A Narrative Review of Key Risk Factors for Severe Illness Following SARS-CoV-2, Influenza Virus, and Respiratory Syncytial Virus Infection

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are highly infectious respiratory viruses that affect people of all ages and are typically associated with mild symptoms and few complications in immunocompetent individuals. However, the risk of severe outcomes (e.g., hospitalization and death) following infection with these respiratory viruses is higher in certain populations, including older adults and individuals of certain race/ethnic and sociodemographic groups. Additionally, immunocompromising conditions and pre-existing comorbidities, including underlying cardiovascular (e.g., congestive heart failure) and respiratory diseases (e.g., chronic obstructive pulmonary disease), diabetes, chronic kidney disease, and obesity, are key factors that predispose individuals to SARS-CoV-2-, influenza-, and RSV-related severe outcomes. Increased risk for severe outcomes associated with advancing age and comorbidities is compounded by residence in long-term care facilities due to the enhanced spread of respiratory infections in congregate living environments. In this narrative review, risk factors associated with severe outcomes following infection with SARS-CoV-2, influenza, and RSV in adult populations are explored. Additionally, distinct clinical outcomes based on underlying comorbidities following infection are discussed in the context of high-risk populations. Factors unique to each virus that underpin distinct risk profiles are described and suggest the potential for tailored surveillance and healthcare approaches to target and ultimately mitigate SARS-CoV-2-, influenza-, and RSV-associated disease burden in vulnerable populations. Mutual risk factors for severe outcomes are also highlighted; these similarities indicate that cohesive risk reduction strategies may also be feasible, particularly since vaccines are available for each of these respiratory viruses. Ultimately, a more thorough understanding of the risk factors that predispose individuals to develop SARS-CoV-2-, influenza-, and RSV-related severe outcomes may improve risk reduction strategies, inform healthcare policy, and contribute to the expansion and refinement of existing surveillance approaches to ultimately mitigate disease burden in vulnerable populations.

Keywords: COVID-19; Comorbidities; Immunocompromised hosts; Influenza; Older adults; Respiratory syncytial virus; Risk factors; SARS-CoV-2.

Fig. 1

Hospitalization rates per 100,000 population among adults with laboratory-confirmed SARS-CoV-2, influenza, or RSV infection during the 2023–2024 RVI season. Data are representative of > 30 million individuals covered by population-based surveillance conducted through acute care hospitals in the United States (RESP-NET) [13]. Independent y-axis ranges were used for the illustration of each respiratory virus. The RESP-NET database is updated frequently; values presented here are accurate as of March 2024. RSV respiratory syncytial virus, RVI respiratory virus infection

Fig. 2

Cumulative hospitalization rates per 100,000 population among individuals with laboratory-confirmed SARS-CoV-2, influenza, or RSV infection during the 2022–2023 and 2023–2024 seasons. Data were obtained from the population-based surveillance systems RSV-NET, COVID-NET, and FluSurv-NET (RESP-NET) that collect data through a network of > 250 acute care hospitals in the United States [56, 59, 164]. Hospitalization rates^a reflect the cumulative rate observed between October 2022 and September 2023 (2022–2023 season) and October 2023 and May 2024 (2023–2024 season) among adults aged ≥ 18 years (SARS-CoV-2 and RSV) and individuals of all ages (influenza).^b Independent x-axis ranges are used for the illustration of each respiratory virus. ^aRates are not adjusted for undertesting of the three RVIs and laboratory testing practices may differ by race/ethnic groups and over time. ^bData stratified by race/ethnicity and age group were not available for influenza and therefore the data presented here reflect individuals of all ages. The RESP-NET database is updated frequently; values presented here are accurate as of May 3, 2024. AI/AN American Indian or Alaska Native, A/PI Asian and Pacific Islander, COVID-19 coronavirus disease 2019, RSV respiratory syncytial virus. A/PI, White, Black, and AI/AN individuals were considered non-Hispanic

Fig. 3

Comorbidities as risk factors for severe outcomes following SARS-CoV-2, influenza-, and RSV infection. Data were obtained from the publication by Hamilton et al. [72] and are representative of individuals of all ages across the following time periods: March–December 2020 (SARS-CoV-2) and 2010–2011 through 2018–2019 RVI seasons (influenza and RSV). a Proportions of comorbidities among individuals with underlying medical conditions who experienced severe outcomes due to SARS-CoV-2, influenza, and RSV infection. b Predictors of in-hospital mortality following RVI. The proportion of patients with ≥ 1 comorbidity and 30-day all-cause in-hospital mortality are shown for patients hospitalized with laboratory-confirmed SARS-CoV-2, influenza, and RSV infection. CHF congestive heart failure, CKD chronic kidney disease, COPD chronic obstructive pulmonary disease, RSV respiratory syncytial virus, RVI respiratory virus infection. ^aA selected number of comorbidities are shown as proportions of individuals with these conditions. The presence of multimorbidity is not reflected and therefore individuals may be represented in > 1 comorbidity category [72]. ^bThe common and divergent predictors of mortality were obtained from adjusted models. Additional common predictors of in-hospital mortality from unadjusted models included COPD, hypertension, diabetes, and dementia/frailty among others [72]