Absence of severe COVID-19 in patients with clonal mast cells activation disorders: effective anti-SARS-CoV-2 immune response

• Published in: bioRxiv
• Main Authors: Rossignol, Julien, Ouedrani, Amani, Bulai-Livideanu, Cristina, Barete, Stéphane, Terriou, Louis, Launay, David, Lemal, Richard, Greco, Celine, Frenzel, Laurent, Meni, Cecile, Bodemere-Skandalis, Christine, Polivka, Laura, Anne-Florence Collange, Hassiba Hachichi, Bouzourine, Sonia, Djazira Nait Messaoud, Negretto, Mathilde, Vendrame, Laurence, Jambou, Marguerite, Gousseff, Marie, Durupt, Stéphane, Lega, Jean-Christophe, Durand, Jean-Marc, Gaudy, Caroline, Gandhi Damaj, Marie-Pierre Gourin, Hamidou, Mohamed, Bouillet, Laurence, Edwige Le Mouel, Alexandre, Maria, Zunic, Patricia, Cabrera, Quentin, Vincent, Denis, Lavigne, Christian, Riviere, Etienne, Clement Gourguechon, Brignier, Anne, Lhermitte, Ludovic, Molina, Thierry J, Bruneau, Julie, Agopian, Julie, Dubreuil, Patrice, Ranta, Dana, Mania, Alexandre, Arock, Michel, Staropoli, Isabelle, Tournilhac, Olivier, Lortholary, Olivier, Schwartz, Olivier, Chatenoud, Lucienne, Olivier Hermine
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 01.09.2021; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Adaptive immunity; Antiviral agents; Cell activation; Coronaviridae; Coronaviruses; COVID-19; Enzyme-linked immunosorbent assay; Immune response; Immune response (humoral); Immunoglobulin A; Immunoglobulin G; Immunology; Innate immunity; Lymphocytes T; Mast cells; Mastocytosis; Mechanical ventilation; Patients; Severe acute respiratory syndrome coronavirus 2; Tryptase; γ-Interferon; COVID-19; Mast cells activation disorders; T-cells; Mastocytosis; Clonal mast cells activation syndrome; B-cells; SARS-CoV-2; Mast cells; Endemic coronaviruses
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2021.09.01.458516

Mast cells are key actors of innate immunity and Th2 adaptive immune response which counterbalance Th1 response, critical for anti-viral immunity. Clonal Mast Cells Activation Disorders (cMCADs) such as mastocytosis and clonal mast cells activation syndrome are characterized by an abnormal mast cells accumulation and/or activation. No data have been published on the anti-viral immune response of patients with cMCADs. The aims of the study were to collected, in a comprehensive way, outcomes of cMCADs patients who experienced a biologically-proven COVID-19 and to characterize both anti-endemic coronaviruses and specific anti-SARS-CoV-2 immune responses in these patients. Clinical follow-up and outcome data were collected prospectively for one year within the French rare disease network CEREMAST encompassing patients from all over the country. Anti-SARS-CoV-2 and anti-endemic coronaviruses specific T-cells were assessed with an enzyme-linked immunospot assay (EliSpot) and anti-SARS-CoV-2 humoral response with dosage of circulating levels of specific IgG, IgA and neutralizing antibodies. Overall, 32 cMCADs patients were identified. None of them required non-invasive or mechanical ventilation; two patients were hospitalized to receive oxygen and steroid therapy. In 21 patients, a characterization of the SARS-CoV-2-specific immune response has been performed. A majority of patients showed a high proportion of circulating SARS-CoV-2-specific interferon (IFN)-γ producing T-cells and high levels of anti-Spike IgG antibodies with neutralizing activity. In addition, no defects in anti-endemic coronaviruses responses were found in patients with cMCADs compared to non-cMCADs controls. Patients with cMCADs frequently showed a spontaneous IFN-γ T-cell production in absence of any stimulation that correlated with circulating basal tryptase levels, a marker of mast cells burden. These findings underscore that patients with cMCADs might be not at risk of severe COVID-19 and the spontaneous IFN-γ production might explain this observation. Competing Interest Statement The authors have declared that no competing interests exist.