Estimating the Cumulative Incidence of SARS-CoV-2 Infection and the Infection Fatality Ratio in Light of Waning Antibodies

Background: Serology tests can identify previous infections and facilitate estimation of the number of total infections. However, immunoglobulins targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to wane below the detectable level of serologic assays (which is not necessarily equivalent to the duration of protective immunity). We estimate the cumulative incidence of SARS-CoV-2 infection from serology studies, accounting for expected levels of antibody acquisition (seroconversion) and waning (seroreversion), and apply this framework using data from New York City and Connecticut.

Methods: We estimated time from seroconversion to seroreversion and infection fatality ratio (IFR) using mortality data from March to October 2020 and population-level cross-sectional seroprevalence data from April to August 2020 in New York City and Connecticut. We then estimated the daily seroprevalence and cumulative incidence of SARS-CoV-2 infection.

Results: The estimated average time from seroconversion to seroreversion was 3-4 months. The estimated IFR was 1.1% (95% credible interval, 1.0%, 1.2%) in New York City and 1.4% (1.1, 1.7%) in Connecticut. The estimated daily seroprevalence declined after a peak in the spring. The estimated cumulative incidence reached 26.8% (24.2%, 29.7%) at the end of September in New York City and 8.8% (7.1%, 11.3%) in Connecticut, higher than maximum seroprevalence measures (22.1% and 6.1%), respectively.

Conclusions: The cumulative incidence of SARS-CoV-2 infection is underestimated using cross-sectional serology data without adjustment for waning antibodies. Our approach can help quantify the magnitude of underestimation and adjust estimates for waning antibodies.