Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections in vaccinated individuals and reinfections in previously infected individuals have become increasingly common. Such infections highlight a broader need to understand the contribution of vaccination, including booster doses, and natural immunity to the infectiousness of individuals with SARS-CoV-2 infections, especially in high-risk populations with intense transmission, such as in prisons. Here we show that both vaccine-derived and naturally acquired immunity independently reduce the infectiousness of persons with Omicron variant SARS-CoV-2 infections in a prison setting. Analyzing SARS-CoV-2 surveillance data from December 2021 to May 2022 across 35 California state prisons with a predominately male population, we estimate that unvaccinated Omicron cases had a 36% (95% confidence interval (CI): 31-42%) risk of transmitting infection to close contacts, as compared to a 28% (25-31%) risk among vaccinated cases. In adjusted analyses, we estimated that any vaccination, prior infection alone and both vaccination and prior infection reduced an index case's risk of transmitting infection by 22% (6-36%), 23% (3-39%) and 40% (20-55%), respectively. Receipt of booster doses and more recent vaccination further reduced infectiousness among vaccinated cases. These findings suggest that, although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection. This study underscores benefit of vaccination to reduce, but not eliminate, transmission.Transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shifted over the course of the pandemic due to widespread vaccination, natural infection and emergence of novel variants 1 . Although the early pandemic was characterized by infections in fully susceptible individuals, SARS-CoV-2 breakthrough infections among vaccinated individuals and reinfections among previously infected individuals are now increasingly frequent 2-4 . After the emergence of the highly infectious Omicron variant in December 2021, the United States observed the largest surge in Coronavirus Disease 2019 (COVID-19) cases to date 5 . Determining the impact of vaccination,

Breakthrough infections in vaccinated individuals and reinfections among previously infected individuals are increasingly prevalent, especially during the Omicron wave. Here, we analyze data from SARS-CoV-2 surveillance across 35 California prisons to understand the impact of vaccination and prior infection on infectiousness of individuals with SARS-CoV-2 Omicron infections in prison settings. We estimate that vaccination, prior infection, and both vaccination and prior infection reduced an index case's risk of transmitting to close contacts by 24% (9-37%), 21% (4-36%) and 41% (23-54%), respectively. Booster vaccine doses and more recent vaccination further reduced infectiousness. These findings suggest that although vaccinated and/or previously infected individuals remain infectious upon SARS-CoV-2 Omicron infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection.

Key Points Question How many COVID-19 cases, hospitalizations, and deaths were averted because of COVID-19 vaccination in California? Findings In this modeling study using data from the California Department of Public Health, COVID-19 vaccination was estimated to have prevented more than 1.5 million COVID-19 cases, 72 000 hospitalizations, and 19 000 deaths during the first 10 months of vaccination, through October 16, 2021. Meaning These findings suggest that COVID-19 vaccination had a large public health benefit in California, which can be generalized across the United States.

Importance: Despite widespread vaccination against COVID-19 in the United States, there are limited empirical data quantifying the public health impact in the population. Objective: To estimate the number of cases of COVID-19 averted due to COVID-19 vaccination Design, Setting, and Participants: The California Department of Public Health (CDPH) provided person-level data on COVID-19 cases and COVID-19 vaccine administration. To estimate the number of COVID-19 cases that would have occurred in the vaccine era in absence of vaccination, we applied a statistical model that estimated the relationship of COVID-19 cases in the pre-vaccine era between the unvaccinated age group (<12 years) and vaccine-eligible groups (≥12 years) to COVID-19 case data after the start of vaccination. The primary study outcome was the difference between predicted number of COVID-19 cases in absence of vaccination and observed COVID-19 cases with vaccination. As a sensitivity analysis, we developed a second independent model that estimated the number of vaccine-averted COVID-19 cases by applying published data on vaccine effectiveness to data on COVID-19 vaccine administration and estimated risk of COVID-19 over time. Intervention: COVID-19 vaccination Main Outcomes and Measures: COVID-19 cases Results: There were 4,585,248 confirmed COVID-19 cases in California from January 1, 2020 to October 16, 2021, during which 27,164,680 vaccine-eligible individuals ≥12 years were reported to have received at least 1 dose of a COVID-19 vaccine in the vaccine era (79.5% of the eligible population). We estimated that 1,523,500 [95% prediction interval (976,800-2,230,800)] COVID-19 cases were averted and there was a 34% [95% prediction interval (25-43)] reduction in cases due to vaccination in the primary model. Approximately 66% of total cases averted occurred after the delta variant became the dominant strain of SARS-CoV-2 circulating in California. Our alternative model identified comparable findings. Conclusions and Relevance: This study provides robust evidence on the public health impact of COVID-19 vaccination in the United States and further supports the urgency for continued vaccination.

