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Comparative hospitalization and mortality risk in the US population during the Omicron and Delta periods

In a recent report published in the United States Centers for Disease Control and Prevention (US-CDC)’s Morbidity and Mortality Weekly Report (MMWR), researchers compared in-hospital mortality across coronavirus disease 2019 (COVID-19) pandemic periods.

Study: Mortality Risk Among Patients Hospitalized Primarily for COVID-19 During the Omicron and Delta Variant Pandemic Periods — United States, April 2020–June 2022. Image Credit: Thaiview/Shutterstock


Studies have evidenced that the risk for severe COVID-19 and in-hospital mortality increases with age, disability, and pre-existing health conditions (comorbidities). The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) Omicron is more infectious but causes much less severe disease. Additionally, by the time Omicron emerged, the majority of the world population had developed high levels of either vaccine- or infection-induced immunity.

Consequently, the proportion of the US population with infection-induced antibodies to SARS-CoV-2 increased from 33% in December 2021 to 57% by February 2022. During the same time, the medical community made several advancements in oral COVID-19 therapies for patients at risk for severe disease. Together, this resulted in marked reductions in other measures of COVID-19 severity during the period of Omicron predominance. For instance, there was a reduction in the number of intensive-care unit (ICU) admissions and intermittent mandatory ventilation (IMV).

About the study

In the present study, researchers retrieved the COVID-19-related hospitalizations and deaths data from 678 US hospitals registered with the Premier Healthcare Database Special COVID-19 Release (PHD-SR). An expired discharge status indicated a COVID-19-related in-hospital death. The researchers used the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1 to identify COVID-19-related hospitalizations.

The team conducted analyses per patient level by selecting each patient’s last hospitalization record for COVID-19 during the Delta (July to October 2021), early Omicron (January to March 2022), and later Omicron periods (April to June 2022).

They described sociodemographics, disease severity, and hospital characteristics to calculate crude mortality risk (cMR), i.e., deaths per 100 hospitalizations, for each pre-specified study period. The cMR computations encompassed total deaths, COVID-19-related deaths, and COVID-19-unrelated deaths. 

The study model estimated adjusted mortality risk differences (aMRDs) and adjusted mortality risk ratios (aMRRs), which quantify absolute risk and relative risk for in-hospital death, respectively. Furthermore, the researchers conducted descriptive analyses for three pre-Delta periods between April 2020 and June 2021.

They used z-tests to compare cMR, aMRDs, and aMRRs across COVID-19 pandemic periods, with p<0.05 indicating statistical significance. Finally, the researchers presented the aMRDs and aMRRs for in-hospital deaths during early Omicron vis-à-vis Delta and later Omicron vis-à-vis Delta periods using multivariable generalized estimating equation (GEE) models.

Study findings         

As per PHD-SR records, 1,072,106 COVID-19-related hospitalizations and 128,517 in-hospital deaths occurred between April 2020 and June 2022. The cMR among patients hospitalized primarily for COVID-19 was 15.1, 13.1, and 4.9 during the Delta, the early Omicron, and the later Omicron periods, with the cMR range of 9.9 to 16.1 during the three pre-Delta periods.

Regarding the pattern of cMRs, cMR was one to two percentage points higher for COVID-19 hospitalizations than for total COVID-19 hospitalizations till December 2021. As COVID-19-related hospitalizations began to decrease during the early Omicron period, the cMR difference increased to up to 3.5 percentage points to return to 1 to 2 percentage points in the later Omicron period.

Compared to the Delta period, in-hospital mortality among patients hospitalized primarily for COVID-19 was 0.69 and 0.24 times as likely during the early and later Omicron periods, respectively. Notably, cMR decreased from 15.1% to 4.9% between Delta and later Omicron periods, despite most hospitalizations of high-risk patient populations.

The mortality risk did not differ between the Omicron and Delta periods for patients less than 18 years old. During the later Omicron period, 81.9% of in-hospital deaths occurred among adults aged more than 65 years. Likewise, 73.4% of individuals with three or more comorbidities died in hospitals during this time. However, the study results could not confirm whether these patients with comorbidities suffered from COVID-19-related respiratory complications or other acute or chronic conditions exacerbated by SARS-CoV-2 infection.


During the Omicron predominance period, the cMR for COVID-19-related hospitalizations decreased to 4.9%. This cMR was nearly one-third of the observed cMR in the Delta predominance period and lower than any other period of the COVID-19 pandemic. Likewise, in-hospital mortality decreased for all patient groups during the later Omicron period. Moreover, most hospitalizations and deaths occurred among patients aged more than 65 years, disabled patients, and those with three or more comorbidities.

Overall, in the later Omicron predominance period, COVID-19 patients at lower risk were not often hospitalized, but those who were had none to minimal severe outcomes and much-lower mortality risk. Thus, the study results highlighted the need for continuous vaccination, early treatment, and non-pharmaceutical interventions to prevent COVID-19-related deaths, especially in high-risk individuals.

Most importantly, there is a need to continue monitoring COVID-19–related hospitalizations and mortality amid the evolution of protective immunity, both infection- and vaccine-induced, and the emergence of new SARS-CoV-2 VOCs to inform public health strategies.

*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.

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