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13.04.2021 | COVID-19 | Original Article Zur Zeit gratis

Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain

verfasst von: Jesús Troya, Paul Bastard, Laura Planas-Serra, Pablo Ryan, Montse Ruiz, María de Carranza, Juan Torres, Amalia Martínez, Laurent Abel, Jean-Laurent Casanova, Aurora Pujol

Erschienen in: Journal of Clinical Immunology | Ausgabe 5/2021

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Abstract

Background

In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta.

Objectives

We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes.

Methods

We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain.

Results

The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%), while they were not found in any of the 118 asymptomatic controls (p = 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p = 5.10e⁻⁰³) and lower lymphocyte counts (p = 1.80e⁻⁰²). No significant association with response to IFN-beta-1b therapy (p = 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%).

Conclusion

Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.

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WHO. Coronavirus disease 2019 (COVID-19). Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed 22 Feb 2021.

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4. https://doi.org/10.1016/S0140-6736(20)30628-0.CrossRefPubMedPubMedCentral

Ciancanelli MJ, Abel L, Zhang SY, Casanova JL. Host genetics of severe influenza: from mouse Mx1 to human IRF7. Curr Opin Immunol. 2016;38:109–20. https://doi.org/10.1016/j.coi.2015.12.002.CrossRefPubMedPubMedCentral

Jouanguy E, Béziat V, Mogensen TH, Casanova JL, Tangye SG, Zhang SY. Human inborn errors of immunity to herpes viruses. Curr Opin Immunol. 2020;62:106–22. https://doi.org/10.1016/j.coi.2020.01.004.CrossRefPubMedPubMedCentral

Ku CL, Chi CY, von Bernuth H, Doffinger R. Autoantibodies against cytokines: phenocopies of primary immunodeficiencies? Hum Genet. 2020;139(6–7):783–94. https://doi.org/10.1007/s00439-020-02180-0.CrossRefPubMedPubMedCentral

Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585. https://doi.org/10.1126/science.abd4585.CrossRefPubMedPubMedCentral

Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4570. https://doi.org/10.1126/science.abd4570.CrossRefPubMedPubMedCentral

Zhang Q, Bastard P, Bolze A, Jouanguy E, Zhang SY, COVID Human Genetic Effort, et al. Life-threatening COVID-19: defective interferons unleash excessive inflammation. Med (NY). 2020;1(1):14–20. https://doi.org/10.1016/j.medj.2020.12.001.CrossRef

Mesev EV, LeDesma RA, Ploss A. Decoding type I and III interferon signalling during viral infection. Nat Microbiol. 2019 Jun;4(6):914–24. https://doi.org/10.1038/s41564-019-0421-x.CrossRefPubMedPubMedCentral

10.

Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004;31:69–75. https://doi.org/10.1016/j.jcv.2004.03.003.CrossRefPubMedPubMedCentral

11.

Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Inf Secur. 2013;67:606–16. https://doi.org/10.1016/j.jinf.2013.09.029.CrossRef

12.

Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59:252–6. https://doi.org/10.1136/thorax.2003.012658.CrossRefPubMedPubMedCentral

13.

Jiménez E, Fontán-Vela M, Valencia J, Fernandez-Jimenez I, Álvaro-Alonso EA, Izquierdo-García E, et al. Characteristics, complications and outcomes among 1549 patients hospitalised with COVID-19 in a secondary hospital in Madrid, Spain: a retrospective case series study. BMJ Open. 2020;10(11):e042398. https://doi.org/10.1136/bmjopen-2020-042398.CrossRefPubMed

14.

Clinical Spectrum of SARS-CoV-2 Infection. Available at: https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/. Accessed 22 Feb 2021.

15.

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81. https://doi.org/10.1016/j.jbi.2008.08.010.CrossRefPubMed

16.

Ruiz-Antorán B, Sancho-López A, Torres F, Moreno-Torres V, de Pablo-López I, García-López P, et al. Combination of tocilizumab and steroids to improve mortality in patients with severe COVID-19 infection: a Spanish, multicenter, cohort study. Infect Dis Ther. 2020;10:1–16. https://doi.org/10.1007/s40121-020-00373-8.CrossRef

17.

Smoke SM, Raja K, Hilden P, Daniel NM. Early clinical outcomes with tocilizumab for severe Covid-19: a two-center retrospective study. Int J Antimicrob Agents. 2020;57(2):106265. https://doi.org/10.1016/j.ijantimicag.2020.CrossRefPubMedPubMedCentral

18.

