《内科学》课程教学资源（新冠文献）Clinical Characteristics of Coronavirus Disease 2019 in China

TRA NEW ENGLAND IOURNAL E MEDICINE ORIGINAL ARTICLE Clinical Characteristics of Coronavirus Disease 2019 in China C.Lei,D.S.C.Hui S.Li,Jin-lin Wang.Z.Liang.Y.Pens YLuYa-hua Hu.P.Per an吗 lian-mi Wang, .Liu.Z.Chen.G.Li.Z.Zheng,S.Qiu,J.Luo,C.Ye,S.Zhu and N.Zhong,for the China Medical Treatment Expert Group for Covid-19* ABSTRACT BACKGROUND Since December 2019,when coronavirus disease 2019(Covid-19)emerged in Wuhan characterist METHODS ted da 53eracted China thr gh January 29.2020.The pri 151Y ang Rd ma to an intensive care unit (CU).the use of mechanical ventilation.or death. DESIITE A时 The median age of the patients was 47 years;419%of the patients were female The primary composite end point occurred in 67 patients (6.1%),including 5.0% who we ere ac mitte d to the ICU,2.3%who underwent invasive mecl hanical ventila ildli who die ally to th 2120 Th ere fever (43 go on admission and gg zo du ing ho NEJM.org. (678%)Diarrhea was uncommon (38%)The median incubation period was 4 dav (interquartile range,2 to 7).On admission,ground-glass opacity was the most O:10.1055/NE]Mo 2002037 common radiologic finding on chest computed tomography(CT)(56.4%).No radic disoser isese Lyphocytopenia was with nonsever frst2 months of the current outbreak,Covid-19 spread rapidly throughout China and caused varying deg es of illness.Patients often without fever,and many did not have abnormal radiologic findings.(Funded by the National Health Commission of China and others.) N ENGLJ MED NEJM.ORG The New England Journal of Medicing Dow loaded from nejm.M s Me All rights

The new england journal o f medicine n engl j med nejm.org 1 The authors’ full names, academic de￾grees, and affiliations are listed in the Appendix. Address reprint requests to Dr. Zhong at the State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Rd., Guangzhou, Guangdong, China, or at nanshan@vip.163.com. *A list of investigators in the China Medi￾cal Treatment Expert Group for Covid-19 study is provided in the Supplementary Appendix, available at NEJM.org. Drs. Guan, Ni, Yu Hu, W. Liang, Ou, He, L. Liu, Shan, Lei, Hui, Du, L. Li, Zeng, and Yuen contributed equally to this article. This article was published on February 28, 2020, and updated on March 3, 2020, at NEJM.org. DOI: 10.1056/NEJMoa2002032 Copyright © 2020 Massachusetts Medical Society. BACKGROUND Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventila￾tion, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radio￾graphic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.) ABSTRACT Clinical Characteristics of Coronavirus Disease 2019 in China W. Guan, Z. Ni, Yu Hu, W. Liang, C. Ou, J. He, L. Liu, H. Shan, C. Lei, D.S.C. Hui, B. Du, L. Li, G. Zeng, K.-Y. Yuen, R. Chen, C. Tang, T. Wang, P. Chen, J. Xiang, S. Li, Jin-lin Wang, Z. Liang, Y. Peng, L. Wei, Y. Liu, Ya-hua Hu, P. Peng, Jian-ming Wang, J. Liu, Z. Chen, G. Li, Z. Zheng, S. Qiu, J. Luo, C. Ye, S. Zhu, and N. Zhong, for the China Medical Treatment Expert Group for Covid-19* Original Article The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

Thr NEW ENGLAND JOURNAL f MEDICINE NEARLY DECEMBER 201 throughput sequencingor real-time reve RT-PCR fied in Wuhan.the capital city of Hubei al swab specimens province The pathogen has been identified as aonly laboratory-confirmed cases were included novel enveloped RNA betacoronavirus'that has in the analysis. currently been named severe acute respiratory We obtained data regarding cases outside syndrom (SARS-C Hubei province from the Nationa has a p sin bec the hig d of cli ented The World Health Organization (WHO)has re tan Hospital where many of the patients with cently declared coronavirus disease 2019 (Covid-19) covid-19 in wuhan were being treated a public health emergency of international con We extracted the recent exposure history e且total f81,109 clinical syn cas ission from el cked se lud me cal re FSARS ments in Co Given the rapid (CT) ead of Covid-19.we the clinical care needs of the patient.We deter throughout mainland China might help identify mined the presence of a radiologic abnormality the defining clinical characteristics and s on the basis of the documentation or description the disea Her we escribe the results of our medical charts;if im aging scans were he clin thr ugh disa nt h ultation with a third revie METHODS Laboratory ass essments consisted of a complete STUDY OVERSIGHT blood count,blood chemical analysis,coagula The study was supported by Natio onal Health tion test ing,assessment of liver and renal func sion of Ch na and esign the tion,and me ap genas H med 1.10 waived in light of the urgent need to collect time of admission using the american Thoraci data.Data were analyzed and interpreted by the Society guidelinesfor communityacquired pneu authors.All the authors reviewed the manuscript monia and vouch for the accuracy and completeness of All medical records were copied and sent t the data and for ble estu this e data-proce an He. cians reviewed and abstracted the data.Data DATA SOURCES were entered into a computerized database and We obtained the medical records and compiled cross-checked.If the core data were missing data for hospitalized patient requests for clarification were sent to the coo ratory-con odcoaoupata -19,as reporte iganchesubscqueaiyoataciadthetmd 11 2920 0. 1302 STUDY OUTCOMES Covid-19 was dias nosed on the basis of the The primary composite end point was admission WHO interim guidance.4A confirmed case of to an intensive care unit (ICU),the use of me- Covid-19 was defined as a positive result on high- chanical ventilation,or death.These outcomes N ENGLI MED NEIM ORO Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY nal us Copyngnt 2020 M