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Background Uptake of COVID-19 bivalent vaccines and oral medication nirmatrelvir-ritonavir (Paxlovid) has remained low across the United States. Assessing the public health impact of increasing uptake of these interventions in key risk groups can guide further public health resources and policy, and determine what proportion of severe COVID-19 is avertable with these interventions. Methods This modeling study used person-level data from the California Department of Public Health on COVID-19 cases, hospitalizations, deaths, and vaccine administration from July 23, 2022 to January 23, 2023. We used a quasi-Poisson regression model calibrated to recent historical data to predict future COVID-19 outcomes and modeled the impact of increasing uptake (up to 70% coverage) of bivalent COVID-19 vaccines and nirmatrelvir-ritonavir during acute illness in different risk groups. Risk groups were defined by age (50+, 65+, 75+ years) and vaccination status (everyone, primary series only, previously vaccinated). We predicted the number of averted COVID-19 cases, hospitalizations, and deaths and number needed to treat (NNT). Results The model predicted that increased uptake of bivalent COVID-19 boosters and nirmatrelvir-ritonavir (up to 70% coverage) in all eligible persons could avert an estimated 15.7% (95% UI 11.2-20.7; NNT: 17,310) and 23.5% (95% UI 13.1-30.0; NNT: 67) of total COVID-19 related deaths, respectively. In the high-risk group of persons 65+ years old alone, increased uptake of bivalent boosters and nirmatrelvir-ritonavir could avert an estimated 11.9% (95% UI 8.4-15.1; NNT: 2,757) and 22.8% (95% UI 12.7-29.2; NNT: 50) of total COVID-19 related deaths, respectively. Conclusions These findings suggest prioritizing uptake of bivalent boosters and nirmatrelvir-ritonavir among the older age groups (65+ years) would be most effective (based on NNT) but would not address the entire burden of severe COVID-19.

Background: Uptake of COVID-19 bivalent vaccines and oral medication nirmatrelvir-ritonavir (Paxlovid) has remained low across the United States. Assessing the public health impact of increasing uptake of these interventions in key risk groups can guide further public health resources and policy. Methods: This modeling study used person-level data from the California Department of Public Health on COVID-19 cases, hospitalizations, deaths, and vaccine administration from July 23, 2022 to January 23, 2023. We modeled the impact of additional uptake of bivalent COVID-19 vaccines and nirmatrelvir-ritonavir during acute illness in different risk groups defined by age (50+, 65+, 75+ years) and vaccination status (everyone, primary series only, previously vaccinated). We predicted the number of averted COVID-19 cases, hospitalizations, and deaths and number needed to treat (NNT). Results: For both bivalent vaccines and nirmatrelvir-ritonavir, the most efficient strategy (based on NNT) for averting severe COVID-19 was targeting the 75+ years group. We predicted that perfect coverage of bivalent boosters in the 75+ years group would avert 3,920 hospitalizations (95%UI: 2,491-4,882; 7.8% total averted; NNT 387) and 1,074 deaths (95%UI: 774-1,355; 16.2% total averted; NNT 1,410). Perfect uptake of nirmatrelvir-ritonavir in the 75+ years group would avert 5,644 hospitalizations (95%UI: 3,947-6,826; 11.2% total averted; NNT 11) and 1,669 deaths (95%UI: 1,053-2,038; 25.2% total averted; NNT 35). Conclusions: These findings suggest prioritizing uptake of bivalent boosters and nirmatrelvir-ritonavir among the oldest age groups would be efficient and have substantial public health impact in reducing the burden of severe COVID-19, but would not address the entire burden of severe COVID-19.

While waning protection from vaccination and natural infection against SARS-CoV-2 infection is well-documented, recent analyses have also found waning of protection against severe COVID-19. This highlights a broader need to understand the optimal timing of COVID-19 booster vaccines specific to an individual to mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age group and immune status. Here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively mitigate the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit. Analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, we estimated that in persons 75+ years, annual and semiannual bivalent boosters would reduce annual absolute risk of severe COVID-19 by 311 (277-369) and 578 (494-671) cases, respectively, compared to a one-time bivalent booster dose. In contrast, for persons 18-49 years, the model estimated that annual and semiannual bivalent boosters would reduce annual absolute risk of severe COVID-19 by 20 (13-26) and 37 (24-50) cases per 100,000 persons, respectively, compared to a one-time bivalent booster dose. Persons with prior infection had a much lower benefit of more frequent boosting, while immunocompromised persons had larger benefit. This study underscores the benefit of customizing timing of COVID-19 booster vaccines based on individual risk.