Effects of Comorbidities on the Elderly Patients with COVID-19: Clinical Characteristics of Elderly Patients Infected with COVID-19 from Sichuan, China

Objectives The co-occurrence of chronic diseases in the elderly is a common problem. However, the relationship between comorbidities and the prognosis of elderly patients with COVID-19 was not clear. This study was supposed to describe the clinical characteristics of elderly patients with COVID-19 infection from Sichuan province and the effects of comorbidity. Design A retrospective study. Settings and participants COVID-19 patients from Public Health Clinical Center of Chengdu between December 16, 2019 and February 26, 2020 were included in this study. Patients were divided into elderly group (≥60 years old) and non-elderly group (< 60 years old). Results Elderly patients with COVID-19 indicated relatively higher proportion of comorbidities, and the most common were atherosclerotic cardiovascular disease (56.5%), hypertension (43.5%) and chronic pulmonary disease (21.7%). The proportion of severe cases was higher in elderly group than that in non-elderly group (73.9% and 42.2%, respectively, P=0.012). During hospitalization, elderly patients indicated relatively higher proportion of complications, such as shock (21.7%), respiratory failure (21.7%). The proportion of patients with a decreased number of CD8+ lymphocytes (82.6%) and B lymphocytes (77.8%) in elderly patients was significantly higher than that in non-elderly group (48.9% and 44.8%, respectively). All 3 deaths were elderly patients with comorbidities and the cell counts of T lymphocyte subsets, B and NK cells of them were significantly decreased at admission. Conclusions Elderly patients with COVID-19 had a high proportion of severe cases and comorbidities, more likely to show low immune function, and indicate higher proportion of complications. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12603-020-1486-1 and is accessible for authorized users.

study were collected. All patients were categorized into two groups according to the age, the elderly group (≥60 years old) and the non-elderly group (< 60 years old). All collected data were compared between the two groups.

Statistical analysis
All data were analyzed using the software SPSS version 20.0. Continuous measurements were represented as mean (x ±s) and analyzed by t-test or median (P25 and P75) and analyzed by Mann-Whitney U test. χ2 test were used to analyze the classified variables. P value < 0.05 was considered to define statistical significance.

The clinical and laboratory characteristics of elderly patients
68 patients who confirmed with COVID-19 infection were included in this study, aged from 19 to 88 years, and 35 (51.1%) male patients. Of the 68 patients, 45 (66.18%) and 23 (33.82%) were categorized into non-elderly group and elderly group, as shown in Table 1. In total, 62 (91.18%) patients had contact history. The most common symptoms in both groups were fever and cough.
The CT and laboratory tests of patients on admission were shown in Table 2. Most patients showed multiple lobe infection in both two groups, and no significant difference between this two groups (P=0.291). The red blood cell count (3.98×1012/L) and hemoglobin (122g/L) in the elderly group were lower than those in non-elderly group (4.64×1012/L and 138 g/L respectively). The C-reactive protein in the elderly group was higher than that in the young group (23.49 VS 9.93 mg/L, P = 0.047), but there was no significant difference in the procalcitonin between the two groups.
82.6% of the elderly patients showed a decrease in CD8+ lymphocyte count, which was much higher than that of in nonelderly group (48.9%), P = 0.009. 77.8% of patients showed the decrease of B lymphocyte in elderly group, which was also higher than that in the non-elderly group (44.8%) (P = 0.036). However, there was no significant difference in cell counts and rates of lymphocyte subsets and NK cells between the two groups, as shown in Table 3.

Comorbidities and the prognosis of elderly patients with COVID-19
The comorbidity of patients was shown in Table 1. Compared with non-elderly patients, old patients were more likely to combine with other basic diseases before infection of COVID-19 (P = 0.017). 13 (56.5%) elderly patients combined with atherosclerotic cardiovascular disease, and the proportion was higher than that in the non-elderly group (9 (20.0%), P = 0.005). The proportion of patients with hypertension was higher in elderly group than in non-elderly group (43.5% and 8.9%, respectively, P = 0.003). Five patients (21.7%) in the elderly group had chronic pulmonary disease, but no in the non-elderly The proportion of severe cases was higher in elderly group than that in non-elderly group (73.9% and 42.2%, respectively, P=0.012). During hospitalization, the proportion of elderly patients with respiratory failure was higher than that of in non-elderly patients (21.7% and 4.4%, respectively, P=0.039). Shock was also more common in older patients than non-elderly patients (21.7% vs 2.2%, P=0.015). And of the 6 patients with shock, 5 had a history of atherosclerotic cardiovascular disease. The proportion of elderly patients requiring mechanical ventilation during treatment was higher than that of younger patients (30.4%, 8.9%, respectively, P=0.020). As shown in table 4, the prognosis of the elderly patients was worse than that of the non-elderly group (P=0.006). All 3 deaths were elderly patients with underlying diseases before admission. The level of C-reactive protein of these dead patients was significantly increased and the cell counts of CD3+, CD4+, and CD8+ T lymphocytes, B lymphocytes and NK cells were significantly decreased at admission, as shown in supplementary table 1.

