Clinical characteristics and severity of influenza infections by virus type, subtype, and lineage: A systematic literature review.

AIM: Studies carried out in the early 2000s found that the number of influenza-associated hospitalizations and deaths was highest in seasons dominated by A(H3N2), suggesting that the clinical presentation and severity of influenza may differ across virus types, subtypes, and lineages. We aimed to review the studies that examined this hypothesis.

METHOD: We conducted a literature review of studies published until January 2017 that compared the clinical presentation, disease severity, and case-fatality ratio of influenza patients infected with different virus types (A, B), subtypes (pre-pandemic A(H1N1), A(H1N1)p, A(H3N2)), and lineages (Victoria, Yamagata).

RESULTS: The literature search resulted in over 1700 entries: After applying in- and exclusion criteria, 47 studies were included in the literature review. Studies showed a wide diversity in setting and populations. Only a minority of studies provided results adjusted by patient's age and other potential confounders. There were very few differences in the clinical presentation of patients infected with different influenza viruses. We found weak evidence that the A(H1N1)p subtype in the post-pandemic period was more often associated with secondary bacterial pneumonia, ICU admission, and death, than the other influenza virus (sub)types.

CONCLUSION: Contrary to what is commonly assumed, the causal virus subtype does not seem to be a major determinant of clinical presentation and severity of influenza illness. However, drawing conclusions was made difficult by the low comparability and methodological shortcomings of included studies, and more well-designed studies are warranted.