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

Abstract

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 e2011 to 2018e2019) 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 e2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54e4.20). 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 e64 years, RR for intensive care 5.42, 95% CI 3.45e8.65, and RR for death 6.19, 95%CI 4.05e9.38). Within the 40e64 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.

Influenza-induced acute respiratory distress syndrome during the 2010-2016 seasons: bacterial co-infections and outcomes by virus type and subtype

“…It has been reported that A(H3N2) particularly affected elderly people, as was found herein, leading to a high mortality and ICU admission rates in this population [9]. Although considered as less severe and mainly responsible for mild presentation in children, B infections can also cause severe and fatal cases [14], notably due to the development of bacterial co-infections [15].…”

“…Since 2009, A(H1N1)pdm09 has also been reported to be the most frequently detected in ICU patients, underscoring the particular virulence of this influenza subtype [4,8,9]. T€ opfer et al found that A(H1N1)pdm09-ARDS led to a more important impairment of gas exchange than non-A(H1N1)pdm09-ARDS; interestingly, the rate of bacterial co-infection between the two groups was not different [10].…”

Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: A systematic review and meta‐analysis

“…The reasons behind this interesting finding are still unclear. We observed that patients with influenza A (H1N1) were more likely to require ICU support than those with either influenza A (H3N2) or influenza B 59‐61 . Therefore, it is plausible that influenza A (H1N1) may reflect more severe illness, which could partly explain the higher risk of IPA in this influenza subtype population.…”

“…We observed that patients with influenza A (H1N1) were more likely to require ICU support than those with either influenza A (H3N2) or influenza B. [59][60][61] Therefore, it is plausible that influenza A (H1N1) may reflect more severe illness, which could partly explain the higher risk of IPA in this influenza subtype population. Considering the high probability of the development of IPA in influenza patients, primary prophylaxis may be considered in select populations with high-risk conditions.…”

Prognostic impact of high sensitive troponin in predicting 30-day mortality among patients admitted to hospital with influenza

“…Furthermore, higher rates of ACS in our study are probably related to the differences in cardio vascular disease (CVD) risk factor profile because patients in our study were older (median age 82 years vs. 77 years in the US study). In addition, these differences in rates of ACS may be related to the virulence of circulating influenza strains in respective epidemiological season [23] . Another study [15] , which included 264 influenza patients admitted over a period of 5 years where hsTnT results were available, found that 31.8% of patients had elevated cardiac biomarkers and 7.6% of these patients developed ACS, however, patients in this study were much younger (68.7 vs. 82 years) as compared to our population.…”