key: cord-275866-m89hgf41
authors: Li, Ping; Chen, Lulu; Liu, Zheming; Pan, Jinghui; Zhou, Dingyi; Wang, Hui; Gong, Hongyun; Fu, Zhenmin; Song, Qibin; Min, Qian; Ruan, Shasha; Xu, Tangpeng; Cheng, Fan; Li, Xiangpan
title: Clinical Features and Short-term Outcomes of Elderly Patients With COVID-19
date: 2020-05-31
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.05.107
sha: 
doc_id: 275866
cord_uid: m89hgf41

Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. Methods 204 elderly patients (≥60 years old) diagnosed with COVID-19 in Renmin Hospital of Wuhan University from January 31st to February 20th, 2020 were included in this study. Clinical endpoint was in-hospital death. Results Of the 204 patients, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD) were the most common coexisting conditions. 76 patients died in the hospital. Multivariate analysis showed that dyspnea (hazards ratio (HR) 2.2, 95% confidence interval (CI) 1.414 to 3.517;p < 0.001), older age (HR 1.1, 95% CI 1.070 to 1.123; p < 0.001), neutrophilia (HR 4.4, 95% CI 1.310 to 15.061; p = 0.017) and elevated ultrasensitive cardiac troponin I (HR 3.9, 95% CI 1.471 to 10.433; p = 0.006) were independently associated with death. Conclusion Although so far the overall mortality of COVID-19 is relatively low, the mortality of elderly patients is much higher. Early diagnosis and supportive care are of great importance for the elderly patients of COVID-19.

The severity of symptoms variable was categorized as mild, severe, or critical. Mild cases included non-pneumonia and mild pneumonia cases. Severe was characterized by dyspnea, respiratory frequency ≥ 30/minute, blood oxygen saturation ≤ 93%, PaO2/FiO2 ratio <300, and/or lung infiltrates >50% within 24-48 hours. Critical cases were those that exhibited respiratory failure, septic shock, and/or multiple organ dysfunction/failure 8 .

Medians and interquartile ranges were calculated as summaries of continuous variables.

For categorical variables, percentages of patients in each category were determined.

Poor outcome was defined as the earliest of death. The time to death were investigated using survival analysis with follow up starting at hospital admission and ending on 20 February 2020. The primary end point was death. Patients were censored if at the end of the end of follow up they were still alive (for mortality). The Kaplan-Meier method was used for time-to-death plot. Comparisons between groups of time-to-death data were made using the Cox proportional hazards model. A multivariate Cox proportional hazards model was used to analyze independent risk factors for mortality from the three variables: age, onset of dyspnea, presence of any comorbidities. The same method was used to identify risk factors for adverse outcomes. SPSS (version 22.0) was used for all statistical analyses. A P value of less than 0.05 is considered statistically significant.

The initial study cohort comprised of 209 elder patients. Five patients who contracted J o u r n a l P r e -p r o o f 5 COVID-19 while in the hospital during a prolonged stay that began well before the The median time between the onset of symptoms and admission was 10 days (7-14 days). The IQR time from self-reported earliest known exposure to onset of symptoms was 11days (7-15days) for prodrome (fatigue or myalgia), 10 days (7-14 days) for selfreported fever, 11 days (8-14 days) for diarrhea, and 10 days (7-14 days) for cough or dyspnea.

Laboratory data on admission are shown in Table 2 The univariate Cox proportional hazards model showed that the mortality risk was 5.3 times of that in those aged above 70 (95% confidence interval (CI) 3.1 to 9.0; p<0.001).