2 n engl j med nejm.org The new england journal o f medicine I n early December 2019, the first pneu￾monia cases of unknown origin were identi￾fied in Wuhan, the capital city of Hubei province.1 The pathogen has been identified as a novel enveloped RNA betacoronavirus2 that has currently been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has a phylogenetic similarity to SARS-CoV.3 Pa￾tients with the infection have been documented both in hospitals and in family settings.4-8 The World Health Organization (WHO) has re￾cently declared coronavirus disease 2019 (Covid-19) a public health emergency of international con￾cern.9 As of February 25, 2020, a total of 81,109 laboratory-confirmed cases had been document￾ed globally.5,6,9-11 In recent studies, the severity of some cases of Covid-19 mimicked that of SARS￾CoV.1,12,13 Given the rapid spread of Covid-19, we determined that an updated analysis of cases throughout mainland China might help identify the defining clinical characteristics and severity of the disease. Here, we describe the results of our analysis of the clinical characteristics of Covid-19 in a selected cohort of patients throughout China. Methods Study Oversight The study was supported by National Health Commission of China and designed by the in￾vestigators. The study was approved by the insti￾tutional review board of the National Health Commission. Written informed consent was waived in light of the urgent need to collect data. Data were analyzed and interpreted by the authors. All the authors reviewed the manuscript and vouch for the accuracy and completeness of the data and for the adherence of the study to the protocol, available with the full text of this article at NEJM.org. Data Sources We obtained the medical records and compiled data for hospitalized patients and outpatients with laboratory-confirmed Covid-19, as reported to the National Health Commission between December 11, 2019, and January 29, 2020; the data cutoff for the study was January 31, 2020. Covid-19 was diagnosed on the basis of the WHO interim guidance.14 A confirmed case of Covid-19 was defined as a positive result on high￾throughput sequencing or real-time reverse-tran￾scriptase–polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens.1 Only laboratory-confirmed cases were included in the analysis. We obtained data regarding cases outside Hubei province from the National Health Com￾mission. Because of the high workload of clini￾cians, three outside experts from Guangzhou performed raw data extraction at Wuhan Jinyin￾tan Hospital, where many of the patients with Covid-19 in Wuhan were being treated. We extracted the recent exposure history, clinical symptoms or signs, and laboratory find￾ings on admission from electronic medical rec￾ords. Radiologic assessments included chest radi￾ography or computed tomography (CT), and all laboratory testing was performed according to the clinical care needs of the patient. We deter￾mined the presence of a radiologic abnormality on the basis of the documentation or description in medical charts; if imaging scans were avail￾able, they were reviewed by attending physicians in respiratory medicine who extracted the data. Major disagreement between two reviewers was resolved by consultation with a third reviewer. Laboratory assessments consisted of a complete blood count, blood chemical analysis, coagula￾tion testing, assessment of liver and renal func￾tion, and measures of electrolytes, C-reactive protein, procalcitonin, lactate dehydrogenase, and creatine kinase. We defined the degree of severity of Covid-19 (severe vs. nonsevere) at the time of admission using the American Thoracic Society guidelines for community-acquired pneu￾monia.15 All medical records were copied and sent to the data-processing center in Guangzhou, under the coordination of the National Health Com￾mission. A team of experienced respiratory clini￾cians reviewed and abstracted the data. Data were entered into a computerized database and cross-checked. If the core data were missing, requests for clarification were sent to the coor￾dinators, who subsequently contacted the attend￾ing clinicians. Study Outcomes The primary composite end point was admission to an intensive care unit (ICU), the use of me￾chanical ventilation, or death. These outcomes The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

CHARACTERISTICS OF CORONAVIRUS DISEASE 2019 IN CHINA were used in a previous study to assess the se-descriptive only.We used ArcGIS.version 10.2.2 verity of other serious infectious diseases,such to plot the numbers of patients with reportedly as H7N9 infection.Secondary end points were the rate of death and the time from symptom em光e 3.6.2 (R Foundation for Statistical Computing) composite end point ReSuLts STUDY DEFINITIONS The incubation period was defined as the inter- DEMOGRAPHIC AND CLINICAL CHARACTERISTICS val between the potential earliest date of contact Of the 7736 patients with Covid-19 who had been of the transmission source (wildlife or person hospitalized at 552 sites as of January 29,2020 ed or confirmed case)and the pote est date of symptoms i.w。ns 132 pital The hosp patients had continuous exposure to contamina. tals that were included in this study accounted tion sources;in these cases,the latest date of for 29.7%of the 1856 designated hospitals exposure was recorded.The summary statistics where patients with Covid-19 could be admitted of incubation periods we e calculated on the in 30 provinces,autonomous regions,or munici- f29 clear information palities across Ch the posure ed of e de phice of37.5℃or higher. e health care and a history of fined as a lymphe ocvte count of less than 1500 contact with wildlife was documented in 1.9% cells per cubic millimeter.Thrombocytopenia was 483 patients (43.9%)were residents of wuhan defined as a platelet coun of less Among the patients who lived outside Wuhan per cubic millimeter.Additional definitions- 2.3%ha conta ct w h residents of Wuhan,in ife,ac ute respirator cluding 3 had vis ute heartm e city nc nd myolysis-are provided in the Supplementary The median incubation period was 4 days Appendix,available at NEJM.org. (interquartile range 2 to 7)The median age of the patients was 47 years(interquartile range,35 LABORATORY CONFIRMATIO to 58);0.9%of the patients were younger than mation of SARS-Co as per 5 years or age.A ota ent in tie 88 The nd m RT-PCR assavs were erformed in accordance was cough (67.8%):nausea or vomiting (5.0%) with the protocol established by the WHO.De-and diarrhea (3.8%)were uncommon.Among tails regarding laboratory confirmation processes the overall population,23.7%had at least one are provided in the Supplementary Appendix. coexisting illness (e.g..hypertension and chronic STATISTICAL ANALYSIS sdiCoid-19 the A of severity in and interquartile ranges or simple ranges,as ap patients and severe in 173 patients.Patients with propriate.Categorical variables were summarized severe disease were older than those with non- as counts and percentages.No imputation was severe disease by a median of 7 years.Moreover made for missing data.Because the cohort of the presence of any coexisting illness was more patients in our s dy wa ed tr ere di se tha dom selection,all stati om ra h nonsevere disease (8.%vs. N ENGLJ MED NEJM.ORG The New England Joumal of Medicine All rights

