Innate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19

Overview

Journal Annu Rev Immunol

Specialty Allergy & Immunology

Date 2024 Jun 28

PMID 38941608

Authors

R K Subbarao Malireddi

Bhesh Raj Sharma

Thirumala-Devi Kanneganti

Affiliations

Soon will be listed here.

Abstract

The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.

Citing Articles

Acute lung injury induced by recombinant SARS-CoV-2 spike protein subunit S1 in mice.

Zhu J, Wu J, Lu M, Jiao Q, Liu X, Liu L Respir Res. 2025; 26(1):59.

PMID: 39972348 PMC: 11837662. DOI: 10.1186/s12931-025-03143-7.

Bronchoalveolar lavage single-cell transcriptomics reveals immune dysregulations driving COVID-19 severity.

Asaba C, Bitazar R, Labonte P, Bukong T PLoS One. 2025; 20(2):e0309880.

PMID: 39928675 PMC: 11809808. DOI: 10.1371/journal.pone.0309880.

Clinical Characteristics During and After COVID-19 Infection Among Healthcare Workers During the First Wave of Omicron in Chongqing, China.

Tang H, Chen Z, Huang T, Yu P, Tang Q, Qiu Y Immun Inflamm Dis. 2025; 13(1):e70141.

PMID: 39871525 PMC: 11772718. DOI: 10.1002/iid3.70141.

References

Davis H, Assaf G, McCorkell L, Wei H, Low R, Reem Y . Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021; 38:101019. PMC: 8280690. DOI: 10.1016/j.eclinm.2021.101019. View

Strich J, Tian X, Samour M, King C, Shlobin O, Reger R . Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial. Clin Infect Dis. 2021; 75(1):e491-e498. PMC: 9890443. DOI: 10.1093/cid/ciab732. View

Banoth B, Tuladhar S, Karki R, Sharma B, Briard B, Kesavardhana S . ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis). J Biol Chem. 2020; 295(52):18276-18283. PMC: 7939383. DOI: 10.1074/jbc.RA120.015924. View

Zhang J, Wu H, Yao X, Zhang D, Zhou Y, Fu B . Pyroptotic macrophages stimulate the SARS-CoV-2-associated cytokine storm. Cell Mol Immunol. 2021; 18(5):1305-1307. PMC: 7976727. DOI: 10.1038/s41423-021-00665-0. View

Lempp F, Soriaga L, Montiel-Ruiz M, Benigni F, Noack J, Park Y . Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies. Nature. 2021; 598(7880):342-347. DOI: 10.1038/s41586-021-03925-1. View

Lee S, Channappanavar R, Kanneganti T . Coronaviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines. Trends Immunol. 2020; 41(12):1083-1099. PMC: 7561287. DOI: 10.1016/j.it.2020.10.005. View

Karki R, Kanneganti T . Innate immunity, cytokine storm, and inflammatory cell death in COVID-19. J Transl Med. 2022; 20(1):542. PMC: 9682745. DOI: 10.1186/s12967-022-03767-z. View

Kariko K, Buckstein M, Ni H, Weissman D . Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity. 2005; 23(2):165-75. DOI: 10.1016/j.immuni.2005.06.008. View

Zheng M, Karki R, Williams E, Yang D, Fitzpatrick E, Vogel P . TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat Immunol. 2021; 22(7):829-838. PMC: 8882317. DOI: 10.1038/s41590-021-00937-x. View

10.

Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H . Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020; 130(5):2620-2629. PMC: 7190990. DOI: 10.1172/JCI137244. View

11.

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

12.

Horby P, Lim W, Emberson J, Mafham M, Bell J, Linsell L . Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 384(8):693-704. PMC: 7383595. DOI: 10.1056/NEJMoa2021436. View

13.

Stanifer M, Kee C, Cortese M, Zumaran C, Triana S, Mukenhirn M . Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells. Cell Rep. 2020; 32(1):107863. PMC: 7303637. DOI: 10.1016/j.celrep.2020.107863. View

14.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

15.

Lu S, Ye Q, Singh D, Cao Y, Diedrich J, Yates 3rd J . The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nat Commun. 2021; 12(1):502. PMC: 7820290. DOI: 10.1038/s41467-020-20768-y. View

16.

Sette A, Crotty S . Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021; 184(4):861-880. PMC: 7803150. DOI: 10.1016/j.cell.2021.01.007. View

17.

Zhang Q, Matuozzo D, Le Pen J, Lee D, Moens L, Asano T . Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia. J Exp Med. 2022; 219(8). PMC: 9206114. DOI: 10.1084/jem.20220131. View

18.

Yamada T, Sato S, Sotoyama Y, Orba Y, Sawa H, Yamauchi H . RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells. Nat Immunol. 2021; 22(7):820-828. DOI: 10.1038/s41590-021-00942-0. View

19.

Abolhassani H, Landegren N, Bastard P, Materna M, Modaresi M, Du L . Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome. J Clin Immunol. 2022; 42(3):471-483. PMC: 8798309. DOI: 10.1007/s10875-022-01215-7. View

20.

Hung I, Lung K, Tso E, Liu R, Chung T, Chu M . Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020; 395(10238):1695-1704. PMC: 7211500. DOI: 10.1016/S0140-6736(20)31042-4. View