For every 5 years increase in age, the risk of death increased by 1.55. However, there was no difference in the proportion of men and women with mortality. The initial State of COVID-19 at admission is closely associated with mortality in the elderly. Severe or critical cases were associated with an increased mortality risk of 10 (95% CI 5.4 to 14.6; p<0.001).The presence of any comorbidities increased the mortality risk (hazards ratio (HR) 3.1, 95% CI 1.6 to 5.8; p=0.001), with COPD (HR 3.1, 95%CI 1.8 to 5.4 ; p< 0.001) and chronic renal failure (HR 4.2, 95% CI 1.7 to 10.5; p=0.002), being the most important comorbidities ( Table 2 ). The presence of cardiovascular disease with an increased mortality of 1.8 (95% CI 1.1 to 2.9; p=0.016), similar to hypertension with an increased mortality of 2.3 (95% CI 1.5 to 3.6; p<0.001)(figure 2).Other J o u r n a l P r e -p r o o f 8 comorbidities factors (cancer and diabetes mellitus) had no significant effects on mortality. In addition, onset of dyspnea before admission increased the mortality risk (HR 2.0, 95% CI 1.3 to 3.2; p=0.002). Leucocytosis, neutrophilia, pH values, CKMB levels, , ultra-TnI, d-dimer, albumin, procalcitonin, partial pressure of carbon dioxide, the partial pressure of oxygen, and oxygen saturation were also associated with death ( 

We conducted a cohort of 204 elder patients over 60 years who were hospitalized with COVID-19 in Wuhan, China. We observed similar clinical features as recently reported COVID-19. The most common symptoms were fever, cough, and dyspnea. Fever was the first symptom reported by many patients (78.9%). The onset of dyspnea might help physicians identify the patients with poor prognosis.35.3% patients were classified as severe or even critical cases on admission. The overall rate of serious illness was higher than those reported in previous studies. In addition, a significant portion of patients showed bilateral infiltrate chest radiograph results on admission.

Univariate analysis showed age of 70 years or older, comorbidity (hypertension, J o u r n a l P r e -p r o o f cardiovascular disease, COPD, chronic renal failure), onset of dyspnea, and several laboratory indices abnormalities were associated with poor outcome. In our multivariable Cox proportional hazards model, dyspnea, older age, neutrophilia and elevated ultra-TnI were independently associated with poor outcomes.

In this study, we reported 76 death of COVID-19. Most patients had pulmonary consolidation and hypoxemia which was difficult to recover. The clinical characteristics of these patients indicated that the age and underlying diseases were the most important risk factors for death. For every 5 years increase in age, the risk of death increased by 1.55. The most common underlying disease was hypertension, followed by cardiovascular disease, diabetes, COPD, malignant tumors, and kidney disease. The effects of age and comorbidities have also been addressed in other cohorts of patients with COVID-19 4,5 . The presence of cancer or diabetes mellitus was related to a higher mortality rate or an adverse outcome in other studies 4 , which could predispose to superimposed nosocomial pneumonia due to Staphylococcus aureus or other agents in these already critically ill patients, although this was not observed in our patients.

However, the presence of COPD, chronic renal failure, cardiovascular disease or hypertension was related to a higher mortality rate in our data.

The patients with underlying disease of lung, heart, and kidney are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), most likely because angiotensin converting enzyme II (ACE2) protein has an abundant expression in many kinds of cells, such as renal tubular epithelial cells, alveolar epithelial cells, heart, artery smooth muscle cells 9 . The coronavirus has a three-dimensional structure of spike J o u r n a l P r e -p r o o f protein, which is closely bound to human cell receptor ACE2. Therefore, the cells with ACE2 expression may act as target cells and be susceptible to COVID-19 infection, such as type II alveolar cells (AT2) in the lung 10 .

In terms of laboratory tests, the count of lymphocytes in most patients was reduced.

This result suggests that COVID-19 is a viral disease characterized by decreased lymphocyte count, like those recently reported 4, 5, 11 . Although lymphopenia has been commonly observed, the absolute lymphocyte count was not associated with poor outcome in our study. Most patients' albumin levels and 84.8% hemoglobin levels were decreased, which indicates that malnutrition is common to elderly patients. Elevated alanine aminotransferase and aspartate aminotransferase levels were prevalent on admission in our cohort. High levels of D-dimer was found in more than half of patients with infection. These findings are quite different from those associated with pneumonia caused by common bacterial pathogens, but similar to those previously observed in patients with SARS-CoV infection 12, 13 . The routine blood test and PCT were used to reflect changes in the inflammatory response in COVID-19. Increased white blood cell and neutrophils count were observed in 30.64% and 33.33% of patients. In particular, a high neutrophil count was an independent predictor for poor outcome. Neutrophilia was observed during the cytokine storm induced by virus infection [14] [15] [16] . In the study of Betsy et al, after autopsy they showed neutrophils infiltrating lung in the context of a cytokine storm triggered ARDS and caused organ damage and mortality in COVID-which will seriously damage the lung function and resulted in dyspnea and acute respiratory failure when fluid builds up in the air sacs in lungs. Elevated levels of ultra-TnI was more commonly seen in COVID-19. Cardiac complications were common in patients with pneumonia in our cohort. The high level of ultra-TnI was another independent predictor for poor outcome. The present understanding of the human cardiovascular response to infections, including pneumonia, is derived mainly from studies of critically ill patients with septic shock 17 . Further research is needed to investigate the pathogenesis of sepsis in COVID-19 illness.

