Human Susceptibility to Influenza Infection and Severe Disease

Abstract

Influenza viruses are a persistent threat to global human health. Increased susceptibility to infection and the risk factors associated with progression to severe influenza-related disease are determined by a multitude of viral, host, and environmental conditions. Decades of epidemiologic research have broadly defined high-risk groups, while new genomic association studies have identified specific host factors impacting an individual's response to influenza. Here, we review and highlight both human susceptibility to influenza infection and the conditions that lead to severe influenza disease.

Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract

“…A number of risk factors for complications have been identified through epidemiological studies or genomic analysis (fig. 1b; reviewed elsewhere 24 ). Individuals >65 years or <6 months of age suffer severe outcomes of influenza virus more often than those not at the extremes of age 25 .…”

“…As a consequence, there is a shift to type 2 immunity characterized by a cytokine profile that suppresses cytotoxic T lymphocytes and alters antibody class switching to result in less effective responses to viral infections 35,36 . Men appear to have disproportionate hospitalization rates compared with non-pregnant women 37 , presumably related to differences in immune responses mediated by sex hormones, which may be age-dependent 24,38 . Comorbid chronic health conditions, including metabolic syndrome 39 , heart failure 40 and chronic obstructive pulmonary disease 41 , also increase an individual's risk of severe disease.…”

Mucosal immune responses to infection and vaccination in the respiratory tract

“…As discussed throughout this review, there is enormous complexity among the cellular and humoral immune responses within the airways following infection and vaccination, which requires a delicate balance between resistance and tolerance. The regulation, potency, and duration of these innate and adaptive facets, however, can be significantly impacted by underlying biological factors including age ( Wu et al., 2021 ), biological sex ( Ursin and Klein, 2021 ), race/ethnicity ( Prata Menezes et al., 2021 ), host genetics ( Patarčić et al., 2015 ; Casanova and Abel, 2021 ), pregnancy ( Sappenfield et al., 2013 ; Liong et al., 2020 ), host microbiome ( de Steenhuijsen Piters, Sanders and Bogaert, 2015 ; de Steenhuijsen Piters, Binkowska and Bogaert, 2020 ), chronic underlying conditions ( Glezen et al., 2000 ; Honce and Schultz-Cherry, 2019 ), and many more ( Mettelman and Thomas, 2021 ). As the lung is a kaleidoscope of heterogeneous cell subsets, each playing a specific and necessary role, it is critical to understand how these biological factors alter aspects of the pulmonary immune response.…”

Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

“…Epidemiological and viral shedding data suggest that obesity may play a role in influenza transmission [ 69 ], a question that could be investigated further using the recently developed obese ferret model [ 70 ]. There is evidence that host genetics can determine the susceptibility to severe influenza [ 71 ] and COVID-19 [ 72 , 73 ]. However, evidence is so far lacking for a role of host genetics in determining the route and propensity of transmission of respiratory viruses.…”