key: cord-323421-67r1qmc9 authors: Liao, Yunfei; Feng, Yong; Wang, Bo; Wang, Hanyu; Huang, Jinsha; Wu, Yaxin; Wu, Ziling; Chen, Xiao; Yang, Chao; Fu, Xinqiao; Sun, Hui title: Clinical Characteristics and Risk factors for developed COVID-19 patients transferring to designated hospital from Jianghan Fangcang shelter Hospital: a retrospective, observational study date: 2020-04-24 journal: nan DOI: 10.1101/2020.04.21.20074724 sha: doc_id: 323421 cord_uid: 67r1qmc9 Background The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. Fangcang shelter hospitals have been applied in COVID-19 to ease ongoing shortage of medical resources in Wuhan since February 2020. Methods This study enrolled all cases (no=1848) with mild or moderate type of COVID-19 in Fangcang shelter hospital of Jianghan in Wuhan from Feb 5th to Mar 9th, 2020. Diagnosis of COVID-19 was based on the National health commission of China. Epidemiological history, comorbidity, vital signs, symptoms and signs were recorded in detail. Laboratory tests included biochemical indicators and nucleic acid tests by throat swabs have been performed as well. Findings A total of 1327 patients reached the criteria of isolation release. Meanwhile, 521 patients have been transferred to the designated hospitals for further treatment, including severe type, fever more than 3 days, and severe comorbidity. The case-severity rate (rate of mild or moderate type transforming to severe type) was 3.0% in the shelter hospital. The patients from mild or moderate type to severe type showed the following clinical characteristics: the median incubation (onset to shelter) period was 10 days; they were all symptomatic at admission; fever, cough, and fatigue were the most common symptoms; hypertension, diabetes and coronary heart diseases were common co-morbidities; most of the patients had elevated levels of CRP at ill onset with 33.3% over 10 mg per L; bilateral distribution and ground-glass opacity were the most common manifestations in chest CT. Interpretation The potential risk factors of fever, fatigue, high level of C-reactive protein were the risk factors to identify the progression of COVID-19 patients with mild or moderate type. Fangcang shelter hospitals have substantially reduced the time from the onset of severe symptoms transfer to a designated hospital. Early application of the Fangcang shelter hospital may contribute to decrease the ratio of mild transforming to severe patients. Funding No specific grant from any funding was applied to this research. The coronavirus disease 2019 (COVID -19) has been shown the ability of human-to-human transmission and become a world-wide emergency. 1 The World Health Organization (WHO) has recently declared COVID-19 outbreak in several countries. Since January 2020, thousands of new patients have been diagnosed every day, which requires enormous medical resources. The surge of infections placed huge pressure on the national medical system. 2 The Fangcang shelter hospitals in Wuhan were large-scale, temporary hospitals, rapidly built by converting existing public venues, such as exhibition centers and stadiums, into health-care facilities. They were served to isolate patients with mild or moderate COVID-19 from their families and communities, while providing basic medical care, disease monitoring, food, shelter, and social activities. 3 Fangcang shelter hospitals presented five essential functions: isolation, triage, basic medical care, frequent monitoring and rapid transfer, and essential living and social engagement. Patients with mild or moderate COVID-19 who met additional admission criteria were isolated and treated in the Fangcang shelter hospitals, whereas patients with severe or critical COVID-19 received medical care in traditional hospitals. [3] [4] [5] [6] Fangcang shelter hospitals provide basic medical care and monitored the progression of disease. As some patients remain experienced progression of COVID-19 or development of severe chronic diseases, they were transferred in a timely manner to the designated higher-level hospitals. The clinical characteristics of patients transferred to the designated hospital were important for the revision of admission criteria of COVID patients in Fangcang shelter hospitals. The case-severity (from mild or moderate to severe case) rate was an important benefit index for therapeutic efficacy assessment in shelter hospital. Dynamic observation the risk factors of mild to severe patients is contribute to great value for early prognosis and treatment. Therefore, a retrospective review of overall medical record was performed in Fangcang shelter hospital of Jianghan, which received the largest number of patients among Fangcang shelter hospitals in Wuhan. A total of 1848 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04. 