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Clinical Context

The COVID-19 pandemic has shifted considerably since the advent of the Omicron variant at the end of 2021. It is clear that Omicron more effectively eludes the primary SARS-CoV-2 vaccination series compared with previous variants, which prompted the development of 2 bivalent booster vaccines designed to improve activity against Omicron. But how effective have these bivalent boosters been? A recent study by Lin and colleagues, published in the February 23, 2023, issue of the New England Journal of Medicine, addressed this issue.^[1]

Researchers had access to a large cohort of more than 6 million individuals living in the US from September 1 to November 3, 2022; 17.0% of eligible patients received the bivalent booster. Booster effectiveness against severe infection peaked at 4 weeks and then waned thereafter. The rates of vaccine effectiveness against severe COVID-19 infection, resulting in hospitalization, in comparing the monovalent older vaccine with the newer bivalent vaccine were 25.2% and 58.7%. The respective rates of vaccine effectiveness against the combination of hospitalization or death were 24.9% and 61.8%. Estimates of efficacy were similar in comparing the Pfizer-BioNTech and Moderna bivalent booster vaccines, and the improved relative effectiveness of the bivalent vaccines was sustained in an analysis of adults at age 65 years or older.

Despite evidence to the contrary, some loud voices continue to state that the clinical sequelae of COVID-19 are no worse than those of influenza. The current study compares hospital outcomes of adults admitted with influenza infection vs infection with SARS-CoV-2 during Omicron predominance.

Study Synopsis and Perspective

COVID-19 remains deadlier than influenza in severe cases requiring hospitalization, a new study shows.

People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die compared with people who were hospitalized with influenza, Swiss researchers found.

The results of the study continue to debunk an earlier belief from the start of the pandemic that influenza was the more dangerous of the 2 respiratory viruses. Researchers noted that the deadliness of COVID-19 compared with influenza persisted “despite virus evolution and improved management strategies.”

The study was published February 15 in JAMA Network Open and included 5212 patients in Switzerland hospitalized with COVID-19 or influenza. All the patients with COVID-19 were infected with the Omicron variant and were hospitalized between January 15, 2022, and March 15, 2022. Influenza data included cases from January 2018 to March 15, 2022. 

Overall, 7.0% of patients with COVID-19 died compared with 4.4% of patients with influenza. Researchers noted that the death rate for hospitalized patients with COVID-19 had declined since their previous study, which was conducted during the first COVID-19 wave in the first half of 2020. At that time, the death rate of hospitalized patients with COVID-19 was 12.8%. 

Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors conclude, as a secondary analysis in this most recent study showed that unvaccinated patients with COVID-19 were twice as likely to die compared with patients with influenza.

“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they write.

Although the death rate among patients with COVID-19 was significantly higher, there was no difference in the rate that patients with COVID-19 or influenza were admitted to the intensive care unit, which was around 8%.

A limitation of the study was that all the COVID-19 cases did not have laboratory testing to confirm the Omicron variant. However, study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors stated that they were confident that their results were not biased by the potential for other variants being included in the data.

JAMA Netw Open. 2023;6(2):e2255599.

Clinical Implications

• A previous study found that the bivalent SARS-CoV-2 booster was more effective than the monovalent booster in the prevention of severe COVID-19 disease during the Omicron-predominant period. Estimates of efficacy were similar in comparing the Pfizer-BioNTech and Moderna bivalent booster vaccines, and the improved relative effectiveness of the bivalent vaccines was sustained in an analysis of adults at age 65 years or older.
• The current study finds an approximate 2-fold increase in the risk for in-hospital mortality among patients admitted with COVID-19 vs influenza. The difference in death rates was even more pronounced for patients admitted specifically for symptomatic COVID-19 vs influenza. There was no significant difference between the COVID-19 and influenza groups for ICU admission.
• Implications for the healthcare team: The healthcare team should be aware that COVID-19 appears to have a higher mortality rate among hospitalized patients compared with influenza. However, patients should continue be educated on the benefits of receiving a COVID-19 vaccine and/or booster.

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