Nielsen Jeschke K, Bonnesen B, Hansen EF, Jensen JS, Lapperre TS, Weinreich UM, et al. Guideline for the management of COVID-19 patients during hospital admission in a non-intensive care setting. Eur Clin Respir J. 2020;7(1):1761677. https://doi.org/10.1080/20018525.2020.1761677.CrossRefPubMedPubMedCentral

19.

Barek MA, Aziz MA, Islam MS. Impact of age, sex, comorbidities and clinical symptoms on the severity of COVID-19 cases: a meta-analysis with 55 studies and 10014 cases. Heliyon. 2020;6(12):e05684. https://doi.org/10.1016/j.heliyon.2020.e05684.CrossRefPubMedPubMedCentral

20.

Petrilli CM, Jones SA, Yang J, Rajagopalan H, O'Donnell L, Chernyak Y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966. https://doi.org/10.1136/bmj.m1966.CrossRefPubMedPubMedCentral

21.

Qu R, Hu L, Ling Y, Fang H, Zhang H, Liang S, et al. C-reactive protein concentration as a risk predictor of mortality in intensive care unit: a multicenter, prospective, observational study. BMC Anesthesiol. 2020;20(1):292. https://doi.org/10.1186/s12871-020-01207.CrossRefPubMedPubMedCentral

22.

Tang Y, Li Y, Sun J, Pan H, Yao F, Jiao X. Selection of an optimal combination panel to better triage COVID-19 hospitalized patients. J Inflamm Res. 2020;13:773–87. https://doi.org/10.2147/JIR.S273193.CrossRefPubMedPubMedCentral

23.

Cao P, Wu Y, Wu S, Wu T, Zhang Q, Zhang R, et al. Elevated serum ferritin level effectively discriminates severity illness and liver injury of coronavirus disease 2019 pneumonia. Biomarkers. 2020;26:1–18. https://doi.org/10.1080/1354750X.2020.1861098.CrossRef

24.

Sallard E, Lescure FX, Yazdanpanah Y, Mentre F, Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antivir Res. 2020;178:104791. https://doi.org/10.1016/j.antiviral.2020.104791.CrossRefPubMed

25.

Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY, et al. 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):1695–04. https://doi.org/10.1016/S0140-6736(20)31042-4.CrossRefPubMedPubMedCentral

26.

Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, et al. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med. 2020;180(10):1345–55. https://doi.org/10.1001/jamainternmed.2020.3539.CrossRefPubMed

27.

Mussini C, Cozzi-Lepri A, Menozzi M, Meschiari M, Franceschini E, Rogati C, et al. Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator. Clin Microbiol Infect. 2020:S1198-743X(20)30765–5. https://doi.org/10.1016/j.cmi.2020.12.010.

28.

Meyerowitz-Katz G, Merone L. A systematic review and meta-analysis of published research data on COVID-19 infection fatality rates. Int J Infect Dis. 2020;101:138–48. https://doi.org/10.1016/j.ijid.2020.09.1464.CrossRefPubMedPubMedCentral

29.

Filardo TD, Khan MR, Krawczyk N, Galitzer H, Karmen-Tuohy S, Coffee M, et al. Comorbidity and clinical factors associated with COVID-19 critical illness and mortality at a large public hospital in New York City in the early phase of the pandemic (March-April 2020). PLoS One. 2020;15(11):e0242760. https://doi.org/10.1371/journal.pone.0242760.CrossRefPubMedPubMedCentral

30.

Bastard P, Lévy R, Henriquez S, Bodemer C, Szwebel T-A, Casanova JL, et al. Interferon-β therapy in a patient with Incontinentia Pigmenti and autoantibodies against type I IFNs infected with SARS-CoV-2. JoCI. 2021; 25:1–3. https://doi.org/10.1007/s10875-021-01023-5.

Titel: Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain
verfasst von: Jesús Troya
Paul Bastard
Laura Planas-Serra
Pablo Ryan
Montse Ruiz
María de Carranza
Juan Torres
Amalia Martínez
Laurent Abel
Jean-Laurent Casanova
Aurora Pujol
Publikationsdatum: 13.04.2021
Verlag: Springer US
Schlagwort: COVID-19
Erschienen in: Journal of Clinical Immunology / Ausgabe 5/2021
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-021-01036-0

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Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain

Abstract

Background

Objectives

Methods

Results

Conclusion

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Abstract

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Conclusion

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