Guedez‐Lopez 2020 [A].

Study characteristics
Patient Sampling	Purpose: Diagnosis of acute COVID‐19 Design: Multiple groups design to estimate sensitivity and specificity: [1] healthcare workers at Hospital Universitario La Paz, who attended the occupational health consultation for the first time between the 24th March and the 2nd of April referring symptoms compatible with COVID‐19 (n = 95) [1a] PCR+ for SARS‐COV‐2 (n = 55); [1b] PCR‐ for SARS‐COV‐2 (n = 40); [2] patients randomly selected who were admitted to the Emergency Department of the Hospital with positive RT‐qPCR or high clinical suspicion of COVID‐19 (n = 50); [2a] PCR+ for SARS‐COV‐2 (n = 46); [2b] PCR‐ for SARS‐COV‐2 (n = 4); [3] Pre‐pandemic patients (n = 20). Recruitment: [1] Healthcare workers at Hospital Universitario La Paz, who attended the occupational health consultation for the first time between the 24th March and the 2nd of April referring symptoms compatible with COVID‐19 [2] Randomly selected patients who were admitted to the Emergency Department of the Hospital with positive RT‐qPCR or high clinical suspicion of COVID‐19 [3] Randomly selected patients from 2018 Prospective or retrospective: [1] and [2] Prospective [3] Retrospective Sample size: 165 (101) Further detail: [1] Healthcare workers at Hospital Universitario La Paz, who attended the occupational health consultation for the first time between the 24th March and the 2nd of April referring symptoms compatible with COVID‐19 [2] Patients who were admitted to the Emergency Department of the Hospital with positive RT‐qPCR or high clinical suspicion of COVID‐19 [3] No further details
Patient characteristics and setting	Setting: [2a] patients attending accident and emergency department, ([2] 47/50 later hospitalised); [1a] Healthcare workers who attended the occupational health consultation for the first time ([1] 93/95 outpatients and 2/95 hospitalised); No separate data for PCR+ cases ([1a] and [2a]) Location: [1a] and [2a] Hospital Universitario La Paz (Madrid, Spain) Country: Spain Dates: [1a] and [2a] Serum samples collected between 8th March and 2nd April 2020 [1a] Attended occupational health consultation between 24th March and the 2nd of April 2020 Symptoms and severity: Only reported for all 95 and 50 patients with suspected COVID‐19, not for 50 and 46 rtPCR+ patients separately: [1] Hospitalised 2/95; pneumonia 12/95 [2] Hospitalised 47/50; pneumonia 48/50 Demographics: Only reported for all 95 and 50 patients with suspected COVID‐19, not for 50 and 46 rtPCR+ patients separately: [1] Healthcare workers; 74/95 female; median age 43 (range 21–79) years [2] ER admissions; 23/50 female; median age 50 (range 28–98) years Exposure history: [1a] Healthcare workers [2a] Unclear Non‐Covid group 1: [3] Pre‐pandemic patients Source: Pre‐pandemic (from 2018), Hospital Universitario La Paz (Madrid, Spain) Characteristics: Not reported (randomly selected patients, so possibly other diseases) Non‐Covid group 2: [1b] and [2b] Suspected COVID patients with negative PCR result Source: Hospital Universitario La Paz (Madrid, Spain), occupational health consultation or ER admissions; 8th of March and the 2nd of April 2020 Characteristics: [1b] 40 healthcare workers [2b] 4 patients admitted to ER department. Futher demographics only reported for all 95 and 50 patients with suspected COVID‐19, not for 40 and 4 rtPCR‐ patients separately: [1] Healthcare workers; 74/95 female; median age 43 (range 21–79) years [2] ER admissions; 23/50 female; median age 50 (range 28–98) years
