Bernasconi 2020.

Study characteristics
Patient Sampling	Purpose: Diagnosis of acute and convalescent‐phase infection of SARS‐CoV‐2 3‐group study to estimate sensitivity and specificity for diagnosis of acute disease and convalescent infection Design: Three groups for two comparisons (COVID cases versus same time period controls or pre‐pandemic controls): [1] COVID‐19 positive ED patients (n = 67) [2] COVID‐19 negative ED patients (with clinical suspicion of acute airway infection) (n = 76, see comment) [3] COVID‐19 negative historical pre‐pandemic controls (n = 100) Recruitment: Unclear [1] and [2] Symptomatic patients presenting to the emergency department of 1 hospital; patients’ enrolment was based on clinical suspicion of acute airway infection. [3] SARS‐CoV‐2 seronegative samples collected between May and October 2018 Prospective or retrospective: Pandemic cases/controls, prospective (consent was obtained from participants). Pre‐pandemic controls, retrospective Sample size: Same time period comparison [1 and [2]: 143 (67) All 3 groups: 243 (67) patients with 315 (135) samples of which 243 (67) samples were included in our analysis Further detail: ED cases/controls: "symptomatic patients presenting to the ED of the Kantonsspital Aarau, Switzerland from March to April 2020... Patients’ enrolment was based on clinical suspicion of acute airway infection." Pre‐pandemic controls: Unclear.("SARS‐CoV‐2 seronegative samples collected between May and October 2018")
Patient characteristics and setting	Setting: Emergency department Location: Kantonsspital Aarau AG, Tellstrasse 25, 5001 Aarau, Switzerland Country: Switzerland Dates: March‐April 2020 Symptoms and severity: "symptomatic" Demographics: Not reported by COVID‐19 status. Whole ED case/control population (n = 143): Sex Male 84 (59%), female 59 (41%) Age, Median, years 69 (range 22‐95 years) Exposure history: not stated Non‐Covid group 1: [2] Contemporaneous ED controls Source: Emergency department, March‐April 2020 Characteristics: Not reported by COVID‐19 status Whole ED case/control population (n = 143): Sex Male 84 (59%), female 59 (41%) Age, Median, years 69 (range 22‐95 years) Non‐Covid group 2: [3] Pre‐pandemic controls Source: Source unclear, May‐October 2018 Characteristics: Not stated
Index tests	Test name: Maccura LFIA SARS‐CoV‐2 IgM/IgG Manufacturer: Maccura Biotechnology, Chengdu, China Antibody: IgM, IgG Antigen target: recombinant spike and nucleocapsid proteins of the SARS‐CoV‐2 Evaluation setting: POC, tested at ED and during hospitalisation (figure 1) Test method: lateral flow immunochromatography assay (LFIA) Timing of samples: [1] COVID‐19‐positive patients (n = 67): < 7 days onset (n = 21), ≥ 7 days onset (n = 46) Fig 1 reported on 135 samples from 1‐31 days pso. [2] COVID‐19 negative patients ‐ not stated Timing of samples: [1] COVID‐19‐positive patients (n = 67): < 7 days onset (n = 21), ≥ 7 days onset (n = 46) Fig 1 reported on 135 samples from 1‐31 days pso. [2] COVID‐19 negative patients ‐ not stated Samples used: not stated Test operator: not stated Definition of test positivity: not stated Blinding reported: Yes, since antibody/RT‐PCR tests were done in parallel and antibody test results are faster than RT‐PCR Unclear for samples taken during hospitalisation Threshold predefined: not stated (visually based)
Target condition and reference standard(s)	Reference standard: RT‐PCR (Seegene Inc., Seoul, Republic of Korea) Diagnosis of COVID‐19 was based on clinical, microbiological and radiological criteria according to in‐house, national and international recommendations and guidelines. Samples used: nasopharyngeal swab samples (transportation medium ESwab, Copan Italia, Brescia, Italy) or nasopharyngeal fluid Timing of reference standard: [1] COVID‐19‐positive patients (n = 67): < 7 days onset (n = 21), ≥ 7 days onset (n = 46) Blinded to index test: Not stated Incorporated index test: No Definition of non‐COVID cases: [2] COVID‐19 negative patients, RT‐PCR (Seegene Inc., Seoul, Republic of Korea) [3] pre‐pandemic controls Samples used: [2] COVID‐19 negative patients, nasopharyngeal swab samples or nasopharyngeal fluid [3] pre‐pandemic controls, not stated Timing of reference standard: [2] COVID‐19‐positive patients ‐ not stated [3] pre‐pandemic controls Blinded to index test: [2] Not stated [3] yes Incorporated index test: No
Flow and timing	Time interval between index and reference tests: [1] and [2] LFIA and molecular testing for SARS‐CoV‐2 by RT‐PCR … was done in parallel for 67 samples. Unclear for the remaining 72 samples (215 samples from 143 patients) [3] Not stated All patients received same reference standard: No Missing data: Not stated Uninterpretable results: None Indeterminate results: Not stated Unit of analysis: Samples for [1] and [2] (215 samples of 143 ED patients)
Comparative
Notes	Funding: None declared Publication status: Published letter Source: Clinical Chemistry & Laboratory Medicine Author COI: Authors stated no conflict of interest
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?	Unclear
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?			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?	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