Study Identifies Patients at Risk for Severe COVID-19 Post-Vaccination

Adults in Alberta, Canada, who completed at least a primary COVID-19 vaccination schedule remained overwhelmingly protected against severe outcomes, but a retrospective cohort study published in PLOS One found that specific subgroups continued to face a meaningfully elevated risk of hospitalization or death.¹

Researchers analyzed population-level administrative health data from more than 2.6 million adults who received a primary vaccination series between December 2020 and March 2023, along with a subgroup of more than 1.5 million adults who went on to receive at least 1 additional dose. The authors said the findings can help health care providers and public health officials target prevention efforts toward those who remain most vulnerable even after vaccination.¹

Study Design and Population

The study used person-level linked administrative health data from the Alberta Health Care Insurance Plan, which covers more than 99% of the province's residents, including records from the province's Immunization and Adverse Reactions to Immunizations database that captures doses given by Alberta Health Services and pharmacist immunizers.¹

Eligible adults had completed a primary schedule of 2 doses of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca); 2 doses of the Novavax COVID-19 vaccine; or 1 dose of Ad26.COV2.S (Janssen). A severe COVID-19 outcome was defined as a COVID-19–related hospitalization or death occurring at least 14 days after completion of the primary series or at least 7 days after a first booster dose in the subgroup analysis.¹

The cohort's mean age was 49 years; just over half were female; and the most common health conditions of interest were dyslipidemia (24.5%), hypertension (23.2%), a mental health disorder (15.5%), cardiovascular disease (10.5%), and diabetes (10.4%).¹

Age and Comorbidity Burden Drove Risk

In fully adjusted analysis, adults 65 years and older had more than 3 times the risk of a severe outcome compared with those younger than 65 years (adjusted hazard ratio [aHR], 3.56; 95% CI, 3.30-3.84). Male sex was independently associated with greater risk than female sex (aHR, 1.14; 95% CI, 1.08-1.20), and each 1-point increase in Charlson Comorbidity Index score raised risk as well (aHR, 1.14; 95% CI, 1.12-1.16).¹

Among the 10 individual health conditions evaluated, dementia carried the greatest adjusted risk (aHR, 2.07; 95% CI, 1.87-2.30), followed by cardiovascular disease (aHR, 2.00; 95% CI, 1.87-2.14), an immunocompromised status (aHR, 1.87; 95% CI, 1.75-2.00), chronic obstructive pulmonary disease (aHR, 1.76; 95% CI, 1.64-1.90), and chronic kidney disease (aHR, 1.74; 95% CI, 1.61-1.87); dyslipidemia was the lone condition negatively associated with risk (aHR, 0.77; 95% CI, 0.72-0.82).¹

Residents of a socioeconomically deprived area faced greater risk than those in the most well-off areas (aHR, 1.39; 95% CI, 1.27-1.52), and long-term care residence was associated with lower overall risk of a severe outcome (aHR, 0.65; 95% CI, 0.53-0.80) but more than double the risk of COVID-19–related death specifically (aHR, 2.03; 95% CI, 1.55-2.66).1 A prior SARS-CoV-2 infection was associated with a lower risk of a severe outcome (aHR, 0.62; 95% CI, 0.54-0.72).¹

Risk Profiles Could Show Greatest Impact

To help translate the statistical findings into practical targeting criteria, the researchers modeled several example risk profiles combining age and health conditions. Adults 65 years and older or living with any health condition of interest made up just 54.7% of the cohort but accounted for 89.6% of all severe outcomes, for a population attributable risk of 77.0% (unadjusted hazard ratio [uHR], 9.34; 95% CI, 8.57-10.19).¹

A narrower profile of age 75 years and older alone represented only 8.3% of the cohort yet captured 34.7% of severe outcomes, with a population-attributable risk of 28.7% (uHR, 11.36; 95% CI, 10.71-12.04). The authors noted that choosing among these risk profiles for public health interventions involves trade-offs between capturing the largest share of at-risk individuals and the feasibility of targeting a narrower, higher-risk population.¹

