condition in that and international studies, it gener- ally was not identified as an independent predictor of mortality. “While evidence for hypertension as a risk factor for severe COVID-19 is mixed, hypertension consistently ranks as one of the most prevalent underlying conditions across numerous studies,” the researchers wrote. “In our study, hypertension was the most frequent significant risk factor observed (present in 82.0% of sig- nificant combinations). The absence of hypertension as a highlighted independent risk factor in official CDC guidance may result in missed opportunities to identify and manage at-risk patients, particularly in terms of encouraging these patients to stay up-to-date on vac- cination and facilitating access to effective COVID-19 antiviral treatment,” the authors advised. They pointed out that heart conditions and smoking often emerged as key contributors to severe COVID-19 outcomes, in combination with other chronic condi- tions. “Hypertension most frequently overlapped with heart conditions, not-up-to date on COVID-19 vacci- nation, and smoking (approx. > 57% of combinations),” the researchers noted. “Additionally, other cardiometa- bolic conditions, such as diabetes mellitus and obesity, were observed in several of the top 20 com- binations of risk factors with the highest risk of 30-day severe COVID-19. Previous work has demon- strated that clusters of car- diometabolic conditions are associated with severe COVID-19. The frequent overlap of these conditions highlights the importance of coordinated approaches to mitigate their collec- tive impact on severe COVID-19.” One of the surpris- ing findings was that the overwhelming majority of the study participants, nearly two-thirds, were not up-to-date on their COVID-19 vaccinations. The authors said that risk factor was among the most frequently observed in significant combinations and that “all of the top 20 combinations linked to the greatest adjusted 30-day risk of severe COVID-19 included both age ≥ 50 years and not being up to date on vaccination.” “Maintaining up-to-date COVID-19 vaccination is critical for preventing severe COVID-19 outcomes and should remain a public health priority to mitigate the burden of COVID-19, especially among older patients and those with underlying conditions,” the study empha- sized. “An online survey of 1,200 previously vaccinated US adults found that among the most common reasons for not receiving a bivalent booster dose were lack of awareness related to eligibility and availability of the vaccine and overconfidence in perceived immunity against COVID-19 infection and severe disease. As such, public health messaging should emphasize not only the availability of updated COVID-19 vaccines but also the importance of staying up to date with vaccination to reduce their risk of hospitalization and death from COVID-19.” In light of declining COVID-19 vaccination uptake and an increasing emphasis on risk-based clinical deci- sion-making rather than simple eligibility criteria, the 9 6 Impact of Risk Factor Combinations on Severe COVID-19 Outcomes Among Outpatients Effects of number of risk factors on 30-day severe COVID-19 in adults with COVID-19 in the outpatient setting. The adjusted odds ratios (aOR) are estimated from multivariable analysis of the data. The multivariable unconditional logistic regression models compared individuals with one risk factor (reference group) to those with two, three, four, and so forth, risk factors and controlled for sex (male or female), race (white or other/unknown), ethnicity (Hispanic/Latino or non-Hispanic/Latino or unknown), region (Northeast, Midwest, South or West), and deprived (yes or no, based on area deprivation index). Analysis conducted in entire cohort (n = 379,144) Source: Impact of Risk Factor Combinations on Severe COVID-19 Outcomes Among Outpatients. Infect Dis Ther. 2026 Mar 25. doi: 10.1007/s40121-026-01328-1. Epub ahead of print. PMID: 41882459.
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