Estimating the cumulative incidence of SARS-CoV-2 infection and the infection fatality ratio in light of waning antibodies

Shioda, Kayoko; Lau, Max SY; Kraay, Alicia NM; Nelson, Kristin N; Siegler, Aaron J; Sullivan, Patrick S; Collins, Matthew H; Weitz, Joshua S; Lopman, Benjamin A

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 serological assays. 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 (NYC) and Connecticut. METHODS: We estimated time from seroconversion to seroreversion and infection fatality ratio (IFR) using mortality data from March-October 2020 and population-level cross-sectional seroprevalence data from April-August 2020 in NYC and Connecticut. We then estimated the daily seroprevalence and cumulative incidence of SARS-CoV-2 infection. FINDINGS: 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 NYC 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%) and 8.8% (7.1–11.3%) at the end of September in NYC and Connecticut, higher than maximum seroprevalence measures (22.1% and 6.1%), respectively. INTERPRETATION: 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. FUNDING: This study was supported by the US National Science Foundation and the National Institute of Allergy and Infectious Diseases.