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

Abstract

BackgroundSerology 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.MethodsWe 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.FindingsThe 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.InterpretationThe 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.FundingThis study was supported by the US National Science Foundation and the National Institute of Allergy and Infectious Diseases.

SARS-CoV-2 Infection Is Asymptomatic in Nearly Half of Adults with Robust Anti-Spike Protein Receptor-Binding Domain Antibody Response

“…Overall, our results indicate that asymptomatic and mostly unsuspected SARS-CoV-2 infections are more prevalent than currently thought. Moreover, the number of asymptomatic cases in the community could be even higher, since the seroprevalence in cross-sectional studies can be underestimated without adjustment for waning antibodies, as previously reported in studies from New York City and Connecticut [ 28 ].…”

Durability of the humoral immune response in recovered COVID-19 patients

“…At odds with our findings, waning humoral immunity in patients with SARS-CoV-2 infection has also been reported. Therefore, this raises the possibility that naturally developed humoral immunity counter to SARS-CoV-2 might not be long-lasting ( Choe et al, 2021 , Shioda et al, 2020 ).…”

Cohort Profile: A national prospective cohort study of SARS-CoV-2 pandemic outcomes in the U.S. - The CHASING COVID Cohort Study

“…However, antibody waning may also make this interpretation challenging, as up to 5 months may have passed between the first and second specimen collection for some participants. Recently, other teams have developed algorithms to correct seroprevalence estimates for waning 20 , and we may be able to use these approaches to correct our estimates of cumulative incidence in our cohort going forward. Limitations of serological assays notwithstanding 21 , recent cross-sectional serosurveys done prior to the relaxing of physical distancing have reported cumulative incidence estimates ranging from 1.7% in Indiana to 21% in New York City, and <10% nationally as of the end of September 2020.…”