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      Comparative subgenomic mRNA profiles of SARS-CoV-2 Alpha, Delta and Omicron BA.1, BA.2 and BA.5 sub-lineages using Danish COVID-19 genomic surveillance data

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          Abstract

          Background

          Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread worldwide in the population since it was first detected in late 2019. The transcription and replication of coronaviruses, although not fully understood, is characterised by the production of genomic length RNA and shorter subgenomic RNAs to make viral proteins and ultimately progeny virions. Observed levels of subgenomic RNAs differ between sub-lineages and open reading frames but their biological significance is presently unclear.

          Methods

          Using a large and diverse panel of virus sequencing data produced as part of the Danish COVID-19 routine surveillance together with information in electronic health registries, we assessed the association of subgenomic RNA levels with demographic and clinical variables of the infected individuals.

          Findings

          Our findings suggest no significant statistical relationship between levels of subgenomic RNAs and host-related factors.

          Interpretation

          Differences between lineages and subgenomic ORFs may be related to differences in target cell tropism, early virus replication/transcription kinetics or sequence features.

          Funding

          The author(s) received no specific funding for this work.

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          Most cited references51

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          Virological assessment of hospitalized patients with COVID-2019

          Roman Wölfel, Victor M Corman, Wolfgang Guggemos … (2020)
          Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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            Regularization Paths for Generalized Linear Models via Coordinate Descent

            Jerome H. Friedman, Trevor J. Hastie, Robert Tibshirani … (2011)
            Article 0 comments Cited 3334 times – based on 0 reviews     Review now
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              Coronavirus biology and replication: implications for SARS-CoV-2

              Philip V’kovski, Annika Kratzel, Silvio Steiner … (2020)
              The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus–host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.
              Article 0 comments Cited 1229 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): eBioMedicine
                Journal ID (iso-abbrev): EBioMedicine
                Title: eBioMedicine
                Publisher: The Author(s). Published by Elsevier B.V.
                ISSN (Electronic): 2352-3964
                Publication date PMC-release: 20 June 2023
                Publication date (Print): July 2023
                Publication date (Electronic): 20 June 2023
                Volume: 93
                Page: 104669
                Affiliations
                [a ]Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
                [b ]Division of Diagnostic Preparedness, Statens Serum Institut, Copenhagen, Denmark
                Author notes
                [∗ ]Corresponding author.
                Article
                Publisher Item ID: S2352-3964(23)00234-7 Publisher ID: 104669
                DOI: 10.1016/j.ebiom.2023.104669
                PMC ID: 10281627
                SO-VID: 16c7daa6-7507-4c9d-a28c-f07071c66fc2
                Copyright © © 2023 The Author(s)
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 8 February 2023
                Date revision received : 30 May 2023
                Date accepted : 6 June 2023
                Categories
                Subject: Articles

                Keywords: sars-cov-2,subgenomic rna,alpha,delta,omicron,association analysis
                Data availability:
                Keywords: sars-cov-2, subgenomic rna, alpha, delta, omicron, association analysis

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