Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023.

BACKGROUND: Non-pharmaceutical interventions implemented during the COVID-19 pandemic resulted in a marked reduction in influenza infections globally. The absence of influenza has raised concerns of waning immunity, and potentially more severe influenza seasons after the pandemic. METHODS: To evaluate immunity towards influenza post-COVID-19 pandemic we have assessed influenza A epidemics in Norway from October 2016 to June 2023 and measured antibodies against circulating strains of influenza A(H1N1)pdm09 and A(H3N2) in different age groups by hemagglutination inhibition (HAI) assays in a total of 3364 serum samples collected in 2019, 2021, 2022 and 2023. RESULTS: Influenza epidemics in Norway from October 2016 until June 2023 were predominately influenza As, with a mixture of A(H1N1)pdm09 and A(H3N2) subtype predominance. We did not observe higher numbers of infections during the influenza epidemics following the COVID-19 pandemic than in pre-COVID-19 seasons. Frequencies of protective HAI titers against A(H1N1)pdm09 and A(H3N2) viruses were reduced in sera collected in 2021 and 2022, compared to sera collected in 2019. The reduction could, however, largely be explained by antigenic drift of new virus strains, as protective HAI titers remained stable against the same strain from one season to the next. However, we observed the development of an immunity gap in the youngest children during the pandemic which resulted in a prominent reduction in HAI titers against A(H1N1)pdm09 in 2021 and 2022. The immunity gap was partially closed in sera collected in 2023 following the A(H1N1)pdm09-dominated influenza seasons of 2022/2023. During the 2022/2023 epidemic, drift variants of A(H1N1)pdm09 belonging to the 5a.2a.1 clade emerged, and pre-season HAI titers were significantly lower against this clade compared to the ancestral 5a.2 clade. CONCLUSION: The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be prioritized for vaccination.

Influenza risk groups in Norway by education and employment status.

AIMS: This study aimed to estimate the size of the risk group for severe influenza and to describe the social patterning of the influenza risk group in Norway, defined as everyone ⩾65 years of age and individuals of any age with certain chronic conditions (medical risk group). METHODS: Study data came from a nationally representative survey among 10,923 individuals aged 16-79 years. The medical risk group was defined as individuals reporting one or more relevant chronic conditions. The associations between educational attainment, employment status, age and risk of belonging to the medical risk group were studied with logistic regression. RESULTS: Nearly a fifth (19.0%) of respondents reported at least one chronic condition, while 29.4% belonged to the influenza risk group due to either age or chronic conditions. Being older, having a low educational level (comparing compulsory education to higher education, odds ratio (OR)=1.4, 95% confidence interval (CI) 1.2-1.8 among women, and OR=1.3, 95% CI 1.1-1.7 among men) and a weaker connection to working life (comparing disability pension to working full-time, OR=6.8, 95% CI 5.3-8.7 among women, and OR=6.5, 95% CI 4.9-8.5 among men) was associated with a higher risk of belonging to the medical risk group for severe influenza. CONCLUSIONS: This study indicates that the prevalence of medical risk factors for severe influenza is disproportionally distributed across the socio-economic spectrum in Norway. These results should influence both public funding decisions regarding influenza vaccination and communication strategies towards the public and health professionals.

Higher educational attainment associated with higher confidence in influenza vaccination in Norway.

AIMS: To explore public confidence in influenza vaccination through the use of attitudinal indicators, and study whether educational attainment is related to attitudes towards influenza vaccination. METHODS: Confidence in influenza vaccination was measured with three questions adapted from the Vaccine Confidence Project. These questions have been included in four study years of a Norwegian nationally representative telephone survey that cover influenza seasons 2016/17, 2019/20, 2020/21 and 2021/22. Over these four years, a total of 8 436 individuals aged 18-79 years responded to the survey and are included in the analysis. Risk differences (RDs) with 95 % confidence intervals were estimated using multivariable Poisson regression. RESULTS: Influenza vaccine confidence increased over time, with approximately 80 % of the general population expressing trust in the vaccine in the 2021/22 season. There was a tendency towards higher confidence in the oldest age group (65-79 years). Moreover, confidence increased with increasing educational attainment. The proportion of participants who agreed that influenza vaccine is compatible with their basic values was close to 20 percentage points lower among those with only compulsory education than among those with higher education at graduate level, RD = -18.4 % (95 % CI -21.4 % to -15.5 %). Educational attainment was consistently associated with influenza vaccine confidence in all seasons, among risk groups 18-64 years, and among health care workers. CONCLUSIONS: We observed an increase in confidence in influenza vaccination over the seasons examined in the study. However, the increase has not been equal in all groups and there is a clear educational gradient in influenza vaccine confidence. These findings indicate that despite efforts to increase influenza coverage over several years, the implemented measures have failed to reach all parts of the population.

Covid-19 and influenza vaccine effectiveness against associated hospital admission and death among individuals over 65 years in Norway: A population-based cohort study, 3 October 2022 to 20 June 2023.

BACKGROUND: Co-circulation of SARS-CoV-2 and influenza virus can lead to double epidemics and increased pressure on health systems. To evaluate the effect of both vaccines, we estimated the adjusted vaccine effectiveness (aVE) of influenza and Covid-19 vaccines against related severe disease in the elderly population in Norway during the 2022/2023 season. METHODS: In this population-based cohort study, we included data from the Emergency preparedness register for Covid-19 (Beredt C19) on all individuals ≥ 65 years living in Norway between 3 October 2022 and 20 June 2023. Using Cox-proportional hazard models, we estimated aVE of both influenza and Covid-19 vaccines (bivalent BA.1 and BA.4-5) against associated hospitalisation and death. Vaccine status was included as a time-varying covariate and all models were adjusted for potential confounders, including the other vaccine. RESULTS: We identified 2,437 influenza-associated hospitalisations and 178 deaths, alongside 5,824 Covid-19-associated hospitalisations and 621 deaths. The aVE was highest in the first three months after receiving either vaccine. Against influenza-associated hospitalisation the aVE was 34 % (26 %-42 %) among 65-79-year-olds and 40 % (30 %-48 %) among ≥ 80-year-olds, and 6.6 % (-64 %-47 %) and 37 % (0.5 %-61 %) against influenza-associated death, respectively. The aVE against Covid-19-associated hospitalisation was 65 % (61 %-69 %) among 65-79-year-olds and 55 % (49 %-60 %) among ≥ 80-year-olds (compared to having received the vaccine ≥ 180 days ago). Similarly, the aVE against Covid-19-associated death was 68 % (48 %-80 %) and 78 % (65 %-86 %), respectively. For Covid-19 we show a reduction in aVE with time since dose. CONCLUSION: Covid-19 and influenza vaccines reduced the risk of severe disease in the same high-risk population. Ensuring high uptake of both vaccines could thus limit the overall health care burden.