key: cord-0934824-iimtc4dt authors: Rui, Li; Sirui, Li; Xuebei, Du; Xujun, Ye; Yanggan, Wang title: Clinical observations in the very elderly patients with COVID‐19 in Wuhan date: 2020-07-07 journal: Geriatr Gerontol Int DOI: 10.1111/ggi.13974 sha: f58a5831c532d451e342f1626f7db5d6bf10de84 doc_id: 934824 cord_uid: iimtc4dt BACKGROUND: In December 2019, the outbreak of coronavirus disease 2019 (COVID‐19) was initiated in Wuhan, now causing a worldwide pandemic. However, the experience in the very elderly patients is very limited, which has important implications for the surveillances of hospital infection in medical and health institutions. METHODS: Seven patients with confirmed COVID‐19 infection in the Department of Geriatrics at Zhongnan Hospital of Wuhan University were included. Clinical data were retrospectively collected and analyzed. The laboratory test and chest CT images from the patients before and after the COVID‐19 infection were compared. RESULTS: The median age of patients was 91 years old (from 87 to 96). Six patients had pneumonia in the last six months. Dyspnea occurred in one patient 64 hours after the onset of the disease. The rest six patients only manifested minor fatigue with low fever. Lymphopenia and a significant reduction in plasma globulin level has been observed compared to the levels before the onset of the disease. None had typical chest CT phenotypes at the early stage, except the mentioned critically ill patient who had a “white lung” development and died. One even showed an absorption of inflammation compared with previous hypostatic pneumonia. CONCLUSIONS: The ratio of fatal cases in the very elderly COVID‐19 infected patients is not higher to that reported in the non‐elderly patients, probably due to low immune response. The elderly patients, however, manifested minor clinical symptoms and atypical changes in chest CT images, which usually lead to misdiagnosis or delayed diagnosis. In December, 2019, an outbreak of a novel coronavirus disease, now known as COVID-19, was reported in Wuhan, China. As of Feb 21, 2020, a total of 75,467 COVID-19 infected patients have been diagnosed in China. The disease is quickly spread out to 29 countries. On Jan 30, the pathogen was identified to be a novel beta-coronavirus by whole genome sequencing the lower respiratory tract samples from the infected patients. 1 Histological examination of patients' lung revealed pulmonary edema and interstitial mononuclear inflammatory infiltrates. 2 Up to date, several studies have reported the clinical features of this quickly spread viral disease. [3] [4] [5] [6] [7] [8] [9] The clinical manifestations included fever, dry cough, fatigue and dyspnea. 4 Leukopenia (9-25%), leukocytosis (24-30%) and lymphopenia (63%) were observed. 3, 4 Typical chest tomography includes bilateral patchy shadows or ground glass opacity. 7 Based on the observation from a total of 8,866 patients, Yang et al reported a median incubation period of 4.75 days, The R0 was estimated to be 3.77. Male patients and patients with This article is protected by copyright. All rights reserved. Accepted Article age more than 50 years were more sensitive to the diseases. 8 Liu et al identified neutrophil-to-lymphocyte ratio as an early risk factors for the severity of the illness. 10 Although age≥50 has been considered as a risk factor for poor prognostic, the clinical features of very elderly patients with age≥85 has not been reported. We reviewed the clinical records from seven very elderly patients in our department, and summarized the clinical features from these patients with confirmed COVID-19. The study was conducted with approval by the ethics board of Zhongnan The clinical outcomes (ie, length of stay, mortality) were followed up to February 21, 2020. The medical data recorded in this study included the demographic data, medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, and chest CT scans. Laboratory results and CT images were obtained before and after the onset of the disease. The date of disease onset was recorded as the day when patient had fever. Throat swab samples were collected for detection of SARS-CoV2. All samples were tested using qRT-PCR with the CDC recommended Kit (BioGerm, Shanghai, China), following WHO guidelines for qRT-PCR. 12 The results were assessed according to the diagnostic criteria based on the recommendation of the This article is protected by copyright. All rights reserved. National Institute for Viral Disease Control and Prevention (China) (http://ivdc.chinacdc.cn/kyjz/202001/t20200121_211337.html). Statistical analysis was performed with Prism Graphpad 6.0c and SPSS 22.0. Continuous variables were directly expressed as a range. Categorical variables were expressed as number (%). Data were recorded as mean ± SEM and analyzed by Wilcoxon rank-sum test, p<0.05 is regarded as significant. All patients were hospitalized before the outbreak of COVID-19. Neither patients nor their recent visitors had direct exposure to Huanan seafood market. The median age was 91 years (IQR, 88-94; range, 87-96), and five (71.4%) were men ( Table 1 ). All patients were quarantined immediately after the diagnosis had been made. Two of them died, one of whom died of ARDS 9 This article is protected by copyright. All rights reserved. Accepted Article days after diagnosis, another died of his ongoing heart failure. One patient was