Population-based serosurveys for SARS-CoV-2 transmission 2021-2022, Massachusetts USA

SARS-CoV-2 has been responsible for extensive morbidity and mortality in Massachusetts, especially during the 2021-2022 time period. The true burden of infection is unknown as official reporting data during 2021 and 2022 was not able to capture subclinical/asymptomatic infections nor the results from home-based lateral flow tests (LFTs).

This study was designed to better characterize the exposure of Massachusetts residents to SARS-CoV-2, and to understand demographic and behavioral factors associated with SARS-CoV-2 exposure during the highest burden years of the pandemic.

A series of five sequential state-wide serosurveys were conducted with oversampling for underrepresented demographic groups from June 2021 to September 2022. These mail-based, repeated cross-sectional surveys (RCSs) captured data at periods of rapid vaccine uptake when different viral variants were predominant. This study also included collection of at-home nasal swabs for PCR-based SARS-CoV-2 virological testing, and collection of dried blood spot cards for ELISA-based testing of SARS-CoV-2 IgG antibody seromarkers including spike and nucleocapsid protein, reported as seroprevelences. Neutralizing antibodies to spike-RBD were also measured.

Of the randomly selected 52,000 Massachusetts households invited to participate in this survey, a total of 2220 participants completed the demographic questionnaire and submitted valid specimens for analysis. Of these participants, ten were PCR-positive for SARS-CoV-2 at time of survey. Across all five repeated cross-sectional surveys (RCS), spike antibody positivity ranged from 83.1 % to 96.4 %. Additionally, levels of the spike neutralizing antibody increased with each RCS; point prevalence values ranged from 20.5 % in RCS 1/2 to 73.5 % in RCS 5. Using weighted data, the seroprevalence of nucleocapsid protein remained relatively constant throughout the RCSs except for RCS 3. Multivariable regression results found a positive association between vaccination status and seromarkers of SARS-CoV-2 exposure; individuals who had been vaccinated were more likely to be seropositive for all seromarkers. Factors including race, age, income, and occupation did not show any statistically significant associations with serostatus.

This survey indicates that while there was an increase in antibodies to spike protein and to associated neutralizing antibodies over time, there were no differences in neutralizing antibodies by socio-demographic factors, suggesting no major health disparities existed at the time of surveys in either vaccine coverage or infection-related antibody titers across the state. Response rates were higher among some demographic groups (Caucasians, households with a high income, and women), thus, oversampling and weighting allowed estimates of the larger Massachusetts population. Our findings that there were no statistically significant differences in neutralizing antibodies across demographic groups suggesting all groups were similarly protected from SARS-CoV-2 infection. These results highlight the success of Massachusetts in protecting individuals across all demographics.