n engl j med nejm.org 3 Char acteristics of Coronavirus Disease 2019 in China were used in a previous study to assess the se￾verity of other serious infectious diseases, such as H7N9 infection.16 Secondary end points were the rate of death and the time from symptom onset until the composite end point and until each component of the composite end point. Study Definitions The incubation period was defined as the inter￾val between the potential earliest date of contact of the transmission source (wildlife or person with suspected or confirmed case) and the poten￾tial earliest date of symptom onset (i.e., cough, fever, fatigue, or myalgia). We excluded incuba￾tion periods of less than 1 day because some patients had continuous exposure to contamina￾tion sources; in these cases, the latest date of exposure was recorded. The summary statistics of incubation periods were calculated on the basis of 291 patients who had clear information regarding the specific date of exposure. Fever was defined as an axillary temperature of 37.5°C or higher. Lymphocytopenia was de￾fined as a lymphocyte count of less than 1500 cells per cubic millimeter. Thrombocytopenia was defined as a platelet count of less than 150,000 per cubic millimeter. Additional definitions — including exposure to wildlife, acute respiratory distress syndrome (ARDS), pneumonia, acute kidney failure, acute heart failure, and rhabdo￾myolysis — are provided in the Supplementary Appendix, available at NEJM.org. Laboratory Confirmation Laboratory confirmation of SARS-CoV-2 was per￾formed at the Chinese Center for Disease Preven￾tion and Control before January 23, 2020, and subsequently in certified tertiary care hospitals. RT-PCR assays were performed in accordance with the protocol established by the WHO.17 De￾tails regarding laboratory confirmation processes are provided in the Supplementary Appendix. Statistical Analysis Continuous variables were expressed as medians and interquartile ranges or simple ranges, as ap￾propriate. Categorical variables were summarized as counts and percentages. No imputation was made for missing data. Because the cohort of patients in our study was not derived from ran￾dom selection, all statistics are deemed to be descriptive only. We used ArcGIS, version 10.2.2, to plot the numbers of patients with reportedly confirmed cases on a map. All the analyses were performed with the use of R software, version 3.6.2 (R Foundation for Statistical Computing). Results Demographic and Clinical Characteristics Of the 7736 patients with Covid-19 who had been hospitalized at 552 sites as of January 29, 2020, we obtained data regarding clinical symptoms and outcomes for 1099 patients (14.2%). The largest number of patients (132) had been ad￾mitted to Wuhan Jinyintan Hospital. The hospi￾tals that were included in this study accounted for 29.7% of the 1856 designated hospitals where patients with Covid-19 could be admitted in 30 provinces, autonomous regions, or munici￾palities across China (Fig. 1). The demographic and clinical characteristics of the patients are shown in Table 1. A total of 3.5% were health care workers, and a history of contact with wildlife was documented in 1.9%; 483 patients (43.9%) were residents of Wuhan. Among the patients who lived outside Wuhan, 72.3% had contact with residents of Wuhan, in￾cluding 31.3% who had visited the city; 25.9% of nonresidents had neither visited the city nor had contact with Wuhan residents. The median incubation period was 4 days (interquartile range, 2 to 7). The median age of the patients was 47 years (interquartile range, 35 to 58); 0.9% of the patients were younger than 15 years of age. A total of 41.9% were female. Fever was present in 43.8% of the patients on admission but developed in 88.7% during hospi￾talization. The second most common symptom was cough (67.8%); nausea or vomiting (5.0%) and diarrhea (3.8%) were uncommon. Among the overall population, 23.7% had at least one coexisting illness (e.g., hypertension and chronic obstructive pulmonary disease). On admission, the degree of severity of Covid-19 was categorized as nonsevere in 926 patients and severe in 173 patients. Patients with severe disease were older than those with non￾severe disease by a median of 7 years. Moreover, the presence of any coexisting illness was more common among patients with severe disease than among those with nonsevere disease (38.7% vs. The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

