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1.
Bioessays ; 43(2): e2000232, 2021 02.
Article in English | MEDLINE | ID: covidwho-1372696

ABSTRACT

Immunity against SARS-CoV-2 that is acquired by convalescent COVID-19 patients is examined in reference to (A) the Th17 cell generation system in psoriatic epidermis and (B) a recently discovered phenomenon in which Th17 cells are converted into tissue-resident memory T (TRM ) cells with Th1 phenotype. Neutrophils that are attracted to the site of infection secrete IL-17A, which stimulates lung epithelial cells to express CCL20. Natural Th17 (nTh17) cells are recruited to the infection site by CCL20 and expand in the presence of IL-23. These nTh17 cells are converted to TRM cells upon encounter with SARS-CoV-2 and continue to exist as ex-Th17 cells, which exert Th1-like immunity during a memory response. G-CSF can induce nTh17 cell accumulation at the infection site because it promotes neutrophil egress from the bone marrow. Hence, G-CSF may be effective against COVID-19. Administration of G-CSF to patients infected with SARS-CoV-2 is worth a clinical trial.


Subject(s)
Granulocyte Colony-Stimulating Factor/therapeutic use , Neutrophils/immunology , SARS-CoV-2/immunology , Th1 Cells/immunology , Th17 Cells/immunology , COVID-19/drug therapy , COVID-19/immunology , Chemokine CCL20/metabolism , Humans , Immunologic Memory/immunology , Interleukin-17/metabolism , Interleukin-23 Subunit p19/immunology , Neutrophils/drug effects , Th17 Cells/drug effects
2.
J Cell Physiol ; 236(7): 5325-5338, 2021 07.
Article in English | MEDLINE | ID: covidwho-995973

ABSTRACT

In novel coronavirus disease 2019 (COVID-19), the increased frequency and overactivation of T helper (Th) 17 cells and subsequent production of large amounts of proinflammatory cytokines result in hyperinflammation and disease progression. The current study aimed to investigate the therapeutic effects of nanocurcumin on the frequency and responses of Th17 cells in mild and severe COVID-19 patients. In this study, 40 severe COVID-19 intensive care unit-admitted patients and 40 patients in mild condition were included. The frequency of Th17 cells, the messenger RNA expression of Th17 cell-related factors (RAR-related orphan receptor γt, interleukin [IL]-17, IL-21, IL-23, and granulocyte-macrophage colony-stimulating factor), and the serum levels of cytokines were measured in both nanocurcumin and placebo-treated groups before and after treatment. A significant decrease in the number of Th17 cells, downregulation of Th17 cell-related factors, and decreased levels of Th17 cell-related cytokines were found in mild and severe COVID-19 patients treated by nanocurcumin compared to the placebo group. Moreover, the abovementioned parameters were significantly decreased in the nanocurcumin-treated group after treatment versus before treatment. Curcumin could reduce the frequency of Th17 cells and their related inflammatory factors in both mild and severe COVID-19 patients. Hence, it could be considered as a potential modulatory compound in improving the patient's inflammatory condition.


Subject(s)
COVID-19/drug therapy , Curcumin/therapeutic use , Immunomodulation/drug effects , Nanoparticles/therapeutic use , Th17 Cells/drug effects , Adult , Cytokines/metabolism , Female , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Male , Middle Aged , Nanoparticles/administration & dosage , SARS-CoV-2/drug effects , Severity of Illness Index , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/virology , Th17 Cells/metabolism
3.
J Immunother Cancer ; 8(2)2020 12.
Article in English | MEDLINE | ID: covidwho-971586

ABSTRACT

The COVID-19 outbreak caused by SARS-CoV-2 challenges the medical system by interfering with routine therapies for many patients with chronic diseases. In patients with cancer receiving immune checkpoint inhibitors (ICIs), difficulties also arise from the incomplete understanding of the intricate interplay between their routine treatment and pathogenesis of the novel virus. By referring to previous ICI-based investigations, we speculate that ICIs themselves are not linked to high-infection risks of respiratory diseases or inflammation-related adverse effects in patients with cancer. Moreover, ICI treatment may even enhance coronavirus clearance in some patients with malignant tumor by boosting antiviral T-cell responsiveness. However, the 'explosive' inflammation during COVID-19 in some ICI-treated patients with cancer was illustrated as exuberant immunopathological damage or even death. In case of the COVID-19 immunopathogenesis fueled by ICIs, we propose a regular monitor of pathogenic T-cell subsets and their exhaustion marker expression (eg, Th17 and interleukin (IL)-6-producing Th1 subsets with surface programmed death 1 expression) to guide the usage of ICI. Here we aimed to address these considerations, based on available literature and experience from our practice, that may assist with the decision-making of ICI administration during the pandemic.


