Absence of severe COVID-19 in patients with clonal mast cells activation disorders: effective anti-SARS-CoV-2 immune response
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Abstract
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.
Author Summary
Mast cells are immune cells involved in many biological processes including the anti-microbial response. However, previous studies suggest that mast cells may have a detrimental role in the response against viruses such as SARS-CoV-2, responsible for COVID-19. When a mutation occurs in mast cells, it can lead to a group of diseases called clonal mast cells activation disorders (cMCADs), characterized by deregulated activation of these cells. Hence, patients with cMCADs might be more susceptible to severe COVID-19 than general population.
We therefore conducted a 1-year study in France to collect data from all cMCADs patients included in the CEREMAST rare disease French network and who experienced COVID-19. Interestingly, we did not find any severe COVID-19 (i.e. requiring non-invasive or mechanical ventilation) in spite of well-known risk factors for severe COVID-19 in a part of cMCADs patients.
We then have studied the immune response against SARS-CoV-2 and other endemic coronaviruses in these patients. We did not observe any abnormalities in the immune response either at the level of T and B lymphocytes. These findings underscore that these patients might not be at risk of severe COVID-19 as one might have feared.
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SciScore for 10.1101/2021.09.01.458516: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the ethics committee of Necker Hospital and was carried out in compliance with the Declaration of Helsinki Principles protocol.
Consent: A written informed consent was obtained (Comité de Protection des Personnes N°93-00).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Humoral characterization, including anti-Spike SARS-CoV-2 IgG and IgA antibodies detection and neutralizing ability of anti-Spike IgG determination, was performed using previously described techniques: S-flow assay and S-pseudotype neutralization … SciScore for 10.1101/2021.09.01.458516: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the ethics committee of Necker Hospital and was carried out in compliance with the Declaration of Helsinki Principles protocol.
Consent: A written informed consent was obtained (Comité de Protection des Personnes N°93-00).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Humoral characterization, including anti-Spike SARS-CoV-2 IgG and IgA antibodies detection and neutralizing ability of anti-Spike IgG determination, was performed using previously described techniques: S-flow assay and S-pseudotype neutralization assays(24). anti-Spike SARS-CoV-2 IgGsuggested: (Sino Biological Cat# 40592-R001, RRID:AB_2857936)IgAsuggested: Noneanti-Spike IgGsuggested: NoneThe viral pseudotypes were incubated with sera to be tested (at a 1:100 dilution), then added on transduced HEK 293T-cells expressing ACE2 and incubated for 48h at 37°c. The test measures the ability of anti-S antibodies to neutralize infection. anti-Ssuggested: NoneExperimental Models: Cell Lines Sentences Resources Pools of peptides derived from Spike glycoprotein of common Human alpha-coronavirus (HCoV-229E and HCoV-NL63) and beta-coronavirus (HCoV-OC43 and HCoV-HKU1) were also tested. HCoV-229Esuggested: NoneBriefly, S-Flow assay used transduced Human embryonic kidney (HEK) 293T-cells encoding SARS-CoV-2 Spike protein. HEKsuggested: NoneThe viral pseudotypes were incubated with sera to be tested (at a 1:100 dilution), then added on transduced HEK 293T-cells expressing ACE2 and incubated for 48h at 37°c. The test measures the ability of anti-S antibodies to neutralize infection. HEK 293T-cellssuggested: NoneSoftware and Algorithms Sentences Resources Positive controls were phytohemagglutinin PHA-P (Sigma-Aldrich) and CEFX Ultra SuperStim Pool (JPT Peptide Technologies GmbH, BioNTech BioNTechsuggested: NoneStatistics: Statistical analyses were performed using GraphPadPrism (version 6.0; GraphPad Software). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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