Thr NEW ENGLAND JOURNAL f MEDICINE 251 015 97 .191 to the National Health Co ion as of February 4.2020.Thenun ator the pPoncanCphiesedbyH2witehcacfhtomorceonimedaciorcachproincauianomoasegono mentary appendix no radiographic or CT abnormality was found in RADIOLOGIC AND LABORATORY FINDINGS 157 of 877 patients (179%)with nonsevere dis- Table 2 shows the radiologi c and laboratory ease and in 5 of 173 patients (2.9%)with severe findings on adn 0n. 0f97 disease were a was presen nia (56.4%)and bilateral patchy shadowing (518%) atients had elevated levels of c-reactive protein Representative radiologie findings in two pa less common were elevated levels of alanine tients with nonsevere Covid-19 and in another aminotransferase,aspartate aminotransferase. N ENGLI MED NEIM ORG Dowloaddm OUTHERN MEDICAL UNIVv No other e nal us Copyngnt 2020 M:

4 n engl j med nejm.org The new england journal o f medicine 21.0%). However, the exposure history between the two groups of disease severity was similar. Radiologic and Laboratory Findings Table 2 shows the radiologic and laboratory findings on admission. Of 975 CT scans that were performed at the time of admission, 86.2% revealed abnormal results. The most common patterns on chest CT were ground-glass opacity (56.4%) and bilateral patchy shadowing (51.8%). Representative radiologic findings in two pa￾tients with nonsevere Covid-19 and in another two patients with severe Covid-19 are provided in Figure S1 in the Supplementary Appendix. No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere dis￾ease and in 5 of 173 patients (2.9%) with severe disease. On admission, lymphocytopenia was present in 83.2% of the patients, thrombocytopenia in 36.2%, and leukopenia in 33.7%. Most of the patients had elevated levels of C-reactive protein; less common were elevated levels of alanine aminotransferase, aspartate aminotransferase, Figure 1. Distribution of Patients with Covid-19 across Mainland China. Shown are the official statistics of all documented, laboratory-confirmed cases of coronavirus disease 2019 (Covid-19) throughout China, according to the National Health Commission as of February 4, 2020. The numerator denotes the number of patients who were included in the study cohort and the denominator denotes the number of laboratory-confirmed cases for each province, autonomous region, or provincial municipality, as reported by the National Health Commission. Tibet (0/1) Guangdong (79/683) Fujian (17/170) Taiwan (0/100) Macau (0/8) Hong Kong (0/15) Xinjiang (3/31) Ningxia Qinghai (4/33) (1/10) Gansu (12/51) Shaanxi (15/128) Yunnan (10/113) Guizhou (5/46) Sichuan (33/271) Chongqing (74/300) Guangxi (28/127) Hunan (60/521) Hubei (308/11,177) Henan (78/566) Shandong (29/246) Jiangxi (35/391) Anhui (40/408) Zhejiang (89/724) Jiangsu (37/254) Shanghai (14/193) Heilongjiang (17/109) Jilin (5/24) Liaoning (22/70) Inner Mongolia (6/31) Shanxi (16/66) Hebei (11/118) Tianjin (11/49) Beijing (21/212) Hainan 0 125 250 (19/70) 0 250 500 750 375 500 Miles Km No. of Confirmed Cases 1–9 10–99 100–499 500–999 1,000–11,177 The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

CHARACTERISTICS OF CORONAVIRUS DISEASE 2019 IN CHINA creatine kinase.and p-dimer.Patients with severe findings and in the severity of disease at the disease had more prominent laboratory abnor-time of presentation.Fever was identified in malities (including lymphocytopenia and leuko- penia)than those with nonsevere disease. oped in 88.7% e 109) No e lost to folloy oitend-pon patients with seve event occurred in67patients (.1%),including with nonsevere disease.Despite the number of 5.0%who were admitted to the ICU,2.3%who deaths associated with Covid-19,SARS-CoV-2 underwent invasive mechanical ventilation,and appears to have a lower case fatality rate than mposite end-poin drome-related isk of t山 omg ite end point was%among those with severe ed with worse outcomes disease the cumulative risk was 206% Approximately 2%of the patients had a history of direct contact with wildlife,whereas more than TREATMENT AND COMPLICATIONS the patients () the city,or had contact with city therapy,and35.8% out an as 6.1%higher percentages of patients with severe disease received these therapies (Table 3).Me- study cannot preclude the presence of patients chanical ventilation was initiated in more pa who have been termed "super-spreaders. tients with severe disease than in those with entional rot utes of transmission of SARS Cov, S-Cov,an influenz tha plets (18.6%),with a higher percentage among those SARS-CoV-2 well.SARS-Cov-2 can be with severe disease than nonsevere disease (44.%detected in the gastrointestinal tract,saliva,and vs.13.7%).Of these 204 patients,33 (16.2%)urine,these routes of potential transmission were admitted to the ICU,17(8.3%)underwent need to be investigated (Tables $1 and S2). invasi and 5)die d-1 has been applied to pa oratory-co (0 59 12.0 days (mean,12.8).During of the disease is needed.sincein of the sion,most of the patients received a diagnosis of patients,SARS-CoV-2 infection was detected be- pneumonia from a physician (91.1%),followed fore the development of viral pneumonia or viral by ARDS (3.4%)and shock (11%).Patients with pneumonia did not develop. 99.4%s.89.5% those ARS-Cov. teristics dominant symptoms and ga rointestinal sy DISCUSSION ence in viral tropism as compared with SARS-CoV. During the initial phase of the Covid-19 out MERS-CoV,and seasonal influenza.2 The ab- maging Co and RCo im SAR-CovdMR- N ENGLJ MED NEJM.ORG e0UE MEDICL6于 Dow

