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Review 1: "Clinical Severity of Omicron Sub-lineage BA.2 Compared to BA.1 in South Africa"

Published onAug 02, 2022
Review 1: "Clinical Severity of Omicron Sub-lineage BA.2 Compared to BA.1 in South Africa"
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key-enterThis Pub is a Review of
Clinical severity of Omicron sub-lineage BA.2 compared to BA.1 in South Africa

ABSTRACTEarly data indicated that infection with Omicron BA.1 sub-lineage was associated with a lower risk of hospitalisation and severe illness, compared to Delta infection. Recently, the BA.2 sub-lineage has increased in many areas globally. We aimed to assess the severity of BA.2 infections compared to BA.1 in South Africa. We performed data linkages for (i) national COVID-19 case data, (ii) SARS-CoV-2 laboratory test data, and (iii) COVID-19 hospitalisations data, nationally. For cases identified using TaqPath COVID-19 PCR, infections were designated as S-gene target failure (SGTF, proxy for BA.1) or S-gene positive (proxy for BA.2). Disease severity was assessed using multivariable logistic regression models comparing individuals with S-gene positive infection to SGTF-infected individuals diagnosed between 1 December 2021 to 20 January 2022. From week 49 (starting 5 December 2021) through week 4 (ending 29 January 2022), the proportion of S-gene positive infections increased from 3% (931/31,271) to 80% (2,425/3,031). The odds of being admitted to hospital did not differ between individuals with S-gene positive (BA.2 proxy) infection compared to SGTF (BA.1 proxy) infection (adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.85-1.09). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ for individuals with S-gene positive infection compared to SGTF infection (aOR 0.91, 95%CI 0.68-1.22). These data suggest that while BA.2 may have a competitive advantage over BA.1 in some settings, the clinical profile of illness remains similar.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.



The information in this manuscript is reliable. The authors compare the risk of disease severity between two omicron strains BA.1 and BA.2 using population level and individual data in the DATCOV database linked with the presence or absence of the S-Gene to serve as a proxy for BA.1 and BA.2. They use multivariable logistic regression models to help assess and control for risk factors known to impact severity of disease. Despite controlling for prior infection, vaccination status among the hospitalized, and across demographics such as age and sex, they found similar odds of hospitalization and severe disease between BA.1 and BA.2. Supporting the idea that though BA.2 may be more transmissible it is not shown to be linked to higher disease severity.

The limitations of this study are reasonable, if we assume that the DATCOV dataset (which was accessed to help determine disease severity and hospitalizations) distinguishes between incidental and attributable admissions for SARS-CoV-2. The authors mention that they only had individual data on vaccinations among those hospitalized (self-report) and so the odds of hospitalization did not take vaccination status into account for the total positive population. Vaccination status is likely to impact the risk of hospitalization and if an increase in vaccination occurred in response to the start of the omicron wave it’s possible that individuals exposed to BA.2 were more likely to have been previously vaccinated than BA.1, which could potentially skew the results. Vaccination status is included in the model assessing disease severity among those hospitalized and was shown to be associated with lower disease severity in general but did not impact the odds of severe disease between the two groups.

Overall, it is an efficient and well-done assessment of odds of severe disease and hospitalization between two different viral strains and answers an important question about the current circulating strain.

Since our solicitation of reviews, an updated version of this preprint has been published in The Lancet journal and the link to the published manuscript can be found here.

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