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      Comparison of secondary attack rate and viable virus shedding between patients with SARS‐CoV‐2 Delta and Omicron variants: A prospective cohort study

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          Abstract

          There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID‐19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS‐CoV‐2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID‐19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1−7], vs. 8.5 days, IQR [5–12 days], p < 0.001). Multivariable analysis revealed that moderate‐to‐critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster‐vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.

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          Is Open Access

          Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

          The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations in its spike protein 2 . Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
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            Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors

            This review summarizes current knowledge about the transmission of SARS-CoV-2. Evidence-based policies and practices should incorporate the accumulating knowledge regarding SARS-CoV-2 transmission to help educate the public and slow spread of this virus.
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              Continuous and Discontinuous RNA Synthesis in Coronaviruses.

              Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein-RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize cis-acting RNA elements mainly located in the highly structured 5' and 3' untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.
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                Author and article information

                Contributors
                manseong.park@gmail.com
                kimsunghanmd@hotmail.com
                Journal
                J Med Virol
                J Med Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                10 December 2022
                January 2023
                10 December 2022
                : 95
                : 1 ( doiID: 10.1002/jmv.v95.1 )
                : e28369
                Affiliations
                [ 1 ] Department of Infectious Diseases, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea
                [ 2 ] Department of Biomedical Sciences, BK21 Graduate Program Korea University College of Medicine Seoul Republic of Korea
                [ 3 ] Department of Microbiology, Institute for Viral Diseases, Vaccine Innovation Center, College of Medicine Korea University Seoul South Korea
                Author notes
                [*] [* ] Correspondence Man‐Seong Park, Department of Microbiology, Institute for Viral Diseases, Vaccine Innovation Center, College of Medicine, Korea University, 73 Goryeodae‐ro, Seongbuk‐gu, Seoul 02841, South Korea.

                Email: manseong.park@ 123456gmail.com

                Sung‐Han Kim, Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic‐ro‐43‐gil, Songpa‐gu, Seoul 05505, Republic of Korea.

                Email: kimsunghanmd@ 123456hotmail.com

                Author information
                https://orcid.org/0000-0002-6596-8253
                Article
                JMV28369
                10.1002/jmv.28369
                9877691
                36458559
                0ce433b0-299d-4434-8955-c2dcaa643ff6
                © 2022 Wiley Periodicals LLC.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 12 November 2022
                : 03 August 2022
                : 28 November 2022
                Page count
                Figures: 2, Tables: 2, Pages: 10, Words: 5760
                Funding
                Funded by: Korea Health Industry Development Institute , doi 10.13039/501100003710;
                Funded by: National Research Foundation of Korea , doi 10.13039/501100003725;
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                January 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.4 mode:remove_FC converted:26.01.2023

                Microbiology & Virology
                covid‐19,infection dynamics,virus shedding
                Microbiology & Virology
                covid‐19, infection dynamics, virus shedding

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