Findings Held Among a Booster Dose

Among the 1,580,110 adults who received at least 1 additional vaccine dose, risk patterns were largely consistent with the primary series cohort. Age 65 years and older remained the strongest driver of risk (aHR, 5.01; 95% CI, 4.70-5.34), followed by dementia (aHR, 2.34; 95% CI, 2.18-2.51), cardiovascular disease (aHR, 1.95; 95% CI, 1.86-2.06), and an immunocompromised status (aHR, 1.93; 95% CI, 1.84-2.03). Male sex was again independently associated with greater risk (aHR, 1.25; 95% CI, 1.19-1.31).¹

Two notable exceptions emerged. Socioeconomic deprivation (most deprived versus most well-off: aHR, 1.04; 95% CI, 0.97-1.11) and obesity (aHR, 1.12; 95% CI, 1.06-1.18) were no longer statistically significant in the fully adjusted booster subgroup, suggesting some factors' influence may attenuate with additional doses. A prior SARS-CoV-2 infection remained protective in this group as well (aHR, 0.46; 95% CI, 0.39-0.54).¹

What This Means for Pharmacists

The study's authors linked their findings directly to Canada's National Advisory Committee on Immunization, which recommends that all adults 65 years and older, along with those with certain health conditions, residents of long-term care and other congregate settings, and members of equity-denied communities, stay up to date with COVID-19 vaccination.¹

That guidance mirrors risk categories identified by the CDC, which advises clinicians to "consider the patient's age, presence of underlying medical conditions and other risk factors, and vaccination status" when assessing a patient's risk of severe COVID-19 illness. The CDC's list of conditions with conclusive evidence of higher risk includes chronic kidney, lung, and liver disease; diabetes; heart conditions; dementia and other neurologic conditions; obesity; and immunosuppressive medication use—closely paralleling the conditions identified in the Alberta cohort.²

Mayo Clinic similarly notes that "staying up to date with the latest vaccine is most important for people at higher risk," specifically citing adults older than 65 years, people with weakened immune systems, and those with chronic conditions such as heart disease, lung disease, and obesity.³

Because the Alberta data source itself included vaccination records entered by pharmacist immunizers, the findings underscore the role community and health-system pharmacists already play in identifying these higher-risk patients at the point of care and encouraging them to remain current on recommended doses.¹

Vaccination's Benefits Extend Beyond Acute Illness

A separate review in Frontiers in Immunology adds further context for pharmacist counseling. Vaccination not only reduces the likelihood of severe acute illness but has also been associated with a lower incidence and symptom burden of long COVID.⁴

The review found that vaccinated individuals showed lower frequencies of fatigue, cough, dyspnea, anxiety, depression, memory dysfunction, and brain fog compared with unvaccinated peers, with effects reported to persist for up to 18 months. A multicentric analysis across the United Kingdom, Spain, and Estonia similarly found that pre-infection vaccination was associated with a markedly lower risk of developing long COVID.⁴

Taken together with the Alberta cohort's findings, this evidence gives pharmacists a broader rationale—beyond preventing hospitalization or death—for encouraging eligible patients, particularly those who are older or living with chronic conditions, to remain current on COVID-19 vaccination.

REFERENCES

1. Aponte-Hao S, Luu H, Martins KJB, et al. Factors associated with severe COVID-19 outcomes among adults with at least a primary vaccination schedule: A retrospective cohort study from Alberta, Canada. PLoS One. 2026;21(8):e0354822. Published 2026 Aug 17. doi:10.1371/journal.pone.0354822

2. Centers for Disease Control and Prevention. Underlying conditions and the higher risk for severe COVID-19. CDC. Updated February 6, 2025. Accessed August 20, 2026. https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html

3. Mayo Clinic Staff. COVID-19 vaccines: get the facts. Mayo Clinic. Updated June 25, 2026. Accessed August 20, 2026. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-vaccine/art-20484859

4. Guimarães GN, Brunetti NS, De Lima DG, Proenca-Modena JL, Farias AS. Vaccination and COVID-19: impact on long-COVID. Front Immunol. 2025;16:1686572. Published 2025 Nov 19. doi:10.3389/fimmu.2025.1686572