Yin and Yang of Interferons: Lessons from the Coronavirus Disease 2019 (COVID-19) Pandemic

Overview

Journal Curr Opin Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2024 May 22

PMID 38776716

Authors

Sara Svensson Akusjarvi

Ivan Zanoni

Affiliations

Soon will be listed here.

Abstract

The host immune response against severe acute respiratory syndrome coronavirus 2 includes the induction of a group of natural antiviral cytokines called interferons (IFNs). Although originally recognized for their ability to potently counteract infections, the mechanistic functions of IFNs in patients with varying severities of coronavirus disease 2019 (COVID-19) have highlighted a more complex scenario. Cellular and molecular analyses have revealed that timing, location, and subtypes of IFNs produced during severe acute respiratory syndrome coronavirus 2 infection play a major role in determining disease progression and severity. In this review, we summarize what the COVID-19 pandemic has taught us about the protective and detrimental roles of IFNs during the inflammatory response elicited against a new respiratory virus across different ages and its longitudinal consequences in driving the development of long COVID-19.

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References

Thompson R, Simons N, Wilkins L, Cheng E, Del Valle D, Hoffman G . Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae. Nat Med. 2022; 29(1):236-246. PMC: 9873574. DOI: 10.1038/s41591-022-02107-4. View

Schuhenn J, Meister T, Todt D, Bracht T, Schork K, Billaud J . Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection. Proc Natl Acad Sci U S A. 2022; 119(8). PMC: 8872780. DOI: 10.1073/pnas.2111600119. View

Santer D, Li D, Ghosheh Y, Zahoor M, Prajapati D, Hansen B . Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity. Nat Commun. 2022; 13(1):6992. PMC: 9667439. DOI: 10.1038/s41467-022-34709-4. View

Jagannathan P, Andrews J, Bonilla H, Hedlin H, Jacobson K, Balasubramanian V . Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat Commun. 2021; 12(1):1967. PMC: 8009873. DOI: 10.1038/s41467-021-22177-1. View

Wang E, Mao T, Klein J, Dai Y, Huck J, Jaycox J . Diverse functional autoantibodies in patients with COVID-19. Nature. 2021; 595(7866):283-288. DOI: 10.1038/s41586-021-03631-y. View

Pan H, Peto R, Henao-Restrepo A, Preziosi M, Sathiyamoorthy V, Abdool Karim Q . Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2020; 384(6):497-511. PMC: 7727327. DOI: 10.1056/NEJMoa2023184. View

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

Wiech M, Chroscicki P, Swatler J, Stepnik D, De Biasi S, Hampel M . Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection. Front Immunol. 2022; 13:886431. PMC: 9226563. DOI: 10.3389/fimmu.2022.886431. View

Combes A, Courau T, Kuhn N, Hu K, Ray A, Chen W . Global absence and targeting of protective immune states in severe COVID-19. Nature. 2021; 591(7848):124-130. PMC: 8567458. DOI: 10.1038/s41586-021-03234-7. View

10.

Wimmers F, Burrell A, Feng Y, Zheng H, Arunachalam P, Hu M . Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth. Cell. 2023; 186(21):4632-4651.e23. PMC: 10724861. DOI: 10.1016/j.cell.2023.08.044. View

11.

Tovo P, Garazzino S, Dapra V, Pruccoli G, Calvi C, Mignone F . COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases. Int J Mol Sci. 2021; 22(14). PMC: 8303145. DOI: 10.3390/ijms22147481. View

12.

Smith N, Posseme C, Bondet V, Sugrue J, Townsend L, Charbit B . Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity. Nat Commun. 2022; 13(1):7254. PMC: 9700809. DOI: 10.1038/s41467-022-34895-1. View

13.

Shin H, Kim S, Jo A, Won J, Gil C, Yoon S . Intranasal inoculation of IFN-λ resolves SARS-CoV-2 lung infection via the rapid reduction of viral burden and improvement of tissue damage. Front Immunol. 2022; 13:1009424. PMC: 9744928. DOI: 10.3389/fimmu.2022.1009424. View

14.

Edahiro R, Shirai Y, Takeshima Y, Sakakibara S, Yamaguchi Y, Murakami T . Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity. Nat Genet. 2023; 55(5):753-767. PMC: 10181941. DOI: 10.1038/s41588-023-01375-1. View

15.

Bosi C, Ferrarese R, De Lorenzo R, Mancini N, Bosi E . Lack of efficacy of Interferon β-1a in COVID-19 patients with mild to moderate pneumonia. Eur J Intern Med. 2022; 110:104-106. PMC: 9715494. DOI: 10.1016/j.ejim.2022.11.033. View

16.

Magalhaes V, Lukassen S, Drechsler M, Loske J, Burkart S, Wust S . Immune-epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children. EMBO Rep. 2023; 24(12):e57912. PMC: 10702842. DOI: 10.15252/embr.202357912. View

17.

Kalil A, Mehta A, Patterson T, Erdmann N, Gomez C, Jain M . Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021; 9(12):1365-1376. PMC: 8523116. DOI: 10.1016/S2213-2600(21)00384-2. View

18.

Ozonoff A, Jayavelu N, Liu S, Melamed E, Milliren C, Qi J . Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study. Nat Commun. 2024; 15(1):216. PMC: 10764789. DOI: 10.1038/s41467-023-44090-5. View

19.

Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y . Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19. Genome Med. 2023; 15(1):22. PMC: 10074346. DOI: 10.1186/s13073-023-01173-8. View

20.

Zhou S, Butler-Laporte G, Nakanishi T, Morrison D, Afilalo J, Afilalo M . A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity. Nat Med. 2021; 27(4):659-667. DOI: 10.1038/s41591-021-01281-1. View