Background Two FDA-authorized mRNA COVID-19 vaccines, BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), have demonstrated high efficacies in large Phase 3 randomized clinical trials. It is important to assess their effectiveness in a real-world setting. Methods This is a retrospective analysis of 136,532 individuals in the Mayo Clinic health system (Arizona, Florida, Iowa, Minnesota, Wisconsin) with PCR testing data between December 1, 2020 and April 20, 2021. We compared clinical outcomes for a vaccinated cohort of 68,266 individuals who received at least one dose of either vaccine (n BNT162b2 = 51,795; n mRNA-1273 = 16,471) and an unvaccinated control cohort of 68,266 individuals propensity-matched based on relevant demographic, clinical, and geographic features. We estimated real-world vaccine effectiveness by comparing incidence rates of positive SARS-CoV-2 PCR testing and COVID-19 associated hospitalization and ICU admission starting 7 days after the second vaccine dose. Findings The real-world vaccine effectiveness in preventing SARS-CoV-2 infection was 86.1% (95% CI: 82.4-89.1%) for BNT162b2 and 93.3% (95% CI: 85.7-97.4%) for mRNA-1273. BNT162b2 and mRNA-1273 were 88.8% (95% CI: 75.5-95.7%) and 86.0% (95% CI: 71.6-93.9%) effective in preventing COVID-19 associated hospitalization. Both vaccines were 100% effective (95% CI BNT162b2 : 51.4-100%; 95% CI mRNA-1273 : 43.3-100%) in preventing COVID-19 associated ICU admission. Conclusions BNT162b2 and mRNA-1273 are both effective in a real-world setting and are associated with reduced rates of SARS-CoV-2 infection and decreased burden of COVID-19 on the healthcare system.

Clinical studies are ongoing to assess whether existing vaccines may afford protection against SARS-CoV-2 infection through trained immunity. In this exploratory study, we analyze immunization records from 137,037 individuals who received SARS-CoV-2 PCR tests. We find that polio, Haemophilus influenzae type-B (HIB), measles-mumps-rubella (MMR), Varicella, pneumococcal conjugate (PCV13), Geriatric Flu, and hepatitis A/hepatitis B (HepA–HepB) vaccines administered in the past 1, 2, and 5 years are associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, comorbidities, and number of other vaccinations. Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI (0.32, 0.64), p-value: 6.9e−05). Overall, this study identifies existing approved vaccines which can be promising candidates for pre-clinical research and Randomized Clinical Trials towards combating COVID-19.

Background Real-world clinical data to support the use of casirivimab–imdevimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) is needed. This study aimed to assess the outcomes of casirivimab–imdevimab treatment of mild to moderate COVID-19. Methods A retrospective cohort of 696 patients who received casirivimab–imdevimab between December 4, 2020 and April 9, 2021 was compared to a propensity-matched control of 696 untreated patients with mild to moderate COVID-19 at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Primary outcome was rate of hospitalization at days 14, 21 and 28 after infusion. Findings The median age of the antibody-treated cohort was 63 years (interquartile range, 52–71); 45·5% were ≥65 years old; 51.4% were female. High-risk characteristics were hypertension (52.4%), body mass index ≥35 (31.0%), diabetes mellitus (24.6%), chronic lung disease (22.1%), chronic renal disease (11.4%), congestive heart failure (6.6%), and compromised immune function (6.7%). Compared to the propensity-matched untreated control, patients who received casirivimab–imdevimab had significantly lower all-cause hospitalization rates at day 14 (1.3% vs 3.3%; Absolute Difference: 2.0%; 95% confidence interval (CI): 0.5–3.7%), day 21 (1.3% vs 4.2%; Absolute Difference: 2.9%; 95% CI: 1.2–4.7%), and day 28 (1.6% vs 4.8%; Absolute Difference: 3.2%; 95% CI: 1.4–5.1%). Rates of intensive care unit admission and mortality at days 14, 21 and 28 were similarly low for antibody-treated and untreated groups. Interpretation Among high-risk patients with mild to moderate COVID-19, casirivimab–imdevimab treatment was associated with a significantly lower rate of hospitalization. Funding Mayo Clinic.

Motivated by the fact that there may be inaccuracies in features and labels of training data, we apply robust optimization techniques to study in a principled way the uncertainty in data features and labels in classification problems and obtain robust formulations for the three most widely used classification methods: support vector machines, logistic regression, and decision trees. We show that adding robustness does not materially change the complexity of the problem and that all robust counterparts can be solved in practical computational times. We demonstrate the advantage of these robust formulations over regularized and nominal methods in synthetic data experiments, and we show that our robust classification methods offer improved out-of-sample accuracy. Furthermore, we run large-scale computational experiments across a sample of 75 data sets from the University of California Irvine Machine Learning Repository and show that adding robustness to any of the three nonregularized classification methods improves the accuracy in the majority of the data sets. We observe the most significant gains for robust classification methods on high-dimensional and difficult classification problems, with an average improvement in out-of-sample accuracy of robust versus nominal problems of 5.3% for support vector machines, 4.0% for logistic regression, and 1.3% for decision trees.

Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st 2020 and February 8th 2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.