21.20074724 doi: medRxiv preprint cases with mild or moderate COVID-19 were included and 521 cases transferred to the designated hospital were analyzed. The risk factors of patients from mild or moderate to severe case were detected as well. The Jianghan Fangcang shelter hospital opened on the 5 th Feb and closed on the 9 th Mar 2020. A total of 1848 cases with COVID-19 were enrolled in Jianghan Fangcang shelter hospital of Wuhan from Feb 5th to Mar 9th, 2020. The admission criteria of Fangcang shelter hospital were COVID-19 patients with mild or moderate type. Diagnosis of COVID-19 was based on the National health commission (NHC) of the People's Republic of China. 7 The clinical classifications are as follows: (1) Before admission into Fangcang shelter hospital, all suspected patients of Covid-2019 were taken upper respiratory throat swab samples. Chest CT scan was performed as well. Clinical and laboratory findings were recorded and carefully checked. Laboratory tests included biochemical Indicators, blood routine, and C-reactive protein (CRP, normal range 0-4 mg per L). Epidemiological history, comorbidity, vital signs, symptoms and signs were recorded in detail. Patients meeting the diagnosis of mild or moderate type were admitted to the mobile cabin hospital. Two reviewers (HW, JH) independently checked all collected data. In case of disagreement among two reviewers, consensus was conducted by a third reviewer (YW). During the following days in Fangcang shelter hospital, the patients were re-examined for laboratory and imaging examination, and recorded symptoms, signs, treatments and outcome events. The throat swab specimens of RT-PCR test and chest CT scan were performed according to the symptoms and signs. The clinical outcomes of patients in the mobile cabin hospital were divided into three ways. They were the patients transferred to the designated hospitals for further treatments, the patients reaching the criteria of isolation release, and the patients kept treatment in the mobile cabin. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04. 21.20074724 doi: medRxiv preprint Throat swab samples were stored in virus transport medium and transported to Wuhan Union Hospital for laboratory diagnosis. Throat swab specimens of all patients were subject to real time PCR tests by amplifying ORF1ab gene and N gene of SARS-CoV-2 (BioGerm, Shanghai, China). The CT examinations were carried out with a 16-row multidetector CT scanner (μCT550, Shanghai LianYing medical technology co., LTD) using the following parameters: detector collimation widths 64 ×0.6 mm, 128×0.6 mm, 64×0.6 mm, and 64×0.6 mm; and tube voltage 120 kV. Continuous variables were represented by mean (standard deviations, SDs) or median (interquartile range, IQR) as appropriate, categorical variables were described as number (%). Significant differences between the 2 groups (mild patients and mild to severe patients) were compared by Student t test, Mann-Whitney U test, chi-square or Fischer exact test where appropriate. In addition, we also used univariable and multivariable logistic regression models to explore potential risk factors related to mild developing to severe. Considering the total included severe patients (n=56) in this study and in order to avoid over-fitting in our multivariable logistic regression models, we chose five variables for this model based on significant results (P<0.05) from the univariate regression. The results were present as odds ratio (OR) [95% confidence interval]. Because all tests were two-sided, P value less than 0.05 was considered statistically significant. Analyses were performed using SPSS 20.0 statistical package. According to the spatial structure, Jianghan Fangcang shelter hospital was is divided into 4 districts. Each district contains about 30 rooms and each room had 10-16 beds. About 300-400 patients were kept in each district per day. At least one nurse was assigned to each room and the distance between the neighboring beds was 1.5-1.8 meters in the room. There were about 25 doctors and 120 nurses on duty by turns in each distract, ensuring that doctors and nurses were available 24 hours a day. Doctors and nurses carried out the daily round separately. The digital ratio of patients to doctors and nurses was about 1.6 (1848/1180). After admission, all patients were given antiviral therapy (e.g., abidor hydrochloride) and other individualized treatments (such as antibiotics, antihypertensive and hypoglycemic therapy) according to the doctor's advice and NHC's interim guidelines. 