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Review
. 2022 Jun 10:13:912336.
doi: 10.3389/fimmu.2022.912336. eCollection 2022.

Hallmarks of Severe COVID-19 Pathogenesis: A Pas de Deux Between Viral and Host Factors

Roberta Rovito  1 , Matteo Augello  1 , Assaf Ben-Haim  1 , Valeria Bono  1 , Antonella d'Arminio Monforte  1 , Giulia Marchetti  1
Affiliations
Review

Hallmarks of Severe COVID-19 Pathogenesis: A Pas de Deux Between Viral and Host Factors

Roberta Rovito et al. Front Immunol. .

Abstract

Two years into Coronavirus Disease 2019 (COVID-19) pandemic, a comprehensive characterization of the pathogenesis of severe and critical forms of COVID-19 is still missing. While a deep dysregulation of both the magnitude and functionality of innate and adaptive immune responses have been described in severe COVID-19, the mechanisms underlying such dysregulations are still a matter of scientific debate, in turn hampering the identification of new therapies and of subgroups of patients that would most benefit from individual clinical interventions. Here we review the current understanding of viral and host factors that contribute to immune dysregulation associated with COVID-19 severity in the attempt to unfold and broaden the comprehension of COVID-19 pathogenesis and to define correlates of protection to further inform strategies of targeted therapeutic interventions.

Keywords: COVID-19; SARS-CoV-2; biomarker; gut-lung axis; immune dysregulation; immunity; microbiota; severity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immune dysregulation in COVID-19 severe patients. The severe/critical form of COVID-19 disease is associated to a multi-layered immune dysregulation involving both innate and adaptive immune responses. Created with BioRender.com.
Figure 2
Figure 2
Underlying mechanisms of immune dysregulation. Several viral and host factors have been described as influencing one or more steps of the immune response during SARS-CoV-2 infection. In particular, the early phases of the immune response may be influenced by i) viral factors, such as viral inoculum, Spike mutations and viral interference of host IFN pathways, as well as ii) host factors, such as ACE2 polymorphisms and URT microbiota. Whereas viral up-regulation of host HLA-G, inborn host mutations, auto-reactive Abs vs IFN, HLA and KIR polymorphisms, past coronavirus infections may influence the later phases of immune responses. In this context, gut-lung axis perturbations may further fuel systemic inflammation. TLRs, Toll-like receptors; IFN, Interferon; Abs: Antibodies; HLA, Human Leukocyte Antigens; KIRs, Killer Cell Immunoglobulin-like Receptors; URT, Upper Respiratory Tract; ACE2, Angiotensin-converting Enzyme 2. Created with BioRender.com.
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References

    1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. . A Novel Coronavirus From Patients With Pneumonia in China, 2019. N Engl J Med (2020) 382(8):727–33. doi: 10.1056/NEJMoa2001017 - DOI - PMC - PubMed
    1. Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, et al. . The Species Severe Acute Respiratory Syndrome-Related Coronavirus: Classifying 2019-Ncov and Naming it SARS-CoV-2. Nat Microbiol (2020) 5(4):536–44. doi: 10.1038/s41564-020-0695-z - DOI - PMC - PubMed
    1. Peiris JS, Guan Y, Yuen KY. Severe Acute Respiratory Syndrome. Nat Med (2004) 10(12 Suppl):S88–97. doi: 10.1038/nm1143 - DOI - PMC - PubMed
    1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a Novel Coronavirus From a Man With Pneumonia in Saudi Arabia. N Engl J Med (2012) 367(19):1814–20. doi: 10.1056/NEJMoa1211721 - DOI - PubMed
    1. Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et al. . A Familial Cluster of Pneumonia Associated With the 2019 Novel Coronavirus Indicating Person-to-Person Transmission: A Study of a Family Cluster. Lancet (2020) 395(10223):514–23. doi: 10.1016/S0140-6736(20)30154-9 - DOI - PMC - PubMed

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