During September to December 2021, school mask policies to mitigate SARS-CoV-2 transmission varied throughout the US. We compared infection-induced seroprevalence estimates and estimated seroconversion among children residing in areas with and without school mask requirements. We estimated infection-induced seroprevalence among children in three age groups (5-17, 5-11, and 12-17 years) in areas with and without school district mask requirements for two time points: September 1-30, 2021 and December 15, 2021 to January 14, 2022. Robust Poisson regression models estimated population seroconversion over the semester among initially seronegative children. Permutation tests assessed for significant differences in the estimated population seroconversion due to incident infections by school district mask policy. Residing in an area with no school mask requirement was associated with higher infection-induced seroprevalence among children aged 5-17 years (adjusted prevalence ratio [aPR] = 1.18, 95% confidence interval [CI]: 1.10, 1.26), and those aged 5-11 years (aPR) = 1.21, 95% CI: 1.10, 1.32) and those aged 12-17 years (aPR = 1.16, 95% CI: 1.07, 1.26), compared with areas requiring masks in school. Estimated population seroconversion during the semester was also significantly higher among children in districts without mask policies than those with school mask requirements among all age groups (5-17 years: 23.7% vs 18.1%, P < 0.001; 5-11 years: 6.4% vs 4.5%, P = 0.002;12-17 years: 27.2% vs 21.0%, P < 0.001). During the U.S. Fall 2021 semester, areas with school mask requirements had lower infection-induced seroprevalence and an estimated lower proportion of seroconversion due to incident infection among school-aged children compared with areas without school mask requirements; causality cannot necessarily be inferred from these associations. IMPORTANCE: During the U.S. Fall 2021 school semester, the estimated proportion of previously uninfected school-aged children who experienced a first infection with SARS-CoV-2 was lower in areas where public school district policies required masks for all staff and students compared with areas where the school districts had no mask requirements. Because children are more likely than adults to experience asymptomatic or mild SARS-CoV-2 infections, the presence of infection-induced antibodies is a more accurate measure of infection history than clinical testing. The proportion of children with these antibodies (i.e., seroprevalence) can improve our understanding of SARS-CoV-2 by detecting more infections and eliminating potential bias due to local testing and reporting practices. Enhanced robustness of surveillance for respiratory infections in children, including records of mitigation policies in communities and schools, as well as seroprevalence data, would establish a better evidence base for policy decisions and response measures during future respiratory outbreaks.

We estimated monthly cross-sectional seroprevalence rates of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies to severe acute respiratory syndrome coronavirus 2 in two U.S. nationwide studies. The nationwide blood donor seroprevalence (NBDS) study included specimens from blood donors, while the nationwide commercial laboratory seroprevalence (NCLS) study included residual serum specimens tested in commercial laboratories for reasons unrelated to the assessment of coronavirus disease 2019 infection. In September-December 2021, specimens collected from both nationwide studies were tested for anti-N antibodies. In September-October 2021, specimens from both studies within a five-state area were tested for anti-S antibodies. We used raking methods to adjust all seroprevalence estimates by the population distribution of key demographics in included states. Seroprevalence estimates of each antibody type were compared across the two studies for specimens drawn in the same U.S. states during the same time period. Our analysis revealed that over a 4-month period, national NCLS monthly anti-N estimates were 0.5-1.9 percentage points higher than NBDS estimates. In contrast, across five states during a 2-month period, NBDS anti-S estimates were 7.6 and 8.2 percentage points higher than NCLS estimates. The observed differences in seroprevalence estimates between the NBDS and NCLS studies may be attributed to variations in the characteristics of the study sample populations, particularly with respect to health status, health behaviors, and vaccination status. These differences should be considered in the interpretation of seroprevalence study results based on blood donors or commercial lab residual specimens. IMPORTANCE: This study was the first systematic comparison between two nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies which estimated seroprevalence, or the proportion of the population with antibodies to the virus, using differing convenience sample populations. One study tested blood donor specimens; the other study tested specimens left over from clinical blood tests. The seroprevalence of anti-nucleocapsid and anti-spike antibodies was compared in the same states during the same months with statistical adjustments based on state demographics. Similar anti-nucleocapsid antibody seroprevalence estimates produced by two independent studies using differing convenience samples build confidence in the generalizability of their anti-nucleocapsid findings. Due to high blood donor vaccine rates, blood donor SARS-CoV-2 anti-spike antibody estimates might overestimate general population seroprevalence, an important consideration for interpreting national seroprevalence study results. Furthermore, because laboratory residuals and blood donations are two common sources of specimens for seroprevalence studies, study findings may be informative for other respiratory virus seroepidemiology studies.

BACKGROUND AND OBJECTIVES: Trends in estimates of US pediatric SARS-CoV-2 infection-induced seroprevalence from commercial laboratory specimens may overrepresent children with frequent healthcare needs. We examined seroprevalence trends and compared seroprevalence estimates by testing type and diagnostic coding. METHODS: Cross-sectional convenience samples of residual sera between September 2021 and February 2022 from 52 U.S. jurisdictions were assayed for infection-induced SARS-CoV-2 antibodies; monthly seroprevalence estimates were calculated by age group. Multivariate logistic analyses compared seroprevalence estimates for specimens associated with ICD-10 codes and laboratory orders indicating well-child care with estimates for other pediatric specimens. RESULTS: Infection-induced SARS-CoV-2 seroprevalence increased in each age group; from 30% to 68% (1-4 years), 38% to 77% (5-11 years), and 40% to 74% (12-17 years). On multivariate analysis, patients with well-child ICD-10 codes were seropositive more often than other patients aged 1-17 years (adjusted prevalence ratio [aPR] 1.04; 95% CI 1.02-1.07); children aged 9-11 years receiving standard lipid screening were seropositive more often than those receiving other laboratory tests (1.05; 1.02-1.08). CONCLUSIONS: Infection-induced seroprevalence more than doubled among children under 12 between September 2021 and February 2022, and increased 85% in adolescents. Differences in seroprevalence by care type did not substantially impact US pediatric seroprevalence estimates.

In December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, became predominant in the United States. Subsequently, national COVID-19 case rates peaked at their highest recorded levels.* Traditional methods of disease surveillance do not capture all COVID-19 cases because some are asymptomatic, not diagnosed, or not reported; therefore, the proportion of the population with SARS-CoV-2 antibodies (i.e., seroprevalence) can improve understanding of population-level incidence of COVID-19. This report uses data from CDC's national commercial laboratory seroprevalence study and the 2018 American Community Survey to examine U.S. trends in infection-induced SARS-CoV-2 seroprevalence during September 2021-February 2022, by age group.