Coronavirus disease 2019 (COVID-19) in older patients: outcomes and risks of mortality

Introduction

Patients of advanced age who are hospitalized with Coronavirus disease 2019 (COVID-19) have a higher risk of hospitalization, morbidity, greater need for a higher level of care, and higher mortality when compared to younger patients. Among 5700 patients hospitalized with COVID-19 in New York, early in the pandemic, mortality was around 43% for those aged 70 years [1]. A large, single-centre study from the western US showed a mortality rate of 37% among patients aged 80 years or older hospitalized with COVID-19 [2]. Previously published studies of COVID-19 in older patients (> 65 years) do not adequately explain the heterogeneity in outcomes related to age sub-groups nor the association of age-related conditions such as immune senescence, frailty, and the prevalence of particular chronic comorbid conditions with unfavourable outcomes [1, 3, 4]. For that reason, we examined the clinical course and characteristics of patients aged 65 years and older who were hospitalized with COVID-19 at a suburban tertiary care centre during the early pandemic.

Material and methods

This is a retrospective cohort study conducted at Westchester Medical Centre, which serves a population of 2.5 million people in the Hudson Valley region of New York State. All hospitalized patients aged 65 years or older from 15 March to 15 May 2020, who tested positive for SARS-CoV-2 by polymerase chain reaction, and were discharged, were included in this study. Clinical characteristics, treatment, and hospital course were recorded, and variables were compared using Student’s t-test, χ², and/or Fisher’s exact test and binary logistic regression. The primary analysis focused on 2 age groups: “Old” (65–76 years) and “Older” (77–105 years). These age groups were selected because the 76-year median age corresponded to the age at which mortality has been shown to rise rapidly in other studies [1, 5]. Statistical significance was accepted at p < 0.05 and corrected using the Bonferroni method.

Results

The study included 196 patients, which comprised 32% of all COVID-19 patients hospitalized during the study period. The median age was 76 years (range: 65–105 years). The majority (70%) of patients arrived from home. The primary diagnosis at time of hospitalization was COVID-19 for 65% of patients and another diagnosis with COVID-19 for the remainder of the group. Atypical clinical presentations were common and included generalized weakness (36%), altered mental status (18%), myalgia (15%), and falls (7%), along with typical symptoms such as shortness of breath (63%) or fever (54%). The mean duration from symptom onset to arrival was 5.6 ±4.4 days. On admission, 70% of patients had bilateral infiltrates on chest X-ray, 27% were febrile, 33% had a respiratory rate over 24, and 53% had a lowest measured oxygen saturation level below 90%. Patients had multiple underlying chronic medical conditions, with a mean of 3.9 ±1.9 medical comorbidities. Common medical comorbidities were hypertension (63%), cardiac conditions (34%), diabetes mellitus (34%), and neurological disorders (inclusive of dementia) (19%). Mean body mass index (BMI) was 27.2 ±5.7 kg/m2 (range: 14.5–44.1). Overall survival was 66.3% and did not differ significantly across various age groups 65–69 (30/40, 75%), 70–74 (37/52, 71%), 75–79 (24/31, 77%), but it was significantly lower in the age group 80 years and above (39/73, 53%, χ² = 9.0, p = 0.003) (Table I).
Comparison of age groups (65–76 “old” vs. 77–105 years “older”)

Presentation

On admission, a greater proportion of older patients arrived from a location other than home (60% vs. 12%, p < 0.001) and had an admission diagnosis other than COVID-19 (34% vs. 15%, p = 0.001). More older patients had a history of dementia (25% vs. 1.0%, p < 0.001), chronic heart disease (42% vs. 28%, p = 0.038), a vascular disorder (20% vs. 9%, p = 0.023), or recurrent bacterial infections (7% vs. 1.0%, p = 0.022). Significant differences in the average number of comorbidities per patient and the proportions of other comorbid conditions were not observed between the 2 age groups. Antipsychotic (14% vs. 5%, p = 0.031) and antidepressant (20% vs. 9%, p = 0.023) drug use was reported more commonly in the older group. Mean body mass was significantly lower in the older group (26.0 ±5.3, vs. 28.4 ±5.8, p = 0.007). Clinical presentations varied significantly between the 2 groups, with a higher proportion of older patients being afebrile (33% vs. 21%, p = 0.047), having altered mentation (30% vs. 7%, p < 0.001), a need for oxygen by non-rebreather mask (27% vs. 8.0%, p = 0.001), having a clear initial chest X-ray (19% vs. 8%, p = 0.029), and reliance on surrogate decision-making (64% vs. 21%, p < 0.001).

