Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients

  1. Konstantina Kitsou
  2. Anastasia Kotanidou
  3. Dimitrios Paraskevis
  4. Timokratis Karamitros
  5. Aris Katzourakis
  6. Richard Tedder
  7. Tara Hurst
  8. Spyros Sapounas
  9. Athanassios Kotsinas
  10. Vassilis Gorgoulis
  11. Vana Spoulou
  12. Sotirios Tsiodras
  13. Pagona Lagiou
  14. Gkikas Magiorkinis

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Abstract

SARS-CoV-2 emerged in late 2019 in China, causing a global pandemic. Severe COVID-19 is characterized by intensive inflammatory responses, and older age is an important risk factor for unfavorable outcomes.

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  1. Version published to 10.1128/spectrum.01260-21
  2. Version published to 10.21203/rs.3.rs-116697/v1 on Research Square
  3. ScreenIT

    SciScore for 10.1101/2020.05.10.20096958: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    For this reason, based on the coordinates we used and the length of endogenous retroviral elements, we considered a length of 9000bp for HML-3, HML-5 and HML-6, 10000bp for HML-1, HML-2, HML-4 and HML-6, HERV-W, HERV-L, HERV-E, HERV-I and HERV-FRD, a length of 9000bp for HML-3, HML-5 and HML-6, 12000bp for HERV-9 and 17000bp for HERV-H for the calculation of -f for each virus, in order to increase the sensitivity of the detection.
    HML-4
    suggested: None
    Software and Algorithms
    SentencesResources
    RNAseq data from BALF samples of healthy individuals were downloaded from Sequence Read Archive (SRA) with accession numbers: SRR10571724, SRR10571730, SRR10571732.
    Sequence Read Archive
    suggested: (DDBJ Sequence Read Archive, RRID:SCR_001370)
    Bioinformatics Analysis: Bowtie2 with default settings for paired-end data was used for the alignment of these data to hg19 human genome assembly (25).
    Bowtie2
    suggested: (Bowtie 2, RRID:SCR_016368)
    Samtools sort and index commands were used with default settings.
    Samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    Bedtools multicov command was used for the quantification of the expression of these genes with the -f option for the detection of reads that overlap with the genes coordinates by at least 80%, the same way as with the endogenous retroviral elements.
    Bedtools
    suggested: (BEDTools, RRID:SCR_006646)
    IBM SPSS Statistics for Windows, Version 23.0.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    One limitation of our study is the small number of samples; thus, our findings need to be replicated in more patients, but also need to be followed up by functional studies. Nevertheless, our findings might also (at least partially) provide a working hypothesis to explain the mechanism of action of Lopinavir/ritonavir which has been shown to inhibit the expression of at least one HERV family (HK2) (23). Interestingly, there is also evidence of the potential benefit of antiretroviral treatment against SARS-CoV-2 infection, as there is an ongoing phase 2b/3 Clinical Trial for the assessment of the effectiveness of leronlimab, a CCR5 antagonist, against COVID-19 (24). We find that multiple HERV families are upregulated in Bronchoalveolar Lavage Fluid (BALF), but not in PBMCs, in patients with COVID-19 compared to healthy individuals. Furthermore, we were able to identify upregulation in the expression of HERVs in senescence induced HBECs in comparison to non-induced cells, a fact that indicates the potential role of increased endogenous retroviral expression as a mediator of inflammatory reactions in older individuals that are at increased risk due to the disease. The findings merit further study regarding the potential involvement of HERVs in COVID-19. It thus seems feasible that should HERV expression be aetiologically linked to COVID-19 this expression could be a therapeutic target that to minimize the likelihood of severe Covid-19 and death. It remains to be seen if HERV exp...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.05.10.20096958 on medRxiv