Fact check: How do underlying health conditions affect fatality rates among vaccinated and unvaccinated individuals?

1. Why vaccinated patients can still have high death rates — the hidden age and comorbidity mix

Analyses of hospitalized cohorts reveal that vaccinated patients are frequently older and carry more comorbidities than unvaccinated patients, which complicates simple comparisons of crude fatality rates. An international study of 83,163 hospitalized patients found vaccinated people were on average older and more multimorbid, producing large between-country variation in in-hospital fatality risk and in the vaccinated-versus-unvaccinated mortality gap ^[3]. This pattern means that unadjusted mortality figures can understate vaccine benefit: when studies adjust for age and comorbidities, vaccination is associated with substantially lower mortality, illustrating the importance of risk adjustment in interpreting outcomes ^[1].

2. Quantifying the benefit: adjusted mortality differences and booster effects

Careful, statistically adjusted analyses demonstrate meaningful reductions in death among vaccinated patients even after accounting for underlying conditions. A large hospitalized cohort analysis reported adjusted in-hospital mortality of 8.3% for unvaccinated versus 5.1% for vaccinated patients, implying a strong protective effect when confounders are controlled ^[1]. Separately, population surveillance among adults aged 65+ showed that receipt of a bivalent booster was associated with a large reduction in mortality versus being unvaccinated, with vaccine effectiveness modestly declining over months but remaining high in the studied interval ^[2]. These results underscore that boosters further lower risk in high-risk age groups.

3. Which comorbidities drive the greatest increases in risk — heart and lung diseases stand out

Systematic reviews and meta-analyses consistently identify cardiovascular disease, diabetes, chronic lung disease, obesity, and smoking as leading comorbid drivers of severe COVID-19 outcomes and death. A meta-analysis from the Omicron era found the highest mortality and hospitalization risks among people with cerebrovascular and cardiovascular disease and heart failure, while obesity and diabetes increased ICU admission risk ^[4]. Another review highlighted hypertension, respiratory disorders and smoking as associated with higher mortality, reflecting convergence across studies that specific chronic conditions qualitatively and quantitatively magnify fatality risk ^{[5] [6]}.

4. Age, comorbidity load and multimorbidity: compounding risks rather than simple add-ons

Evidence indicates that multimorbidity multiplies rather than merely adds to risk, with younger infected individuals experiencing higher infection rates but older, multimorbid patients suffering much higher fatality. Analyses show that combinations of comorbidities—particularly cardiac disease plus diabetes or chronic lung disease—escalate the likelihood of severe outcomes and death ^{[6] [4]}. This interaction changes the vaccinated-versus-unvaccinated comparison: vaccinated older adults with multiple conditions still have lower adjusted mortality than unvaccinated counterparts, yet their absolute risk remains elevated compared with healthier peers.

5. Geographic variation and healthcare context change the vaccinated-versus-unvaccinated gap

The magnitude of vaccine-associated mortality reduction varies substantially across countries and health systems, driven by differences in population age structure, prevalence of comorbidities, timing of vaccine rollout, and hospital capacity. The multi-country hospitalization analysis highlighted considerable between-country variation in in-hospital fatality risk and in vaccinated-versus-unvaccinated differences ^[3]. These contextual factors mean that policy conclusions drawn from one jurisdiction may not generalize; local demographics and healthcare resources shape observed fatality patterns and the measurable benefit of vaccines.

6. What’s missing from the studies and why it matters for interpretation

Several analyses note limitations that could influence measured effects, including residual confounding, variable case ascertainment, and changing dominant variants and treatments over time. While adjusted analyses point to vaccine benefit, heterogeneity in comorbidity measurement, evolving clinical care, and selection into hospitalization can bias comparisons, especially when vaccinated patients differ systematically in health-seeking behavior or baseline frailty ^{[1] [3]}. Recognizing these methodological gaps is essential for accurate risk communication and for designing targeted protective strategies.

7. Practical takeaway for patients, clinicians and policymakers

Synthesis of these studies supports the clear conclusion that vaccination and boosters reduce mortality even among people with comorbidities, but individuals with cardiovascular disease, diabetes, chronic lung disease, obesity, or multiple conditions remain at substantially higher absolute risk and merit prioritized preventive measures. Public health strategies should combine vaccination, timely boosters, and tailored clinical management for multimorbid patients while accounting for local population risk profiles and healthcare capacity to maximize reductions in COVID-19 fatalities ^{[1] [2] [4] [5]}.