Effectiveness of Sotrovimab in Preventing COVID-19-related Hospitalizations or Deaths Among U.S. Veterans (preprint)

Background: Data on effectiveness of sotrovimab preventing COVID-19-related hospitalization or mortality, particularly after the emergence of the Omicron variant, are limited. Method: Determine the real-world clinical effectiveness of sotrovimab for prevention of 30-day COVID-19 related hospitalization or mortality using a retrospective cohort within the U.S. Department of Veterans Affairs (VA) healthcare system. Veterans aged [≥]18 years, diagnosed with COVID-19 between December 1, 2021, and April 4, 2022, were included. Sotrovimab recipients (n=2,816) were exactly matched to untreated controls (n=11,250) on date of diagnosis, vaccination status, and region. The primary outcome was COVID-19-related hospitalization or all-cause mortality within 30 days from diagnosis. Cox proportional hazards modeling estimated the hazard ratios (HR) and 95% Confidence Interval (CI) for the association between receipt of sotrovimab and outcomes. Results: During BA.1 dominance, compared to matched controls, sotrovimab-treated patients had a 70% lower risk hospitalization within 30 days or mortality (HR 0.30; 95%CI, 0.23-0.40), a 66% lower risk of 30-day hospitalization (HR 0.34; 95%CI, 0.25-0.46), and a 77% lower risk of 30-day all-cause mortality (HR 0.23; 95%CI, 0.14-0.38). During BA.2 dominance sotrovimab-treated patients had a 71% (HR .29; 95%CI, 0.08-0.98) lower risk of 30-day COVID-19-related- hospitalization, emergency, or urgent care. Limitations include confounding by indication. Conclusions: Using national real-world data from high risk and predominantly vaccinated Veterans, administration of sotrovimab, compared with no treatment, was associated with reduced risk of 30-day COVID-19-related hospitalization or all-cause mortality during the Omicron BA.1 period and reduced risk of progression to severe COVID-19 during the BA.2 dominant period.

Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data (preprint)

Background: Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in this population, particularly after the emergence of the Omicron variant. Objective: To determine the effectiveness of tixagevimab/cilgavimab for prevention of SARS-CoV-2 infection and severe disease among immunocompromised patients. Design: Retrospective cohort study with propensity matching and difference-in-difference analyses. Setting: U.S. Department of Veterans Affairs (VA) healthcare system. Participants: Veterans age [≥]18 years as of January 1, 2022, receiving VA healthcare. We compared a cohort of 1,848 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to matched controls selected from 251,756 patients who were on immunocompromised or otherwise at high risk for COVID-19. Patients were followed through April 30, 2022, or until death, whichever occurred earlier. Main Outcomes: Composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used cox proportional hazards modelling to estimate the hazard ratios (HR) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. Results: Most (69%) tixagevimab/cilgavimab recipients were [≥]65 years old, 92% were identified as immunocompromised in electronic data, and 73% had [≥]3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to propensity-matched controls, tixagevimab/cilgavimab-treated patients had a lower incidence of the composite COVID-19 outcome (17/1733 [1.0%] vs 206/6354 [3.2%]; HR 0.31; 95%CI, 0.18-0.53), and individually SARS-CoV-2 infection (HR 0.34; 95%CI, 0.13-0.87), COVID-19 hospitalization (HR 0.13; 95%CI, 0.02-0.99), and all-cause mortality (HR 0.36; 95%CI, 0.18-0.73). Limitations: Confounding by indication and immortal time bias. Conclusions: Using national real-world data from predominantly vaccinated, immunocompromised Veterans, administration of tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection, COVID-19 hospitalization, and all-cause mortality during the Omicron surge.

Relative effectiveness of booster vs. 2-dose mRNA Covid-19 vaccination in the Veterans Health Administration: Self-controlled risk interval analysis (preprint)

ABSTRACT Importance Previous studies have analyzed effectiveness of booster mRNA Covid-19 vaccination and compared it with 2-dose primary series for both Delta and Omicron variants. Observational studies that estimate effectiveness by comparing outcomes among vaccinated and unvaccinated individuals may suffer from residual confounding and exposure misclassification. Objective To estimate relative effectiveness of booster vaccination versus the 2-dose primary series with self-controlled study design Design, Setting and Participants We used the Veterans Health Administration (VHA) Corporate Data Warehouse to identify U.S. Veterans enrolled in care ≥2 years who received the 2-dose primary mRNA Covid-19 vaccine series and a mRNA Covid-19 booster following expanded recommendation for booster vaccination, and who had a positive SARS-CoV-2 test during the Delta (9/23/2021-11/30/2021) or Omicron (1/1/22-3/1/22) predominant period. Among them, we conducted a self-controlled risk interval (SCRI) analysis to compare odds of SARS-CoV-2 infection during a booster exposure interval versus a control interval. Exposures control interval (days 4-6 post-booster vaccination, presumably prior to gain of booster immunity), and booster exposure interval (days 14-16 post-booster vaccination, presumably following gain of booster immunity) Outcomes and Measures Positive PCR or antigen SARS-CoV-2 test. Separately for Delta and Omicron periods, we used conditional logistic regression to calculate odds ratios (OR) of a positive test for the booster versus control interval and calculated relative effectiveness of booster versus 2-dose primary series as (1-OR)*100. The SCRI approach implicitly controlled for time-fixed confounders. Results We found 42 individuals with a positive SARS-CoV-2 test in the control interval and 14 in the booster exposure interval during Delta period, and 137 and 66, respectively, in Omicron period. For the booster versus 2-dose primary series, the odds of infection were 70% (95%CI: 42%, 84%) lower during the Delta period and 56% (95%CI: 38%, 67%) lower during Omicron. Results were similar for ages <65 and ≥65 years in the Omicron period. In sensitivity analyses among those with prior Covid-19 history, and age stratification, ORs were similar to the main analysis. Conclusions Booster vaccination was more effective relative to a 2-dose primary series, the relative effectiveness was consistent across age groups and was higher during the Delta predominant period than during the Omicron period.

