Clinical severity of SARS-CoV-2-Omicron infection found to be lower than Delta infection

By Pooja Toshniwal PahariaReviewed by Aimee MolineuxMar 21 2022

In a recent study published in The Lancet, researchers evaluated the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by the Omicron variant compared to the Delta variant.

Several SARS-CoV-2 variants have emerged with variable severity and transmissibility. Previous studies reported that the Omicron variant has higher transmissibility, but lower severity than the Delta variant. However, the age-stratified difference in coronavirus disease 2019 (COVID-19)-associated morbidity and mortality by the two variants is not clear.

About the study

In the present study, researchers evaluated the age-stratified Omicron infection severity relative to the Delta infection.

English residents diagnosed with COVID-19 between November 29, 2021, and January 9, 2022, were selected for the study. Data on their vaccination status, hospital attendances, hospital admissions, and deaths were obtained from sources such as the UK Health Security Agency (UKHSA), polymerase chain reaction (PCR) testing laboratories, National Immunisation Management Service, hospital datasets (Secondary Uses Service dataset and Emergency Care Data Set). They linked these data sources using the National Health Service (NHS) number.

Additionally, data were searched in PubMed, pre-print servers such as SSRN and medRxiv, and peer-reviewed publications without any language or date restrictions. Cases with confirmed COVID-19 caused by the Omicron or Delta variants by whole-genome sequencing and S-gene determination were included.

The relative risks of hospital attendance or admission within two weeks, and death within four weeks post-infection, were estimated as hazard ratios (HR). Additionally, data were stratified based on the test date, age groups, ethnicity, vaccination status, and residential areas. The data were further adjusted for sex, index of multiple deprivations, previous infections, and year within each age group.

Cases with missing or invalid NHS numbers or missing relevant information were excluded. Additionally, cases were excluded if they were primarily vaccinated by vaccines other than Pfizer–BioNTech, Moderna, or Oxford–AstraZeneca or had received greater than three vaccine doses or if the third dose was not of Moderna or Pfizer vaccines or was less than 80 days post-second vaccination dose.

The primary outcomes assessed were hospital attendance, hospital admission, and death. Additionally, the data were secondarily analyzed to determine vaccine efficacy based on the type of primary vaccination and the causative variant. Moreover, the relative risk for unvaccinated COVID-19 patients by the Omicron and Delta variants was also calculated which indicated the inherent relative severity of the Omicron variant. Additionally, sensitivity analysis was performed.

Results

Of the 4,135,347 COVID-19 cases detected, 37% were eligible for the analysis of which 70% and 30% were Omicron and Delta infections, respectively.

For Omicron, the HR values were 0.6, 0.4, and 0.3 for hospital attendance, admission, and death across all ages and primary vaccination types, respectively. On age-stratification, the HR values of hospital admission for individuals below 10 years, 60 to 69 years, and above 80 years were 1.1, 0.3, and 0.5, respectively. A similar trend was observed for the mortality outcome.

The relative risk of death or hospitalization in vaccinated individuals compared to those unvaccinated was greater for Omicron compared to Delta infections. This indicates that the reductions in mortality and hospitalization risks understate the intrinsic decrease in the risk of severe infection associated with the transition of Delta to the Omicron variant. This decrease was partially counterbalanced by a decrease in vaccine efficacy. Notably, the greatest reductions in vaccine efficacy against novel infections were observed in individuals who received the Oxford–AstraZeneca vaccine for primary vaccination without a booster dose.

The relative protection (versus unvaccinated) for Omicron against hospital admission due to novel infections post booster remained greater than 70% (HR 0.2). Previous infections conferred protection to unvaccinated individuals with HR values 0.6 and 0.2 for hospital admission and death, respectively. However, for vaccinated individuals, previous infections did not confer added protection against hospital admission (HR 0.96) but did against death (HR 0.8). The protection conferred against death and hospitalization by previous infections was similar by both variants.

The sensitivity analysis gave marginally greater HR values for Omicron compared to Delta than the secondary analysis, but marginally lower HR values for vaccinated versus unvaccinated individuals for Omicron, and lower HR values for reinfections versus primary infections.

To summarize, Omicron infection had lower disease severity with an overall 59%, 44%, and 69% reduction in the risks of hospital admission, hospital attendance, and death compared to Delta infections, respectively, across all ages above 10 years. Also, prior SARS-CoV-2 infections and vaccination conferred immunity against novel SARS-CoV-2 infections.