discharged, the other four were still under quarantine. The median time from first symptoms to diagnosis was 10 days (IQR, 3-18, range, 1-22). All patients had more than two comorbidities, such as hypertension (4 patients Accepted Article patient is due to progress of his ongoing heart failure. The laboratory results were analyzed from the data collected from each patient, one month prior to COVID-19 infection and 2-5 days after the manifestation of the first symptom (Table 2) . A significant decrease in white blood cells, lymphocytes and monocytes after the onset of the disease was observed, while no significant change in neutrophils was noticed ( Figure 1 ). No changes in the creatinine level were found. In contrast, a remarkable decrease in globulin level was observed without noticeable changes in the total protein levels. Abnormalities in chest CT images were detected in all patients. Only one patient (Patient 2) showed newly emerged ground grass opacity in the left upper lobe, a typical change as reported in the non-elderly COVID-19 patients This article is protected by copyright. All rights reserved. Accepted Article ( Figure 2 ). The rest either manifested a minor progression of the previously existed pulmonary disorders or atypical changes, and one patient even showed an absorption of the inflammation. To our knowledge, this is the first study to report the clinical features of COVID-19 in the very elderly patients. The time from onset to confirmed diagnosis was 10 days in average, which is longer than that reported in the non-elderly patients. Wang et al reported the median time from first symptoms to hospital admission to be 7 days in patients with a median age of 56 years 7 . The reason for the delay of diagnosis in the very elderly patients is due to the atypical manifestation of clinical symptoms, laboratory tests and chest CT. Most of these patients have comorbidities, especially the chronic pulmonary infection or pneumonia, which interfered with the diagnosis of the disease. In these seven patients, one was critically ill after the onset of the disease, with the PaO 2 /FiO 2 less than 300 mmHg. Two of the patients received non-invasive This article is protected by copyright. All rights reserved. All the paitents were local people whose residence were located in Wuchang district near the hospital. None of them had any direct or indirect exposure to the Huanan Seafood Marcket, where the initial cases of COVID-19 in Wuhan were reported. However, all these patients had lived in hospital for certain periods of time before the onset of the symptoms for other purpose, such as controlling blood pressure, glucose level, or dementia. The This article is protected by copyright. All rights reserved. Barthel ADL Index were assessed, with a result of 20 (IQR 10-35), suggesting that these very old paitents all need assited living. One paitent had normal cognitive function (Patient 1). The other six paitents had dementia, among which one had mild dementia, two had moderate dementia and three had severe dementia. This give rise to difficulties in medical history taking. All patients had fever, and two had dry cough at the onset of COVID-19. However, since most of the patients had dysphagia and chronic cough, cough could not serve as a typical symptom in these patients. Thus, fever may be an important sign and should be followed with complete laboratory examinations. The main mode of transmission has been proven to be person to person by respiratory droplet and physical contact of contaminations, while faecal-oral transmission has also been proposed. 13 Based on the early reports between December 10 and January 4, R 0 was estimated to be approximately 2.2, which means each infected patient can spread the infection to 2.2 other people. 5 In a later study with larger population analysis, R 0 was estimated to be 3.77. 8 This article is protected by copyright. All rights reserved. The number of infected patients stopped increasing in our department seven days after shutting down the central air-conditioner and visiting from patients' relatives. In this study, person-to-person transmission was considered the most important approach although the airborne transmission at the early stage could not be ruled out. The most common laboratory abnormalities in reported COVID-19 patients include decreases in total lymphocytes, prolonged prothrombin time, elevated D-Dimers and lactate dehydrogenase. 7 In our very elderly patients, we found decreases in white blood cells (3 patients), total lymphocytes (6 patients) and monocytes (1 patient), as well as the globulin levels after the viral infection. This may indicate a reduced immune and inflammatory activity. Chest CT scan is the most important approach to diagnose pulmonary lesion caused by the COVID-19. The most common abnormality was bilateral ground-glass opacities. 4 However, only one of these patients (one out of seven, This article is protected by copyright. All rights reserved. Our study has some limitations. First, this is only a single center clinical study and the number of patients is limited. Second, the diagnosis was made Scatter plots illustrate the laboratory parameters in 7 patients before and after the onset of illness. P<0.05 for each parameter collected before and after the illness, by the 2-tailed paired Student's t test. 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