SARS-CoV-2 Omicron BA.2 less severe than Delta and original Omicron

In a recent JAMA Network Open study, researchers estimate the severity of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 subvariant compared to that caused by the Delta and Omicron variants.

Study: Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England. Image Credit: CI Photos /

Study: Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England. Image Credit: CI Photos /


The SARS-CoV-2 Omicron (B.1.1.529) variant has been reported to be more contagious but often, less harmful than previous variants in numerous countries, including Canada, England, and Scotland.

More recently, several Omicron subvariants have become dominant circulating strains throughout the world, thus making it difficult to determine the severity of infections with these new subvariants. In addition, cohort studies that have sought to measure the Omicron BA.2 lineage severity have shown inconsistent results, thus necessitating further research.

About the study

In the present study, researchers consider several confounding factors, including the adjusted risks of death, hospitalization, admission to an intensive care unit (ICU), and invasive ventilation to compare the severity of infections between SARS-CoV-2 Omicron BA.2, Delta, and Omicron variants.

Coronavirus disease 2019 (COVID-19) cases in adults and children were identified between March 3, 2020, and May 21, 2022. Eligible participants either had a positive polymerase chain reaction (PCR) test or the electronic health record (EHR) had flagged them with a verified or suspected COVID-19 status. When the disease was discovered, cases were classified into one of three groups: Delta, Omicron, or Omicron subvariant-infected.

By analyzing the dominance of variants on residual diagnostic tests, period barriers were identified. Delta cases occurred between June 27, 2021, and December 5, 2021. Omicron cases were identified between December 26, 2021, and February 21, 2022. The Omicron BA.2 subvariant was assigned to any case between March 21, 2022, and May 21, 2022.

The incident date of the infection was the first positive PCR or flag corresponding to a patient. A patient was considered newly infected with SARS-CoV-2 if they reported another positive PCR test or new flag more than 90 days after the incident date.

A minimum data floor requirement of at least two diagnosis records six months apart in the three years before the COVID-19 diagnosis was necessary to postulate sufficient information related to a patient to assess their comorbidity history and record their outcomes. In addition, each patient's vaccination status was divided into one of four categories 21 days prior to the patient's COVID-19 incident date, which included unvaccinated, the first dose only, fully vaccinated, or fully vaccinated with a booster vaccine dose.

In-hospital mortality within 30 days since COVID-19 diagnosis was the primary outcome. Hospitalization, invasive ventilation, and ICU hospitalizations were considered secondary outcomes. The patient was classified as having secondary outcomes if these events occurred within 30 days of the COVID-19 incident date.

Study findings

The SARS-CoV-2 Delta, Omicron, and Omicron BA.2 strains were assigned to 20,770, 52,605, and 28,940 cases, respectively.

Each group's demographics differed slightly from the others. For example, the Omicron variant had the lowest percentage of men who tested positive for SARS-CoV-2, while the Delta variant had the most significant proportion. In addition, Omicron subvariant patients were slightly older, with an average age of 49.5 years.

All three populations infected by the three assessed variants reported similar comorbidities. Notably, a significant number of cases involving individuals suffering from chronic pulmonary disease, including 4,529, 2,829, and 7,877 patients from the Omicron BA.2, Delta, and Omicron cohorts, respectively.

The Delta variant was associated with 148 documented fatalities within 30 days after infection, whereas the Omicron and Omicron BA.2 variants were associated with 203 and 76 recorded deaths, respectively. This accounted for 0.7% of the Omicron BA.2 subvariant cases, 0.4% of the Omicron cases, and 0.3% of the identified Delta infections.

After utilizing entropy balancing to account for factors like sex, gender, race and ethnicity, comorbidities, vaccination status, therapies, and prior infection, Delta mortality was higher than Omicron subvariant mortality, while Omicron variant mortality was higher than Omicron subvariant mortality.

After adjusting for covariates, the Omicron BA.2 subvariant was associated with a significantly lower risk of hospitalization than Delta. However, the Omicron variant was more likely than the subvariant to cause hospitalization.

ICU admission was more likely for Delta than Omicron subvariant infections. Similarly, Omicron variant infections were more likely to result in ICU admission than those due to the subvariant. 


The study findings showed that the SARS-CoV-2 Omicron BA.2 subvariant was much less severe than the Delta and Omicron variants after considering many confounding variables linked to SARS-CoV-2 outcomes. After accounting for several variables, such as medications, vaccines, and prior infections, the severity profile of SARS-CoV-2, about these novel variants, appears to be decreasing.

Journal reference:
  • Strasser, Z. H., Greifer, N., Hadavand, A., et al. (2022). Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England. JAMA Network Open 5(10):e2238354. doi:10.1001/jamanetworkopen.2022.38354
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.


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