Lower Risk of Severe COVID-19 Associated With Omicron vs Delta Variant


Vaccination was shown to lower risk of developing severe COVID-19 in both variants, with the largest difference in risk observed in patients aged 40 to 59 years.

Patients infected with the SARS-CoV-2 Omicron variant showed reduced risk of developing severe COVID-19 compared with those who had the Delta variant in Italy, according to study findings published recently in International Journal of Infectious Diseases.

As of February 21, 2022, approximately 12 million confirmed cases and 150,000 deaths from COVID-19 have been recorded in Italy. Several variants of concern have been identified in the country, but only 3 of them have become dominant: Alpha, Delta, and Omicron.

Researchers note that previous studies have associated Omicron’s mutations with a higher probability of reinfection and with reduced severity, including lower risk of hospitalization and death compared with the Delta variant.

“Despite this emerging evidence, there is wide variation in the published estimates of severe disease risk between Omicron and previous variants, and [it] is still not well understood how individual factors such as age could modulate such risk,” said the study authors.

Seeking to provide further evidence on this potential association, they conducted a retrospective cohort study using individual data retrieved from the Italian National COVID-19 Integrated Surveillance System.

“This system collects individual demographic and clinical information on all the notified cases of SARS-CoV-2 infection tested positive in the country, including the variant responsible of infection, if the positive sample has been sequenced, and clinical outcomes (hospitalization, admission to intensive care unit [ICU], recovery, or death),” explained researchers.

“We also used individual information about vaccination status, retrieved from the National Vaccination Registry coordinated by the Italian Ministry of Health, that was linked to the surveillance data through the individual tax code.”

For the analysis, all cases of SARS-CoV-2 infection diagnosed from November 15, 2021, to February 1, 2022 for whom sequencing had detected the Omicron or the Delta variant as the cause of infection and who were eligible for vaccination at the beginning of the study period (12 years or older) were eligible for inclusion.

A multilevel negative binomial model adjusting for sex, age group (12-19 years, 20-39 years, 10-year age groups from 40-49 to 70-79 years, and ≥ 80 years), vaccination status, occupation, prior infection, weekly incidence, and geographical area, was used to assess risk of developing severe COVID-19 with Omicron infection compared with Delta in individuals 12 years or older. Additional analyses were conducted to examine the interaction between the sequenced variant, age, and vaccination status.

A total of 21,645 eligible cases of SARS-CoV-2 infection where genome sequencing found Delta (n = 10,728) or Omicron (n = 10,917), diagnosed from November 15, 2021, to February 1, 2022, were included. Overall, 3021 cases developed severe COVID-19.

Between the 2 groups, Omicron cases were seen more frequently among health care workers than Delta cases (5.0% vs 2.2%) and among those vaccinated with at least 1 dose of a COVID-19 vaccine. Omicron cases were also generally younger than Delta cases and more likely to have had a prior diagnosis of SARS-CoV-2 infection (4.9% vs 1.7%). All the events analyzed—hospitalizations, ICU admissions, and deaths—were less frequent in Omicron cases than in Delta cases.

Findings of the multivariable analysis showed that patients ases infected with the Omicron variant were 23% less likely to develop severe COVID-19 compared with Delta cases (incidence rate ratio [IRR], 0.77; 95% CI, 0.70-0.86). The largest difference in risk of developing severe COVID-19 among Omicron cases vs Delta cases was shown among individuals aged 40 to 59 years (IRR, 0.66; 95% CI, 0.55-0.79), whereas no protective effect was found in those aged 12 to 39 years (IRR, 1.03; 95% CI, 0.79-1.33).

Regarding other assessed covariates, a higher risk of developing severe COVID-19 was shown among males compared with females (IRR, 1.25; 95% Cl, 1.16-1.35) and among unvaccinated individuals, of which those infected with the Omicron variant were at lower risk of develop severe COVID-19 compared with Delta cases (IRR, 0.68; 95% CI, 0.59-0.79). Vaccination was associated with a lower risk of developing severe COVID-19 in both variants.

Given the relatively low number of admissions to ICU and deaths, analyses were not able to provide robust outcome-specific estimates. The underascertainment and underreporting, due to the introduction of house testing in Italy from the end of 2021, could also serve as limitation of the study findings, noted the researchers.


Petrone D, Mateo-Urdiales A, Sacco C, et al. Reduction of the risk of severe COVID-19 due to Omicron compared to Delta variant in Italy (November 2021 – February 2022). Int J Infect Dis. Publilshed online January 25, 2023. doi:10.1016/j.ijid.2023.01.027

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