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. 2023 Oct 14:7:100219.
doi: 10.1016/j.jtauto.2023.100219. eCollection 2023 Dec.

Role of autoantibodies targeting interferon type 1 in COVID-19 severity: A systematic review and meta-analysis

Abolfazl Akbari  1 , Alireza Hadizadeh  2   3 , Mahdi Amiri  1 , Neshat Najaf Najafi  1 , Zahra Shahriari  1 , Tannaz Jamialahmadi  4 , Amirhossein Sahebkar  4   5
Affiliations

Role of autoantibodies targeting interferon type 1 in COVID-19 severity: A systematic review and meta-analysis

Abolfazl Akbari et al. J Transl Autoimmun. .

Abstract

Introduction: Impairment of the type I interferon (IFN-I) signaling pathway is associated with increased severity of COVID-19 disease. Here we have undertaken a systematic review and meta = analysis on the association between the severity of COVID-19 and IFN-1 autoantibodies (AAbs; aIFN-1, aIFN-α, aIFN-ω, and aIFN-β).

Methods: Four databases, including Medline [PubMed], Embase, Web of Science, and Scopus, were systematically searched to find papers on the role of aIFN-1 and its subtype AAbs in the severity of COVID-19 infection. Data on the prevalence of aIFN-1, aIFN-α, aIFN-ω, and aIFN-β were pooled using random- or fixed-effects models. Subgroup analysis was performed based on disease severity. Odds ratios (OR) for COVID-19 disease outcome, including length of hospital stay, ICU admission and death, were calculated in relation to positive or negative plasma IFN-1 AAbs.

Results: A total of 33 studies with 13023 patients were included. The overall prevalence of circulating aIFN-1, aIFN-α, and aIFN-ω AAbs was 17.8 % [13.8, 22.8], 7.2 % [4.7, 10.9], and 4.4 % [2.1, 8.6], respectively, and the overall prevalence of neutralizing aIFN-1, aIFN-α, aIFN-ω, and aIFN-β AAbs was 7.1 % [4.9, 10.1], 7.5 % [5.9, 9.5], 8.0 % [5.7, 11.1] and 1.2 % [0.4, 3.5], respectively. Circulating aIFN-α (OR = 4.537 [2.247, 9.158]), neutralizing aIFN-α (O = 17.482 [8.899, 34.342]), and neutralizing aIFN-ω (OR = 12.529 [7.397, 21.222]) were significantly more frequent in critical/severe patients than in moderate/mild patients (p < 0.001 for all). Anti-IFN-1 was more common in male subjects (OR = 2.248 [1.366, 3.699], p = 0.001) and two COVID-19 outcomes including ICU admission (OR = 2.485 [1.409, 4.385], p = 0.002) and death (OR = 2.593 [1.199, 5.604], p = 0.015) occurred more frequently in patients with positive anti-IFN-1.Conclusion: aIFN-1 and its subtypes AAbs are associated with severe and critical COVID-19 disease and may be a predictive marker for a poor prognosis, particularly in men.

Keywords: Autoantibody; COVID-19; Interferon.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram.
Fig. 2
Fig. 2
Prevalence of circulating autoantibodies against interferon α2 (A) and ω (B) in COVID -19 patients with different disease severity.
Fig. 2
Fig. 2
Prevalence of circulating autoantibodies against interferon α2 (A) and ω (B) in COVID -19 patients with different disease severity.
Fig. 3
Fig. 3
Prevalence of neutralizing autoantibodies against interferon α2 (A), ω (B), and β (C) among COVID -19 patients with different disease severity.
Fig. 3
Fig. 3
Prevalence of neutralizing autoantibodies against interferon α2 (A), ω (B), and β (C) among COVID -19 patients with different disease severity.
Fig. 3
Fig. 3
Prevalence of neutralizing autoantibodies against interferon α2 (A), ω (B), and β (C) among COVID -19 patients with different disease severity.
Fig. 4
Fig. 4
Association between sex, death, ICU admission, and length of hospital stay with positive serum autoantibodies against IFN-1 or IFN-α.
Fig. 4
Fig. 4
Association between sex, death, ICU admission, and length of hospital stay with positive serum autoantibodies against IFN-1 or IFN-α.
Fig. 4
Fig. 4
Association between sex, death, ICU admission, and length of hospital stay with positive serum autoantibodies against IFN-1 or IFN-α.
Fig. 5
Fig. 5
Overall prevalence of circulating aIFN-1 (A), aIFN-α (B), and aIFN-ω (C) autoantibodies regardless of disease severity.
Fig. 5
Fig. 5
Overall prevalence of circulating aIFN-1 (A), aIFN-α (B), and aIFN-ω (C) autoantibodies regardless of disease severity.
Fig. 5
Fig. 5
Overall prevalence of circulating aIFN-1 (A), aIFN-α (B), and aIFN-ω (C) autoantibodies regardless of disease severity.
Fig. 6
Fig. 6
Overall prevalence of neutralizing aIFN-1 (A), aIFN-α (B), aIFN-ω (C), and aIFN-β (D) autoantibodies regardless of disease severity.
Fig. 6
Fig. 6
Overall prevalence of neutralizing aIFN-1 (A), aIFN-α (B), aIFN-ω (C), and aIFN-β (D) autoantibodies regardless of disease severity.
Fig. 6
Fig. 6
Overall prevalence of neutralizing aIFN-1 (A), aIFN-α (B), aIFN-ω (C), and aIFN-β (D) autoantibodies regardless of disease severity.
Fig. 6
Fig. 6
Overall prevalence of neutralizing aIFN-1 (A), aIFN-α (B), aIFN-ω (C), and aIFN-β (D) autoantibodies regardless of disease severity.
Fig. 7
Fig. 7
Circulating aIFN-α prevalence in critical/severe patients compared with moderate/mild patients.
Fig. 8
Fig. 8
Neutralizing aIFN-α prevalence in critical/severe patients compared with moderate/mild patients.
Fig. 9
Fig. 9
Circulating aIFN-ω prevalence in critical/severe patients compared with moderate/mild patients.
See this image and copyright information in PMC

References

    1. Organization W.H. 2023. COVID-19 Weekly Epidemiological Update. [141:[
    1. Galani I.-E., Rovina N., Lampropoulou V., Triantafyllia V., Manioudaki M., Pavlos E., et al. Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nat. Immunol. 2021;22(1):32–40. - PubMed
    1. Tajbakhsh A., Gheibi Hayat S.M., Taghizadeh H., Akbari A., Inabadi M., Savardashtaki A., et al. COVID-19 and cardiac injury: clinical manifestations, biomarkers, mechanisms, diagnosis, treatment, and follow up. Expert Rev. Anti-infect. Ther. 2021;19(3):345–357. - PubMed
    1. Ghale R., Spottiswoode N., Anderson M.S., Mitchell A., Wang G., Calfee C.S., et al. Prevalence of type-1 interferon autoantibodies in adults with non-COVID-19 acute respiratory failure. Respir. Res. 2022;23(1):354. - PMC - PubMed
    1. Zhang Q., Pizzorno A., Miorin L., Bastard P., Gervais A., Le Voyer T., et al. Autoantibodies against type I IFNs in patients with critical influenza pneumonia. J. Exp. Med. 2022;219(11) - PMC - PubMed

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