key: cord-303799-9hh17k86 authors: Huang, Ying; Yang, Rui; Xu, Ying; Gong, Ping title: Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China date: 2020-02-29 journal: nan DOI: 10.1101/2020.02.27.20029009 sha: doc_id: 303799 cord_uid: 9hh17k86 Background Although the outbreak of Coronavirus disease 2019 (COVID-19) has caused over 2200 deaths in China, there was no study about death yet. We aimed to describe the clinical characteristics of non-survivors with COVID-19. Methods For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed by real-time RT-PCR between Jan 21 and Feb 10, 2020 according to the recommended protocol. The epidemiological, demographic, clinical, laboratory, radiological and treatment data were collected and analyzed. Outcomes were followed up until Feb 14, 2020. This study was approved by the ethics commissions of the Fifth Hospital of Wuhan, with a waiver of informed consent due to a public health outbreak investigation. Results We included 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Lymphopenia occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83-225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had acute respiratory distress syndrome (ARDS). The median time from onset to ARDS was 11 days. One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. Interpretation Lots of patients died from COVID-19 till now. The median survival time of these non-survivors from onset to death was about 2 weeks. Most patients were older males with comorbidities. They finally progressed to ARDS. The median time from onset to ARDS was 11 days. Gradually decreased lymphocytes and increased inflammation biomarkers were common, and need to be monitored in the routine treatment. Although the outbreak of Coronavirus disease 2019 has caused over 2200 deaths in China, there was no study about death yet. We aimed to describe the clinical characteristics of non-survivors with COVID-19. For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed by real-time RT-PCR between Jan 21 and Feb 10, 2020 according to the recommended protocol. The epidemiological, demographic, clinical, laboratory, radiological and treatment data were collected and analyzed. Outcomes were followed up until Feb 14, 2020 . This study was approved by the ethics commissions of the Fifth Hospital of Wuhan, with a waiver of informed consent due to a public health outbreak investigation. We included 36 patients who died from COVID- 19 author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the Lots of patients died from COVID-19 till now. The median survival time of these non-survivors from onset to death was about 2 weeks. Most patients were older males with comorbidities. They finally progressed to ARDS. The median time from onset to ARDS was 11 days. Gradually decreased lymphocytes and increased inflammation biomarkers were common, and need to be monitored in the routine treatment. There is no any funder involved in this study. The outbreak of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) happened since December 2020 in Wuhan 1 . 2 SARS-CoV-2 has been spreading in China as well as in other countries [3] [4] [5] [6] . The outbreak of SARS-CoV-2 infection has been declared as a Public Health Emergency of International Concern by the World Health Organization (WHO) on 30 January 2020. According to the situation report from WHO, as of 21 February 2020, SARS-Cov-2 infection has caused 76769 confirmed cases in 27 countries and 2247 deaths globally 7 . Severity of COVID-19 varied from mild to severe. 8 Mortality rate of COVID-19 can be reduced, by timely identifying those who are at higher risk of developing into critically ill patients, closely monitoring changes of their disease course, and applying intensive care treatment to these patients. However, reports about dead cases of COVID-19 were limited but warranted, considering the large amount of confirmed cases, which is still increasing. In this single-centered study, we retrospectively analysed specific clinical information of 36 non-survivors infected with SARS-CoV-2. For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed between Jan 21 and Feb 10, 2020 according to All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint the recommended protocol. This study was approved by the ethics commissions of hospital, with a waiver of informed consent due to a public health outbreak investigation. COVID-19 was confirmed by real-time RT-PCR using the same protocol described previously 9 . Additionally, all patients were given chest computed tomography (CT). We obtained epidemiological, demographic, clinical, laboratory, treatment and outcome data from patients' medical records. Clinical outcomes were followed up to Feb 14, 2020. We analysed epidemiological, demographics, exposure history, smoking history, chronic medical illness, signs and symptoms on admission, comorbidity, chest CT findings, laboratory findings and treatment measures. Categorical variables were described as count (%). Continuous variables were described using mean (SD) if they are normally distributed, median (IQR) if they are not. All statistical analyses were performed using R (version 3.6.1). All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint We included 36 patients who died from COVID-19 in the Fifth Hospital of Wuhan. One (2.78%) patients had a history of exposure to the Huanan seafood market in Wuhan. