Centenarians in nursing homes during the COVID-19 pandemic

Introduction

Since December 2019, there has been a growing number of patients worldwide infected with the novel coronavirus 2019 (SARS-CoV-2). The recent literature confirms that older adults appear to be more susceptible to the virus [1], as well as more likely to present the most severe cases, in particular those with comorbidities (hypertension, diabetes, cancer, cardiological and respiratory diseases) [2] and/or frailties such as functional or cognitive impairments [3]. Among older adults, the number of centenarians has increased over the past 20 years. In France, there were 20 944 centenarians in 2017 [4]. Their susceptibility to the disease is different from that of other older people. Previous surveys have shown that thirty percent of centenarians are not affected by major age-related diseases including dementia. Others have described a phenomenon of “compression of morbidity” (including cancer) in centenarians leading them to spend a relatively short period of their lives with age-related diseases or disabilities [5, 6]. Genomic and genetic studies carried out in this particular population have described several mechanisms underlying this exceptional longevity [7].

We conducted a search in PubMed for articles on screening and cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in centenarians published between January 1 and November 10, 2020. We identified three studies that had included centenarians with COVID-19 [8–10] and three others that had included patients over 90 years [11–13]. None described specific characteristics and outcomes in centenarians managed for COVID-19 in nursing homes.

The objectives of this study carried out by the geriatric and therapeutic department at Marseille University Hospital (AP-HM) were (1) to describe and (2) to compare comorbidities, clinical and biological characteristics, treatment measures, and outcomes in centenarians and other residents diagnosed with COVID-19 in 15 nursing homes in the Marseille area.

Results

In our study, 321 residents were diagnosed with COVID-19 including 12 centenarians. The median age in centenarians was 101 years (interquartile range (IQR) 100-102.75) and 11 out of 12 were women. The median age of the other residents was 89 years (IQR 82-93) and 70.2% were women. Irrespective of the age group, the most frequent comorbidities were cognitive impairment, depression, and hypertension. Centenarians had chronic renal disease more often than younger residents (33.3% vs. 12.5%) but none had chronic pulmonary disease. The demographic, clinical, and geriatric characteristics and comorbidities in centenarians and younger residents are detailed in Table 1. Even though the differences were not statistically significant, centenarians were more likely to be malnourished according to the body mass index (BMI) than younger residents at the time of COVID-19 infection (58.3% vs. 43.4%) and to have impaired autonomy (75% belonged to an iso-resource group ≤ 3 vs. 69% of younger residents). Concerning chronic medications, only four centenarians (33.3%) were exposed to polypharmacy compared to 74.8% of younger residents (p = 0.004).

Table 2 describes COVID-19 related symptoms, biology, and treatment among the centenarians and the other residents. The most common symptoms were asthenia (50% of centenarians and 51.2% of younger residents) and fever (50% of centenarians and 42.4% of younger residents). Anorexia was more common among centenarians (41.7%) than among the others (21.4%) but, unlike the younger residents, the centenarians did not suffer from headaches, myalgia, or falls. Three centenarians (25%) experienced a worsening of pre-existing depression (vs. 5.5% of younger residents; p = 0.032).

Ten centenarians received azithromycin, one received hydroxychloroquine, and 4 received preventive anticoagulation. None received antiviral drugs. Moreover, 5 centenarians had oxygen therapy and 9 received intravenous or subcutaneous hydration. Regarding supportive care, 4 centenarians were given analgesics and/or anxiolytics. Drug-drug interactions were detected between azithromycin and psychotic drugs and/or antidepressants for five centenarians. COVID-19 care was comparable among the younger residents even if they received hydroxychloroquine more often (32%) and hydration (48.5%) less often.

Hospitalization concerned 24.6% of younger residents and only one centenarian (to manage dyspnea). Four centenarians received palliative care, perfusions for hydration, and hydroxychloroquine treatment initiation within the context of home hospitalization. Finally, 50% of centenarians (n = 6) and 21.3% of younger residents died from COVID-19 during hospitalization or in nursing homes (p = 0.031) and centenarians were more likely to die in nursing homes (Table 2).

The comparison of the 12 centenarians showed that three out of the six deceased centenarians only had one COVID-19-related symptom (fever, cough, or dyspnea). Lymphopenia was more prevalent in deceased centenarians than surviving centenarians. Centenarians who died from COVID-19 were more likely to have hypertension, diabetes, obesity or severe malnutrition (according to BMI), and severe disability (according to the iso-resource group) than those who survived (Table 3). Deceased centenarians received more oxygen therapy than survivors and conversely, surviving centenarians had more preventive anticoagulation.

A complementary comparative analysis dividing the population into four age groups (65-79, 80-89; 90-99 and >100 years old) suggests that anorexia increased with age (p = 0.036) and that, compared to other groups, centenarians were mostly treated with a combination of antibiotics (p = 0.024) and were more often offered hydration (p < 0.001). Moreover, the death rate increased with age (p = 0.029). The worsening of depression was not significantly different between the four age groups but was nevertheless more prevalent in the centenarian age group (25% vs. 7.0%, 4.1%, 6.2% in the 65-79, 80-89, and 90-99 age groups, respectively) (Supplementary Table 1).

Discussion

To our knowledge, this is the first multicenter study to describe and compare the clinical, geriatric, and biological characteristics and outcomes in centenarians and other residents with COVID-19 in nursing homes.

The centenarians studied had a poorer survival rate than the other residents but had a low hospitalization rate, as home hospitalization was favored.

