Insight into the practical performance of RT-PCR testing for SARS-CoV-2 using serological data: a cohort study

Background Virological detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through RT-PCR has limitations for surveillance. Serological tests can be an important complementary approach. We aimed to assess the practical performance of RT-PCR-based surveillance protocols and determine the extent of undetected SARS-CoV-2 infection in Shenzhen, China. Methods We did a cohort study in Shenzhen, China and attempted to recruit by telephone all RT-PCR-negative close contacts (defined as those who lived in the same residence as, or shared a meal, travelled, or socially interacted with, an index case within 2 days before symptom onset) of all RT-PCR-confirmed cases of SARS-CoV-2 detected since January, 2020, via contact tracing. We measured anti-SARS-CoV-2 antibodies in serum samples from RT-PCR-negative close contacts 2-15 weeks after initial virological testing by RT-PCR, using total antibody, IgG, and IgM ELISAs. In addition, we did a serosurvey of volunteers from neighbourhoods with no reported cases, and from neighbourhoods with reported cases. We assessed rates of infection undetected by RT-PCR, performance of RT-PCR over the course of infection, and characteristics of individuals who were seropositive on total antibody ELISA but RT-PCR negative. Findings Between April 12 and May 4, 2020, we enrolled and collected serological samples from 2345 (53.0%) of 4422 RT-PCR-negative close contacts of cases of RT-PCR-confirmed SARS-CoV-2. 1175 (50.1%) of 2345 were close contacts of cases diagnosed in Shenzhen with contact tracing details, and of these, 880 (74.9%) had serum samples collected more than 2 weeks after exposure to an index case and were included in our analysis. 40 (4.5%) of 880 RT-PCR-negative close contacts were positive on total antibody ELISA. The seropositivity rate with total antibody ELISA among RT-PCR-negative close contacts, adjusted for assay performance, was 4.1% (95% CI 2.9-5.7), which was significantly higher than among individuals residing in neighbourhoods with no reported cases (0.0% [95% CI 0.0-1.1]). RT-PCR-positive individuals were 8.0 times (95% CI 5.3-12.7) more likely to report symptoms than those who were RT-PCR-negative but seropositive, but both groups had a similar distribution of sex, age, contact frequency, and mode of contact. RT-PCR did not detect 48 (36% [95% CI 28-44]) of 134 infected close contacts, and false-negative rates appeared to be associated with stage of infection. Interpretation Even rigorous RT-PCR testing protocols might miss a substantial proportion of SARS-CoV-2 infections, perhaps in part due to difficulties in determining the timing of testing in asymptomatic individuals for optimal sensitivity. RT-PCR-based surveillance and control protocols that include rapid contact tracing, universal RT-PCR testing, and mandatory 2-week quarantine were, nevertheless, able to contain community spread in Shenzhen, China. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Automated summary

The study in Shenzhen, China, found a substantial proportion of undetected SARS-CoV-2 infections among PCR-negative close contacts as well as in the community. PCR testing protocols may miss infected individuals, but comprehensive surveillance and control measures, including rapid contact tracing, universal testing, and mandatory quarantine, proved effective in containing community spread.