Serology tests were better at detecting the presence of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients when they were tested 15 to 35 days post-symptom onset, according to the findings of a recently published review on the Cochrane Database of Systematic Reviews.  

The review aimed to evaluate the diagnostic accuracy of antibody tests at detecting current or previous SARS-CoV-2 infection, as well as the potential use of these tests in seroprevalence surveys. An electronic search of the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern yielded 54 relevant studies, 38 of which were analyzed in detail. 

“We included test accuracy studies of any design that evaluated antibody tests (including enzyme‐linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS‐CoV‐2 infection, or where tests were used to screen for infection,” the study authors stated. They added, “We included all reference standards to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction tests [RT‐PCR] and clinical diagnostic criteria).”

Findings of the study revealed that the sensitivity of antibody tests were low 1 week after symptom onset, but increased in the second and third week. It was noted that data analyzed after 3 weeks post-symptom onset was obtained from fewer studies with  smaller sample sizes and that there was insufficient evidence to estimate the sensitivity of tests after 35 days. 

The authors reported the sensitivity of the combination of IgG/IgM tests to be 30.1% (95% CI, 21.4-40.7) for days 1 to 7, 72.2% (95% CI, 63.5-79.5) for days 8 to 14, 91.4% (95% CI, 87.0-94.4) for days 15 to 21, and 96.0% (95% CI, 90.6-98.3) for days 21 to 35. 

“Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post‐symptom onset,” the authors also reported. At a 5% prevalence, which would be a likely value in national surveys, 4 (3-7) would be missed (false negative result) of the 1000 tested and 12 (6-27) would be a false positive result. 

In their review, the authors also highlighted their concerns surrounding the risk of bias present in the studies included in their analysis. Common issues identified included use of multigroup designs, inclusion of COVID-19 cases only, lack of index test and reference standard blinding, differential verification, and lack of clarity surrounding participant characteristics. Additionally, the majority of studies were conducted in hospitalized patients and no studies included asymptomatic patients only.

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According to findings of this analysis, antibody tests appear to be useful in detecting previous SARS-CoV-2 infection if utilized between 15 to 35 days post-symptom onset. Because evidence regarding the sensitivity of these tests after 35 days is lacking, these tests are not recommended for seroprevalence surveys for public health management purposes at this time. Additionally, it is imperative that the design, execution, and reporting of studies evaluating the accuracy of antibody tests is improved in order to properly analyze their performance in the near future. 

Reference

Deeks  JJ, Dinnes  J, Takwoingi  Y, Davenport, et al. Antibody tests for identification of current and past infection with SARS‐CoV‐2 [published online June 25, 2020]. Cochrane Database of Systematic Reviews 2020. doi: 10.1002/14651858.CD013652.