The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as coronavirus disease-2019 (COVID-19). SARS-CoV-2 infects the lungs and may cause several immune-related complications such as lymphocytopenia and cytokine storm which are associated with the severity of the disease and predict mortality . The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is not fully understood. Here we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells in a mechanism that also requires ACE2 and TMPRSS2. Once inside T helper cells, SARS-CoV-2 assembles viral factories, impairs cell function and may cause cell death. SARS-CoV-2 infected T helper cells express higher amounts of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID- 19 patients.
BackgroundEmerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) pathogenesis.ObjectiveTo investigate whether CD19+ B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8+ T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients.MethodsIn this study, 104 RRMS patients during different treatments and 58 healthy donors were included. CD8, CD19, Runx3, and GzmB expression was assessed by flow cytometry analyses.ResultsRRMS patients during fingolimod (FTY) and natalizumab (NTZ) treatment showed increased percentage of circulating CD8+GzmB+ T lymphocytes when compared to healthy volunteers. An increase in circulating CD19+GzmB+ B cells was observed in RRMS patients during FTY and NTZ therapies when compared to glatiramer (GA), untreated RRMS patients, and healthy donors but not when compared to interferon-β (IFN). Moreover, regarding Runx3, the transcriptional factor classically associated with cytotoxicity in CD8+ T lymphocytes, the expression of GzmB was significantly higher in CD19+Runx3+-expressing B cells when compared to CD19+Runx3- counterparts in RRMS patients.ConclusionsCD19+ B cells may exhibit cytotoxic behavior resembling CD8+ T lymphocytes in MS patients during different treatments. In the future, monitoring “cytotoxic” subsets might become an accessible marker for investigating MS pathophysiology and even for the development of new therapeutic interventions.
To the Editor, We read with interest the report by Blagova et al. 1 and would like to share some ideas and comments regarding the immunological features possibly involved in the post-COVID manifestations. The authors showed the detection of SARS-CoV-2 RNA in 12 of 14 patients exhibiting longterm post-COVID-19 myocarditis (diagnosed 2-18 months after the acute infection). Although these individuals did not present severe respiratory failure or cardiac injury in the acute phase, the biopsies (performed 5.5 months later) revealed viral particles, along with lymph histiocytic elements (with eosinophils and mainly macrophages, T-lymphocytes, and B cells in the infiltrates). Coronariitis, microvascular thrombosis and parietal thrombi in the right ventricle were also observed. Strikingly, high levels of antiheart (AHA) autoantibodies (auto-Abs) were detected in 93% of patients. The authors suggested that this could be involved in the physiopathology of post-COVID-19 myocarditis (summarized in Figure 1). Interestingly, Fagyas et al. 2 recently reported the occurrence of AHA in 68% of patients during the severe clinical course of COVID-19. In this cohort, the IgM isotype was more prevalent (51%) than IgG (39%). The authors did not find any apparent correlation between COVID-19
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