ABSTRACT
Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower programmed cell death protein 1 (PD-1) expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM-CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3-HLA-DR- lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4â11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.
Subject(s)
CD8-Positive T-Lymphocytes/virology , COVID-19/blood , Leukocytes, Mononuclear/virology , SARS-CoV-2/pathogenicity , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Cell Lineage/genetics , Cell Lineage/immunology , Female , Gene Expression Regulation/immunology , Granzymes/genetics , Humans , Interferon-gamma/genetics , Leukocytes, Mononuclear/pathology , Male , Middle Aged , T-Box Domain Proteins/genetics , Th1 Cells/immunology , Th1 Cells/virology , Th17 Cells/immunology , Th17 Cells/virology , Th2 Cells/immunology , Th2 Cells/virologyABSTRACT
Today, Coronavirus Disease 2019 (COVID-19) is a global public health emergency and vaccination measures to counter its diffusion are deemed necessary. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the disease, unleashes a T-helper 2 immune response in those patients requiring intensive care. Here, we illustrate the immunological mechanism to train the immune system towards a more effective and less symptomatic T-helper 1 immune response, to be exploited against SARS-CoV-2.
Subject(s)
BCG Vaccine/administration & dosage , Bacterial Vaccines/administration & dosage , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunity, Innate/drug effects , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Propionibacteriaceae/immunology , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Corynebacterium , Humans , Immunization Schedule , Immunogenicity, Vaccine , Interleukins/genetics , Interleukins/immunology , Patient Safety , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/virology , Th1-Th2 Balance/drug effects , Th2 Cells/drug effects , Th2 Cells/immunology , Th2 Cells/virology , Vaccination , Viral Vaccines/administration & dosage , Viral Vaccines/biosynthesisSubject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Fever/immunology , Myalgia/immunology , Olfaction Disorders/immunology , Pneumonia, Viral/immunology , Adult , COVID-19 , Case-Control Studies , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/virology , Disease Progression , Female , Fever/complications , Fever/diagnosis , Fever/virology , Humans , Immunity, Innate , Myalgia/complications , Myalgia/diagnosis , Myalgia/virology , Olfaction Disorders/complications , Olfaction Disorders/diagnosis , Olfaction Disorders/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Pregnancy , SARS-CoV-2 , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/virology , Th1-Th2 Balance , Th2 Cells/immunology , Th2 Cells/virologyABSTRACT
Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.