On the association between SARS-COV-2 variants and COVID-19 mortality during the second wave of the pandemic in Europe

  1. Katarzyna Jabłońska
  2. Samuel Aballéa
  3. Pascal Auquier
  4. Mondher Toumi

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Abstract

BACKGROUND

Preliminary clinical evidence suggests an increased COVID-19 mortality associated with the variant of concern 20I/501Y.V1. The evidence outside the UK and a real-world comparison of variants spread and mortality is sparse. This study aims at investigating the association between COVID-19 mortality and SARS-COV-2 variants spread during the second wave of the COVID-19 pandemic in Europe.

METHODS

For 38 European countries, publicly available data were collected on numbers of COVID-19 deaths, SARS-COV-2 variants spread through time using Nextstrain classification and countries’ demographic and health characteristics. The cumulative number of COVID-19 deaths and the height of COVID-19 daily deaths peak during the second wave of the pandemic were considered as outcomes. Pearson correlations and multivariate generalized linear models with selection algorithms were used.

FINDINGS

The average proportion of 20I/501Y.V1 variant (B.1.1.7) was found to be a significant predictor of cumulative number of COVID-19 deaths within two months before the deaths peak and between 1 January – 25 February 2021, as well as of the deaths’ peak height when calculating the proportion during the second wave and the pre-peak period. The average proportion of 20A.EU2 variant (S:477N) was a significant predictor of cumulative COVID-19 deaths in the pre-peak period.

INTERPRETATION

Our findings suggest that the spread of a new variant of concern 20I/501Y.V1 had a significant impact on the mortality during the second wave of COVID-19 pandemic in Europe and that proportions of 20A.EU2 and 20I/501Y.V1 variants were associated with increased mortality in the initial phase of that wave.

Research in context

Evidence before this study

Emerging evidence suggests that the new variant of concern 20I/501Y.V1 (B.1.1.7) may be associated with an increased risk of death. The 20A.EU2 variant (S:447N), observed firstly in July 2020 in western Europe, was found to be capable of increasing SARS-COV-2 infectivity. The evidence outside the UK is still sparse, same as a real-world comparison of distinct variants spread and mortality through time.

Added value of this study

In this study we investigated whether the change of the proportion of any SARS-COV-2 variant, including 20I/501Y.V1 and 11 other variants identified by Nextstrain up to 25 February 2021, has an association with COVID-19 cumulative mortality or with the height of the second wave COVID-19 mortality peak.

Implications of all the available evidence

Our findings shed light on the causes of the increased COVID-19 mortality during the second wave of the pandemic in Europe. It shows the need for early containment strategies when the variant 20I/501Y.V1 emerges. These findings also support the need for systematic SARS-CoV-2 regular genome sequencing to control the COVID-19 pandemic.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.25.21254289: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Analyses were performed using SAS 9.4 software.
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)

    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:
    Limitations: One of the study limitations is that data on limited number of countries were used. Since the course of the pandemic differs sorely between continents, and so do the virus variants spread, we focused on the European region to avoid data inconsistency issues. However, the number of observations is enough to draw conclusions based on multivariate regression models. Stability of results was tested with sensitivity analyses, being highly consistent with base case findings. The limited number of covariates were included in the multivariate analysis, while other factors could be potentially influential. The selection of covariates was based on the literature search and only factors which previously were found to have a significant association with COVID-19 mortality were included. Another limitation concerns the reliability of the data. The proportions of variants were calculated across strains obtained from GISAID and sampling of virus strains may not be equal across countries. However, the number of countries with less than 30 observations was only 5 (13·2%), and the average number of sequences per country in the database was 64. There also exists the variability of data quality between countries, as well as between-country differences on data on daily deaths due to COVID-19 collection methods. In addition, the date of death occurrence and date of reporting can differ. Conclusions: Our findings suggest that the development and spread of a new virus variant of concern...

    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.

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  2. Version published to 10.1101/2021.03.25.21254289v1 on medRxiv
  3. Version published to 10.1080/20016689.2021.2002008