Study suggests SARS-CoV-2 Omicron is as deadly as past variants

A recent article under review at the Nature Portfolio journal and currently posted to the Research Square* preprint server compared the severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant with prior mutants.

Study: SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities. Image Credit: NIAIDStudy: SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities. Image Credit: NIAID


In various countries, including Scotland, South Africa, Canada, and England, the SARS-CoV-2 Omicron (B.1.1.529) variant has been documented to be more transmissible, albeit less severe than prior variants. The inherent severity of the Omicron variant, on the other hand, is difficult to comprehend. Moreover, since the beginning of the SARS-CoV-2 pandemic, numerous confounding elements, including healthcare usage and vaccination status, determining CoV disease 2019 (COVID-19) severity have altered and might persist the variance.

A comparison of SARS-CoV-2 variants without proper control and adjustment of crucial confounders that may change over time might mislead both medical specialists and the general public about the actual danger of the variant. In addition, it might contribute to public distrust and bad policy decisions by health experts.

About the study

The present study aimed to eliminate various confounding biases when comparing the severity of the SARS-CoV-2 Omicron variant to prior variants. The researchers used a causal modeling technique employing inverse probability of treatment weighting (IPTW) with data sources from the Massachusetts interstate vaccination registry, curated results, and longitudinal electronic health records (EHR) from the Mass General Brigham (MGB). 

The team combined state-level vaccination records with quality-controlled EHR from an extensive healthcare system, MGB, in Massachusetts, United States of America (USA), comprising 13 hospitals. They conducted a weighted case-control analysis in more than 130,000 COVID-19 patients to assess the odds of hospitalization and death throughout the SARS-CoV-2 waves. 

Using a multi-hospital network medical system permits the maintenance of a steady healthcare utilization factor, and the MGB hospital systems followed similar practices. Further, the reasons for using IPTW as the model for determining COVID-19 severity were as follows:

First, given the significant number of covariates in the current COVID-19 model, the propensity score-based technique may summarize multiple variables to a single covariate, which was beneficial. Second, the IPTW study did not discard unmatched people relative to other propensity-score matching procedures, leading to enhanced sample size. Lastly, various weighing formulas were devised into the IPTW model to solve different concerns, such as substantially large weights. Depending on the situation, these formulations may aid in discovering various treatment effects.


The study results demonstrated that between December 1, 2020, and February 28, 2022, 148,876 patients in the MGB system had a positive COVID-19 polymerase chain reaction (PCR) test result. More females than males were diagnosed with SARS-CoV-2 infection varying from 57.8 to 61.5% in each COVID-19 wave. Compared to other times, the patients infected in Winter 2020-2021 were older. The number of SARS-CoV-2-infected non-whites was reduced in the initial two waves relative to the last two. 

The four COVID-19 periods had comparable Charlson comorbidity index ratings. Nevertheless, in the Winter 2020-2021 period, few patients had a zero score, and the majority had scores above four. Given the commencement of COVID-19 vaccinations in the Winter 2020-2021 season, the proportion of vaccinated patients varied dramatically with each following period as predicted. In the initial two periods, only a few SARS-CoV-2-infected patients had been vaccinated, but in the third and fourth waves, significant amounts of infected patients had been vaccinated.

The proportion of diagnosed SARS-CoV-2 cases was comparatively substantial in the Winter months versus the Spring and Summer. Besides, despite the higher number of COVID-19 cases in the Omicron phase, the risk of hospitalization and death was lower than in the other three periods. Hospitalization risk, however, followed a less constant trend during the Omicron dominancy.

Despite popular belief that Omicron was less severe, the hospitalization probability of the Omicron dominancy was quite similar to the earlier timeframes after controlling for confounding factors. The hospitalization incidence was low in the Winter 2020-2021 season than in the Omicron period. Contrasting the adjusted hospitalization probability of Omicron to Spring 2021 or Delta dominant phase, there was no discernible difference. The risk of death in the Winter 2020-2021 and Delta periods was very close to that in the Omicron period. Furthermore, while Omicron had a statistically relevant lower mortality risk in Spring 2021, the adjusted odds ratio was approximately equal.


The study findings illustrated that the unadjusted hospitalization and mortality rates were significant in prior SARS-CoV-2 waves relative to the Omicron timeframe. Nonetheless, after controlling for confounding variables, including several demographics, COVID-19 vaccination status while keeping healthcare utilization steady, and Charlson comorbidity index scores, the authors discovered that the odds of hospital admission and fatality were almost similar among the Omicron and previous SARS-CoV-2 waves.

Overall, the current research depicted that the Omicron variant's inherent severity may be comparable to the prior SARS-CoV-2 variants. This study accounted for COVID-19 vaccinations, comorbid conditions, demographics, and medical care utilization, adopted IPTW weighted matching, and demonstrated that the severity of the existing SARS-CoV-2 variants was very similar.

*Important notice

Preprints with Research Square publish 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.

Journal reference:
  • Zachary Strasser, Aboozar Hadavand, Shawn Murphy et al. SARS-CoV-2 Omicron Variant is as Deadly as Previous Waves After Adjusting for Vaccinations, Demographics, and Comorbidities, May 02 2022, PREPRINT (Version 1) available at Research Square [],
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.


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