Autoantibodies Neutralizing Type I Interferons in 20% of COVID-19 Deaths in a French Hospital.

Angélique Chauvineau-Grenier,Jean-Laurent Casanova,Aurélie Cobat,Jérémie Rosain,Benjamin Rossi,Adrian Gervais,Paul Bastard,Emmanuelle Jouanguy,Antoine Servajean

doi:10.1007/s10875-021-01203-3

Abstract

Recent studies reported the presence of pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in at least 15% of patients with critical COVID-19 pneumonia. In one study, these auto-Abs were found in almost 20% of deceased patients across all ages. We aimed to assess the prevalence and clinical impact of the auto-Abs to type I IFNs in the Seine-Saint-Denis district, which was one of the most affected areas by COVID-19 in France during the first wave. We tested for the presence of auto-Abs neutralizing type I IFNs in a cohort of patients admitted for critical COVID-19 pneumonia during the first wave in the spring of 2020 in the medicine departments at Robert Ballanger Hospital, Aulnay sous Bois. We found circulating auto-Abs that neutralized 100 pg/mL IFN-α2 and/or IFN-ω in the plasma (diluted 1/10) of 7.9% (11 of 139) of the patients hospitalized for critical COVID-19. The presence of neutralizing auto-Abs was associated with an increased risk of mortality, as these auto-Abs were detected in 21% of patients who died from COVID-19 pneumonia. Deceased patients with and without auto-Abs did not present overt clinical differences. These results confirm both the importance of type I IFN immunity in host defense against SARS-CoV-2 infection and the usefulness of detection of auto-Abs neutralizing type I IFNs in the management of patients.

Highlights

Since the onset of the COVID-19 pandemic in December 2019, at least 220 million people have been infected, and most likely many more
A cohort of 246 patients admitted for critical COVID-19 pneumonia was constituted in Robert Ballanger Hospital, Aulnay sous Bois, France, during the first wave of the pandemic in order to assess factors associated with clinical outcomes in patients hospitalized for COVID-19 [16]
We found that 107 (77%) patients with critical COVID-19 have auto-Abs against IFN-α and/or IFN-ω by Gyros technology

Summary

Introduction

Since the onset of the COVID-19 pandemic in December 2019, at least 220 million people have been infected, and most likely many more. Only about 10% of these individuals developed hypoxemic COVID-19 pneumonia (severe or critical in about 3% of cases). There have been at least 5 million deaths, and most likely closer to 8–10 million. The clinical spectrum of SARS-CoV-2 infection is vast, ranging from silent infection to lethal disease. A few epidemiological risk factors have been identified. The most important one is age, with a risk of life-threatening disease doubling every 5 years. Gender as well as several other risk factors have been described (e.g., obesity) but with relatively modest effects [1, 2].

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