In our study, the mortality rate was 50% among the 12 centenarians, which is higher than among the other residents (24.6%). In the literature, the mortality rate of COVID-19 for hospitalized older adults varies from 14.8% to 31% [13, 14] but little is known about the COVID-19-related mortality rate in nursing homes. On June 1, 2020, the COVID-19-related death rate was 27.4% in France [15] and up to 40% in nursing homes in the USA [16]. A study of centenarians’ in Lombardy (comparing community-dwelling patients with nursing home residents) showed that COVID-19-related mortality was high for the oldest old adults [17]. A majority of the centenarians who died in our study received home hospitalization at the nursing home. Currently, the hospitalization of centenarians is avoided whenever possible [18]. The hospitalization rate in centenarians varies between 18% and 50% in the literature [18, 19] and the increased number of care home beds has been associated with fewer deaths of older residents in hospital [20]. Moreover, the centenarians who received home hospitalization in our survey had a severe form of COVID-19 and their poor clinical state could contra-indicate hospitalization. This could explain the low hospitalization rate in centenarians. With the COVID-19 pandemic, older persons, and in particular very old persons or those with severe comorbidities, are at particular risk of severe infection and poor outcomes [2, 21]. Despite successful aging, centenarians have a higher mortality rate than younger residents. Nevertheless, there is no concrete evidence that the low hospitalization rate in our study could actually be linked to the higher mortality rate of the centenarian group compared to the younger residents, as our study sample was too small to draw any conclusions. The mortality rate of the centenarians in our study shows the importance of implementing effective COVID-19 prevention measures, especially for nursing home residents.

Concerning demographics and comorbidities, in the centenarian group [22] 91.7% were women compared with only 70.2% in the 65 to 99 years age group, which is in accordance with the literature [23, 24]. Little is known regarding the great longevity of women centenarians but it is thought that it could be more related to environmental conditions than genetic factors [24, 25]. All the more, centenarians had fewer cardiovascular and depression comorbidities than other residents [25], and polypharmacy was less frequent in centenarians (p = 0.004) than in other residents in our survey, which is consistent with previous results in older patients living in nursing homes [26]. However, centenarians in nursing homes were more dependent according to the iso-resource group classification and more often suffered from malnutrition than other residents.

Concerning symptoms, centenarians had a fever and asthenia in 50 % of cases, followed by anorexia (41.7%) and dyspnea (33.3%). Anorexia was more frequent in centenarians than in other residents. In the literature, asthenia was particularly frequent in older patients with COVID-19, which is in accordance with our work [2, 13, 27]. Despite our small sample size, the worsening of depression was significantly more prevalent in centenarians than in other residents. Depression has not been described in the literature on older patients with COVID-19, except in a study using the depression score to predict older inpatient mortality [11]. The particularity of this symptom is the increased worry and sadness in residents with pre-existing comorbid depression. However, the worsening of depression can also be associated with asthenia and delirium in older adults. Delirium was present in two centenarians and is commonly under-recognized when superimposed on major neurocognitive disorders, especially during the severe stages of the disease, as it is difficult to find a clear distinction between symptoms attributable to delirium or underlying dementia [28, 29]. Due to the small sample of centenarians and the lack of power of our comparative analysis with the 65 to 99-year-olds, few symptoms were significantly associated with age.

Chronic inflammation (inflammaging) increases with age and is known to play a major role in the physiopathology of COVID-19 [30]. Inflammaging is lower than expected in centenarians, as they develop anti-inflammatory markers that may delay diseases and can partially explain successful aging [31, 32]. The only inflammation marker available in our survey was CRP and we did not find any significant difference in CRP levels according to the age of the residents. However, this is not conclusive, as we collected the biological data retrospectively from the medical files at the nursing homes, and C-reactive protein levels were missing for 26.2% of the residents.

Concerning COVID-19 treatment, a majority of the centenarians received antibiotics, in particular azithromycin, and hydration. Specific treatments (including hydroxychloroquine, antiviral therapy, or immunomodulatory agents) were used less in centenarians than in other residents, which is in accordance with the treatment of hospitalized older patients described in the literature [13, 33].

This study is limited as it was retrospective with a limited number of centenarians. However, the COVID-19 screening policy implemented in French nursing homes involved the systematic screening of all the residents each time a case was detected among staff, health care workers, or residents. Consequently, our sample of residents with symptomatic or asymptomatic coronavirus disease included all COVID-19 cases during the study period. The other strengths of the study concern the detailed collection of clinical, biological, management, and survival data among centenarians with COVID-19 at the time of the pandemic, which is rare in the geriatric literature. The small number of patients did not allow multivariable analysis to highlight factors that may influence deaths or hospitalizations in this population. Moreover, our centenarians with COVID-19 were all living in nursing homes and are more frail than community-dwelling centenarians. However, taking into account that data on centenarians are sparse and that only 305 centenarians were living in the Marseille area in 2017 [4], our small sample was worth describing. We compared their data with other residents and showed differences among symptoms and outcomes. However, our results need to be validated on a larger population from other areas.

Conclusion: Centenarians with COVID-19 in nursing homes had a high mortality rate (50%) but a low hospitalization rate. Home hospitalization was preferred to avoid hospitalizations and allowed patients to receive supportive care. Even in our small sample, clinical differences were observed between centenarians and younger residents regarding COVID-19 symptoms. These specificities should be studied clinically and genetically in larger samples of both nursing home and community-dwelling centenarians to improve detection and management of the disease in this frail population.

Materials and Methods

Supplementary Materials

Supplementary Table 1