Daily Respiratory Research Analysis

In early 2024, clade 2.3.4.4b highly pathogenic avian influenza (HPAI) A H5N1 virus was detected in United States dairy cattle. Although so far the public health threat of contemporary clade 2.3.4.4b H5N1 virus strains remains low, continued circulation in mammals and frequent spillover into humans poses a threat of pandemic H5N1. The United States and other countries have stockpiled vaccines and have plans in place to rapidly produce additional vaccine doses should a pandemic H5N1 virus emerge. However, the continued antigenic drift of clade 2.3.4.4b H5N1 antigens compared with historical antigens used by stockpiled vaccines has raised questions of whether these vaccines will confer protection or whether stockpiles need to be updated. We recently evaluated a replicating RNA (repRNA) vaccine against lethal contemporary 2.3.4.4b H5N1 virus challenge in mice and found that a homologous, but not historical, H5 hemagglutinin (HA)-based vaccine conferred protection. Here, we further evaluated the protective capacity of a repRNA expressing the contemporary 2.3.4.4b HA or a repRNA expressing a historical H5 HA (A/Vietnam/1203/2004) in a recently developed lethal nonhuman primate (NHP) challenge model. We found that both vaccines conferred robust protection against lethal 2.3.4.4b H5N1 virus challenge, reducing viral loads and signs of respiratory illness. Our data show that the repRNA platform can elicit protective immunity against lethal influenza virus challenge in NHPs and that historical H5 HAs can elicit cross-protective immunity.

IMPORTANCE: People who are critically buried by an avalanche typically die of asphyxia within 35 minutes, often making timely rescue impossible. The development of new strategies to delay asphyxiation is crucial to improve survival rates. OBJECTIVE: To investigate the efficacy of a novel, user-carried avalanche safety device that delivers airflow from avalanche debris to the user's airway without requiring supplemental oxygen or a mouthpiece. DESIGN, SETTING, AND PARTICIPANTS: This randomized, blinded, clinical trial was organized by 4 institutions and conducted at 1 field location in Italy from January to March 2023. Healthy volunteers aged 18 to 60 years were enrolled. Trial participants underwent a critical snow burial simulation while in a prone position covered by at least 50 cm of snow. Vital parameters were continuously monitored throughout the simulation to ensure participant safety and to collect physiological data. INTERVENTIONS: Participants were randomized to the safety device group (using the Safeback SBX device) or the control group (using a sham device). The safety device group completed an unblinded control in which the participants who remained buried after 35 minutes were seamlessly transferred to the sham device. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the time to oxygen saturation as measured by pulse oximetry (Spo2) less than 80% (event) during 35 minutes of monitoring, comparing intervention and control groups. Secondary outcomes included oxygen and carbon dioxide concentrations at different distances in the snow.

BACKGROUND: Amid the declining clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and diminishing public uptake of annual coronavirus disease 2019 (Covid-19) vaccines, contemporary evidence on vaccine effectiveness against clinically relevant outcomes is needed. METHODS: We conducted an observational study that used the electronic health records of the Department of Veterans Affairs to evaluate the effectiveness of the 2024-2025 Covid-19 vaccine among veterans who received the Covid-19 and influenza vaccines on the same day (164,132 participants) and in an active-comparator group of veterans who received the influenza vaccine only (131,839 participants), between September 3 and December 31, 2024. Participants were followed for 180 days or until the occurrence of an outcome, whichever came first. We used inverse-probability-weighted models to estimate vaccine effectiveness (calculated as 1 minus the risk ratio) against Covid-19-associated emergency department visits, hospitalizations, and deaths at 6 months. RESULTS: At 6 months of follow-up, the estimated vaccine effectiveness was 29.3% (95% confidence interval [CI], 19.1 to 39.2) against Covid-19-associated emergency department visits (risk difference per 10,000 persons, 18.3; 95% CI, 10.8 to 27.6), 39.2% (95% CI, 21.6 to 54.5) against Covid-19-associated hospitalizations (risk difference per 10,000 persons, 7.5; 95% CI, 3.4 to 13.0), and 64.0% (95% CI, 23.0 to 85.8) against Covid-19-associated deaths (risk difference per 10,000 persons, 2.2; 95% CI, 0.5 to 6.9). Vaccine effectiveness against a composite of these outcomes was 28.3% (95% CI, 18.2 to 38.2), with a risk difference per 10,000 persons of 18.2 (95% CI, 10.7 to 27.5). The Covid-19 vaccine was associated with decreased risks of these outcomes across prespecified subgroups defined according to age (<65 years, 65 to 75 years, and >75 years), the presence or absence of major coexisting conditions, and immunocompetence status. CONCLUSIONS: In this national cohort of U.S. veterans, the receipt of the 2024-2025 Covid-19 vaccine was associated with decreased risks of severe clinical outcomes. (Funded by the Department of Veterans Affairs.).