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 (preprint)

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.

Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes (preprint)

Background: Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes during the Omicron surge is limited. We sought to determine the effectiveness of nirmatrelvir-ritonavir and molnupiravir for the outpatient treatment of COVID-19. Methods: We conducted three retrospective target trial emulation studies comparing matched patient cohorts who received nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir in the Veterans Health Administration (VHA). Participants were Veterans in VHA care at risk for severe COVID-19 who tested positive for SARS-CoV-2 in the outpatient setting during January and February 2022. Primary outcomes included all-cause 30-day hospitalization or death and 31-180-day incidence of acute or long-term care admission, death, or post-COVID-19 conditions. For 30-day outcomes, we calculated unadjusted risk rates, risk differences, and risk ratios. For 31-180-day outcomes, we used unadjusted time-to-event analyses. Results: Participants were 90% male with median age 67 years and 26% unvaccinated. Compared to matched untreated controls, nirmatrelvir-ritonavir-treated participants (N=1,587) had a lower 30-day risk of hospitalization (27.10/1000 versus 41.06/1000, risk difference [RD] -13.97, 95% CI -23.85 to -4.09) and death (3.15/1000 versus 14.86/1000, RD -11.71, 95% CI -16.07 to -7.35). Among persons who were alive at day 31, further significant reductions in 31-180-day incidence of hospitalization (sub-hazard ratio 1.07, 95% CI 0.83 to 1.37) or death (hazard ratio 0.61, 95% CI 0.35 to 1.08) were not observed. Molnupiravir-treated participants aged [≥]65 years (n=543) had a lower combined 30-day risk of hospitalization or death (55.25/1000 versus 82.35/1000, RD -27.10, 95% CI -50.63 to -3.58). A statistically significant difference in 30-day or 31-180-day risk of hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants. Incidence of most post-COVID conditions was similar across comparison groups. Conclusions: Nirmatrelvir-ritonavir was highly effective in preventing 30-day hospitalization and death. Short-term benefit from molnupiravir was observed in older groups. Significant reductions in adverse outcomes from 31-180 days were not observed with either antiviral.

Differences in COVID-19 Risk by Race and County-Level Social Determinants of Health Among Veterans (preprint)

COVID-19 disparities by area-level social determinants of health (SDH) may be impacting U.S. Veterans. This retrospective analysis utilized COVID-19 data from the U.S. Department of Veterans Affairs (VA)s EHR and geographically linked county-level data from 18 area-based socioeconomic measures. The risk of testing positive with Veterans county-level SDHs adjusting for demographics, comorbidities, and facility characteristics was calculated using generalized linear models. We found an exposure-response relationship whereby individual COVID-19 infection risk increased with each increasing quartile of adverse county-level SDH such as the percentage of residents in a county without a college degree, eligible for Medicaid, and living in crowded housing.

Racial and ethnic disparities for SARS-CoV-2 positivity in the United States: a generalizing pandemic (preprint)

The coronavirus pandemic has disproportionally impacted racial and ethnic minority communities in the United States. These disparities may be changing over time as outbreaks occur in different communities. Using electronic health record data from the Department of Veterans Affairs, we estimated odds ratios, stratified by region and time period, for testing positive for SARS-CoV-2 among 951,408 individuals tested for SARS-CoV-2 between February 12, 2020 and February 12, 2021. Our study found racial and ethnic disparities for testing positive were most pronounced at the beginning of the pandemic and decreased over time. A key finding was that the disparity among Hispanic individuals attenuated but remained elevated over the entire study period. We identified variation in racial and ethnic disparities in SARS-CoV-2 positivity by time and region independent of underlying health status and other key factors in a nationwide cohort, which provides important insight for strategies to contain and prevent further outbreaks.

Association of Mortality and Aspirin Prescription for COVID-19 Patients at the Veterans Health Administration (preprint)

There is growing evidence that thrombotic and inflammatory pathways contribute to the severity of COVID-19. Common medications such as aspirin, that mitigate these pathways, may decrease COVID-19 mortality. This assessment was designed to quantify the correlation between aspirin and mortality for COVID-19 positive patients in our care. Data from the Veterans Health Administration national electronic health record database was utilized for the evaluation. Veterans from across the country with a first positive COVID-19 polymerase chain reaction lab result were included in the evaluation which comprised 28,350 patients from March 2, 2020 to September 13, 2020 for the 14-day mortality cohort and 26,346 patients from March 2, 2020 to August 28, 2020 for the 30-day mortality cohort. Patients were matched via propensity scores and the odds of mortality were then compared. Among COVID-19 positive Veterans, preexisting aspirin prescription was associated with a statistically and clinically significant decrease in overall mortality at 14-days (OR 0.38, 95% CI 0.32-0.46) and at 30-days (OR 0.38, 95% CI 0.33-0.45), cutting the odds of mortality by more than half. Findings demonstrated that pre-diagnosis aspirin prescription was strongly associated with decreased mortality rates for Veterans diagnosed with COVID-19. Prospective evaluation is required to more completely assess this correlation and its implications for patient care.