The literature concerning gestational maternal influenza virus infection and risk of autism spectrum disorders (ASD) is inconclusive. To address this uncertainty, we obtained information from questionnaires and samples from the Autism Birth Cohort, a prospective birth cohort comprising mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaires, referrals, and linkages to the Norwegian National Patient Registry, we identified 338 mothers of children with ASD and 348 frequency-matched controls for whom plasma samples that had been collected midpregnancy and after delivery were available for influenza virus serology via luciferase immunoprecipitation and hemagglutinin inhibition assays for influenza virus strains circulating during the study period. Assay data were combined to define serological status and integrated with self-reports of influenza-like illness to estimate ASD risk. Neither influenza A nor influenza B virus infection was associated with increased ASD risk. Integration of reports of symptoms of influenza-like illness with serology revealed an increase in risk for seropositive women with symptoms, but this increase did not achieve statistical significance (a level of P < 0.05) in the comparison with seronegative women without symptoms (adjusted odds ratio, 1.93; 95% confidence interval, 0.95 to 3.89; P = 0.068). Although chance may explain our findings, the magnitude of the potential association may be of biological importance, and dismissing our findings could result in failure to detect a bona fide association (type II error). If the association is true, we posit that the risk is due to activation of the maternal immune system following infection rather than direct fetal infection. Data on levels of cytokines or other mediators of inflammation would allow us to test the validity of this hypothesis. IMPORTANCE The causes of most cases of autism spectrum disorders (ASD) are unknown. Some epidemiological studies suggest that maternal gestational influenza virus infection may increase the risk of ASD in offspring. Here, we describe an analysis of a large birth cohort with results based on questionnaires that prospectively addressed subjective reports of influenza-like illness and serological assays for objective determination of influenza virus infection. Although serologic evidence of gestational influenza virus infection alone was not associated with risk, positive serology and symptoms of influenza-like illness cannot yet be definitely ruled out as a risk factor.

Immune responses in people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies, including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators, attenuate Ab responses after vaccination. Evaluation of cellular responses after vaccination, therefore, is of particular importance in these populations. In this study, we used flow cytometry to analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy control study participants and pwMS receiving 5 different DMTs. Although pwMS receiving rituximab and fingolimod therapies had low Ab responses after both 2 and 3 vaccine doses, T cell responses in pwMS taking rituximab were preserved after a third vaccination, even when an additional dose of rituximab was administered between vaccine doses 2 and 3. PwMS taking fingolimod had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that, even in the absence of robust Ab responses, vaccination can generate immune responses in pwMS.

Background: Understanding how booster vaccination can prevent moderate and severe illness without hospitalization is crucial to evaluate the full advantage of mRNA boosters. Methods: We followed 85 801 participants (aged 31–81 years) in 2 large population-based cohorts during the Omicron BA.1/2 wave. Information on home testing, PCR testing, and symptoms of coronavirus disease 2019 (COVID-19) was extracted from biweekly questionnaires covering the period 12 January 2022 to 7 April 2022. Vaccination status and data on previous SARS-CoV-2 infection were obtained from national registries. Cox regression was used to estimate the effectiveness of booster vaccination compared to receipt of 2-dose primary series >130 days previously. Results: The effectiveness of booster vaccination increased with increasing severity of COVID-19 and decreased with time since booster vaccination. The effectiveness against severe COVID-19 was reduced from 80.9% shortly after booster vaccination to 63.4% in the period >90 days after vaccination. There was hardly any effect against mild COVID-19. The effectiveness tended to be lower among subjects aged ≥60 years than those aged <50 years. Conclusions: This is the first population-based study to evaluate booster effectiveness against self-reported mild, moderate, and severe COVID-19. Our findings contribute valuable information on duration of protection and thus timing of additional booster vaccinations.

The effects of maternal influenza infection on the fetus remain unclear. We studied mild influenza and influenza antibodies in relation to birth weight and risks of pre-eclampsia, preterm birth (PTB), and small for gestational age (SGA) birth among the unvaccinated participants in the Norwegian Influenza Pregnancy Cohort. Pregnant women attending a routine ultrasound were recruited from four hospitals in Norway shortly after the 2009 A(H1N1) pandemic. The present study was restricted to unvaccinated participants who were pregnant during the pandemic. Information on the participants was obtained through questionnaires and linkage with national registries. Maternal blood samples were collected at delivery. Women with laboratory-confirmed A(H1N1)pdm09 influenza, a clinical diagnosis of influenza, or self-reported influenza during the pandemic were classified as having had influenza. A(H1N1)pdm09-specific antibodies in serum were detected with the hemagglutination-inhibition assay. Detection of antibodies was considered an indicator of infection during the pandemic in the unvaccinated participants. Odds ratios were estimated with logistic regression. Quantile regression was used to estimate differences in the distribution of birth weight. Among the 1258 women included in this study, there were 37 cases of pre-eclampsia, 41 births were PTB, and 103 births were SGA. 226 women (18.0%) had influenza during the pandemic. The majority of cases did not receive medical care, and only a small proportion (1.3%) of the cases were hospitalized. Thus, the cases consisted primarily of women with mild illness. No significant associations between influenza and risk of pre-eclampsia, PTB, or SGA birth were observed. Detection of A(H1N1)pdm09-specific antibodies was associated with a lower 10th percentile of birth weight, β = − 159 g (95% CI − 309, − 9). Mild influenza illness during pregnancy was not associated with increased risk of pre-eclampsia, PTB or SGA birth. However, influenza infection during pregnancy may reduce the birth weight of the smallest children.