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Association Between First MMR Vaccination Before Age 2 Years and Childhood Autism in a U.S. EHR Cohort of 2.5 Million Children
In this large U.S. cohort, age-anchored landmark analyses show no association between MMR vaccination before 24 months and childhood autism. These are the results of a very large retrospective cohort study using the Cosmos electronic health record database, including 2,560,035 U.S. children with linked birth-parent data and follow-up through age 8 years. To minimize bias related to exposure timing and healthcare utilization, they performed prespecified age-based landmark analyses evaluating the first MMR vaccination administered between 11.5 and 24 months. Adjusted hazard ratios (aHRs) for autism were estimated. In the primary 11.5–24 month landmark cohort, the first MMR vaccination was not associated with increased autism risk (aHR 0.97; 99% confidence interval 0.91–1.03). Across all age-specific landmark cohorts, aHRs remained near the null. The negative control analysis yielded a similarly near-null estimate (aHR 1.01; 99% confidence interval 0.99–1.04), supporting that residual bias is unlikely to explain the findings.
Moderna's mRNA Flu Shot mFlusiva Snags FDA Approval after Refusal-to-file Imbroglio
Despite a major curveball thrown by the FDA earlier this year, Moderna gained U.S. approval for its mRNA-based influenza vaccine. The FDA signed off on Moderna’s vaccine, christened mFlusiva, to prevent seasonal influenza in all adults ages 50 years and older. This clears the way for the first-ever flu shot leveraging mRNA technology in the United States. The vaccine’s odds of approval were thrown into flux in February when the FDA issued Moderna a rare refusal to file (RTF) letter, citing concerns with the design of the phase 3 trial for the shot, at the time known as mRNA-1010.
Household Transmission of SARS-CoV-2 in Washington and Oregon, United States, 2022-2024
Authors conducted a prospective observational household study in Oregon and Washington, USA, during 2022–2024. Participants completed enrollment, weekly, and follow-up symptom surveys, and submitted sera and weekly nasal swabs. Swabs were tested for SARS-CoV-2 by PCR; a subset of positive specimens underwent whole genome sequencing. Sera was tested for SARS-CoV-2 antibodies. They identified 617 households with a distinct index case, of which 90% were symptomatic and 41% were children. The estimated secondary infection rate was 16% (95% CI 13.6, 18.8%), reflecting 203 secondary infections among 1,267 household contacts. Among household contacts, factors associated with secondary infection included low anti-nucleocapsid antibody titers (RR: 1.88, 95% CI 1.34, 2.64), or residing with an index case who was symptomatic (RR: 1.85; 95% CI 1.04, 3.23), or had viral detection > 1 week (RR: 2.15, 95% CI 1.55, 2.97). Among 136 sequenced index-secondary case pairs, 128 (94%) shared SARS-CoV-2 lineages.
Virus Reactivation in Acute and Long COVID-19
SARS-CoV-2 infection has been shown to reactivate chronic viruses such as Epstein–Barr virus and cytomegalovirus, yet the full extent, temporal dynamics and immunological impact of viral reactivation in COVID-19 remain incompletely understood. Here, leveraging multi-omic longitudinal data from 1,154 hospitalized patients with COVID-19 from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, authors reveal significant reactivation of Herpesviridae and Anelloviridae during acute COVID-19, with distinct temporal dynamics for different viruses, and demonstrate that reactivation correlates with disease severity, host immune effects and clinical outcomes. Although results do not establish causation between virus reactivation and clinical outcomes, they highlight the prevalence of chronic viral reactivation during acute COVID-19 and Long COVID. These findings challenge the prevailing view that chronic viral reactivation is primarily a consequence of immunosuppression, demonstrating that reactivations occur frequently in immunocompetent individuals during severe illness and in association with increased systemic inflammation. Additionally, they demonstrate persistence of viral reactivation in convalescence, and report an association of Anelloviridae with Long COVID. This study provides immune, transcriptomic and metabolomic signatures of viral reactivation that could inform future strategies to prognosticate and treat acute COVID-19 and Long COVID.
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