A standardised protocol for relative SARS-CoV-2 variant severity assessment, applied to Omicron BA.1 and Delta in six European countries, October 2021 to February 2022

Abstract

During the COVID-19 pandemic, several variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved. These had different risks of causing severe disease [1-18], possibly due to differences in symptom profile [19-22], viral load [23,24], vaccine effectiveness [3,5,22,25,26] or via other mechanisms. A wide range of estimates of the relative risks of severe outcomes such as hospitalisation and death associated with new variants have been reported, often with moderate precision. Some countries have published variant severity assessments based on national data, but many countries have not. Thus, there are likely observational data available on COVID-19 cases and their outcomes which could further inform about variant severity, if analysed within a valid study design and statistical analysis framework to minimise potential biases.

During the spring and summer of 2022, mass testing for COVID-19, as well as sequencing capacity, was reduced in many countries where the pandemic appeared to recede [27-30]. As data on cases and the virus variants become less available, collaborative international efforts will become more important. Such collaborations can provide larger effective sample sizes than those available in single-country datasets, which may enable more rapid identification of differences in virulence between virus variants.

To address these issues, a Joint World Health Organization (WHO) Regional Office for Europe and European Centre for Disease Prevention and Control (ECDC) Infection Severity Working Group was formed. This was an ad hoc group comprised of public health agencies and academic collaborators in countries working on assessing differences in severity of COVID-19 by virus variants. The aim of the group was to produce a standardised protocol to be used by investigators in individual countries to analyse locally available data on COVID-19 cases using comparable methods and definitions. This decentralised approach overcomes potential issues in sharing individual-level data between countries. The intended application of the standardised protocol is for the comparison of the disease risks between two SARS-CoV-2 variants, during calendar periods when both variants are circulating and individual-level data on which virus variant caused the infection of each case are available. Outcomes include indicators of severe disease, such as hospital admission, intensive care unit (ICU) admission or death. The objective was to assess differences in the severity of COVID-19 by virus variants, but the approach is applicable also to the study of severity of other similar diseases, such as influenza, by various virus subtypes. This approach enables direct contrasting of relative risk (RR) estimates based on consistently analysed data from several countries and allows international organisations and researchers to pool those estimates. Pooled estimates can provide greater precision due to a larger sample size compared with estimates from separate countries.

The primary aim of this report was to describe the development of the standardised protocol. The protocol was further applied in a pilot study of data on the full national cohorts of cases with Delta (Phylogenetic Assignment of Named Global Outbreak (Pango) lineage designation B.1.617.2) and Omicron (Pango lineage designation B.1.1.529) BA.1 variants from six European countries.

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DOI

https://doi.org/10.2807/1560-7917.ES.2023.28.36.2300048