In a recent study posted to the medRxiv* preprint server, an interdisciplinary team of researchers from the United Kingdom (UK) conducted a retrospective study on a cohort of patients in England with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test results.

They aimed to determine the relative risk of coronavirus disease 2019 (COVID-19)-induced mortality following SARS-CoV-2 Omicron infection (B.1.1.539/BA.1) as compared to SARS-CoV-2 Delta infection (B.1.617.2) using death registration data.

The Omicron variant, including its sublineages BA.1, BA.2, and BA.3, has been reported to be more transmissible than the Delta variant. With the rapid emergence of Omicron variants, there is an urgent need to quantify the risk of COVID-19 deaths relative to other SARS-CoV-2 variants for healthcare requirements that will support the COVID-19 pandemic response planning.

Study design

In the current study, the researchers collected data from the Office of National Statistics (ONS) Public Health Data Asset (PHDA) that combined the mortality records, 2011 census, Hospital Episode Statistics (HES), General Practice Extraction Service (GPES), trace data, National Health Service (NHS) and from National Immunisation Management Service (NIMS).

The study population included 1,035,163 individuals living in England who had a positive COVID-19 polymerase chain reaction (PCR) test between 1 December 2021 and 31 December 2021, when SARS-CoV-2 Delta and Omicron BA.1 variants were co-circulating, with a rare circulation of the Omicron BA.2 variant.

COVID-19 death as identified by the International classification of disease- 10 (ICD-10) code mentioned on the death certificate was used as the primary outcome. The SARS-CoV-2 variant type detected as trace PCR positive tests were the exposure of interest.

Overall characteristics of the study population were summarized and stratified according to the type of variant using continuous variables mean and percentage of categorical variables. The authors used a regression model specific to Cox proportional hazard to determine the hazard ratio of mortality induced by COVID-19 for Omicron- and Delta-infected individuals.

They used four models:

• Model 1 – sequentially adjusted for sex, age, the status of vaccination, and, former infection;
• Model 2 – additionally adjusted for calendar time;
• Model 3 – with additional socio-economic features; and
• Model 4 – for pre-existing health features.

Findings

The researchers observed that out of the studied population, 78.6% had Omicron infection, and 21.4% had Delta infection, which covered 36.7% of all positive COVID-19 tests in England in December 2021. In individuals with Omicron infection, there were 128 deaths attributable to COVID-19 and 53 deaths not attributable to COVID-19, while in Delta infection, the numbers were 189 and 28 deaths, respectively. For Omicron infection, the meantime from positive report to COVID-19-induced death was 13 days, while for Delta, it was 16 days.

In a fully adjusted model (Model 4) for Omicron infection, the risk of death due to COVID-19 was 67% lower than Delta infection. For the minimally adjusted model (Model 1), this risk was 78% lower for Omicron than Delta. In contrast, for Models 2 and 3, no relative difference was observed between Omicron and Delta infection mortality.

For Omicron and Delta infection, a higher reduction in COVID-19-induced mortality was observed for individuals under 18-59 years [hazard ratio (HR) =0.13] and 60-69 years (HR=0.14) of age as compared to the age group of 70 years and above (HR=0.45). A more pronounced reduction in mortality risk due to COVID-19 was observed in males [(HR=0.25, 95% confidence interval (CI)] as compared to the females (HR=0.44, 95% CI).

The team noted that regardless of the age, administration with SARS-CoV-2 booster vaccination reduced the risk of mortality more in Omicron infection relative to Delta as compared to those who have received two doses of COVID-19 vaccine.

Interestingly, the authors observed that for all age groups, the COVID-19-induced mortality risk was lower in Omicron infection than Delta regardless of the number of comorbidities.

Conclusion

The findings of the study illustrated a lower risk of hospitalizations and deaths with Omicron-driven COVID-19 infection as compared to that by Delta. The study was the first that assessed cause-specific COVID-19 deaths through death certification to capture COVID-19-related deaths accurately.

Notably, the relative risk of COVID-19 deaths following Omicron versus Delta infection was lower in younger individuals and the female population. The study also highlighted the importance of the COVID-19 booster vaccination program as there was a more pronounced reduction in the risk of deaths involving COVID-19 in the population who have received a booster dose.

However, the authors have warranted the need to investigate the long-term outcome of infections like long COVID-19 prevalence following Omicron infection compared to Delta apart from the mortality metric assessed in this study.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Sangeeta Paul

Sangeeta Paul is a researcher and medical writer based in Gurugram, India. Her academic background is in Pharmacy; she has a Bachelor’s in Pharmacy, a Master’s in Pharmacy (Pharmacology), and Ph.D. in Pharmacology from Banasthali Vidyapith, Rajasthan, India. She also holds a post-graduate diploma in Drug regulatory affairs from Jamia Hamdard, New Delhi, and a post-graduate diploma in Intellectual Property Rights, IGNOU, India.