n engl j med nejm.org 5 Char acteristics of Coronavirus Disease 2019 in China creatine kinase, and d-dimer. Patients with severe disease had more prominent laboratory abnor￾malities (including lymphocytopenia and leuko￾penia) than those with nonsevere disease. Clinical Outcomes None of the 1099 patients were lost to follow-up during the study. A primary composite end-point event occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died (Table 3). Among the 173 patients with severe disease, a primary composite end-point event occurred in 43 patients (24.9%). Among all the patients, the cumulative risk of the compos￾ite end point was 3.6%; among those with severe disease, the cumulative risk was 20.6%. Treatment and Complications A majority of the patients (58.0%) received intra￾venous antibiotic therapy, and 35.8% received oseltamivir therapy; oxygen therapy was admin￾istered in 41.3% and mechanical ventilation in 6.1%; higher percentages of patients with severe disease received these therapies (Table 3). Me￾chanical ventilation was initiated in more pa￾tients with severe disease than in those with nonsevere disease (noninvasive ventilation, 32.4% vs. 0%; invasive ventilation, 14.5% vs. 0%). Sys￾temic glucocorticoids were given to 204 patients (18.6%), with a higher percentage among those with severe disease than nonsevere disease (44.5% vs. 13.7%). Of these 204 patients, 33 (16.2%) were admitted to the ICU, 17 (8.3%) underwent invasive ventilation, and 5 (2.5%) died. Extracor￾poreal membrane oxygenation was performed in 5 patients (0.5%) with severe disease. The median duration of hospitalization was 12.0 days (mean, 12.8). During hospital admis￾sion, most of the patients received a diagnosis of pneumonia from a physician (91.1%), followed by ARDS (3.4%) and shock (1.1%). Patients with severe disease had a higher incidence of physi￾cian-diagnosed pneumonia than those with non￾severe disease (99.4% vs. 89.5%). Discussion During the initial phase of the Covid-19 out￾break, the diagnosis of the disease was compli￾cated by the diversity in symptoms and imaging findings and in the severity of disease at the time of presentation. Fever was identified in 43.8% of the patients on presentation but devel￾oped in 88.7% after hospitalization. Severe ill￾ness occurred in 15.7% of the patients after ad￾mission to a hospital. No radiologic abnormalities were noted on initial presentation in 2.9% of the patients with severe disease and in 17.9% of those with nonsevere disease. Despite the number of deaths associated with Covid-19, SARS-CoV-2 appears to have a lower case fatality rate than either SARS-CoV or Middle East respiratory syn￾drome–related coronavirus (MERS-CoV). Com￾promised respiratory status on admission (the primary driver of disease severity) was associat￾ed with worse outcomes. Approximately 2% of the patients had a history of direct contact with wildlife, whereas more than three quarters were either residents of Wuhan, had visited the city, or had contact with city residents. These findings echo the latest reports, including the outbreak of a family cluster,4 transmission from an asymptomatic patient,6 and the three-phase outbreak patterns.8 Our study cannot preclude the presence of patients who have been termed “super-spreaders.” Conventional routes of transmission of SARS￾CoV, MERS-CoV, and highly pathogenic influenza consist of respiratory droplets and direct con￾tact,18-20 mechanisms that probably occur with SARS-CoV-2 as well. Because SARS-CoV-2 can be detected in the gastrointestinal tract, saliva, and urine, these routes of potential transmission need to be investigated21 (Tables S1 and S2). The term Covid-19 has been applied to pa￾tients who have laboratory-confirmed symptom￾atic cases without apparent radiologic manifes￾tations. A better understanding of the spectrum of the disease is needed, since in 8.9% of the patients, SARS-CoV-2 infection was detected be￾fore the development of viral pneumonia or viral pneumonia did not develop. In concert with recent studies,1,8,12 we found that the clinical characteristics of Covid-19 mimic those of SARS-CoV. Fever and cough were the dominant symptoms and gastrointestinal symp￾toms were uncommon, which suggests a differ￾ence in viral tropism as compared with SARS-CoV, MERS-CoV, and seasonal influenza.22,23 The ab￾sence of fever in Covid-19 is more frequent than in SARS-CoV (1%) and MERS-CoV infection The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

Thr NEW ENGLAND JOURNAL Of MEDICINE (0S-0'sS 09t (059-008)07S a 16.99)r6/t6 ()6/ 255925/005 6uo16101 6 -840 O'85-0'SE)O 215501 6)66095 (E)99/6 E811500 (S'E)8o/8 88)66070 'ou >a 6 N ENGLJ MED NEJM.ORG OUTERN MEDCAL UNTVTY .No other useswithout p opyngnt 202