Hospital course

The proportions of old versus older patients who had ever utilized intensive care, mechanical ventilation, vasopressors, or renal replacement therapy did not differ significantly during their hospitalization. However, survival was significantly lower for those in the older age group who required mechanical ventilation (20% vs. 46%, p = 0.029), vasopressors (15% vs. 41%, p = 0.046), had new renal failure (29% vs. 56%, p = 0.015), or new hepatic dysfunction (24% vs. 65%, p < 0.001). On admission, 94% of old patients and 70% of older patients placed no restrictions on potential resuscitative measures. During hospitalization, older patients were more likely than younger patients to change their wishes for cardiopulmonary resuscitation (18% vs. 12%). The average number of individual COVID-19-directed medication doses given to older patients was significantly lower than for old patients (7 ±9 vs. 16 ±15, p < 0.001) with fewer older patients receiving azithromycin (54% vs. 78%, p < 0.001), hydroxychloroquine (56% vs. 82%, p < 0.001), non-pulse dose steroids (25% vs. 43%, p = 0.006), or tocilizumab (2% vs. 14%, p = 0.003). However, the proportion of old vs. older patients who had ever received at least 1 dose of a COVID-19-directed medication was not significantly different (Table II).

Outcomes

Overall survival for the cohort was 66%, but it was significantly lower (59% vs. 74%, p = 0.026) for the older group (77–105 years) compared to the old group (65–76 years). The mean duration of hospitalization (14.1 vs. 13.5, p = 0.754), mean BMI (27.21 vs. 27.23 kg/m2, p = 0.984), proportions of survivors versus non-survivors with a primary diagnosis of COVID-19 on admission (67% vs. 33%, p = 0.975), male sex (67% v 33%, p = 0.908), or of different racial/ethnic groups did not differ significantly between the older/old groups. However, survival was significantly higher among older compared to old patients with BMI less than 23 (63% vs. 38%, p = 0.033). Survival was higher among those with no initial restrictions on resuscitation (69% vs. 31%, p = 0.014) and for those whose resuscitation wishes did not change during hospitalization (73% vs. 27%, p < 0.001). We did not observe significant differences in survival between patients treated versus not treated with azithromycin (64% vs. 36%, p = 0.102), hydroxychloroquine (68 vs. 32%, p = 0.482), tocilizumab (63% vs. 38%, p = 0.605), or convalescent plasma (64% vs. 36%, p = 0.761). However, survival was lower among those treated with steroids (non-pulse dose, 55% vs. 45%, p = 0.018) or pulse dose (38% vs. 62%, p < 0.001).
Factors associated with significantly higher mortality in a univariate analysis included older age group (59% vs. 41%, p = 0.026), pre-admission use of antidepressants, or presence of delirium or dementia on admission and the following admission parameters: oxygen saturation < 90% (68% vs. 46%, p = 0.004), elevated procalcitonin (64% vs. 16%, p < 0.001), elevated aspartate transaminase (AST) ≥ 2× upper limit of normal (39% vs. 17%, p = 0.001), elevated total white blood count (46% vs. 13%, p < 0.001), and elevated D-dimer ≥ 5× upper normal (54% vs. 20%, p < 0.001). The prevalence of these factors by incremental 5-year age subgroups and by age group 80 years and older is displayed in Figure 1. In a multivariable regression model that included each of these factors, elevated procalcitonin (odds ratio = 9.8, 95% CI: 2.4–40), D-dimer (odds ratio = 4.2, 95% CI: 1.1–16), and total white cell count (odds ratio = 5.3, 95% CI: 1.3–21) were significantly associated with mortality (Table III). During hospitalisation, the proportion of patients who survived versus died was significantly higher among those with improving organ function: oxygenation (98% vs. 3%, p < 0.001), renal function (89% vs. 11%, p < 0.001), hepatic function (84% vs. 16%, p < 0.001), or delirium (95% vs. 5%, p < 0.001) (Supplementary Table I).

