key: cord-1038609-0ejs05e8 authors: Wang, Xiong; Liu, Wei; Zhao, Jinzhu; Lu, Yanjun; Wang, Xu; Yu, Caizheng; Hu, Shuhua; Shen, Na; Liu, Weiyong; Sun, Ziyong; Li, Wengang title: Clinical characteristics of 80 hospitalized frontline medical workers infected with COVID-19 in Wuhan, China date: 2020-04-14 journal: J Hosp Infect DOI: 10.1016/j.jhin.2020.04.019 sha: ec43d5e5443a59845771aea8aeb25c83b47733b9 doc_id: 1038609 cord_uid: 0ejs05e8 Summary More than 1,000 medical workers have been infected with COVID-19 in China. The 80 hospitalized patients included 57 SARS-CoV-2 confirmed and 23 clinically diagnosed. The median age was 39 years, 49 (61.25%) were women, and one patient died. The most common symptoms at onset were fever (65, 81.25%), cough (47, 58.75%), fatigue (28, 35%), myalgia (19, 23.75%), expectoration (19, 23.75%), and diarrhea (15, 18.75%). Patients of frontline medical workers at a single-center hospital showed some unique clinical and laboratory findings compared with other patients in Wuhan and outside of Wuhan. This study provides our experience for other frontline medical workers. In December 2019, coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread rapidly 1, 2 . Up to April 3, 2020, 82,857 confirmed cases have been reported in China. Human to human transmission has been confirmed, though initial epidemiological evidence suggested animal to human transmission in patients who had visited the Huanan seafood market in Wuhan 3 . SARS-Cov-2 shows close similarity to bat coronaviruses and belongs to β-coronavirus genus, but is divergent from severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV) 4 . The main clinical manifestations of COVID-19 include fever, cough, fatigue, myalgia, and bilateral distribution of ground glass opacity. Acute respiratory distress syndrome (ARDS) and death occur in severe patients. A number of studies have reported the clinical characteristics of infected patients in both Wuhan and other cities in China 1,3,5-7 . The frontline medical workers were in high risk of infection, and 1,716 medical workers were infected up to February 11, 2020 8 , and 11 of them died up to February 24, 2020. However, the clinical investigation of this special group of population was insufficient 3 . We aimed to describe the clinical characteristics of 80 hospitalized frontline medical workers at single-center hospital with COVID-19 and to compare SARS-CoV-2 confirmed cases with clinically diagnosed cases. Data collection COVID-19 was diagnosed based on positive SARS-CoV-2 nucleic acid test from Respiratory tract specimen or based on clinical diagnosis with fever and bilateral involvement on chest radiographs according to the fifth version of COVID-19 diagnosis and control plan published by the government. Epidemiological, clinical, laboratory, radiological, treatment and outcome data of the infected frontline medical workers at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were obtained from electronic medical records. Information recorded included occupation, exposure history, medical history, symptom, durations from onset to hospital admission, laboratory test, chest computed tomographic (CT) scan, treatment measure, and outcome. Laboratory findings and chest CT scan were collected on admission to hospital. Acute respiratory distress syndrome (ARDS) was defined according to the Berlin definition 9 . The study was approved by Tongji Hospital Ethics Committee (No.TJ-C2030). SARS-CoV-2 nucleic acid detection Throat swab samples were collected, stored in 5 mL virus preservation solution, and virus RNA was extracted with 24 hours on Tianlong PANA9600 automatic nucleic acid extraction system (Tianlong, Xi'an, China) with ready to use reagents. The open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes were simultaneously tested with commercial real-time reverse transcription polymerase chain reaction (RT-PCR) kit from DAAN GENE (Guangzhou, China). RT-PCR assay was performed on Tianlong Gentier 96E real-time PCR system with the following conditions: incubation at 50 °C for 15 minutes, pre-denaturation at 95 °C for 15 minutes, 45 cycles of denaturation at 94 °C for 15 seconds, and extension at 55 °C for 45 seconds (collecting fluorescence signal). A cycle threshold value (Ct-value) of 40 or more for both genes was defined as negative, and a Ct-value less than 40 for both gene was