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Background Returning university students represent large-scale, transient demographic shifts and a potential source of transmission to adjacent communities during the COVID-19 pandemic. Methods In this prospective longitudinal cohort study, we tested for IgG antibodies against SARS-CoV-2 in a non-random cohort of residents living in Centre County prior to the Fall 2020 term at the Pennsylvania State University and following the conclusion of the Fall 2020 term. We also report the seroprevalence in a non-random cohort of students collected at the end of the Fall 2020 term. Findings Of 345 community participants, 19 (5·5%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 7 August and 2 October. Of 625 student participants who returned to campus for fall instruction, 195 (31·2%) were positive for SARS-CoV-2 antibodies between 26 October and 23 November. Twenty-eight (8·1%) community participants returned a positive IgG antibody result by 9 December. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20–50 individuals) were significant predictors of detecting IgG antibodies among returning students (aOR, 95% CI: 3·24, 2·14–4·91; 1·62, 1·08–2·44; respectively). Interpretation Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure. The study implies that heterogeneity in SARS-CoV-2 transmission can occur in geographically coincident populations. Funding The Pennsylvania State University Office of the Provost, Social Science Research Institute, Huck Institute for the Life Sciences, and Clinical and Translational Science Institute; National Institutes of Health.

Importance The Coronavirus Disease 2019 (COVID-19) pandemic has had wide-spread impacts on health and behavioral patterns. Returning university students represent large-scale, transient demographic shifts and a potential source of transmission risk to adjacent communities. Objective Test the a priori hypothesis that the Fall 2020 student return-to-campus would correlate with an increase in infection rates in the surrounding community; identify risk factors for SARS-CoV-2 infection within and between the subgroups. Design Prospective longitudinal cohort study. Setting Conducted in Centre County, Pennsylvania, USA from August 2020 to December 2020. Participants Non-random cohorts of county residents 18 years of age or older living in Centre County prior to the return to in-person instruction at the Pennsylvania State University and returning students who were enrolled during the Fall 2020 term. Exposure(s) Contact with known SARS-CoV-2-positive and COVID-symptomatic individuals, attending gatherings of various sizes, and adherence to public health non-pharmaceutical interventions. Main Outcome(s) and Measure(s) Presence of IgG antibodies against the SARS-CoV-2 surface spike glycoprotein (S) receptor-binding domain (S/RBD), measured using an indirect isotype-specific (IgG) screening enzyme immunoassay. Results Of 345 community participants, 19 (5.5%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 7 August and 2 October. Of 625 returning student participants, 195 (31.2%) were positive for SARS-CoV-2 antibodies between 26 October and 23 November. 28 (8.1%) of the community participants had returned a positive result by 9 December. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20-50 individuals) were significant predictors of IgG antibodies among returning students (aOR, 95% CI: 3.24, 2.14-4.91, p Conclusions and Relevance Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure, implying limited transmission between these cohorts. This implies the potential to minimize the transmission of SARS-CoV-2 from high prevalence, geographically coincident sub-populations. Future work should investigate the relative efficacy of specific measures to reduce risk of transmission from itinerant to resident populations and guide communities with high levels of episodic migration and similar social configurations. KEY POINTS Question What was the effect of a large population influx on SARS-CoV-2 seroprevalence in an immunologically naive resident population? Findings Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents remained low and stable from before student arrival for the Fall term to after their departure, implying limited transmission between these subpopulations. Contact with an individual known to be SARS-CoV-2 positive and attending small gatherings were the only significant risk factors among returning students. Meaning The demographic shift associated with student return to campus was not associated with increased SARS-CoV-2 seroprevalence in this cohort of community residents.