This is the first study that comprehensively describe the clinical presentation of COVID-19 and the risk factors for complications and death in octogenarian hospitalized patients across the different waves of the disease. Thus, the most frequently reported symptoms in all waves were fever, cough, dyspnea, and asthenia. Laboratory and radiological findings consistently showed abnormal bilateral chest X-ray results and elevated inflammatory markers such as LDH, CRP, and ferritin. Among the observed complications, ARDS, renal failure, and alterations in baseline mental status were the most frequent. The overall mortality rate was 41.4% and declined across the epidemic waves.
In our study, age, DM, heart failure, dyspnea, and higher baseline levels of creatinine were identified as risk factors for general complications, while a higher Barthel index and presence of cough were found to be protective. Similarly, age, dyspnea, abnormal bilateral chest x-ray, CRP, and sodium were risk factors for death. In terms of specific complications, dementia and sodium levels were identified as risk factors for confusional syndrome, while female sex was a protective factor. Additionally, dementia and elevated sodium levels were identified as risk factors for cardiological complications, and DM, heart failure, and elevated creatinine levels for renal complications.
The comorbidities most frequently found in our study (hypertension and dyslipidemia) are also considered common elderly patients without COVID-19, suggesting that these conditions may not be related to the disease.21 However, hospitalized patients in this cohort had a higher prevalence of overweight or obesity in contrast to general elderly Spanish population without COVID-19.22
Regarding the clinical symptoms, the most frequently observed in our study (fever, cough, dyspnea, and asthenia) have also been reported as the most common symptoms in cohorts of elderly Spanish patients hospitalized for COVID-19.23–25 Consistent with the findings of other studies, the elderly individuals in our cohort predominantly presented elevated inflammatory markers, such as ferritin and CRP, and frequent elevation of D-dimer and LDH.23,24 This laboratory profile did not differ across the various epidemic waves.
One in ten patients in our sample presented with acute confusional syndrome at admission, with a higher incidence during the initial two waves of the epidemic compared to the subsequent two. The decrease in clinical severity among hospitalized elderly patients in each new wave could explain the decreasing incidence. Furthermore, the relaxation of hospital regulations in later waves allowed companions in patient rooms. Nevertheless, delirium is frequently underdiagnosed and underreported, suggesting its actual incidence during COVID-19 could be higher than detected in our study 26.Moreover, the methods used for delirium detection vary across studies, lacking rigor, leading to highly heterogeneous reported frequencies. Gutiérrez-Rodríguez and Annweiler reported a similar frequency of delirium to our study in the subgroup of patients aged 80 or older, while other authors found higher frequencies.17, 23,24,27,28
A decrease in the prevalence of complications was observed in the third and fifth waves possibly due to the emergence of vaccines, more effective treatments, changes in virus variants and reduced assistance pressure in hospitals. The proportion of patients experiencing ARDS (40%) was similar to other studies.8,23,24 Despite being high, the incidence of ARDS in hospitalized patients is likely underestimated in most studies, as physicians do not always document this diagnosis in the medical records.29 After ARDS, the most common complications were altered mental status and renal failure, with one-fifth of the hospitalized elderly patients developing acute kidney injury. Other cohort studies assessing hospitalized elderly patients have reported acute kidney injury, which is likely related to tubular injury caused by local and systemic inflammation and immune systems, aggravated by hemodynamic instability.23,24,30 Moreover, underlying chronic kidney disease is frequent among octogenarians, further contributing to an increased risk of developing acute kidney injury during hospitalization.
Elderly patients are particularly vulnerable to developing severe forms of the disease. 31 The current study further confirms the clinical presentation, severity, and high mortality rate associated with COVID-19 infection in very elderly patients during the SARS-CoV-2 pandemic. The mortality rate, exceeding 40% in our hospitalized octogenarian group, aligns with the findings reported by two other Spanish cohorts.17,32 Notably, the mortality rate decreased with the progression of the epidemic waves, likely reflecting the successful use of vaccines (starting massively in March 2021) and more effective treatments as the pandemic advanced. Only one previous study has analyzed the clinical presentation, mortality, and associated factors of COVID-19 in octogenarian patients during the different waves of the pandemic.24 This mentioned study, that focused only on the first two epidemic waves and did not analyze risk factors for complications, found a slightly higher overall fatality rate than ours (46.9%), possibly because the study did not include vaccinated patients, which is associated with lower mortality.
Regarding the risk of mortality during hospitalization, this study found that age and elevated levels of CRP and sodium were associated with a higher risk of death. These findings have been consistent with previous studies conducted on elderly patients.25,33,34 During the hospitalization of COVID-19 patients, both hyponatremia and hypernatremia have been associated with worse prognoses and increased mortality rates. 35,36 In our study, elevated sodium levels emerged as a risk factor for death and complications, possibly because patients in a more severe condition may experience tachypnea, fever, and dehydration. On the other hand, patients who presented with a cough at the time of hospitalization and those with higher Barthel index scores had a lower risk of death. While no studies specifically analyze cough as a risk factor for mortality in older patients, studies encompassing patients of all ages have yielded contradictory results.37,38 Regarding the Barthel index score, other studies have reported similar findings to ours, indicating a higher degree of dependence as a risk factor for mortality.25,33
This study was limited by the use of secondary data obtained from medical records, which could introduce information biases related to underreporting certain symptoms or pathologies, in addition to missing information. For the same reason, variables associated with geriatric syndromes (such as malnutrition, falls, or frailty) could not be studied. However, the pre-existing functional status (Barthel index) and acute confusional syndrome were adequately recorded in terms of frequency and quality, allowing their inclusion in our analysis and confirming their significant role in COVID-19 among the elderly. Additionally, the heterogeneity in the collection of certain laboratory parameters across different hospitals (with varying units or reference levels) and throughout the different waves posed a challenge for analysis. Therefore, some laboratory parameters that could not be standardized across the databases were excluded from the analysis, precluding their inclusion in the multivariate analysis. It is important to note that our findings exclusively apply to elderly patients hospitalized with COVID-19 and may not be applicable to elderly individuals with milder forms of the disease who did not require hospitalization.
Despite these limitations, a substantial number of hospitalized octogenarian patients with COVID-19 were included across different waves of the disease in various hospital centers, yielding robust results. Thus, this study offers valuable insights into the disease among the elderly population, specifically regarding the characteristics of hospitalized patients, the clinical manifestations of the disease, abnormalities observed in laboratory and radiological assessments, the frequency and types of complications, as well as the in-hospital mortality rate and prognostic factors, which may help identify elderly individuals who are at risk of developing complications or death during their hospital stay.