In the largest case series to date of COVID-19, a total of 1,023 deaths have occurred among 44,672 confirmed cases for an overall case fatality rate of 2.3% 3 , and the ≥80 age group had the highest case fatality rate of all age groups at 14.8%. However, in our case series,≥ 60 years old age group had a case fatality rate of 37.3% which is much higher. The possible explanation is that the cases in our cohort are from the stage of the epidemic outbreak. Most of the patients have to be isolated at home without medical support due to a lack of inpatient beds in the hospital. Two-third of patients in our studies had received empirical therapy out of hospital over ten days before their admission with COVID-19. So that their illness was from mild to severe. Moreover, the case fatality rate of is unsurprisingly highest among critical cases at 75%. However, it is difficult to calculate the true mortality rate of the disease while the epidemic is continuing and it is impossible to ascertain which of the remaining patients will eventually die or be discharged.

Until now, no specific antiviral treatment has been recommended for coronavirus J o u r n a l P r e -p r o o f infection. Once infected, the Older patients are harder to treat without supportive care.

Currently, the approaches to control this disease is to prevent the sources; use of personal protective equipment to reduce the transmission; and early diagnosis, isolation, and supportive treatments. This study suggests that the elderly patients of COVID-19 have a rapid course of the disease and a higher case fatality ratio. Severe cases on admission were often subjected to higher death rates. According to current diagnostic criteria, viral nucleic acid test results confirmed by RT-PCR assay play a vital role in determining whether to hospitalize a patient. The overall sensitivity of the RT-PCR test for coronavirus in patients was only 59% 18 which needs to be improved. This might be affected by sample quality, the methods of obtaining the samples, as well as the viral load. Early diagnosis and supportive care in the hospital are of great importance for the elderly COVID-19 patients. The elderly patient with acute dyspnea should seek medical attention immediately.

The results of this study must be interpreted with caution and this research is subject to several limitations. This was a retrospective case series study based on data from medical records. clinical notes and patient charts. Accordingly, certain information was missing for various patients, and certain data that may have been based on patient memory, such as details concerning exposure history and timing of onset of symptoms, maybe affected by recall bias. Not all laboratory tests were done in all patients.

Laboratory parameter is not all documented in our studies. Finally, in an effort to quickly disseminate information to clinicians worldwide, we only assessed short-term outcomes. The follow-up evaluation to determine the long-term repercussions of this 

World Health Organization. Novel coronavirus(2019-nCoV): situation report 51

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of

Cases From the Chinese Center for Disease Control and Prevention

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interimguidance

The Novel Coronavirus Pneumonia Emergency Response Epidemiology T. The (COVID-19) -China

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan

A major outbreak of severe acute respiratory syndrome in Hong Kong

Preliminary clinical description of severe acute respiratory syndrome

New fronts emerge in the influenza cytokine storm

On the alert for cytokine storm: Immunopathology in COVID-19

Targeting potential drivers of COVID-19: Neutrophil extracellular traps

Acute pneumonia and the cardiovascular system

Correlation of Chest CT and RT-PCR Testing in Monocyte count

Abbreviations: IQR, interquartile range; INR, international normalized ratio; CKMB, creatine kinase-MB; ultra-TnI, Ultrasensitive cardiac troponin I; PH, Pondus Hydrogenii; pCO 2 , partial pressure of carbon dioxide

Abbreviations: COPD, chronic obstructive pulmonary disease

95% CI, 95% confidence interval; CKMB, creatine kinase-MB; ultra-TnI, Ultrasensitive cardiac troponin I; PH, Pondus Hydrogenii