Fiel‐Ozores 2021.

Study characteristics
Patient Sampling	Purpose: diagnosis of SARS‐CoV‐2 infection (mild COVID‐19 disease) ‐ to identify the main differential clinical features of infection by SARS‐CoV‐2 Design: cross‐sectional cohort study, retrospective data collection Recruitment: every paediatric patient (ages 0‐15 years) that had undergone a RT‐PCR test for detection of SARS‐CoV‐2 in a nasopharyngeal sample due to suspected infection was invited for a serology test and interview, setting unclear Sample size: n = 126 (33 cases) Inclusion criteria: patients aged 0‐15 years who underwent RT‐PCR test due to clinical suspicion of SARS‐CoV‐2 during the period under study whose parents/legal guardians provided consent and did not meet any of the exclusion criteria Exclusion criteria: patients with serum immunoglobulin (Ig) deficiency. Patients who underwent the RT‐PCR test when asymptomatic in the context of contact tracing. Study period: March‐May 2020, the months that followed the declaration of the state of alert and the population‐wide lock down
Patient characteristics and setting	Facility cases: RT‐PCR‐positive for SARS‐CoV‐2 Facility controls: RT‐PCR‐negative for SARS‐CoV‐2 Country: Spain Dates: March 2020‐May 2020 Symptoms and severity: not specified, mild to moderate severity Demographics: mean age cases 8.4 years, controls 6.5 years M%/F%: cases 66.7/33.3, controls 59.1/40.9 Exposure history cases: 66.7% had close contact with a positive person (pos RT‐PCR test), 81.8% had relatives with symptoms controls: 19.4% had close contact with a positive person (pos RT‐PCR test), 9.7% had relatives with symptoms
Index tests	All registered at onset of symptoms and during the course of disease Fever Headache Cough Asthenia Diarrhoea Myalgia Breathing difficulty Cutaneous manifestations Odynophagia Chills Wheezing Anosmia/hyposmia Rhinorrhoea Dysgeusia Abdominal pain Vomiting
Target condition and reference standard(s)	TC: SARS‐CoV‐2 infection RS: RT‐PCR for SARS‐CoV‐2 (nasopharyngeal swab) + serology: IgA and IgG antibodies 3‐4 weeks after the RT‐PCR test (blood)
Flow and timing	Timing not specified
Comparative
Notes	Median time elapsed to the PCR was 8 days and to the first antibody test was 51 days, but interviews were done at time of serology testing (asking about onset of symptoms and evolution); unclear which test (PCR or serology) was eventually used as RS Funding: none declared
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Did the study avoid inappropriate inclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Unclear
DOMAIN 2: Index Test (All 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?	No
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?			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
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?	Yes
Were all patients included in the analysis?	Unclear
Could the patient flow have introduced bias?		High risk