Reduced replication but increased interferon resistance of SARS-CoV-2 Omicron BA.1

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The IFN system constitutes a powerful antiviral defense machinery. Consequently, effective IFN responses protect against severe COVID-19 and exogenous IFNs inhibit SARS-CoV-2 in vitro. However, emerging SARS-CoV-2 variants of concern (VOCs) may have evolved reduced IFN sensitivity. Here, we determined differences in replication and IFN susceptibility of an early SARS-CoV-2 isolate (NL-02-2020) and the Alpha, Beta, Gamma, Delta, and Omicron VOCs in Calu-3 cells, iPSC-derived alveolar type-II cells (iAT2) and air–liquid interface (ALI) cultures of primary human airway epithelial cells. Our data show that Alpha, Beta, and Gamma replicated to similar levels as NL-02-2020. In comparison, Delta consistently yielded higher viral RNA levels, whereas Omicron was attenuated. All viruses were inhibited by type-I, -II, and -III IFNs, albeit to varying extend. Overall, Alpha was slightly less sensitive to IFNs than NL-02-2020, whereas Beta, Gamma, and Delta remained fully sensitive. Strikingly, Omicron BA.1 was least restricted by exogenous IFNs in all cell models. Our results suggest that enhanced innate immune evasion rather than higher replication capacity contributed to the effective spread of Omicron BA.1.

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  1. SciScore for 10.1101/2021.11.16.468777: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationFirst, 1 µl random hexamers (50 ng/µl), 1 µl dNTPs mix (10 mM each), and 11 µl template RNA (diluted 1:10 in DNase/RNase free water) were mixed, incubated at 65°C for 5 min and placed on ice for 1 min.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    Vero E6 cells (Cercopithecus aethiops derived epithelial kidney, ATCC) and TMPRSS2-expressing Vero E6 cells (kindly provided by the National Institute for Biological Standards and Control (NIBSC), No. 100978) were grown in Dulbecco’s modified Eagle’s medium (DMEM, Gibco, Cat#41965039) supplemented with 2.5% (upon and after viral infection) or 10% (during all other times) heat-inactivated FBS (Gibco, Cat#10270106), 100 units/ml penicillin, 100 µg/ml streptomycin (ThermoFisher, Cat#15140122), 2 mM L-glutamine (Gibco, Cat#25030081), 1 mM sodium pyruvate (Pan Biotech, Cat# P04-8010), 1x non-essential amino acids (Sigma, Cat#M7145) and 1 mg/mL Geneticin (Gibco, Cat#10131-019) (for TMPRSS2-expressing Vero E6 cells).
    Vero E6
    suggested: RRID:CVCL_XD71)
    Caco-2 cells (human epithelial colorectal adenocarcinoma, kindly provided by Prof. Holger Barth (Ulm University)) were grown in the same media as Vero E6 cells but with supplementation of 10% heat-inactivated FBS.
    suggested: None
    24 h post-seeding, Calu-3 cells were infected with the different variants of SARS-CoV-2 (MOI 0.05).
    suggested: BCRJ Cat# 0264, RRID:CVCL_0609)
    Software and Algorithms
    The obtained sequenced reads were demultiplexed and mapped against the SARS-CoV-2 reference genome (NC_045512.2) with BWA-MEM[36].
    suggested: None
    The mapped reads and the pileup file were used to construct the consensus sequence with the iVar package[38] using default settings.
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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