Discussion

In this report, we provide a detailed description of characteristics and clinical outcomes in patients aged 65 years and older hospitalized with COVID-19, with further sub-group analysis among 2 different chronological age groups. In this early-pandemic cohort, overall survival was 66% but was significantly lower for those 77 years of age and above. Our findings are consistent with earlier studies which have shown that patients in the higher age groups, particularly those over age 80 years, had a significantly greater risk of death compared to younger patients [1, 2, 6–10]. We did not observe differences in survival related to hypertension, diabetes, cardiovascular disease, or total number of medical comorbidities, which have been described in prior reports [11–13]. Body mass index was not associated with differences in survival except that survival was higher among older compared to old patients with low BMI (< 23 kg/m2). The proportions of patients who received advanced therapies (e.g. haemodialysis, mechanical ventilation) did not differ significantly by age group. However, the total number of per-patient doses of COVID-19-directed medications was lower among older patients. Survival was similar for patients receiving most medications, except that those who received corticosteroids had lower survival. This was probably due to greater use of steroids among the sickest patients, a pattern that shifted to general use in the later pandemic following publication of the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial [14]. Overall lower medication use in the older group may have been due to factors such as patient/family preferences or higher potential for medication side effects in the older age group.
Of note, survival was lower for older versus old patients who received mechanical ventilation (66% vs. 34%). In prior studies, mortality was 97% for those older than 65 years who received mechanical ventilation, and in a meta-analysis that included over 50,000 patients mortality was 84% for those age > 80 years [1, 15]. These differences may have been related to factors such as inclusion of patients who remained hospitalized, differences in steroid use, or intubation strategies.
Identification of prognostic, clinical, and laboratory indicators on admission and throughout the course of hospitalisation can assist provider discussions with COVID-19 patients and their families. We found a number of presenting factors including dementia [16], new loss of decision-making capacity, depression, myalgia, and hypoxia [17], and elevations in inflammatory markers, total white blood cell count, and procalcitonin to be associated with reduced survival in univariate analysis. In a prior meta-analysis, liver function-related tests and inflammatory markers were among the most important mortality predictors [13]. After adjusting for age and other factors, we found that even modest elevations of AST and D-dimer levels or total white blood cell count were independent predictors of mortality. Elevations in total white blood cell count in COVID-19 were found to be predictive of mortality in another recent study [18]. Worsening clinical status, such as the need for mechanical ventilation or pressor support or the development of acute kidney injury or new hepatic dysfunction, increased mortality 2–3-fold in older versus old patients in this study. Conversely, in both older and old patients, improving mentation, oxygenation, as well as hepatic and renal function were highly significant and favourable prognostic indicators. In our cohort, around 90% of patients for whom these clinical indicators were improving during hospitalization survived to discharge.
The prevalence of atypical symptoms among patients aged 65 years and over reaffirms the need for physicians to have a high index of suspicion for COVID-19 diagnosis. Almost half of all patients had no fever or cough, and over one-third did not complain of shortness of breath. Atypical symptoms such as anorexia, altered mental status, and generalized weakness were common. In addition, older patients were less likely to be diagnosed with COVID-19 as the primary diagnosis on admission. They also presented with more subtle symptoms initially than their younger counterparts, including lack of fever and normal CXR. In addition, the older patients were more likely to have comorbidities such as dementia, and chronic cardiac and vascular disease, which can obscure COVID 19 symptoms.
In a large meta-analysis, the only symptom that was associated with decreased survival in hospitalized COVID-19 patients was dyspnoea [13]. Consistent with a recent report, we found that that hypoxaemia on admission (rather than respiratory symptoms) predicted poor outcome [17]. We also found that although myalgia was uncommon among the oldest patients, its presence was significantly associated with mortality – even after adjusting for other factors. It is plausible that muscle pain may represent a previously unrecognized, early marker of severe disease.
Consistent with earlier reports, we found that dementia was associated with higher mortality in a univariate analysis [16, 19–21]. This association, however, was less clear when other factors were considered as well. Patients with dementia appear to be more easily infected and harmed by SARS-CoV-2 than those with normal mental function [16]. It has been speculated that pre-existing brain damage may permit greater viral entry into the nervous system, which is worsened by hypoxia and other organ failure. On admission, over one-third of older patients in this study lacked decision-making capacity due to underlying dementia and/or delirium. Older patients were also more likely to change their advance care directives/resuscitation wishes during their hospitalization. The potential for rapid mental decline in the setting of COVID-19 underscores the need for patients and their families to proactively anticipate circumstances in which surrogate decision-making could be necessary, and to timely craft suitable advanced directives [22, 23].
An important concern during the pandemic has been the possibility that members of racial and ethnic minority groups have been disproportionately impacted. Racial disparities in terms of hospitalizations and death due to COVID-19 have been reported [24, 25]. In the present study, the highest number of COVID-19 admissions were among white (66%) patients followed by Hispanic (17%), black (11%), and Asian/Pacific Islander (4%). We did not observe significant differences in survival across racial and ethnic groups (black 29%, Hispanic 28%, white 35%, Asian 36%).
This study had several limitations. First, this was a single-centre, retrospective cohort study with a relatively small sample size, which could influence the generalizability of results. Secondly, practice guidelines and patterns during the COVID-19 pandemic have continued to evolve. Such changes could render certain results less applicable to patients currently hospitalized with COVID-19. While the factor of age over or under 77 years was associated with higher mortality in a univariate analysis, after adjustment for other laboratory and clinical factors it was no longer significantly related to mortality. These findings suggest that other factors must be taken into account with age in order to more accurately predict mortality. Given the modest sample size, these results will require confirmation in larger studies.
In conclusion, among patients aged 65 years and older, age and other factors should be considered together to estimate the risk of mortality.

Conflict of interest

The authors declare no conflict of interest.

References