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      SARS-CoV-2 Disease through Viral Genomic and Receptor Implications: An Overview of Diagnostic and Immunology Breakthroughs

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          Abstract

          The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which is believed to have originated in China towards the end of November 2019, has now spread across the globe, causing a pandemic in 192 countries. The World Health Organization has called it the SARS-CoV-2 pandemic. Rapid dissemination of the virus occurs mainly through the saliva (Flügge’s droplets) and aerosol, together with nasal and lachrymal passages. The literature associated with the recent advancement in terms of rapid diagnostics and SARS-CoV-2 vaccines has thoroughly studied the role of ACE2 receptors and Furin, as well as viral agent access into the host cell and its significant persistence at the level of the oral mucosa, which represents the main access to the virus. The purpose of this review was to underline the processes of SARS-CoV-2 infection mechanisms and novel breakthroughs in diagnostics and vaccines. Different technologies, such as the RT-PCR molecular test and the antigenic test, have been developed to identify subjects affected by the SARS-CoV-2 in order to improve the tracking of infection geographical diffusion. Novel rapid and highly sensitive diagnostic tests has been proposed for the detection of SARS-CoV-2 to improve the screening capability of suspected contagions. The strengthening of the vaccination campaign represents the most effective means to combat the SARS-CoV-2 infection and prevent severe manifestations of the virus—different classes of vaccines have been developed for this purpose. Further attention on the novel SARS-CoV-2 variant is necessary in order to verify the protection efficacy and virulence reduction of the infective agent in the recent vaccine campaign.

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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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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

              Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                10 April 2021
                April 2021
                : 9
                : 4
                : 793
                Affiliations
                [1 ]Department of Interdisciplinary Medicine, University of Medicine Aldo Moro, 70124 Bari, Italy; ad.inchingolo@ 123456libero.it (A.D.I.); angeloinchingolo@ 123456gmail.com (A.M.I.); drciroisacco@ 123456gmail.com (C.G.I.); graziamarinelli@ 123456live.it (G.M.); mtdoria51@ 123456gmail.com (M.T.D.); denisahazballa@ 123456gmail.com (D.H.); luigi.santacroce@ 123456uniba.it (L.S.); francesco.inchingolo@ 123456uniba.it (F.I.); giannadipalma@ 123456tiscali.it (G.D.)
                [2 ]Department of Oral Rehabilitation, Faculty of Dentistry, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
                [3 ]Department of Dental Prosthesis, Medical University of Tirana, Rruga e Dibrës, U.M.T., 1001 Tirana, Albania; editxhajanka@ 123456yahoo.com
                [4 ]Department of Innovative Technologies in Medicine and Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy; a.scarano@ 123456unich.it
                [5 ]UOC Maxillo-Facial Surgery and Dentistry, Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, University of Milan, 20100 Milan, Italy; marco.farronato@ 123456unimi.it (M.F.); gianluca.tartaglia@ 123456unimi.it (G.M.T.)
                [6 ]Director of Research at Human Stem Cells Research Center HSC, Ho Chi Minh 70000, Vietnam
                [7 ]Embryology and Regenerative Medicine and Immunology at Pham Chau Trinh University of Medicine, Hoi An 51300, Vietnam
                [8 ]Department of Medical and Biological Sciences, University of Udine, Via delle Scienze, 206, 33100 Udine, Italy
                [9 ]Kongresi Elbasanit, Rruga: Aqif Pasha, 3001 Elbasan, Albania
                [10 ]Department of Biosciences, Biotechnologies and Biopharmaceutics, Campus Universitario Ernesto Quagliariello, University of Bari “Aldo Moro”, 70125 Bari, Italy; andrea.ballini@ 123456uniba.it
                [11 ]Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
                [12 ]Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania Luigi Vanvitelli, Via Luigi de Crecchio, 6, 80138 Naples, Italy; maria.contaldo@ 123456unicampania.it
                Author notes
                [* ]Correspondence: roxana.bordea@ 123456ymail.com (I.R.B.); giuseppinamalcangi@ 123456libero.it (G.M.); felice.lorusso@ 123456unich.it or drlorussofelice@ 123456gmail.com (F.L.); Tel.: +40-74-4919319 (I.R.B.); +39-34-0334-8500 (G.M.); +39-32-8213-2586 (F.L.)
                [†]

                These authors contributed equally to this work as co-first authors.

                [‡]

                These authors contributed equally to this work as co-last authors.

                Author information
                https://orcid.org/0000-0002-6366-1039
                https://orcid.org/0000-0001-7166-9949
                https://orcid.org/0000-0001-9745-7506
                https://orcid.org/0000-0002-0843-5231
                https://orcid.org/0000-0002-6209-9873
                https://orcid.org/0000-0001-9163-2350
                https://orcid.org/0000-0002-9376-8152
                https://orcid.org/0000-0002-8160-3342
                https://orcid.org/0000-0001-5671-8124
                https://orcid.org/0000-0001-8758-1415
                https://orcid.org/0000-0002-4773-6694
                https://orcid.org/0000-0003-3797-5883
                https://orcid.org/0000-0002-5947-8987
                Article
                microorganisms-09-00793
                10.3390/microorganisms9040793
                8070527
                33920179
                10d11355-8013-4685-9046-51454b390de5
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 14 March 2021
                : 07 April 2021
                Categories
                Review

                sars-cov-2 (covid-19 pandemic),ace2,tmprss2,oral mucosa (salivary glands),furin,cytokine storm syndrome (css),microbiome,vaccines

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