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      Type 2 Diabetes Contributes to Altered Adaptive Immune Responses and Vascular Inflammation in Patients With SARS-CoV-2 Infection

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          Abstract

          SARS-CoV-2, which initially emerged in November of 2019, wreaked havoc across the globe by leading to clinical acute respiratory distress syndrome and continues to evade current therapies today due to mutating strains. Diabetes mellitus is considered an important risk factor for progression to severe COVID disease and death, therefore additional research is warranted in this group. Individuals with diabetes at baseline have an underlying inflammatory state with elevated levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines, both of which cause these individuals to have higher susceptibility to SARS- CoV2 infection. The detrimental effects of SARS-CoV-2 has been attributed to its ability to induce a vast cell mediated immune response leading to a surge in the levels of pro-inflammatory cytokines. This paper will be exploring the underlying mechanisms and pathophysiology in individuals with diabetes and insulin resistance making them more prone to have worse outcomes after SARS- CoV2 infection, and to propose an adjunctive therapy to help combat the cytokine surge seen in COVID-19. It will also look at the immunomodulatory effects of glutathione, an antioxidant shown to reduce immune dysregulation in other diseases; Vitamin D, which has been shown to prevent COVID-19 patients from requiring more intensive care time possibly due to its ability to decrease the expression of certain pro-inflammatory cytokines; and steroids, which have been used as immune modulators despite their ability to exacerbate hyperglycemia.

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          Cell entry mechanisms of SARS-CoV-2

          Significance A key to curbing SARS-CoV-2 is to understand how it enters cells. SARS-CoV-2 and SARS-CoV both use human ACE2 as entry receptor and human proteases as entry activators. Using biochemical and pseudovirus entry assays and SARS-CoV as a comparison, we have identified key cell entry mechanisms of SARS-CoV-2 that potentially contribute to the immune evasion, cell infectivity, and wide spread of the virus. This study also clarifies conflicting reports from recent studies on cell entry of SARS-CoV-2. Finally, by highlighting the potency and the evasiveness of SARS-CoV-2, the study provides insight into intervention strategies that target its cell entry mechanisms.
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            Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

            Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
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              Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China

              An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1424303
                URI : https://loop.frontiersin.org/people/1718114
                URI : https://loop.frontiersin.org/people/1719155
                URI : https://loop.frontiersin.org/people/1417024
                URI : https://loop.frontiersin.org/people/120423
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                24 March 2022
                2022
                24 March 2022
                : 13
                : 833355
                Affiliations
                [1] 1St. Barnabas Hospital Health System, Department of Emergency Medicine , Bronx, NY, United States
                [2] 2Western University of Health Sciences College of Osteopathic Medicine of the Pacific-Pomona , Pomona, CA, United States
                Author notes

                Edited by: Esmaeil Mortaz, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Iran

                Reviewed by: Galileo Escobedo, General Hospital of Mexico, Mexico; Kamlendra Singh, University of Missouri, United States

                *Correspondence: Vishwanath Venketaraman, vvenketaraman@ 123456westernu.edu

                †These authors have contributed equally to this work

                This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.833355
                8986985
                35401518
                9c2acb6e-fd6e-4834-9761-c2389946fb07
                Copyright © 2022 Singh, Barrera Adame, Nickas, Robison, Khatchadourian and Venketaraman

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 December 2021
                : 28 February 2022
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 101, Pages: 11, Words: 0
                Categories
                Immunology
                Review

                Immunology
                type 2 diabetes,sars-cov-2 infection,immune response,inflammation,oxidative stress
                Immunology
                type 2 diabetes, sars-cov-2 infection, immune response, inflammation, oxidative stress

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