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Review
. 2023 Jan 7;15(1):175.
doi: 10.3390/v15010175.

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Levente Zsichla  1   2 , Viktor Müller  1   2
Affiliations
Review

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Levente Zsichla et al. Viruses. .

Abstract

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.

Keywords: COVID-19; age; coinfections; comorbidities; disease severity; host genetics; risk factors; sex; socioeconomic status; viral variants.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The network of interactions between identified and proposed risk factors of severe COVID-19. Host (green), viral (blue) and environmental (yellow) factors are connected by arrows indicating three types of interactions between the factors: some factors might modulate the effect of other factors (blue arrows), e.g., advanced age shortens the duration of effective adaptive immune responses; some interactions may affect the occurrence of factors (red arrows), e.g., lifestyle choices influence the likelihood of certain comorbidities; finally, some factors act as the major determinant of another (black arrows), e.g., biological sex determines the possibility of pregnancy, and sex itself is genetically determined in humans. The width of the arrows indicates the perceived magnitude of these effects. The pictogram of microbiota alterations is faded out to illustrate the uncertainty of its causal role in the development of severe COVID-19. The figure was created with BioRender.com.
See this image and copyright information in PMC

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