ministry of Health and Welfare, Changhua Christian Hospital, Nantou Hospital, Ministry of Health and Welfare, and China Medical University Hospital. Country: Taiwan Dates: 23 January 2020 to 31 May 2020 Symptoms and severity: All 74 enrolled COVID‐19 patients reported at least one COVID‐19‐compatible symptom. Lower respiratory tract symptoms were the predominant symptom at the time of diagnosis (66.2%), followed by upper airway symptoms (62.2%), and fever (45.9%). 28 (37.8%) patients developed pneumonia during hospitalisation, among whom five (6.8%) required ventilator support and intensive care. 1/74 received ECMO support Demographics: Mean patient age was 38.5 years (SD, 16.2 years). 41 (55.4%) patients were men and 67 (90.5%) of them had no significant comorbid or surgical condition. Exposure history: Not stated Non‐Covid group 1: [2] Non‐COVID patients Source: [2a] Treated between 31 January and 31 May 2020, source not stated [2b] 1 May to 31 May 2020, source not stated [2c] Treated between 1 August and 31 December 2019, source not stated Characteristics: [2a] Acute respiratory infection and negative rt‐PCR without other confirmed aetiologies (n = 70); Acute respiratory infection and negative rt‐PCR with microbiological aetiologies (n = 50): Coronavirus n = 3 Cytomegalovirus (CMV) n = 18 CMV and herpes simplex virus (HPV) n = 2 CMV and HPV and Epstein‐Barr virus (EBV) n = 1 HSV n = 1 EBV n = 5 Mycoplasma pneumoniae n = 5 Chlamydophila trachomatis n = 5 Respiratory syncytial virus n = 2 Influenza A n = 4 Influenza B n = 4 [2b] Patients showing the presence of any specific auto‐antibodies (n = 36) [2c] Pre‐pandemic patients showing the presence of specific antigens/antibodies (n = 38): Mycoplasma pneumoniae n = 15 Chlamydophila pneumophila n = 5 EBV n = 10 Respiratory syncytial virus n = 1 Influenza A n = 3 Influenza B n = 4
Index tests	Test name: [A] Roche Elecsys® Anti‐SARS‐CoV‐2 Test [B] Abbott SARS‐CoV‐2 IgG [C] Wondfo SARS‐CoV‐2 Antibody Test [D] ASK COVID‐19 IgG/IgM Rapid Test [E] Dynamiker 2019‐nCoV IgG/IgM Rapid Test Manufacturer: [A] Roche Diagnostics Basel, Switzerland [B] Abbott Laboratories, IL, USA [C] Guangzhou Wondfo Biotech Co., Ltd., China [D] TONYAR Biotech Inc. Taiwan [E] Dynamiker Biotechnology [Tianjin] Antibody: [A] Total antibodies (including IgG) [B] IgG [C] Total antibodies [D] IgG and IgM [E] IgG and IgM Antigen target: [A] N‐protein [B] N‐protein [C] spike‐protein [D] spike‐protein [E] N‐protein Evaluation setting: [A] Lab test used in lab [B] Lab test used in lab [C] POCT used in lab [D] POCT used in lab [E] POCT used in lab Test method: [A] Electrochemiluminescence immunoassay [B] Chemiluminescent microparticle immunoassay [C]‐[E] Lateral flow tests Timing of samples: Median 7 days pso (range 1‐93 days pso) Mean 11.4 (SD 14.8) days pso 0‐7 days pso: 61/346 8‐14 days pso: 73/346 15‐21 days pso: 61/346 22‐28 days pso: 64/346 29‐35 days pso: 32/346 36‐93 days pso: 55/346 Samples used: [A]‐[E] Serum (Residual blood samples; the serum of the collected blood samples was stored at −20°C before testing) Test operator: Not stated (possibly lab personnel) Definition of test positivity: [A] and [B] Test results were interpreted as positive if the electrochemiluminescent signal value of the Roche Test (cut‐off index, COI) ≧ 1.0, or the chemiluminescent signal value of the Abbott Test (index [sample/calibrator], S/C) ≧ 1.4, as manufacturers’ instructions [C]‐[E] Positive results were interpreted as the presence of control line and either IgG or IgM test line for ASK Test and Dynamiker Test, or control line and total antibody test line in Wondfo Test. A weakly positive result (any shade of colour in the test lines) of an antibody rapid testing was considered positive according to the manufacturers’ instructions. Blinding reported: Not stated Threshold predefined: [A]‐[E] yes
Target condition and reference standard(s)	Reference standard: In Taiwan, the respiratory tract specimens from patients who meet the reporting criteria for COVID‐19 have to be submitted to virology laboratories validated and associated with the Centers for Diseases Control of Taiwan (Taiwan CDC) for SARS‐CoV‐2 qRT‐PCR assay. Three sets of primers and probes targeting the SARS‐CoV‐2 envelope (E), nucleocapsid (N), and RNA‐dependent RNA polymerase (RdRp) genes were used. If the result of the first sample was negative for SARS‐CoV‐2, an additional SARS‐CoV‐ 2 qRT‐PCR assay for another respiratory tract sample from the patient suggested of having COVID‐19 was performed to minimise the risk of false‐negative results using the qRT‐PCR assay. Samples used: Respiratory tract specimens Timing of reference standard: Not stated Blinded to index test: yes, prior Incorporated index test: no Definition of non‐COVID cases: Current patients with acute respiratory infections: tested negative ≥ 2 times using SARS‐CoV‐2 qRT‐PCR Current patients with auto‐antibodies: not tested Pre‐pandemic samples Samples used: Not stated (possibly as cases) or not tested Timing of reference standard: Not stated or not tested Blinded to index test: yes, prior Incorporated index test: no
Flow and timing	Time interval between index and reference tests: Not stated All patients received same reference standard: No Missing data: Not stated Uninterpretable results: Not stated Indeterminate results: Not stated Unit of analysis: Samples (48 patients had sequential serum samples; 1 to 38 samples per patient, median 4 samples)
Comparative
Notes	Funding: Not stated Publication status: Published paper Source: Emerging Microbes & Infections Author COI: No potential conflict of interest was reported by the authors.
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?	No
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?		High 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?	Unclear
Did all participants receive a reference standard?	Unclear
Were results presented per patient?	No
Could the patient flow have introduced bias?		High risk