Infection With the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta Variant Is Associated With Higher Recovery of Infectious Virus Compared to the Alpha Variant in Both Unvaccinated and Vaccinated Individuals

  1. Chun Huai Luo
  2. C Paul Morris
  3. Jaiprasath Sachithanandham
  4. Adannaya Amadi
  5. David C Gaston
  6. Maggie Li
  7. Nicholas J Swanson
  8. Matthew Schwartz
  9. Eili Y Klein
  10. Andrew Pekosz
  11. Heba H Mostafa

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Abstract

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) B.1.617.2 (Delta) displaced B.1.1.7 (Alpha) and is associated with increases in coronavirus disease 2019 (COVID-19) cases, greater transmissibility, and higher viral RNA loads, but data are lacking regarding the infectious virus load and antiviral antibody levels in the nasal tract.

Methods

Whole genome sequencing, cycle threshold (Ct) values, infectious virus, anti-SARS-CoV-2 immunoglobulin G (IgG) levels, and clinical chart reviews were combined to characterize SARS-CoV-2 lineages circulating in the National Capital Region between January and September 2021 and differentiate infections in vaccinated and unvaccinated individuals by the Delta, Alpha, and B.1.2 (the predominant lineage prior to Alpha) variants.

Results

The Delta variant displaced the Alpha variant to constitute 99% of the circulating lineages in the National Capital Region by August 2021. In Delta infections, 28.5% were breakthrough cases in fully vaccinated individuals compared to 4% in the Alpha infected cohort. Breakthrough infections in both cohorts were associated with comorbidities, but only Delta infections were associated with a significant increase in the median days after vaccination. More than 74% of Delta samples had infectious virus compared to <30% from the Alpha cohort. The recovery of infectious virus with both variants was associated with low levels of local SARS-CoV-2 IgG.

Conclusions

Infection with the Delta variant was associated with more frequent recovery of infectious virus in vaccinated and unvaccinated individuals compared to the Alpha variant but was not associated with an increase in disease severity in fully vaccinated individuals. Infectious virus was correlated with the presence of low amounts of antiviral IgG in the nasal specimens.

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  1. Version published to 10.1093/cid/ciab986
  2. ScreenIT

    SciScore for 10.1101/2021.08.15.21262077: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical considerations and Data availability: The research Johns Hopkins Medical Institutions Institutional Review Board-X
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cell culture: Vero-TMPRSS2 cells were cultured and infected with aliquots of swab specimens as previously described for VeroE6 cells (23).
    Vero-TMPRSS2
    suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analyses were conducted using GraphPad prism.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We detected the following sentences addressing limitations in the study:
    The limitations of our study include the lower numbers of Delta variant specimens due to the lower positivity in the month of July, 2021, the infrequent specimens collected after 5 days of symptoms onset for the Delta vaccine breakthrough infections, and the relatively shorter time frame of Delta circulation that limited the clinical evaluation of some of the hospitalized patients. In addition, the phenotypes with cell culture experiments are usually dependent on the cell lines used, however Vero-TMPRSS-2 cells have been shown to enhance the isolation of SARS-CoV-2 (34). Moreover, the lack of serum and localized SARS-CoV-2 IgG data prior to infection for vaccine breakthrough cases in our cohort does not allow for the differentiation between waning immune responses and low initial responses to vaccines. Taken together, we hypothesize that the notable increase in the time since receiving the vaccines combined with increased fitness of the Delta variant predisposes both vaccinated and unvaccinated individuals to symptomatic SARS-CoV-2 infections that are associated with high viral loads and transmission. Non-pharmaceutical interventions that include universal masking and social distancing to diminish transmission might be warranted to help control the summer 2021 Delta surge in the US. Booster vaccinations in groups at high risk of severe COVID-19 should be investigated to help reduce the burden of COVID-19 on the medical infrastructure.

    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.
    • 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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  3. Version published to 10.1101/2021.08.15.21262077v1 on medRxiv