defined as positive. Samples with a single Ct-value less than 40 required confirmation by retesting. Analyzers used to measure laboratory results The blood cell count was analyzed using Sysmex XE-2100 hematology analyzer (Sysmex, Kobe, Japan). Coagulation tests were detected by STA-R MAX coagulation analyzer (Diagnostica Stago, Saint-Denis, France). Biochemical items were analyzed with Cobas C8000 (Roche, Mannheim, Germany). Antibodies against SARS-CoV-2 including IgM and IgG was tested using iFlash3000 (Shenzhen YHLO Biotech Co., Ltd., Shenzhen, China). Statistical Analysis SARS-CoV-2 nucleic acid confirmed patients were grouped as NAC and clinically diagnosed patients were classified as CD group. The inclusion criteria of CD were listed in Table S1 . Continuous variables were presented as medians with interquartile (IQR) ranges or means and standard deviations. Student t test was used for data were normally distributed; otherwise, the Wilcoxon Rank-Sum test was used. Categorical variables were analyzed using the χ2 or Fisher's exact test. All analyses were done with SPSS 16. P value less than 0.05 was considered statistically significant. The patients were admitted from January 10 to February 24, 2020. The median age was 56 years (IQR, 32-48.5 years), and 49 (61.25%) were women (Table 1) . Nurses accounted for 51.25% of all cases. Hypertension (10, 12.50%) and renal disease (3, 3.75%) were the most common coexisting diseases. The most common symptoms at onset were fever (65, 81.25%), cough (47, 58.75%), fatigue (28, 35%), myalgia (19, 23.75%), expectoration (19, 23.75%), diarrhea (15, 18.75%), and headache (8, 10%). The median durations from onset to hospital admission was 7 days. In NAC group, 17 (29.82%) patients presented myalgia, while only 2 (8.70%) patients had myalgia in CD group (p=0.044). 28 (49.12%) NAC patients had cough, and 19 (82.61%) CD patients had cough (p=0.006). Expectoration occurred differently between the two groups (17.54% vs 39.13% for NAC and CD groups, p=0.040). The clinical characteristics were stratified by sex (Table S2) . Composition was quite different between males and females. Doctors accounted for 61.29% of males affected, whilst they accounted 8.16% of females affacted. Moreover, 22.58% of males had hypertension, and only 6.12% of females suffered with hypertension. Other aspects of clinical characteristics were similar between males and females. Laboratory tests were performed on hospital admission, 19 of the 80 (23.75%) patients showed leucopenia and 38 (47.5%) showed lymphopenia. The platelet and D-dimer levels were within normal range. 12 (15%) patients showed prolonged prothrombin time (PT), and 13 (26.53%) showed shortened activated partial thromboplastin time (APTT). 19 (23.75%) patients showed increased serum creatinine level, and 30 (37.5%) had decreased creatine kinase (CK). Levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were increased in 37 (46.25%), 14 (17.5%), and 21 (26.25%) patients respectively. Bilateral involvement on chest radiographs were observed in all patients except for one (Table 2) . NAC and CD groups showed similar laboratory findings except for lymphocyte count, which was lower in NAC group. 30 (52.63%) of NAC patients showed lymphopenia, while only 8 (34.78%) showed lymphopenia in CD group. Laboratory findings showed significant difference between males and females (Table S3) . Females had higher platelet count than males. 19.35% of males had decreased platelet count, while it was only 4.08% for females. APTT was slightly different between males and females. Males had higher levels of creatinine than females. 54.84% of males had increased creatinine, whilst only 4.08% of female showed increased creatinine. Moreover, males had higher level of CK, ALT, and AST than females. Four of the 80 patients were transferred to intensive care unit (ICU) for acute respiratory distress syndrome (ARDS). 78 (97.5%) patients received antiviral treatment including Arbidol, Kaletra, and interferon-α, 75 (93.75%) were given antibiotic treatment, and 46 (57.5%) were given corticosteroid treatment. 