Insights into the practical effectiveness of RT PCR testing for SARS CoV 2 from serologic data, a cohort study

Background Virologic detection of SARS-CoV-2 through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) has limitations for surveillance. Serologic tests can be an important complementary approach. We assess the practical performance of RT-PCR based surveillance protocols, and the extent of undetected SARS-CoV-2 transmission in Shenzhen, China. Methods We followed close-contacts of all PCR-confirmed cases detected since January 2020 and measured anti-SARS-CoV-2 antibodies in PCR-negative contacts 2-15 weeks after initial virological testing by RT-PCR using total Ab ELISA. We assessed rates of undetected infection, performance of RT-PCR over the course of infection, and characteristics of seropositive but PCR-negative individuals. Findings The adjusted seropositivity rate for total Ab among 880 PCR-negative close-contacts was 4·1% (95%CI 2·8%-5·7%), significantly higher than among residents without known exposure to cases (0·0%, 95%CI 0·0%-1·0%). PCR-positive cases were 8·0 times (RR; 95% CI 5·3-12·7) more likely to report symptoms than the PCR-negative individuals who were seropositive, but otherwise similar. RT-PCR missed 36% (95%CI 28%-44%) of infected close-contacts, and false negative rates appear to be highly dependent on stage of infection. Interpretation Even rigorous RT-PCR testing protocols may miss a significant proportion of infections, perhaps in part due to difficulties timing testing of asymptomatics for optimal sensitivity. Surveillance and control protocols relying on RT-PCR were, nevertheless, able to contain community spread in Shenzhen. Funding 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Bill & Melinda Gates Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Key Project of Shenzhen Science and Technology Innovation Commission, Shenzhen, China ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All close-contacts and local residents gave written informed consent before participating in the serological testing. Contact tracing and RT-PCR testing is part of the continuing public health investigation of an emerging outbreak and therefore the individual informed consent was waived. The study was approved by the ethics committees of Shenzhen CDC. This work was done in support of an ongoing public health response, and hence was determined not to be human subjects research after consultation with the Johns Hopkins Bloomberg School of Public Health institutional review board. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Summary data are available upon reasonable request