Risk of Suicide Attempts and Self-Directed Violence after SARS-CoV-2 Infection: Outcomes from an Emulated Trial of a Nationwide Observational Matched Cohort of US Veterans

Importance The negative health-related effects of SARS-CoV-2 infection may include increased risk for self-directed violence. Objective To assess suicide attempts and other self-directed violence risk among US Veterans with a positive polymerase chain reaction (PCR) test for SARS-CoV-2 infection compared to matched uninfected Veterans. Design, Setting, and Participants Using a target trial emulation design supported by comprehensive electronic health records from the US Veterans Health Administration, Veterans who had a positive PCR test between March 1, 2020 and March 31, 2021 were matched with non-infected comparators. Monthly matching was anchored to first positive PCR test for each patient. Groups were followed for one-year thereafter. Exposure Positive SARS-CoV-2 PCR. Main Outcomes and Measures Suicide attempts and self-directed violence documented in electronic health records by a VHA provider. Hazard ratios (HR) for time to first suicide attempt and self-directed violence (separate models) for the infected versus comparator group were measured using Cox regression models. Analyses were performed for short-term (days 1-30), long-term (days 31-365) and one-year (days 1-365) and further stratified by age and prior self-directed-violence history. Sensitivity analyses included censoring to address comparators crossing over by later testing positive for SARS-CoV-2. Results Among the 1,190,974 Veterans included, during the one-year period after the index date; 3,078 (0.258%) had a suicide attempt and 2,887 (0.242%) had self-directed violence. Regardless of follow-up duration, the HRs for suicide attempts and self-directed violence were higher for the infected group. For suicide attempts, short-term HR=2.54 (95% Confidence Interval [CI]: 2.05 to 3.15), long-term HR=1.30 (CI: 1.19 to 1.43) and one-year HR= 1.41 (CI: 1.30, 1.54). For self-directed violence, short-term HR=1.94 (CI: 1.51 to 2.49), long-term HR=1.32 (CI: 1.20 to 1.45), and one-year HR=1.38 (CI:1.26, 1.51). Conclusions and Relevance In matched cohorts, Veterans who had a positive SARS-CoV-2 PCR test had a higher risk of suicide attempt and self-directed violence that were greatest within the first 30 days and present for at least one year following. These findings highlight the importance of assessing patient experiences of suicide attempt and other forms of self-directed violence during different time periods post-infection to identify opportunities to augment prevention efforts and support those affected. Trial Registration Not applicable Question What were the risks of suicide attempts and self-directed violence among US Veterans with SARS-CoV-2 infection compared to a matched cohort? Findings In this target trial emulation study of a nationwide observational cohort of 1,190,974 matched US Veterans in the Veterans Health Administration from 3/1/2020-3/31/2021, those with a confirmed PCR test for SARS-CoV-2 infection had increased risk of both suicide attempts and self-directed violence that was greatest within 30 days after infection and persisted over the following year. Over the year, those in the infected group had 1.40 times risk of a suicide attempt and 1.38 times risk of experiencing self-directed violence versus those in the comparison group. Meaning COVID-19 survivors may require additional screening and prevention resources for suicide attempts and other forms of self-directed violence. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by funding from the US Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) Service awards for the COVID Observational Research Collaborative (C19-21-278; C19-21-279); and for use of the VA-linked Medicare data (SDR 02-237; SDR 98-004). Drs. Hynes and Maciejewski were supported in part by a VA Research Career Scientist Award (RCS 10-391 and RCS 21-136, respectively). Dr. Chen was supported by a VA Career Development Award. The authors all have employment or compensation arrangements with the US Department of Veterans Affairs. All statements in this article, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs or the US government, Oregon State University, Oregon Health & Science University, Portland State University, Duke University, the University of Washington, Johns Hopkins University, and the University of Michigan. No copyrighted material was included in this article. We also appreciate the data made available by the VHA Office of Mental Health and Suicide Prevention/Program Evaluation and Resource Center. ### Author Declarations 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 Portland Department of Veterans Affairs Medical Center (Portland VAMC) Research and Development Board (R&D) along with the Portland VAMC Institutional Review Board (IRB) gave ethical approval for this work. No informed consent was obtained because the project is secondary analysis of data. The Portland VAMC Institutional Review Board granted waivers for informed consent, HIPAA information, and HIPAA research on decedents. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The datasets generated and/or analyzed during the current study are not publicly available due to Department of Veterans Affairs data restrictions prohibiting sharing. Contact the corresponding author, Dr. Denise Hynes, for data requests.