Earliest infections predict the age distribution of seasonal influenza A cases
- University of Chicago, United States
- Marshfield Clinic Research Institute, United States
Abstract
Seasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza.
Data availability
Code and data for calculation of imprinting probabilities, vaccination coverage, and model fitting are available on GitHub at https://github.com/cobeylab/FluAImprinting.
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Data and code from Earliest infections predict the age distribution of seasonal influenza A casesGitHub repository, cobeylab/FluAImprinting.
Article and author information
Author details
Funding
National Institutes of Health (DP2AI117921,HHSN272201400005C)
- Sarah Cobey
National Institutes of Health (F32AI145177-01)
- Philip Arevalo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ben S Cooper, Mahidol University, Thailand
Ethics
Human subjects: Study procedures for the vaccine effectiveness study was approved by the IRB at the Marshfield Clinic Research Institute. Informed consent was obtained from all participants at the time of enrollment into the vaccine effectiveness study. This analysis was subsequently approved by the Marshfield Clinic Research Institute IRB with a waiver of informed consent. The analysis of data was approved by the University of Chicago IRB under protocol number IRB17-1134-CR001.
Version history
- Received: July 10, 2019
- Accepted: June 29, 2020
- Accepted Manuscript published: July 7, 2020 (version 1)
- Version of Record published: July 17, 2020 (version 2)
Copyright
© 2020, Arevalo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Earliest infections predict the age distribution of seasonal influenza A cases
eLife 9:e50060.
https://doi.org/10.7554/eLife.50060
Further reading
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- Epidemiology and Global Health
Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0%-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
