Levels of SARS-CoV-2 population exposure are considerably higher than suggested by seroprevalence surveys

Abstract

Accurate knowledge of levels of prior population exposure will inform preparedness plans for subsequent SARS-CoV-2 epidemic waves and vaccination strategies. Serological studies can be used to estimate levels of past exposure and thus position populations in their epidemic timeline. To circumvent biases introduced by decaying antibody titers over time, population exposure estimation methods should account for seroreversion. Here, we present a new method that combines multiple datasets (serology, mortality, and virus positivity ratios) to estimate seroreversion time and infection fatality ratios and simultaneously infer population exposure levels. The results indicate that the average time to seroreversion is five months, meaning that true exposure may be more than double the current seroprevalence levels reported for several regions of England.SummarySARS-CoV-2 exposure in England could be double the reported seroprevalence, with implications for the impact of vaccines/other interventions.

Non-pharmaceutical interventions, vaccination, and the SARS-CoV-2 delta variant in England: a mathematical modelling study

“…We examined varying assumptions about the duration of infection-induced immunity: lifelong or average of 6-year or 3-year duration ( appendix pp 38, 42 ). 35 , 36 , 37 Furthermore, we accounted for the increased severity of delta relative to alpha by assuming a 1·85-fold increased risk of hospital admission. 12…”

SARS-CoV-2 serology across scales: a framework for unbiased seroprevalence estimation incorporating antibody kinetics and epidemic recency

“…We previously raised this issue and performed simulations to demonstrate how relying on validation samples that do not represent the distribution of severity and time since infection in a population can introduce spectrum bias into seroprevalence estimation (10). Various modeling approaches have since been proposed to reduce the effects of spectrum bias stemming from antibody waning over time and seroreversion on various serologic platforms (11)(12)(13)(14)(15). A key advance of our approach is the ability to parametrize seroreversion using longitudinal antibody kinetic data generated from the same assays used in large-scale serosurveys.…”

Quantifying previous SARS-CoV-2 infection through mixture modelling of antibody levels

“…By contrast, many survey participants will have been infected several months earlier and their antibody levels may have waned in the meantime. Antibody waning has been reported in a number of studies [8][9][10][11]13,14 , and those that have specifically accounted for waning by assuming a constant rate of seroreversion-rather than by accounting for spectrum bias more generally as we have done-have predicted a significant impact on seroprevalence estimates 10,15,16 . In general, waning is greatest for anti-nucleocapsid antibodies, but it can also be significant for anti-spike protein antibodies.…”