7 Among 1848 enrolled patients, the age range was from 15 to 81 years, and 49.0% were men. From Feb 5th to Mar 9th, 521 patients were transferred to designated hospitals for further treatment. Meanwhile, the other 1327 patients reached the criteria of isolation release or discharge, (Figure 1 ). Among 521 patients transferring to the designated hospitals, 10.7% patients with severe type from mild or moderate type (56 cases), 6.9% (36 cases) patients with body temperature more than 38.5°C for 3 days or more after treatment, 15.0% (78 cases) patients with cancer or severe liver/kidney/heart disease, 45.9% (239 cases) patients with the persistent positive nucleic acid testing after 2 weeks treatment, and 21.5% (112 cases) patients with other reasons (including new onset severe symptoms or mental illness or tremendous mental pressure or pregnant woman). The basic clinical characteristics of patients transferring to the designated hospitals were in Table 1 . The case-severity rate was identified as the proportion of mild or moderate type progressing to severe type in this study. A total of 56 patients have progressed from mild or moderate type to the All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. The risk factors from univariable analysis with statistic difference were included in multiple regression analysis. Compared with mild or moderate patients, odds of mild-to-severe were higher in patients with cough and fatigue in univariable analysis. Patients of fever on cabin admission, and high level of CRP (≥10 mg per L) were also associated with mild-to-severe type (Table 4) . Furthermore, the shelter period of patients less than 7 days was related with high odds transforming severe type. We then included those 148 patients with complete data for top five most statistically significant variables in the multivariable logistic regression model. The results showed that patients with fever on admission of Fangcang shelter hospital, less shelter period (7 days), fatigue and high level of CRP (≥10 mg per L) were associated with increased odds of mild-to-severe type (Table 4) . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. The novel coronavirus COVID-19 rapidly spread globally, affecting now nearly every continent. The number of patients with severe type determines the final mortality rate of COVID-19. In this study, the case-severity rate was observed with a relatively large prospective cohort, which might be a valuable complement to the characteristics of COVID-19. In the Fangcang shelter hospital of Jianghan, about 3.0% of the patients transformed to severe, which was significantly lower than the 14% cases classified as severe or critical in the spectrum of COVID-19 disease. 8,9 Furthermore, the median incubation (onset to shelter ) period was 10 days and over half of the patients were less than 14 days. Meanwhile, the median time of staying in mobile cabin was 4 days, (21.8%) less than 3 days, 52.7% between 3-7 days, 25.5% more than 7 days. This suggests that the difference in incubation time at the onset of the disease is more indicative for the mild or ordinary patients transforming to severe type. The important function of Fangcang shelter hospital is frequent monitoring and rapid referral. The Jianghan Fangcang shelter hospitals were integrated into the overall health systems of Wuhan via simple pathways of transfer. Overall, Fangcang shelter hospitals had substantially reduced the time from the onset of severe symptoms to admission to a designated hospital, compared to the alternative of home isolation. 10, 11 Previously, older age (over 65 years) was associated with higher odds of progression to severity of COVID-19, which also has been reported as an important independent predictor of mortality in SARS and MERS. [12] [13] [14] In order to better display the clinical characteristics of mild or moderate to severe patients below 65 years old, 92 age-and sex-matched mild or moderate patients stayed in the Fangcang shelter hospital at the same time. In this study, several factors in adults who were hospitalized in Fangcang shelter hospital were associated with mild progressed to severe COVID-19. In particular, All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04. 21.20074724 doi: medRxiv preprint patients aged 40-65 years constituted the highest proportion within the severe group in this study. It have reported that 75% of COVID-19 death cases previously suffered 1-2 underlying diseases, a majority of which were diabetes and cardiovascular diseases. 15 In line with above evidence, our study also found that 42.9% of the mild to severe patients had 1-2 basic diseases, such as cardiovascular diseases, cerebrovascular diseases and endocrine system diseases. The most common symptom on admission was fever and 76.8% (43/56 cases) mild to severe patients got fever on cabin admission. However, some patients with Covid-19 did not have fever abnormalities on initial presentation, which has complicated the diagnosis. 16 In this study, 55.4% patients were with peek temperature more than 38.0°C, while 12.5% of patients were once with fever over 39.0°C. High fever was associated with the development of severity and critical death. [17] [18] [19] Therefore, keep vigilance of those mild patients whose peak temperature over 38.0°C. They were quickly transferred to designated higher-level hospitals once the blood oxygen saturation of those patients was less than 93% in Fangcang shelter hospital of Jianghan. For more specialized monitoring, chest imaging and laboratory services were applied in the Fangcang shelter hospitals. Ground-glass opacity (53/56, 94.6%) was the most common morphological depiction in CT scan on admission. However, only 19.6% of patients showed multiple lesions, 42.9 % patients presented bilateral lesions. Compared with mild patients, most severe patients took CT scan in this study within seven days. The lesions that were present in asymptomatic individuals progressed to bilateral diffuse disease with consolidation around day 10 after the symptom onset. [20] [21] [22] The predominant CT pattern was unilateral and multifocal ground-glass opacities in early stage, then lesions quickly evolved to bilateral, diffuse ground-glass opacity in later stage. 