Risk-based prediction for optimal timing of booster vaccination for COVID-19 to prevent severe disease (preprint)

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.

Predicting the public health impact of bivalent vaccines and nirmatrelvir-ritonavir against COVID-19 (preprint)

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.

Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave (preprint)

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.