6 n engl j med nejm.org The new england journal o f medicine Table 1. Clinical Characteristics of the Study Patients, According to Disease Severity and the Presence or Absence of the Primary Composite End Point.* Characteristic All Patients (N=1099) Disease Severity Presence of Primary Composite End Point† Nonsevere (N=926) Severe (N=173) Yes (N=67) No (N=1032) Age Median (IQR) — yr 47.0 (35.0–58.0) 45.0 (34.0–57.0) 52.0 (40.0–65.0) 63.0 (53.0–71.0) 46.0 (35.0–57.0) Distribution — no./total no. (%) 0–14 yr 9/1011 (0.9) 8/848 (0.9) 1/163 (0.6) 0 9/946 (1.0) 15–49 yr 557/1011 (55.1) 490/848 (57.8) 67/163 (41.1) 12/65 (18.5) 545/946 (57.6) 50–64 yr 292/1011 (28.9) 241/848 (28.4) 51/163 (31.3) 21/65 (32.3) 271/946 (28.6) ≥65 yr 153/1011 (15.1) 109/848 (12.9) 44/163 (27.0) 32/65 (49.2) 121/946 (12.8) Female sex — no./total no. (%) 459/1096 (41.9) 386/923 (41.8) 73/173 (42.2) 22/67 (32.8) 437/1029 (42.5) Smoking history — no./total no. (%) Never smoked 927/1085 (85.4) 793/913 (86.9) 134/172 (77.9) 44/66 (66.7) 883/1019 (86.7) Former smoker 21/1085 (1.9) 12/913 (1.3) 9/172 (5.2) 5/66 (7.6) 16/1019 (1.6) Current smoker 137/1085 (12.6) 108/913 (11.8) 29/172 (16.9) 17/66 (25.8) 120/1019 (11.8) Exposure to source of transmission within past 14 days — no./ total no. Living in Wuhan 483/1099 (43.9) 400/926 (43.2) 83/173 (48.0) 39/67 (58.2) 444/1032 (43.0) Contact with wildlife 13/687 (1.9) 10/559 (1.8) 3/128 (2.3) 1/41 (2.4) 12/646 (1.9) Recently visited Wuhan‡ 193/616 (31.3) 166/526 (31.6) 27/90 (30.0) 10/28 (35.7) 183/588 (31.1) Had contact with Wuhan residents‡ 442/611 (72.3) 376/522 (72.0) 66/89 (74.2) 19/28 (67.9) 423/583 (72.6) Median incubation period (IQR) — days§ 4.0 (2.0–7.0) 4.0 (2.8–7.0) 4.0 (2.0–7.0) 4.0 (1.0–7.5) 4.0 (2.0–7.0) Fever on admission Patients — no./total no. (%) 473/1081 (43.8) 391/910 (43.0) 82/171 (48.0) 24/66 (36.4) 449/1015 (44.2) Median temperature (IQR) — °C 37.3 (36.7–38.0) 37.3 (36.7–38.0) 37.4 (36.7–38.1) 36.8 (36.3–37.8) 37.3 (36.7–38.0) Distribution of temperature — no./total no. (%) 39.0°C 38/1081 (3.5) 30/910 (3.3) 8/171 (4.7) 3/66 (4.5) 35/1015 (3.4) Fever during hospitalization Patients — no./total no. (%) 975/1099 (88.7) 816/926 (88.1) 159/173 (91.9) 59/67 (88.1) 916/1032 (88.8) Median highest temperature (IQR) — °C 38.3 (37.8–38.9) 38.3 (37.8–38.9) 38.5 (38.0–39.0) 38.5 (38.0–39.0) 38.3 (37.8–38.9) 39.0°C 114/926 (12.3) 88/774 (11.4) 26/152 (17.1) 10/54 (18.5) 104/872 (11.9) The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

CHARACTERISTICS OF CORONAVIRUS DISEASE 2019 IN CHINA 原目销身厚月自里 ~期目 日。 星果839目 用围 。 买 N ENGLJ MED NEJM.ORG The New England Joumal of Medicine onal use only.No other uses without permission

n engl j med nejm.org 7 Char acteristics of Coronavirus Disease 2019 in China Symptoms — no. (%) Conjunctival congestion 9 (0.8) 5 (0.5) 4 (2.3) 0 9 (0.9) Nasal congestion 53 (4.8) 47 (5.1) 6 (3.5) 2 (3.0) 51 (4.9) Headache 150 (13.6) 124 (13.4) 26 (15.0) 8 (11.9) 142 (13.8) Cough 745 (67.8) 623 (67.3) 122 (70.5) 46 (68.7) 699 (67.7) Sore throat 153 (13.9) 130 (14.0) 23 (13.3) 6 (9.0) 147 (14.2) Sputum production 370 (33.7) 309 (33.4) 61 (35.3) 20 (29.9) 350 (33.9) Fatigue 419 (38.1) 350 (37.8) 69 (39.9) 22 (32.8) 397 (38.5) Hemoptysis 10 (0.9) 6 (0.6) 4 (2.3) 2 (3.0) 8 (0.8) Shortness of breath 205 (18.7) 140 (15.1) 65 (37.6) 36 (53.7) 169 (16.4) Nausea or vomiting 55 (5.0) 43 (4.6) 12 (6.9) 3 (4.5) 52 (5.0) Diarrhea 42 (3.8) 32 (3.5) 10 (5.8) 4 (6.0) 38 (3.7) Myalgia or arthralgia 164 (14.9) 134 (14.5) 30 (17.3) 6 (9.0) 158 (15.3) Chills 126 (11.5) 100 (10.8) 26 (15.0) 8 (11.9) 118 (11.4) Signs of infection — no. (%) Throat congestion 19 (1.7) 17 (1.8) 2 (1.2) 0 19 (1.8) Tonsil swelling 23 (2.1) 17 (1.8) 6 (3.5) 1 (1.5) 22 (2.1) Enlargement of lymph nodes 2 (0.2) 1 (0.1) 1 (0.6) 1 (1.5) 1 (0.1) Rash 2 (0.2) 0 2 (1.2) 0 2 (0.2) Coexisting disorder — no. (%) Any 261 (23.7) 194 (21.0) 67 (38.7) 39 (58.2) 222 (21.5) Chronic obstructive pulmonary disease 12 (1.1) 6 (0.6) 6 (3.5) 7 (10.4) 5 (0.5) Diabetes 81 (7.4) 53 (5.7) 28 (16.2) 18 (26.9) 63 (6.1) Hypertension 165 (15.0) 124 (13.4) 41 (23.7) 24 (35.8) 141 (13.7) Coronary heart disease 27 (2.5) 17 (1.8) 10 (5.8) 6 (9.0) 21 (2.0) Cerebrovascular disease 15 (1.4) 11 (1.2) 4 (2.3) 4 (6.0) 11 (1.1) Hepatitis B infection¶ 23 (2.1) 22 (2.4) 1 (0.6) 1 (1.5) 22 (2.1) Cancer‖ 10 (0.9) 7 (0.8) 3 (1.7) 1 (1.5) 9 (0.9) Chronic renal disease 8 (0.7) 5 (0.5) 3 (1.7) 2 (3.0) 6 (0.6) Immunodeficiency 2 (0.2) 2 (0.2) 0 0 2 (0.2) * The denominators of patients who were included in the analysis are provided if they differed from the overall numbers in the group. Percentages may not total 100 because of rounding. Covid-19 denotes coronavirus disease 2019, and IQR interquartile range. † The primary composite end point was admission to an intensive care unit, the use of mechanical ventilation, or death. ‡ These patients were not residents of Wuhan. § Data regarding the incubation period were missing for 808 patients (73.5%). ¶The presence of hepatitis B infection was defined as a positive result on testing for hepatitis B surface antigen with or without elevated levels of alanine or aspartate aminotransferase. ‖ Included in this category is any type of cancer. The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

