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      Recent developments in the immunopathology of COVID‐19

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          Abstract

          There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID‐19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID‐19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID‐19. The efficacy of the COVID‐19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID‐19 vaccines have changed the clinical scenario of COVID‐19. Multisystem inflammatory syndrome in children (MIS‐C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long‐term symptoms of COVID‐19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID‐19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID‐19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID‐19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID‐19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID‐19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS‐CoV‐2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high‐risk groups, the development of MIS‐C and long COVID‐19.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

              Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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                Author and article information

                Contributors
                gaoyadong@whu.edu.cn
                Journal
                Allergy
                Allergy
                10.1111/(ISSN)1398-9995
                ALL
                Allergy
                John Wiley and Sons Inc. (Hoboken )
                0105-4538
                1398-9995
                05 December 2022
                February 2023
                : 78
                : 2 ( doiID: 10.1111/all.v78.2 )
                : 369-388
                Affiliations
                [ 1 ] Department of Allergology, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital Third Hospital of Shanxi Medical University Taiyuan China
                [ 2 ] Department of Allergology Zhongnan Hospital of Wuhan University Wuhan China
                [ 3 ] Department of Pediatrics, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital Third Hospital of Shanxi Medical University Taiyuan China
                [ 4 ] Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
                [ 5 ] Division of Pediatric Allergy and Immunology, Department of Pediatrics, Faculty of Medicine University of Kirikkale Kirikkale Turkey
                [ 6 ] Department of Virology, Faculty of Veterinary Medicine University of Kirikkale Kirikkale Turkey
                [ 7 ] Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou China
                [ 8 ] Intensive Care Unit The Second Hospital of Shanxi Medical University Taiyuan China
                Author notes
                [*] [* ] Correspondence

                Ya‐dong Gao, Department of Allergology, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, Hubei, China.

                Email: gaoyadong@ 123456whu.edu.cn

                Author information
                https://orcid.org/0000-0003-2263-6774
                https://orcid.org/0000-0002-4396-9087
                https://orcid.org/0000-0002-5597-8917
                https://orcid.org/0000-0002-1805-4360
                https://orcid.org/0000-0003-0554-9943
                https://orcid.org/0000-0001-8020-019X
                https://orcid.org/0000-0003-1251-7608
                Article
                ALL15593 ALL-2022-00872.R2
                10.1111/all.15593
                10108124
                36420736
                31f1be5e-e434-44e2-9861-dae7ec81692e
                © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 01 November 2022
                : 20 August 2022
                : 22 November 2022
                Page count
                Figures: 4, Tables: 3, Pages: 20, Words: 13770
                Funding
                Funded by: Scientific Research Initiative Funds of Shanxi Bethune Hospital (Number: 2020RC004).
                Funded by: Shanxi Medical University , doi 10.13039/501100008549;
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                February 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:17.04.2023

                Immunology
                allergy,angiotensin‐converting enzyme 2,covid‐19,immunity,vaccine
                Immunology
                allergy, angiotensin‐converting enzyme 2, covid‐19, immunity, vaccine

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