What this trial measures

• Receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivirJanuary and February 2022

  The odds of receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivir were estimated using multivariable logistic regression

• Incidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 daysJanuary through July 2022

  Three retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir- ritonavir versus molnupiravir.

• Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab)January 2022 through January 2023

  To analyze trends and factors associated with prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA).

• Cumulative incidence of 31 potential PCCs at 31 -180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditionsJanuary through July 2022

  Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment.

• Incidence of any hospitalization or all-cause mortality at 30 daysApril 2022 through March 2023

  target trial emulation study in the Veterans Health Administration comparing nirmatrelvir-ritonavir treated versus matched untreated Veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

• Prediction of 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applicationsMarch 1, 2022, and March 31, 2023

  Full models incorporated 84 predictors, including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to fit prediction models. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset.

• RSVPreF3 or RSVpreF vaccination compared with no RSV vaccination for the prevention of documented RSV infection and associated health-care use among VeteransMarch 1, 2022, and March 31, 2023

  The primary outcome was any positive RSV test result occurring from day 14 following the index date until the end of the study period.7,8 Secondary outcomes included RSV-associated emergency department or urgent care encounters, RSV-associated acute hospitalisations, RSV associated intensive care unit (ICU) admissions, and death. RSV-associated health-care encounters were defined as any corresponding encounter occurring the day before until 1 day after the eligible positive RSV test result. Death was defined as any death occurring on the day of until 30 days after the eligible positive RSV test result.

• compare disease severity of COVID-19, influenza, and RSV among US VeteransAugust 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024.

  This retrospective cohort study analyzed national US Veterans Health Administration electronic health record data of nonhospitalized Veterans who underwent same-day testing for SARS-CoV-2, influenza, and RSV, and were diagnosed with a single infection between August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024. Following inverse probability weighting, the cumulative incidence and risk differences (RDs) were calculated for the primary outcomes of 30-day hospitalization, intensive care unit admission, and death, as well as the secondary outcome of long-term death extending through 180 days.

• Determine XBB.1.5 COVID-19 VE and the extent to which it declines over timeOctober 2,2023- January 3, 2024

  Outcomes were ascertained through 10 May 2024 and included any positive result on a SARS-CoV-2 test from day 10 after the matched index date, subsequent hospitalization within 1 day before or 10 days after the positive result, or death within 30 days after the positive result. Vaccine effectiveness was estimated as 100x (1-risk ratio).

• Determine if severe SARS-CoV-2 infection increases risk of selected PCCs or death up to 1 year after infection in wild-type (WT), Alpha-transition, Delta, and Omicron erasMarch 2020 and April 2022

  Investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the risk of selected PCCs or death up to 1 year after infection, separately in the wild-type (WT), Alpha-transition, Delta, and Omicron eras and by vaccination status.

• Determined budget cost of providing nirmatrelvir-ritonavir to Veterans with COVID-19 on 30-day healthcare costs to inform procurement strategies in large healthcare systemsApril 2022 through March 2023

  The decision tree analysis included transition states from cohort entry (ie, infection and treatment) to ED visit, hospitalization without ICU admission, hospitalization with ICU admission, recovery, and death (Figure 1). Decision trees were created for each subgroup and treatment allocation and parameterized with subgroup and treatment specific transition probabilities. In total, 26 trees (13 subgroups and 2 treatment scenarios) were created and parameterized with over 150 transition probabilities.

• Evaluate the impact of different time zero designations on results and inferences from a cohort study comparing the effectiveness of nirmatrelvir ritonavir treatment versus no COVID-19 antiviral treatment in preventing 30-day hospitalization and deathApril 2022-March 2023

  Identified US Veterans who tested positive for SARS-CoV-2 from April 2022-March 2023 and compared nirmatrelvir-ritonavir versus no treatment using 5 time zero approaches: test-date (treated) versus test-date (untreated) with matching allowing treatment on days 0-5 (approach 1a) or day 0 only (1b), test-date versus test-date with a clone-censor-weight method (1c), treatment date versus test-date (2) with matching, or treatment date versus matched index date (3).

• Asses the long-term effectiveness of a single respiratory syncytial virus (RSV) vaccine dose against RSV illness and associated health care useSeptember 2023 to March 2024.

  The primary outcome was any positive RSV test result from day 14 following the matched index date. Secondary outcomes included RSV-associated emergency department or urgent care visits, hospitalizations, or intensive care unit admissions. Vaccine effectiveness was estimated as 100 × (1 - risk ratio).

• Estimate the long-term vaccine effectiveness (VE) of the 2024-2025 COVID-19 vaccines targeting the KP.2 Omicron variant within the Veterans Health AdministrationAugust 1, 2024- April 12, 2025

  Vaccine effectiveness against documented SARS CoV-2 infection, SARS-CoV-2 associated ED/UC visit, SARS-CoV-2 associated hospitalization or SARS-CoV-2 associated death