Association between type-specific influenza circulation and incidence of severe laboratory-confirmed cases; which subtype is the most virulent?

OBJECTIVES

Excess population mortality during winter is most often associated with influenza A(H3N2), though susceptibility differs by age. We examined differences between influenza types/subtypes in their association with severe laboratory-confirmed cases, overall and by age group, to determine which type is the most virulent.

METHODS

We used nine seasons of comprehensive nationwide surveillance data from Greece (2010-2011 to 2018-2019) to examine the association, separately for influenza A(H1N1)pdm09, A(H3N2) and B, between the number of laboratory-confirmed severe cases (intensive care hospitalizations or deaths) per type/subtype and the overall type-specific circulation during the season (expressed as a cumulative incidence proxy). Quasi-Poisson models with identity link were used, and multiple imputation to handle missing influenza A subtype.

RESULTS

For the same level of viral circulation and across all ages, influenza A(H1N1)pdm09 was associated with twice as many intensive care hospitalizations as A(H3N2) (rate ratio (RR) 1.89, 95% CI 1.38-2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54-4.20). Similar associations were observed for laboratory-confirmed deaths. A(H1N1)pdm09 affected adults over 40 years at similar rates, whereas A(H3N2) affected elderly people at a much higher rate than younger persons (≥65 vs. 40-64 years, RR for intensive care 5.42, 95% CI 3.45-8.65, and RR for death 6.19, 95%CI 4.05-9.38). Within the 40-64 years age group, A(H1N1)pdm09 was associated with an approximately five times higher rate of severe disease than both A(H3N2) and B.

DISCUSSION

Influenza A(H1N1)pdm09 is associated with many more severe laboratory-confirmed cases, likely due to a more typical clinical presentation and younger patient age, leading to more testing. A(H3N2) affects older people more, with cases less often recognized and confirmed.