Index tests	Test name: [A] Sienna 2019‐nCoV IgG/IgM Rapid Test [B] Wondfo, SARS‐CoV‐2 Antibody Test [C] Prometheus, 2019‐nCoV IgG/IgM Test Manufacturer: [A] T&D Diagnostics, Sienna, Halifax, Nova Scotia, Canada; [B] Wondfo, Luogang District, Guangzhou, China; [C] Prometheus Bio Inc., Zhejiang, China Antibody: [A] IgG and IgM separately; [B] Total antibody; [C] IgG and IgM separately Antigen target: Not reported Evaluation setting: Designed as POC. Unclear where it was performed Test method: Lateral flow assay (immunochromatographic assay) Timing of samples: [1] Median 5 (range 1–24) days pso [2] Median 11 (range 3–18) days pso [1a] and [2a] Early stage (first week): n = 41; intermediate stage (second week: n = 48; late stage (third week) n = 9 Samples used: Serum Test operator: Unclear. Interpretation was done by two observers. Definition of test positivity: After a short time (no longer than 20 min), the interpretation of the results was done by two observers based on appearance of a coloured band according to manufacturer's protocol. Weakly positive results (appearance of a blurred band) was considered as a positive result according to the manufacturer's protocol. Blinding reported: Unclear Threshold predefined: Yes, according to manufacturer’s protocol
Target condition and reference standard(s)	Reference standard: [1a] and [1b] RT‐qPCR (which detects N, S, E, Orf1ab and RdRp genes); no further details RNA was extracted using an automated system and analysed using selected RT‐qPCR commercial kits routinely used for diagnosis of COVID‐19. Samples used: Nasopharyngeal swabs Timing of reference standard: Not stated (all COVID suspects in [1] Median 0 (range 0–17) days before index test; All COVID suspects in [2] Median 4 (range 0–13) days before index test) Blinded to index test: Unclear for Group [1a] and [2a] Incorporated index test: No Definition of non‐COVID cases: 1b] and [2b] RT‐qPCR (which detects N, S, E, Orf1ab and RdRp genes); no further details RNA was extracted using an automated system and analysed using selected RT‐qPCR commercial kits routinely used for diagnosis of COVID‐19. [3] Pre‐pandemic Samples used: [1b] and [2b] Nasopharyngeal swabs [3] Pre‐pandemic Timing of reference standard: All COVID suspects [1] Median 0 (range 0–17) days before index test All COVID suspects in [2] Median 4 (range 0–13) days before index test; [3] Pre‐pandemic Blinded to index test: [1b] and [2b] Unclear [3] yes, prior index test Incorporated index test: no
Flow and timing	Time interval between index and reference tests: Group [1]: serum samples and nasopharyngeal swabs were collected at the same time in 82 patients, while in the other 13 patients, the average time since the nasopharyngeal swab collection and the serum extraction was 7.5 days; median 0 (range 0‐17) days. Group [2] in 48 patients, serum samples were taken days after the swab collection in an average time of 4.3 days, while in two patients, both samples were collected at the same time; median 4 (range 0‐13) days. All patients received same reference standard: Yes for [1] and [2]; no for [3] Missing data: 20 extra serum samples of randomly selected patients from 2018 not tested with Wondfo® test [B] due to lack of reagents 89 samples, which belonged to the group of healthcare workers, were tested with the three ICT assays, 28 samples (6 from the first and 22 from the second group of patients) were tested with Sienna® [A] and Wondfo® [B} and the other 28 samples from the second group of patients were tested only with Sienna [A]. Uninterpretable results: Not reported Indeterminate results: Weakly positive results (appearance of a blurred band) was considered as a positive result according to the manufacturer's protocol Unit of analysis: Patients
Comparative
Notes	Funding: Not reported Publication status: Published article Source: European Journal of Clinical Microbiology & Infectious Diseases Author COI: The authors declared that they had 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?	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?	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?	Unclear
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?	Yes
Did all participants receive a reference standard?	No
Were results presented per patient?	Yes
Could the patient flow have introduced bias?		High risk