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8 n engl j med nejm.org The new england journal o f medicine Table 2. Radiographic and Laboratory Findings.* Variable All Patients (N=1099) Disease Severity Presence of Composite Primary End Point Nonsevere (N=926) Severe (N=173) Yes (N=67) No (N=1032) Radiologic findings Abnormalities on chest radiograph — no./total no. (%) 162/274 (59.1) 116/214 (54.2) 46/60 (76.7) 30/39 (76.9) 132/235 (56.2) Ground-glass opacity 55/274 (20.1) 37/214 (17.3) 18/60 (30.0) 9/39 (23.1) 46/235 (19.6) Local patchy shadowing 77/274 (28.1) 56/214 (26.2) 21/60 (35.0) 13/39 (33.3) 64/235 (27.2) Bilateral patchy shadowing 100/274 (36.5) 65/214 (30.4) 35/60 (58.3) 27/39 (69.2) 73/235 (31.1) Interstitial abnormalities 12/274 (4.4) 7/214 (3.3) 5/60 (8.3) 6/39 (15.4) 6/235 (2.6) Abnormalities on chest CT — no./total no. (%) 840/975 (86.2) 682/808 (84.4) 158/167 (94.6) 50/57 (87.7) 790/918 (86.1) Ground-glass opacity 550/975 (56.4) 449/808 (55.6) 101/167 (60.5) 30/57 (52.6) 520/918 (56.6) Local patchy shadowing 409/975 (41.9) 317/808 (39.2) 92/167 (55.1) 22/57 (38.6) 387/918 (42.2) Bilateral patchy shadowing 505/975 (51.8) 368/808 (45.5) 137/167 (82.0) 40/57 (70.2) 465/918 (50.7) Interstitial abnormalities 143/975 (14.7) 99/808 (12.3) 44/167 (26.3) 15/57 (26.3) 128/918 (13.9) Laboratory findings Median Pao2:Fio2 ratio (IQR)† 3.9 (2.9–4.7) 3.9 (2.9–4.5) 4.0 (2.8–5.2) 2.9 (2.2–5.4) 4.0 (3.1–4.6) White-cell count Median (IQR) — per mm3 4700 (3500– 6000) 4900 (3800–6000) 3700 (3000–6200) 6100 (4900– 11,100) 4700 (3500– 5900) Distribution — no./total no. (%) >10,000 per mm3 58/978 (5.9) 39/811 (4.8) 19/167 (11.4) 15/58 (25.9) 43/920 (4.7) <4000 per mm3 330/978 (33.7) 228/811 (28.1) 102/167 (61.1) 8/58 (13.8) 322/920 (35.0) Lymphocyte count Median (IQR) — per mm3 1000 (700–1300) 1000 (800–1400) 800 (600–1000) 700 (600–900) 1000 (700–1300) Distribution — no./total no. (%) <1500 per mm3 731/879 (83.2) 584/726 (80.4) 147/153 (96.1) 50/54 (92.6) 681/825 (82.5) The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

CHARACTERISTICS OF CORONAVIRUS DISEASE 2019 IN CHINA (8'85)8vL/Ov 010000 (50960320 1927 (69)6/ve (ZT-OE) 0:20具8：0008：80 0t811192 (S'T8)SET/OT (Et)/L 060t212 965160750 (04013.66)1:50t DCtne 861-0.021015511081-0.6t)O 5915/65 (oT)t9/9 ()Is/s6T .(5:501/:66k201 9701-7669620 p/-ooway sau puy jayto jo uognq!ns!c /owr t'Lt<uqn oww-wnpos up N ENGLJ MED NEJM.ORC Dow loaded from nejm org at No other uses without permission

