Severity and inpatient mortality of COVID-19 pneumonia from Beta variant infection: a clinical cohort study in Cape Town, South Africa

  1. Linda Boloko
  2. Aimee Lifson
  3. Francesca Little
  4. Timothy De Wet
  5. Nectarios Papavarnavas
  6. Gert Marais
  7. Nei-yuan Hsiao
  8. Michael-John Rosslee
  9. Deelan Doolabh
  10. Arash Iranzadeh
  11. Carolyn Williamson
  12. Sipho Dlamini
  13. Marc Mendelson
  14. Ntobeko Ntusi
  15. Robert J. Wilkinson
  16. Hannah Hussey
  17. Mary-Ann Davies
  18. Graeme Meintjes
  19. Sean Wasserman

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Abstract

Background

The SARS-CoV-2 Beta variant, associated with immune escape and higher transmissibility, drove a more severe second COVID-19 wave in South Africa. Individual patient level characteristics and outcomes with the Beta variant are not well characterized.

Methods

We performed a retrospective cohort study comparing disease severity and inpatient mortality of COVID-19 pneumonia between the first and second wave periods at a referral hospital in Cape Town, South Africa. Beta variant infection was confirmed by genomic sequencing. Outcomes were analyzed with logistic regression and accelerated failure time models.

Results

1,182 patients were included: 571 during the first wave period and 611 from the second wave. Beta variant accounted for 97% of infections in the second wave. There was no difference in crude in-hospital mortality between wave periods (first wave 22.2%, second wave 22.1%; p = 0.9). Time to death was decreased with higher weekly hospital admissions (16%; 95% CI, 8 to 24 for every 50-patient increase), age (18%; 95% CI, 12 to 24 for every 10-year increase) and hypertension (31%; 95% CI, 12 to 46). Corticosteroid use delayed time to death by 2-fold (95% CI, 1.5 to 3.0). Admission during the second wave decreased time to death after adjustment for other predictors, but this did not reach statistical significance (24%; 95% CI, 47 to -2). There was no effect of HIV on survival.

Conclusions

There was a trend towards earlier mortality during the second COVID-19 wave driven by the Beta variant, suggesting a possible biological basis. Use of oral prednisone was strongly protective.

Key points

In Cape Town, South Africa, the second wave of COVID-19, dominated by the Beta variant, was associated with decreased time to inpatient death after adjustment for age, comorbidities, steroid use, and admission numbers. Use of oral prednisone was strongly protective.

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  1. ScreenIT

    SciScore for 10.1101/2021.11.04.21265916: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the University of Cape Town Human Research Ethics Committee (HREC 285/2020).
    Sex as a biological variablenot detected.
    RandomizationScreening for potentially eligible cases was done on randomly selected medical records generated from lists of consecutive hospital COVID-19 admissions during each study period.
    Blindingnot detected.
    Power AnalysisA power calculation was done based on data collected during the first wave, where in-hospital mortality was 22% among a sample of 571 patients.

    Table 2: Resources

    Antibodies
    SentencesResources
    No patients received remdesivir, IL-6 inhibitors, or monoclonal antibodies.
    remdesivir, IL-6
    suggested: None
    monoclonal
    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: We detected the following sentences addressing limitations in the study:
    However, this was not seen in smaller hospitalized cohorts with more granular clinical data [18, 19], and importantly, less confounding related to resource limitations in these higher income settings. Disentangling an isolated effect of VOC from dynamic factors that strongly influence clinical outcomes, such as health system strain, treatment practices, vaccination, and population behaviors, is challenging [20]. Laboratory data have demonstrated that variants with mutations in the receptor-binding domain including Alpha, Beta, and Gamma likely have increased transmissibility and reduced sensitivity to neutralization by natural and vaccine-induced antibodies [6, 9, 21, 22]. These characteristics have resulted in higher infection peaks, and increased hospitalization and mortality associated with these variants, including in South Africa [2, 23, 24]. High viral loads may further predict the probability of progression of disease during hospitalization [25], as shown in our study those who died had higher viral loads than survivors. Although lower RT-PCR amplification cycles have been reported with VOC, including the Beta variant [26], a causal relationship between Ct values, VOC, and mortality is not yet established. Dynamic measures of Ct values provide better insights into VOC biology. We did not have longitudinal viral testing data and similar Ct values between wave periods observed in our study may have been influenced by time course of illness or sampling differences. In lin...

    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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  2. Version published to 10.1101/2021.11.04.21265916v1 on medRxiv