68 (85%) patients received noninvasive ventilation, and 2 (2.5%) received invasive ventilation who further received extracorporeal membrane (ECMO). At this point, 78 (97.5%) patients had been discharged, one patient had died, and one was still in ICU ( Table 1 ). The median time for hospitalization was 20.5 days. No significant difference was found between NAC and CD groups in treatment and outcome. No significant difference was found between males and females in treatment and outcome. This is the first report of hospitalized frontline medical workers with COVID-19 including 57 SARS-CoV-2 confirmed and 23 clinically diagnosed cases. None of these workers visited Huanan seafood market in Wuhan. The median age was 39 years (IQR: 32-48.5 years), similar with a report from Zhejiang province, China, which showed a median age of 41 years (IQR: 32-52 years) 7 , but different from local study from Wuhan including 138 patients with a median age of 56 years (IQR: 42-68 years). Female patients accounted for the majority (61.25%) of all cases in our study, quite different from other studies 1, 3, 7 . It suggests that the infected frontline medical workers were younger than other patients, and female workers were infected more than male, consistent with the large number of nurses serving in hospital. Hypertension was the most common comorbidity, consistent with other studies from Wuhan 3 , while liver disease was the most common comorbidity in Zhejiang province 7 . Wuhan is an inland city and Zhejiang included several coastal cities, whether the difference of comorbidity is caused by the geographic difference is unknown. The most common symptoms were similar with other studies, however, a higher ratio of diarrhea was observed in the frontline medical workers (18.75%) than other patients in Wuhan (10.1%) 3 and Zhejiang province (8%) 7 . The median time from onset to hospital admission was 2 days in Zhejiang province, shorter than that in our study (7 days), which may be caused by urgent alarm of the government from January 23 2020. The NAC group had higher ratio of myalgia but lower ratio of cough and expectoration than the CD group. The clinical features varied between male and female patients. These data indicate that the frontline medical workers showed some unique characteristics. Laboratory findings were consistent with previous studies, including leucopenia, lymphopenia, increased LDH, ALT, and AST. Yet, some results were different from other studies. D-dimer were all in normal range, and several studies showed increased D-dimer 6 . In a recent study by Tang et al, they found that Non-survivors showed significantly higher level of D-dimer than survivors in patients with COVID-19 10 . Some medical workers had already taken actions before hospital admission, and most patients were mild to moderate in our study. 12 (15%) patients showed prolonged PT and 3 (3.75%) showed decreased PT, while these numbered 5% and 30% respectively in a previous study including 99 patients in Wuhan 6 . Slightly prolonged PT was also observed in another study in our center 10 . Coagulation test may be influenced by several factors of patients. The laboratory findings also varied between male and female patients. Moreover, NAC group had lower level of lymphocyte than CD group. The treatments were different in this hospital than other regions. Antibiotics were given for 93.75% of all cases, and this number was 45% in Zhejiang province 7 . Moreover, corticosteroid treatment was carried out in 57.5% of all patients, which was only 26% in Zhejiang 7 and 44.9% in another hospital in Wuhan 6 . The mortality was 1.25% in our study, low than 4.3% in other patients in Wuhan 6 . Both NAC and CD groups received similar treatments and showed similar outcome. 16 of the 23 CD patients received antibodies test against SARS-CoV-2 including IgM and IgG. All the 16 patients showed positive IgG, and 5 of 16 patients had positive IgG and IgM. Therefore, the negative nuclear acid result of SARS-CoV-2 in CD patients might be caused by the low sensitivity of its method. In conclusion, patients of frontline medical workers at a single-center hospital showed some unique clinical and laboratory findings compared with other patients in Wuhan and outside of Wuhan. This study provides our experiences for other frontline medical workers. We declare no competing interests. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China First Case of 2019 Novel Coronavirus in the United States Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series Acute respiratory distress syndrome: the Berlin Definition We thank all patients involved in the study.