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). Twenty-five (69.44%) patients were males, and 11 (30.56%) female. Four (11.11%) patients have smoking history. Twenty-six (72.22%) patients had chronic diseases. The most common chronic diseases were hypertension (21, 58.33%), cardiovascular (8, 22 .22%) and diabetes (7, 19.44%) ( Table 1 ). On admission, most patients had fever, cough and more than half of them had shortness of breath (Table 2 ). Other symptoms included fatigue, dyspnea, sputum production, disturbance of consciousness, diarrhea, hemoptysis and myalgia. (Table 2) According to chest CT scan, 31 (96.88%, N=32) patients showed bilateral pneumonia (75%). On admission, leucocytes were below the normal range in 5 (14.71%) patients and above the normal range in 11 (32.35%) patients (Table 3 ). Neutrophils showed above the normal range in 16 (47.06%) patients. Lymphocytes and hemoglobin were below the normal range in many patients (Table 3) . Twelve (35.39%) patients' platelets were below the normal range. 22 patients had varying degrees of liver function abnormality, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) rose above the normal range ( Table 3) . Elevation of lactate dehydrogenase were showed in 26 (100%, N=26) patients. About 30% of these patients had different degrees of renal function damage, with elevated blood urea nitrogen or serum creatinine. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint Regarding the infection index, procalcitonin (PCT) rose above the normal range in 28 (100%) patients. 11 patients were tested for IL-6, most of whose index were above the normal range (Table 3) . 32 patients had increased C-reactive protein (CRP). Thirty-five (35, 97.22%) patients received antiviral treatment, including oseltamivir, ganciclovir, ribavirin or umifenovir hydrochloride. All patients were given antibiotic treatment ( Table 2) Table 2 ). The median time from onset to death was 17 days (Figure 1 ). We reported on 36 patients who died from SARS-CoV-2 infection in a single hospital of Wuhan. All these patients had ARDS and 28 (77.78%) patients needed mechanical ventilation. Bilateral pneumonia was detected in most patients on admission. Previous studies have shown that elder patients and males who were confirmed with coronavirus infection are at higher risk of ARDS, 10 All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint which was consistent with our study. Antibiotic treatment was used to prevent secondary infections since these patients were critically ill. Antiviral regimes were also used in most patients which we hoped may have roles but still need more data. However, there were no specific remedies for SARS-CoV-2 yet 11, 12 . Therefore, most patients were treated with supportive treatment and intensive care. Unfortunately, due to restrictions of hospital's conditions and the heavy burden of COVID-19 in Wuhan City, neither were we able to provide patients in need with advanced life support systems like Extracorporeal Membrane Oxygenation (ECMO), nor were able to transport all serious patients to superior hospital for better medical treatments in time. The median survival time of the patients in our study was only 2 weeks approximately, which was shorter compared to previous reports 13 will decrease as the clinical capacity improves. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint As reported in previous studies, patients who are male, elder or have a history of cerebrovascular disease are at higher risk of SARS-CoV-2 infection 2,14,15 . In our study, we found that the majority of coronavirus non-survivors were male patients, elder patients and patients with chronic diseases, which indicated that these patients might be also at increased risk of becoming critically ill or death. Cerebrovascular diseases were the most common comorbidities. Twentytwo (61.11%) non-survivors had cerebrovascular diseases in our report, and the percentage of cerebrovascular diseases among non-survivors was higher than that reported by Yang et al 13 . Besides, there were 4 (11.11%) non-survivors who had smoking history and 4 (11.11%) had preexisting COPD. According to previous studies on middle east respiratory syndrome