Discussion
This study collected the clinical information of 68 patients with COVID-19 infection who hospitalized in Public Health Clinical Center of Chengdu, Sichuan. The clinical characteristics of elderly patients with COVID-19 were descripted by compared with non-elderly patients.
We observed more patients with COVID-19 were men which was same as the results of previous study (13)(14)(15). The proportion of elderly patients was 33.82%, which was similar to other studies (16,15). In our study, the most common symptom were fever (78.3%) and cough (60.9%) in elderly patients, which was similar to other researches (17)(18)(19). A previous study found that the incidence of multilobe lesions in elderly patients was significantly higher than in non-elderly patients (16). We also observed the higher incidence of multilobe lesions in elderly patients, although no statistically difference.
In this study, the proportion of patients with decreased leucocytes count was 11.8%, lymphocytes 35.3%, lower than that of in a previous study (33.7% and 83.2%, respectively) (20). The proportion of patients with a decreased number of CD8+ T lymphocytes and B lymphocytes in elderly patients was significantly higher than that in non-elderly group, suggesting that elderly patients were more likely to indicate low immune function. The previous study observed that the acute phase of SARS in humans was associated with a severe reduction in the number of T cells in the blood (21).The level of C-reactive protein in elderly patients was significantly higher than that in the non-elderly group, which was consistent with previous study and similar to MERS-CoV infection (22,16).
We found that the prognosis of patients with COVID-19 in elderly patients was worse, which was in accordance with the results of other studies (23,24,16). All 3 dead cases were elderly patients, and had multi-system disease before infected by COVID-19, with decreased umber of T lymphocyte subsets, B lymphocytes and NK cells. An investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, T lymphocyte subsets in the severe type patients (25). Therefore, patients with COVID-19 should actively deal with their comorbidities, prevent bacterial infection and strengthen immune support treatment.
This study found that older patients with COVID-19 indicated relatively higher proportion of comorbidities than non-elderly patients, and the most common comorbidities were atherosclerotic cardiovascular disease (56.5%), hypertension (43.5%) and chronic pulmonary disease (21.7%), which was consistent with other studies (26,15). These multiple disease coexisting in elderly patients affected each other and leaded to complicated and complex diseases. Severe patients were significantly more in elderly patients than non-elderly patients, which was in accordance with previous researches (27,19). Comorbidities was a risk factor for severe cases (OR=2.95, P=0.035). We also observed that elderly patients indicated relatively higher proportion of complications, such as shock The co-occurrence of chronic diseases in the elderly is a common problem in the field of global public health (7). It was reported that more than half of the elderly in developed countries had more than three chronic diseases, meaning an individual suffers from two or more diseases with different pathology and no mutual dependence at the same time (8,9). Studies in China such as Beijing and Shanghai suggest that more than 70 percent of elderly people in the community have two or more chronic diseases (10,11). Compared with patients with a single disease, the hospitalization rate and fatality rate of patients with comorbidities are higher, and the clinical prognosis is significantly lower. A cohort study showed that comorbidities were independent predictors of clinical prognosis in patients with cardiovascular disease (28). Comorbidities make medical decisions more complex and difficult. And, comorbidities often involve multiple medications, and the interactions between drugs and diseases often lead to worse final efficacy, worse prognosis, more adverse reactions and more medical costs (28).
At present, there are no guidelines for comorbidity management. In 2012, the American geriatrics society organized an expert group to formulate the guiding principles for clinical management of comorbidity in the elderly, such as considering the complexity and feasibility of the treatment plan; optimize the treatment plan to choose the one that benefits the most, does the least damage and can improve the quality of life, and carry on the elaboration explanation one by one (9). Doctors should be reminded that the treatment of comorbidities should emphasize patient-centered treatment, considering the whole patient and giving the most appropriate individual treatment.

Limitations
There are some limitations in our study. First, not all COVID-19 cases in Sichuan were enrolled in this study, but only patients admitted to Public Health Clinical Center of Chengdu. And the sample size of our study is relatively small. A study which cover wide population is needed to get more accurate results. Secondly, more detailed patient information was not analyzed, especially different treatment methods and their outcomes.

Conclusions
In this study we observed elderly patients infected with COVID-19 had a high proportion of severe cases and comorbidities, more likely to show low immune function and indicated higher proportion of complications during the course of COVID-19 infection. All dead cases were elderly patients and with low immunity and comorbidities. Therefore, we should pay more attention to elderly patients, especially their comorbidities, and try to give the most appropriate individual treatment for older patients with COVID-19 infection.