Effectiveness of mRNA COVID-19 Booster Vaccines against Omicron and Delta Variants among US Veterans (preprint)

Background We estimated vaccine effectiveness (VE) of mRNA vaccines among US Veterans during periods of Delta and Omicron variant dominance. Patients included in this study were largely 65 years or older (62,834, 55%), male (101,259, 88%), and non-Hispanic white (66,986, 58%). Methods We used SARS-CoV-2 laboratory test results to conduct a matched test-negative case-control study to estimate VE of three and two doses of mRNA vaccines against infection (regardless of symptoms), and a matched case-control study to estimate VE against COVID-19-related hospitalization and death. We estimated VE as (1-odds ratio) x 100%. Severity of disease was measured using hospital length of stay (LOS) and admission to an intensive care unit (ICU). Results Against infection, booster doses had 7-times higher VE - 59% (95% confidence interval [CI], 57 to 61) - than 2-dose VE (7%; 95% CI, 3 to 10) during the Omicron period. For the Delta period, estimated VE against infection was 90% (95% CI, 88 to 92) among boosted vaccinees, 64% higher than VE among 2-dose vaccinees [55% (95% CI, 51 to 58)]. Against hospitalization, booster dose VE was 87% (95% CI, 80 to 91) during Omicron and 95% (95% CI, 91 to 97) during Delta; the 2-dose VE was 44% (95% CI, 26 to 58) during Omicron and 75% (95% CI, 70 to 80) during Delta. Against death, estimated VE with a booster dose was 94% (95% CI, 85 to 98) during Omicron and 96% (95% CI, 88 to 99) during Delta, while the 2-dose VE was 75% (95% CI, 52 to 87) during Omicron and 93% (95% CI, 85 to 97) during Delta. During the Omicron period, average hospital LOS was 4 days shorter [3 days (95%CI, 3 to 4 days)] than during the Delta period. Conclusions A mRNA vaccine booster is more effective against infection, hospitalization, and death than 2-dose vaccination among an older male population with comorbidities.

Coverage and Effectiveness of mRNA COVID-19 Vaccines among Veterans (preprint)

Importance The effectiveness of mRNA vaccination in a large and diverse American population, with older age and higher co-morbidity has not been assessed. Objective To describe the scope of the mRNA vaccination rollout among the diverse U.S. Veterans population, and to study the mRNA COVID-19 vaccine effectiveness (VE) against infection, symptomatic disease, hospitalization, and death. Methods Vaccination histories were obtained from medical records to determine if patients tested for SARS-CoV-2 were unvaccinated, partially vaccinated (first dose of mRNA COVID-19 vaccine), or fully vaccinated (two doses) at time of testing. First, coverage with any COVID-19 vaccination was described for all Veterans enrolled in Veterans Health Administration (VHA). Second, to evaluate VE, a matched test-negative case-control evaluation was conducted utilizing SARS-CoV-2 positive (cases [n=16,690]) and SARS-CoV-2 negative (controls [n=61,610]) tests from Veterans aged ≥18 years old who routinely sought care at a VHA facility and were tested from December 14, 2020, through March 14, 2021. VE was calculated from odds ratios (ORs) with 95% confidence intervals (CI). Results By March 7, 2021, among 6,170,750 Veterans, 1,547,045 (23%) received at least one COVID-19 vaccination. mRNA COVID-19 VE against infection, regardless of symptoms, was 94% (95% CI 92-95) and 58% (95%CI 54-62) for full and partial vaccination (vs. no vaccination), respectively. VE against infection was similar across subpopulations, and it was not significantly different from VE against symptomatic disease. VE against COVID-19-related hospitalization and death for full vs. no vaccination was 89% (95%CI 81-93) and 99% (95%CI 87-100), respectively. Conclusions and Relevance The VHA’s efficient and equitable distribution of effective vaccines decreased COVID-19 infections, hospitalization, and mortality similarly for all Veterans, including Veterans with low income, homeless Veterans, immunocompromised, the elderly, minorities, and rural Veterans thus reducing health inequalities.