Abstract
SummaryBackgroundVirological 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.MethodsWe 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.FindingsBetween 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.InterpretationEven 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.FundingThe Bill & Melinda Gates Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province, and Key Project of Shenzhen Science and Technology Innovation Commission.
Highlights
Virological detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through RT-PCR is the gold standard for diagnosing infection.[1]
RT-PCR might be highly accurate at identifying those who are currently infectious, individuals must be tested at the right time during their infection to be detected, which reduces the utility of virological testing for measuring overall SARS-CoV-2 incidence
We found that approximately 4% of PCR-negative close contacts of cases of SARS-CoV-2 were seropositive for anti-SARS-CoV-2 antibodies on ELISA
Summary
Virological detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through RT-PCR is the gold standard for diagnosing infection.[1] Almost all diagnostic testing for COVID-19 is done using PCRbased methods. RT-PCR has imperfect sensitivity,[2,3,4] and patterns of viral shedding mean that the chance of testing positive varies over the course of infection.[5,6] RT-PCR might be highly accurate at identifying those who are currently infectious, individuals must be tested at the right time during their infection to be detected, which reduces the utility of virological testing for measuring overall SARS-CoV-2 incidence. Serological tests offer an alternative approach for detecting SARS-CoV-2 infection by measuring circulating antibodies against the virus. By contrast with virological tests, serological tests can detect if an individual has been infected even months after viral clearance, though serological tests have imperfect sensitivity and specificity.[7]
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