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      COVID-19 vaccination and myocarditis: A review of current literature

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          Abstract

          Vaccination for coronavirus disease 2019 (COVID-19) is a critical strategy in controlling the current pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). After widespread COVID-19 vaccine imple-mentation, isolated case reports about myocarditis as a potential adverse reaction started coming. As of November 12, 2021, Centers for Disease Control and Prevention (CDC) has reported 1793 cases of myocarditis or pericarditis among young people with age 12-29 years, most cases have been reported in the male adolescent age group after the second dose of mRNA COVID-19 vaccines. It is very important to monitor the safety standards and adverse reactions of vaccines to effectively implement the vaccination policies. The CDC and the United States Food and Drug Administration actively monitor vaccine-associated adverse reactions a well-known platform such as Vaccine Adverse Event Reporting System. CDC continues to recommend COVID-19 vaccines and booster doses for eligible individuals (age limit according to the type of vaccine) after careful consideration from risk-benefit assessment and favorable outcomes from vaccination. Mechanisms behind COVID-19 vaccine-induced myocarditis are not clear yet but several possibilities such as molecular mimicry between the spike protein of SARS-CoV-2 and self-antigens, immune response to mRNA, and activation of host immunological system, trigger of the pre-existing dysregulated immunological system have been documented in the literature. Overall, data suggests a good prognosis, especially in young patients. In this review article, we cover currently available data on COVID-19 vaccine-related myocarditis incidence, concerns, possible mechanisms of myocarditis, current treatment, and outcome trends, risk vs benefit assessment of COVID-19 vaccination in this current pandemic.

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          Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA.

          DNA and RNA stimulate the mammalian innate immune system through activation of Toll-like receptors (TLRs). DNA containing methylated CpG motifs, however, is not stimulatory. Selected nucleosides in naturally occurring RNA are also methylated or otherwise modified, but the immunomodulatory effects of these alterations remain untested. We show that RNA signals through human TLR3, TLR7, and TLR8, but incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine ablates activity. Dendritic cells (DCs) exposed to such modified RNA express significantly less cytokines and activation markers than those treated with unmodified RNA. DCs and TLR-expressing cells are potently activated by bacterial and mitochondrial RNA, but not by mammalian total RNA, which is abundant in modified nucleosides. We conclude that nucleoside modifications suppress the potential of RNA to activate DCs. The innate immune system may therefore detect RNA lacking nucleoside modification as a means of selectively responding to bacteria or necrotic tissue.
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            Myocarditis With COVID-19 mRNA Vaccines

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              Myocarditis after Covid-19 Vaccination in a Large Health Care Organization

              Background Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored. Methods We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer–BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient’s electronic health record. We performed a Kaplan–Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose. Results Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function. Conclusions Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)
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                Author and article information

                Contributors
                Journal
                World J Virol
                WJV
                World Journal of Virology
                Baishideng Publishing Group Inc
                2220-3249
                25 July 2022
                25 July 2022
                : 11
                : 4
                : 170-175
                Affiliations
                Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18702, United States. kartikdhaduk@ 123456gmail.com
                Department of Cardiology, University of Oklahoma, Oklahoma, OK 73019, United States
                Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18702, United States
                Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18702, United States
                Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18702, United States
                Department of Internal Medicine, Carolina East Medical Center, North Carolina, NC 28560, United States
                Department of Medicine, Westchester Medical Center, Valhalla, NY 10595, United States
                Department of Internal Medicine, University of New Mexico, New Mexico, NM 87106, United States
                Author notes

                Author contributions: Dhaduk K conceptualized the manuscript; Dhaduk K, Khosla J, Hussain M and Mangaroliya V wrote the manuscript; Chauhan S, Kumar A and Gupta R performed the literature review, concept modification; Pal S provided expert review of the manuscript; All authors have read and approved the final manuscript.

                Corresponding author: Kartik Dhaduk, MD, Staff Physician, Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, 1000 E Mountain Dr, Wilkes-Barre, PA 18702, United States. kartikdhaduk@ 123456gmail.com

                Article
                jWJV.v11.i4.pg170
                10.5501/wjv.v11.i4.170
                9372786
                e9ea8ae3-31bc-4e9d-afd1-133f99bda800
                ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 24 December 2021
                : 25 March 2022
                : 22 May 2022
                Categories
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                coronavirus disease 2019 vaccine,myocarditis,mrna vaccine,severe acute respiratory syndrome coronavirus-2,vaccine complications,risk assessment

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