Subject(s)
Antineoplastic Agents, Immunological/pharmacology , COVID-19/immunology , Cytokine Release Syndrome/prevention & control , Neoplasms/drug therapy , SARS-CoV-2/immunology , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Clinical Decision-Making , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Drug Monitoring , Humans , Lung/diagnostic imaging , Neoplasms/blood , Neoplasms/immunology , Pandemics , Patient Selection , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/isolation & purification , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/drug effects , Th17 Cells/immunology , Th17 Cells/metabolism , Tomography, X-Ray Computed
4.
Front Immunol ; 11: 2056, 2020.
Article in English | MEDLINE | ID: covidwho-769214

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19), a disease which causes severe lung injury and multiple organ damage, presents an urgent need for new drugs. The case severity and fatality of COVID-19 are associated with excessive inflammation, namely, a cytokine storm. Metformin, a widely used drug to treat type 2 diabetes (T2D) mellitus and metabolic syndrome, has immunomodulatory activity that reduces the production of proinflammatory cytokines using macrophages and causes the formation of neutrophil extracellular traps (NETs). Metformin also inhibits the cytokine production of pathogenic Th1 and Th17 cells. Importantly, treatment with metformin alleviates various lung injuries in preclinical animal models. In addition, a recent proteomic study revealed that metformin has the potential to directly inhibit SARS-CoV-2 infection. Furthermore, retrospective clinical studies have revealed that metformin treatment reduces the mortality of T2D with COVID-19. Therefore, metformin has the potential to be repurposed to treat patients with COVID-19 at risk of developing severe illness. This review summarizes the immune pathogenesis of SARS-CoV-2 and addresses the effects of metformin on inhibiting cytokine storms and preventing SARS-CoV-2 infection, as well as its side effects.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Lung Injury/drug therapy , Metformin/therapeutic use , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/antagonists & inhibitors , Drug Repositioning/methods , Extracellular Traps/drug effects , Humans , Immunologic Factors/adverse effects , Immunologic Factors/pharmacology , Inflammation/drug therapy , Macrophages/drug effects , Macrophages/immunology , Metformin/adverse effects , Metformin/pharmacology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Th1 Cells/drug effects , Th1 Cells/immunology , Th17 Cells/drug effects , Th17 Cells/immunology
5.
Aging Clin Exp Res ; 32(10): 2115-2131, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-738008

ABSTRACT

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/diet therapy , Coronavirus Infections/prevention & control , Cytokines/immunology , Pandemics/prevention & control , Pneumonia, Viral/diet therapy , Pneumonia, Viral/prevention & control , Vitamins/immunology , Vitamins/therapeutic use , Aged , Ascorbic Acid/immunology , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Th17 Cells/drug effects , Th17 Cells/immunology , Vitamin A/immunology , Vitamin A/pharmacology , Vitamin A/therapeutic use , Vitamin D/immunology , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamin E/immunology , Vitamin E/pharmacology , Vitamin E/therapeutic use , Vitamins/pharmacology
6.
J Dtsch Dermatol Ges ; 18(8): 795-807, 2020 08.
Article in English | MEDLINE | ID: covidwho-697169

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 has far-reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS-CoV-2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors. Against this background we summarize here the current state of knowledge on the interaction of SARS-CoV-2/COVID-19 with mediators of the acute phase of inflammation (TNF, IL-1, IL-6), type 1 and type 17 immune responses (IL-12, IL-23, IL-17, IL-36), type 2 immune reactions (IL-4, IL-13, IL-5, IL-31, IgE), B-cell immunity, checkpoint regulators (PD-1, PD-L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non-specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte-mediated innate immune mechanisms. From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS-CoV-2/COVID-19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID-19 pandemic; some even appear to alleviate COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/prevention & control , Cytokines/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , COVID-19/therapy , Cytokine Release Syndrome/immunology , Humans , Immunotherapy , Th1 Cells/drug effects , Th1 Cells/immunology , Th17 Cells/drug effects , Th17 Cells/immunology
7.
J Immunol ; 205(4): 892-898, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-638521

ABSTRACT

SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age >65. The mechanisms underlying the susceptibility to critical illness are poorly understood. Of interest, these comorbidities have previously been associated with increased signaling of Th17 cells. Th17 cells secrete IL-17A and are important for clearing extracellular pathogens, but inappropriate signaling has been linked to acute respiratory distress syndrome. Currently there are few treatment options for SARS-CoV-2 infections. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. These findings provide a basis for testing the potential use of therapies directed at modulation of Th17 cells and IL-17A signaling in the treatment of COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Interleukin-17/antagonists & inhibitors , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Th17 Cells/drug effects , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Critical Illness , Female , Humans , Interleukin-17/metabolism , Male , Pandemics , Pneumonia, Viral/virology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/virology , Risk Factors , SARS-CoV-2 , Signal Transduction/drug effects , Signal Transduction/immunology , Th17 Cells/immunology
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