Type I Interferons in COVID-19 Pathogenesis
Abstract
:Simple Summary
Abstract
1. Introduction
2. In Vitro Inhibition of the IFN-I System by SARS-CoV-2
3. Sex Differences, Inborn Errors and Anti-IFNs Auto-Antibodies in COVID-19
3.1. Inborn Errors in COVID-19
3.2. Auto-Antibodies against Type-I IFN in COVID-19
4. IFN Expression in SARS-CoV-2-Infected Patients
5. IFN-Based Therapy for COVID-19
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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SARS-CoV-2 Protein | Cellular Target | Mechanism | References |
---|---|---|---|
Nsp1 | 40s ribosomal subunit; STAT1; IRF3; STAT2; Tyk2 | Translation inhibition by interfering with host mRNA binding; blocks IRF3 nuclear translocation; blocks nuclear export of host mRNAs; inhibition of STAT1 phosphorylation; reduced expression of STAT2 and Tyk2 | [18,31,32,33,34] |
Nsp5 | STAT1; STAT2 | Induces phospho-STAT1/2 accumulation imparing type I IFN signaling | [29] |
Nsp6 | IRF3; STAT1; STAT2 | Inhibition of IRF3, STAT1 and STAT2 phosphorylation | [18] |
Nsp13 | TBK1; IRF3; STAT1; STAT2 | Inhibition of TBK-1, STAT1 and STAT2 phosphorylation; blocks IRF3 nuclear translocation | [18,22] |
Nsp14 | IRF3 | Inhibits IRF3 nuclear translocation; induces lysosomal degradation of IFNAR1 | [22,29] |
Nsp15 | IRF3 | Inhibits IRF3 nuclear translocation | [22] |
ORF3a | STAT1 | Inhibits STAT1 phosphorilation | [18] |
ORF3b | IRF3 | Inhibits IRF3 nuclear translocation | [23] |
M | MAVS; STAT1 | Impairs MAVS aggregation and recruitment of downstream components; inhibits STAT1 phosphorilation | [18,26] |
ORF6 | IRF3; ISGF3 | Blocks IRF3 and ISGF3 nuclear translocation | [18,19,20,22,30] |
ORF7a | STAT2 | Inhibits STAT2 phosphorilation | [18] |
ORF7b | STAT1; STAT2 | Inhibits STAT1 and STAT2 phosphorilation | [18] |
ORF9b | NEMO; TBK-1; IRF-3 | Interrupts K63-linked polyubiquitination and inhibits NF-κB signaling; blocks activation of TBK-1 and IRF-3 | [27,28] |
N | RIG-I | Binds to the DExD/H domain and represses IFN-β production | [21] |
Authors | IFN Therapy | IFN Administration | Type of Study | N. Patients | Disease Stage | Outcome (Intervention vs. Control) |
---|---|---|---|---|---|---|
Hung, I.F.-N. et al. [87] | IFN-β-1b 5 days from symptoms onset | Subcutaneous | Multicentre prospective open-label randomized phase 2 Trial | 86 intervention group 41 control group | Hospitalized | Hospitalization: 9 vs. 14.5 days Mortality: 0% vs. 0% Serious adverse effects: 0% vs. 2% |
Malhani, A.A. et al. [88] | IFN-β-1b 4 days from symptoms onset | Subcutaneous | Observational study IFN-based vs. FPV treatment | 68 treated with IFN 154 treated with FPV | Mild–moderate–severe | Mortality: 9% vs. 12% Need of systemic corticosteroids: 57% vs. 77% |
Davoudi-Monfared, E. et al. [90] | IFN-β-1a 10 days from symptoms onset | Subcutaneous | Open-label randomized clinical trial | 42 intervention group 39 control group | Severe | Hospitalization: 14.8 vs. 12.2 days Mortality: 19% vs. 43.6% Serious adverse effects: no differences between groups |
Dastan, F. et al. [92] | IFN-β-1a 6.5 days from symptoms onset | Subcutaneous | Prospective non-controlled trial | 20 intervention group only | Severe | Hospitalization: 16.8 days Mortality: 0% Serious adverse effects: 0% |
Ader, F. et al. [93] | IFN-β-1a 10 days from symptoms onset | Subcutaneous | Open-label randomized adaptive clinical trial | 145 intervention group 148 control group | Moderate–severe | Hospital discharge at day 29 significantly higher than control arm |
Meng, Z. et al. [94] | Recombinant human (rh) IFN-α Preventive Therapeutic Strategy | Intranasal | Prospective, open-label study | 2944 intervention group only | None | 28-day incidence of COVID-19/new-onset clinical symptoms: 0% Serious adverse effects: 0% |
Zhou, Q. et al. [95] | IFN-α2b 8 days from symptoms onset | Inhaled | Uncontrolled, exploratory study | 53 intervention group 24 control group | Moderate | Accelerated viral clearance/reduction in systemic inflammation markers (circulating IL-6 and CRP levels) |
Monk, P.D. et al. [96] | IFN-β-1a 24 h from SARS-CoV-2 positive test | Inhaled | Randomized, double-blind, placebo-controlled, phase 2 pilot trial | 50 intervention group 51 control group | Moderate–severe | Greater odds of improvement in OSCI scale for intervention group Mortality: 0% vs. 6% Serious adverse effects: 15% vs. 28% |
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Palermo, E.; Di Carlo, D.; Sgarbanti, M.; Hiscott, J. Type I Interferons in COVID-19 Pathogenesis. Biology 2021, 10, 829. https://doi.org/10.3390/biology10090829
Palermo E, Di Carlo D, Sgarbanti M, Hiscott J. Type I Interferons in COVID-19 Pathogenesis. Biology. 2021; 10(9):829. https://doi.org/10.3390/biology10090829
Chicago/Turabian StylePalermo, Enrico, Daniele Di Carlo, Marco Sgarbanti, and John Hiscott. 2021. "Type I Interferons in COVID-19 Pathogenesis" Biology 10, no. 9: 829. https://doi.org/10.3390/biology10090829