Past pandemic experience at an individual or population level may affect health outcomes in future pandemics. In this study, we focus on how the influenza pandemic of 1968 (H3N2), which killed up to 100,000 people in the US, may have produced differential COVID-19 (SARS-CoV-2) outcomes. Our analysis finds that areas with high influenza-related mortality in 1968 experienced 1-2% lower COVID-19 death rates. We employ an identification strategy that isolates variation in COVID-19 rates across age cohorts born before and after 1968. Locales in the US with high 1968 influenza mortality have lower COVID-19 death rates among older cohorts relative to younger ones. The relationship holds using county-level and patient-level data, as well as data from hospitals and nursing homes. Results do not appear to be driven by systemic or policy-related factors that would affect a population, but instead suggest a potential individual-level response to prior influenza pandemic exposure. The findings merit substantial further investigation into potential biological, immunological, or other mechanisms that can account for these differential outcomes.
Background Past pandemic experience at an individual or population level could affect health outcomes in future pandemics. In this paper we test whether people who lived through local outbreaks of the influenza pandemic of 1968 (H3N2), which resulted in 100,000 deaths in the US, experience better outcomes when infected by the SARS-CoV-2 virus.
Methods We employ econometric techniques on county-level and patient-level data, further validated by aggregated data from hospitals and nursing home, to explain differential COVID-19 outcomes. Given the cross-sectional nature of this study, we address endogeneity and omitted variable bias con-cerns in the relationship between the 1968 flu and COVID-19 outcomes by utilizing as our outcome variable the difference by age group in death rates, number of medical procedures, and hospital admissions. We choose the age cutoff based on whether someone was born before or after 1968 in an attempt to isolate those people more likely exposed to the 1968 pandemic.
Findings We find a persistent negative relationship between US locales’ ex-posure to the 1968 flu pandemic and COVID-19 mortality. This relationship is robust to various controls and holds across populations (i.e., county level aggregates, hospital admittees, and nursing home residents, subset of pa-tients), as well as specifications that exploit age-based variation in exposure. Further analysis supports a possible individual-level mechanism—rather than policy-related, systemic, or population-level factors—as drivers of this phenomenon.
Interpretation Results suggest a potential biological or immunological mechanism that may mitigate the severity of COVID-19 in individuals who survived the 1968 flu pandemic. Further research should explore possible explanations for this phenomenon in the hopes of uncovering new avenues of prevention and treatment.
Competing Interest Statement
The authors have declared no competing interest.
This study did not receive any funding.
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Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv