The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis
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Abstract
The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this.
Methods
In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1 st November 2020 and 30 th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death.
Results
Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants).
Conclusions
The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.
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SciScore for 10.1101/2021.08.17.21260128: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Each lineage was randomly subsampled to a maximum of 5 sequences per epiweek (resulting in 52 to 103 sequences per subsample, depending on the lineage), and 10 subsamples replicates analysed per lineage in a joint exponential growth rate population model. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources The estimates were carried out utilising sequences from November 2020 – March 2021 in BEAST with an exponential growth rate population model, strict molecular clock model and TN93 with four gamma rate distribution categories. BEASTsuggested: (BEAST, RRID:SCR_010228)Resul…
SciScore for 10.1101/2021.08.17.21260128: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Each lineage was randomly subsampled to a maximum of 5 sequences per epiweek (resulting in 52 to 103 sequences per subsample, depending on the lineage), and 10 subsamples replicates analysed per lineage in a joint exponential growth rate population model. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources The estimates were carried out utilising sequences from November 2020 – March 2021 in BEAST with an exponential growth rate population model, strict molecular clock model and TN93 with four gamma rate distribution categories. BEASTsuggested: (BEAST, RRID:SCR_010228)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:There are some limitations to our study. Our dataset is drawn from first-line local NHS diagnostic (pillar 1) testing which over-represents patients presenting for hospital care (59%) while those sampled in the community represented 41% of the dataset. Further, the analysis dataset employed a non-standardised approach to sampling across the study period as sequencing was carried out both as systematic randomised national surveillance and sampling following outbreaks of interest. Finally, the cumulative model used in this analysis assumes a homogenous application of therapeutic intervention across the population. Despite these limitations, our results remain consistent with previous work on the mortality of Alpha, and this study provides new information regarding differences in infection severity. In summary, the B.1.1.7 lineage was found to be associated with a rapid increase in SARS-CoV-2 cases in Scotland and an increased risk of severe infection requiring supportive care. This has implications for planning for outbreaks in countries with low vaccine uptake where the B.1.1.7 lineage is not yet dominant. Our study has shown the value of the collection of higher resolution patient outcome data linked to genetic sequences when looking for clinically relevant differences between viral variants.
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.
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