Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs
Jonathan Lopez, Marine Mommert, William Mouton, Andrés Pizzorno, Karen Brengel‐Pesce, Mehdi Mezidi, Marine Villard, Bruno Lina, Jean‐Christophe Richard, Jean‐Baptiste Fassier, Valérie Cheynet, Blandine Padey, Victoria Dulière, Thomas Julien, Stéphane Paul, Paul Bastard, Alexandre Bélot, Antonin Bal, Jean‐Laurent Casanova, Manuel Rosa‐Calatrava, Florence Morfin, Thierry Walzer, Sophie Trouillet‐Assant
Abstract
IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.