Background: The COVID-19 pandemic served as a global, uncontrolled social isolation experiment, with especially pernicious effects on mental health in young adults. We sought to understand how the COVID-19 pandemic and associated social restrictions impacted the wellbeing of university undergraduate students. Methods: 277 total U.S. undergraduate students enrolled in a course on mental wellbeing and resilience that was offered once each year from 2020 to 2024. Students anonymously completed surveys of anxiety, depression, and wellbeing on a weekly basis. These behavioral data were aggregated and investigated for associations with local COVID-19 case levels and a university social gathering meter. Results: Average student wellbeing declined a few months into the COVID-19 pandemic in Fall 2020, remaining low in Fall 2021 and Spring 2022, with 63.7% of students at-risk for poor wellbeing based on standard cut-offs over these three semesters. Depression and anxiety peaked during Fall 2021 with 39.0% and 34.5% of students at-risk for anxiety and depressive disorders, respectively. Mental health gradually improved following the return to in-person learning in mid-Spring 2022. Over all five semesters, survey questions reflecting anhedonia strongly associated with social gathering restrictions whereas questions assessing acute anxiety most strongly associated with local COVID-19 case levels. Conclusions: Our findings highlight the negative impact of the COVID-19 pandemic on university student wellbeing and suggest partially separable influences of COVID-19 infection prevalence and social isolation on levels of student anxiety and anhedonia. More research is needed to minimize the mental costs of future pandemics in an increasingly interconnected world.

The authors have declared no competing interest.

This study did not receive any funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board of Emory University reviewed this study and determined it to be exempt from further review and approval.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Student datasets in the present study cannot be shared for legal, ethical, or privacy reasons.