As of May 3, 2023, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had resulted in >764 million cases and 6.9 million deaths, with the omicron variant dominating worldwide [https://covid19.who.int/]. Fortunately, with the advancements of the vaccination campaign and the succession of SARS-CoV-2 mutations, the percentage of patients admitted to hospitals due to coronavirus disease 2019 (COVID-19) and the COVID-19-associated mortality rates changed significantly over the course of the pandemic, and the current trend in confirmed cases and mortality rates continues to decrease globally [https://covid19.who.int/].

Multiple contributors to severe outcomes due to COVID-19 infection (e.g., diabetes mellitus, arterial hypertension, cardiovascular and oncological burden) have been identified (1). Dementia is a well-established predictor of a higher mortality rate globally (2), and individuals with dementia may be a particularly high-risk subgroup for both infection (2,3) and negative consequences due to COVID-19 infection (4,5). This is most likely attributed to a larger comorbidity burden (6), a greater vulnerability to pneumonia (7), and an inability to adhere to safety measures, such as social isolation (3). However, during the early stages of the pandemic, the associations between dementia and the risk of mortality of patients with COVID-19 were less consistent (1,8).

The impact of dementia on COVID-19-related mortality has shifted over time, particularly as vaccinations became widely available and were widely administered, and as new strains of SARS-CoV-2 developed (9). The association of dementia with the risk of COVID-19-related mortality has now been confirmed in a large number of patients treated over a lengthy period of time during the pandemic (10).

However, data on the prognostic factors for the poor outcomes of patients with dementia hospitalized due to COVID-19-associated pneumonia in all pandemic waves are limited. The aim of the present study was to shed light on the factors associated with the mortality of elderly patients with dementia hospitalized due to COVID-19-associated pneumonia over a long period of time during the pandemic.

During the study period, a total of 1,144 elderly individuals were hospitalized in COVID-19 Unit, Laiko General Hospital (Athens, Greece) due to COVID-19-associated pneumonia, of whom 105 (9.2%) patients (60 females, 57.1%) were suffering from dementia. The mean age of the patients was 84.03±7.61 years, and the median value of the CCI was 5 (range, 3-9). A total of 8 patients (7.6%) were hospitalized during the period of wild-type variant predominance period, 24 (22.9%) patients were hospitalized during the alpha variant predominance period, 21 (20%) patients were hospitalized during the delta variant predominance period, and 52 (49.5%) patients were hospitalized during the omicron variant predominance period.

As regards the vaccination status, only 27 (25.7%) patients were fully vaccinated (at least three doses). In total, 38 (36.2%) patients succumbed during their hospitalization, while a total of 52 (49.5%) patients succumbed during the first 90 days following diagnosis. The demographics and clinical characteristics of the study population are presented in Table I.

According to the univariate regression analysis, the period of omicron variant prevalence [hazard ratio (HR), 2.126; 95% confidence interval (CI), 1.073-4.213; P=0.031] and the absence of full vaccination (HR, 6.231; 95% CI, 1.500-25.87; P=0.012) were associated with in-hospital mortality (Table II); however, in the multivariate regression analysis, only the absence of complete vaccination exhibited an independent association with in-hospital mortality (HR, 5.182; 95% CI, 1.205-22.28; P=0.027) (Table III).

According to the univariate regression analysis, age (HR, 1.045; 95% CI, 1.006-1.085; P=0.023) and the absence of full vaccination (HR, 3.254; 95% CI, 1.294-8.181; P=0.012) were associated with the 90-day mortality (Table IV). In addition, by multivariate regression analysis, age (HR, 1.047; 95% CI, 1.007-1.048; P=0.021) and the absence of full vaccination (HR, 3.286; 95% CI, 1.307-8.265; P=0.011) exhibited an independent association with the 90-day mortality (Table V).

According to some studies from the first pandemic waves, the mortality rate of patients with dementia hospitalized due to COVID-19-associated pneumonia ranges between 22.4-37.5% (12-14). In their study, Kostev et al (10) reported that in patients with dementia and COVID-19 from all the pandemic waves, the in-hospital mortality rate was 26.5%, while in the present study, the in-hospital mortality rate was 36.2%. This difference may be attributed to different health systems and geographical settings.

In the present study, the 90-day mortality rate was 49.5%. The post-discharge out-of-hospital mortality among patients with dementia with COVID-19 has been reported to be considerably higher than that among non-dementia patients (15). Patients with dementia are an older, more vulnerable population, having a higher CCI value than elderly patients without dementia (15). As a result, patients with dementia will have a higher mortality rate, despite the fact that the majority did not meet the severity requirements at the time of admission. As a result, patients with dementia who are discharged need to be monitored closely, since they are at a high risk of mortality.

Studies from the first pandemic waves have reported comorbidities, such as chronic kidney disease, medications such as antipsychotics and benzodiazepines, and laboratory biomarkers such as CRP, WBC, neutrophil count, serum sodium and calcium as prognostic factors for the mortality of patients with dementia and COVID-19 (9,12,16). The study by Kostev et al (10), which included patients with dementia diagnosed with COVID-19 across a long time period of the pandemic, identified age, the non-omicron variant, obesity, liver cirrhosis and cancer as prognostic factors for mortality. However, that study did not take into account the vaccination status, as it is already mentioned in its limitations (10).

In the present study, age was an independent prognostic factor for the 90-day mortality rate, while the absence of full vaccination was an independent prognostic factor for both in-hospital and 90-day mortality among patients with dementia with COVID-19-assocaited pneumonia. An older age is a recognized prognostic factor for COVID-19-associated mortality, and COVID-19 is responsible for disproportionately high rates of mortality among the elderly, particularly those with multiple comorbidities (17-20). The absence of vaccination is a known risk factor for the mortality of patients with COVID-19(21). Moreover, it has been demonstrated that vaccines against COVID-19 are highly effective in preventing hospitalization and mortality among the elderly (22,23).

To the best of our knowledge, the present study is the first to report the protective role of full vaccination in elderly patients with dementia hospitalized due to COVID-19 in all the pandemic waves. However, the present study is also subject to some limitations. Although the CCI was used for adjustment in the regression analysis, other entities, such as anemia, that were not included could have affected the study outcomes. No detailed data are available regarding the causes of mortality for those individuals who did not survive. In addition, no medications regarding COVID-19 or other medications for the underlying disease were included in the analysis. Furthermore, considering that the present study only enrolled hospitalized patients, the association between dementia and a fatal course of COVID-19 cannot be generalized to indicate an association between dementia and COVID-19 severity in individuals treated as outpatients. Finally, viral variants were not identified individually for patients. The assignment of variants was based on the predominant variant at the time the patient was diagnosed with SARS-CoV2 infection, and a distinction was only made based on whether patients were diagnosed before or since the omicron variant emerged.

In conclusion, the present study demonstrates that in-hospital and the 90-day mortality rates of elderly patients with dementia and COVID-19-associated pneumonia are high. An older age and a lack of full vaccination are independently associated with poor outcomes.