20 However, those characteristics were not consistent with what we had expected in this study. Therefore, the value of lung CT in determining the prognosis of mild COVID-19 patients still needs further research. Meanwhile, most of the patients had elevated levels of CRP at ill onset with 33.3% over 10 mg/L. Similarly, compared to mild or moderate cases, severe cases more frequently had higher levels of CRP. 16 ,23-24 Therefore, imaging and laboratory results could contribute to make the quick decision of transferring to the designated hospitals. Notably, several clinical manifestations were identified as risk factors for progression from mild to severe in the univariate logistic regression analysis. We found that fatigue on admission was associated with increased odds of mild to severe (Table 4) . Furthermore, 57.1% patients had the manifestation fatigue. Report had showed that 45% severe survivors still had cough on discharge and 72% severe non-survivors still had cough at the time of death. 16, 17 In this study, we found cough is associated with case-severity outcome of COVID-19 in univariable analysis. Less common symptoms include a sore throat myalgia or arthralgia, poor appetite. However, respiratory system affection remained as the primary symptom. 23,25-26 Overall, onset of fever and fatigue symptoms should be closely monitored among cabin hospital, more attention should also be paid to patients on those isolation patients at home. Moreover, the shelter period of patients less than 7 days was related with high odds transforming severe type. There were some limitations in this study. Firstly, due to limited medical resources in Fangcang shelter hospital, not all laboratory tests have been performed, such as lactate dehydrogenase, IL-6, and serum ferritin. Secondly, the study was limited to the patients with mild or moderate infection in a single center study. However, we focused on the therapeutic and preventive value of mobile cabin hospital in the COVID-19 patients with mild or moderate type. The study population is representative of cases mild developed to severe in Wuhan. To the best of our knowledge, this is the largest All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04. 21.20074724 doi: medRxiv preprint retrospective cohort study to disclose the clinical characteristics and risk factors for developed COVID-19 patients transferring to the designated hospital in Fangcang shelter hospital. Overall, Fangcang shelter hospitals have substantially reduced the time from the onset of severe symptoms to admission to a designated hospital. Early application of the Fangcang shelter hospital may contribute to alleviate the shortage of medical resources and decrease the ratio of severe patients. We believe that the information in the article will provide valuable data for other countries facing the COVID-19 pandemic, when they are establishing the national public health emergency management for COVID-19. HS designed the study and had full access to all of the data in the study and was responsibility for the integrity of the data and the accuracy of the data analysis. HW, JH, YW, ZW, XC, CY and XF collected data. BW, YL and YF analyzed data. YL and YF wrote the Article. All authors critically revised the manuscript for important content and gave final approval for the version to be published. We declare no competing interests. COVID-19: too little, too late? National Health Commission of the People's Republic of China. Updates on the epidemic (in Chinese) Fangcang shelter hospitals: a novel concept for responding to public health emergencies Novel Coronavirus Pneumonia Emergency Response Key Places Protection and Disinfection Technology Team CCfDCaP. 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The Lancet Respiratory medicine 2020 Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study COVID-19 pneumonia: what has CT taught us? The Lancet No specific grant from any funding was applied to this research. The Jianghan Fangcang shelter hospital was managed daily by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and twenty-one medical teams from other provinces associated with six local hospitals participated in the work. We thank 1573 staff in the Jianghan Fangcang shelter hospital, including 308 doctors, 872 nurses, 120 medical technician, 16 hospital infection-control staff and 257 administrative logistical staff.