coronavirus (MERS-CoV), smokers and COPD patients might be susceptible to MERS. Further, compared to non-smokers, smokers and COPD patients had a higher dipeptidyl peptidase IV (DPP4) expression, which was inversely correlated with lung function and diffusing capacity parameters 16 . Although the relationship between smoking history and susceptibility as well as worse outcomes in COVID-19 remains unclear, we cautioned that the prognosis of COVID-19 in patients with smoking history might be more severe. In our cohort, lymphocytopenia occurred in more than 70% of patients at admission, which is a main laboratory feature in COVID-19 patients 15, 17 . Lymphocytopenia have been identified in the critically ill patients with SARS-CoV and MERS infection 18, 19 . As mentioned in previous studies, the severity of lymphocytopenia might indicate the severity of COVID-19, under the assumption of SARS-CoV-2 viral could attack and destroy the lymphocyte targetedly 2 . Further studies are warranted to confirm these findings. Increased levels of serum CRP, PCT, IL-6 were also found. It indicated the obvious inflammatory response among these patients. In addition, we noticed that All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint the increased CRP, PCT concentration and decreased lymphocyte count from admission to death (Supplementary Figure 2) , which may represent more prominent inflammation in severe patients. Therefore, intravenous glucocorticoids therapy, intravenous immunoglobulin therapy and interferon-alpha (α-IFN) aerosol inhalation were also used to restore homeostasis, without solid evidence. To our knowledge, there is still no specific medicine for COVID-19 till now. Clinical trials on promising regimens for COVID-19, such as remdesivir, lopinavir, and chloroquine phosphate are ongoing, which shed light on conquering the COVID-19 epidemic 12 . This study has several limitations. First, only 36 dead cases were included. However, this is the largest cohort about the non-survivors of COVID-19 up to now. Second, some specific clinical information was insufficient, such as mechanical ventilation settings, oxygen concentration, and detailed medication history. Third, this is a retrospective, single-centered study. It may be limited to the hospital critical care resources. Further studies are still needed. In conclusion, most non-survivors are older men with comorbidities (especially cardiovascular diseases). They finally progressed to ARDS. The median time from onset to ARDS was 11 days. The mean survival time in our cohort of COVID-19 non-survivors was about 2 weeks. Gradually decreased lymphocytes and increased inflammation biomarkers were found in these patients, and need to be monitored in the routine treatment. Early detection and intervention of patients are especially important which can delay the development from mild to severe cases. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint YH, RY,YX collected the epidemiological and clinical data. YH summarised all data. YH, RY, YX, and PG drafted the manuscript. YH and PG revised the final manuscript. We declare no competing interests. The data will be made available to others on reasonable requests to the corresponding author. Deidentified participant data will be provided after approval from the corresponding author and the Fifth Hospital of Wuhan. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint author/funder, who has granted medRxiv a license to display the preprint in perpetuity. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.27.20029009 doi: medRxiv preprint A Novel Coronavirus from Patients with Pneumonia in China Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study COVID-19 in Singapore-Current Experience: Critical Global Issues That Require Attention and Action Journey of a Thai Taxi Driver and Novel Coronavirus First Case of 2019 Novel Coronavirus in the United States Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany Presumed Asymptomatic Carrier Transmission of COVID-19 COVID-19) SARS and MERS: recent insights into emerging coronaviruses Therapeutic options for the 2019 novel coronavirus (2019-nCoV) More than 80 clinical trials launch to test coronavirus treatments Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Clinical Characteristics of 138 Hospitalized Patients With Novel Coronavirus-Infected Pneumonia in Wuhan, China DPP4, the Middle East Respiratory Syndrome Coronavirus Receptor, is Upregulated in Lungs of Smokers and Chronic Obstructive Pulmonary Disease Patients Clinical characteristics of 2019 novel coronavirus infection in China Multiple organ infection and the pathogenesis of SARS T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV We thank all patients and their families involved in the study. We thank all the doctors and