n engl j med nejm.org 9 Char acteristics of Coronavirus Disease 2019 in China Platelet count Median (IQR) — per mm3 168,000 (132,000–207,000) 172,000 (139,000–212,000) 137,500 (99,000–179,500) 156,500 (114,200–195,000) 169,000 (133,000–207,000) Distribution — no./total no. (%) 40 U/liter 168/757 (22.2) 112/615 (18.2) 56/142 (39.4) 26/52 (50.0) 142/705 (20.1) Alanine aminotransferase >40 U/liter 158/741 (21.3) 120/606 (19.8) 38/135 (28.1) 20/49 (40.8) 138/692 (19.9) Total bilirubin >17.1 μmol/liter 76/722 (10.5) 59/594 (9.9) 17/128 (13.3) 10/48 (20.8) 66/674 (9.8) Creatine kinase ≥200 U/liter 90/657 (13.7) 67/536 (12.5) 23/121 (19.0) 12/46 (26.1) 78/611 (12.8) Creatinine ≥133 μmol/liter 12/752 (1.6) 6/614 (1.0) 6/138 (4.3) 5/52 (9.6) 7/700 (1.0) d-dimer ≥0.5 mg/liter 260/560 (46.4) 195/451 (43.2) 65/109 (59.6) 34/49 (69.4) 226/511 (44.2) Minerals§ Median sodium (IQR) — mmol/liter 138.2 (136.1–140.3) 138.4 (136.6–140.4) 138.0 (136.0–140.0) 138.3 (135.0–141.2) 138.2 (136.1–140.2) Median potassium (IQR) — mmol/liter 3.8 (3.5–4.2) 3.9 (3.6–4.2) 3.8 (3.5–4.1) 3.9 (3.6–4.1) 3.8 (3.5–4.2) Median chloride (IQR) — mmol/liter 102.9 (99.7–105.6) 102.7 (99.7–105.3) 103.1 (99.8–106.0) 103.8 (100.8–107.0) 102.8 (99.6–105.3) * Lymphocytopenia was defined as a lymphocyte count of less than 1500 per cubic millimeter. Thrombocytopenia was defined as a platelet count of less than 150,000 per cubic millime￾ter. To convert the values for creatinine to milligrams per deciliter, divide by 88.4. † Data regarding the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Pao2:Fio2) were missing for 894 patients (81.3%). ‡ Data regarding hemoglobin were missing for 226 patients (20.6%). § Data were missing for the measurement of sodium in 363 patients (33.0%), for potassium in 349 patients (31.8%), and for chloride in 392 patients (35.7%). The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved

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10 n engl j med nejm.org The new england journal o f medicine Table 3. Complications, Treatments, and Clinical Outcomes. Variable All Patients (N=1099) Disease Severity Presence of Composite Primary End Point Nonsevere (N=926) Severe (N=173) Yes (N=67) No (N=1032) Complications Septic shock — no. (%) 12 (1.1) 1 (0.1) 11 (6.4) 9 (13.4) 3 (0.3) Acute respiratory distress syndrome — no. (%) 37 (3.4) 10 (1.1) 27 (15.6) 27 (40.3) 10 (1.0) Acute kidney injury — no. (%) 6 (0.5) 1 (0.1) 5 (2.9) 4 (6.0) 2 (0.2) Disseminated intravascular coagulation — no. (%) 1 (0.1) 0 1 (0.6) 1 (1.5) 0 Rhabdomyolysis — no. (%) 2 (0.2) 2 (0.2) 0 0 2 (0.2) Physician-diagnosed pneumonia — no./total no. (%) 972/1067 (91.1) 800/894 (89.5) 172/173 (99.4) 63/66 (95.5) 909/1001 (90.8) Median time until development of pneumonia (IQR) — days* After initial Covid-19 diagnosis 0.0 (0.0–1.0) 0.0 (0.0–1.0) 0.0 (0.0–2.0) 0.0 (0.0–3.5) 0.0 (0.0–1.0) After onset of Covid-19 symptoms 3.0 (1.0–6.0) 3.0 (1.0–6.0) 5.0 (2.0–7.0) 4.0 (0.0–7.0) 3.0 (1.0–6.0) Treatments Intravenous antibiotics — no. (%) 637 (58.0) 498 (53.8) 139 (80.3) 60 (89.6) 577 (55.9) Oseltamivir — no. (%) 393 (35.8) 313 (33.8) 80 (46.2) 36 (53.7) 357 (34.6) Antifungal medication — no. (%) 31 (2.8) 18 (1.9) 13 (7.5) 8 (11.9) 23 (2.2) Systemic glucocorticoids — no. (%) 204 (18.6) 127 (13.7) 77 (44.5) 35 (52.2) 169 (16.4) Oxygen therapy — no. (%) 454 (41.3) 331 (35.7) 123 (71.1) 59 (88.1) 395 (38.3) Mechanical ventilation — no. (%) 67 (6.1) 0 67 (38.7) 40 (59.7) 27 (2.6) Invasive 25 (2.3) 0 25 (14.5) 25 (37.3) 0 Noninvasive 56 (5.1) 0 56 (32.4) 29 (43.3) 27 (2.6) Use of extracorporeal membrane oxygenation — no. (%) 5 (0.5) 0 5 (2.9) 5 (7.5) 0 Use of continuous renal-replacement therapy — no. (%) 9 (0.8) 0 9 (5.2) 8 (11.9) 1 (0.1) Use of intravenous immune globulin — no. (%) 144 (13.1) 86 (9.3) 58 (33.5) 27 (40.3) 117 (11.3) Admission to intensive care unit — no. (%) 55 (5.0) 22 (2.4) 33 (19.1) 55 (82.1) 0 Median length of hospital stay (IQR) — days† 12.0 (10.0–14.0) 11.0 10.0–13.0) 13.0 (11.5–17.0) 14.5 (11.0–19.0) 12.0 (10.0–13.0) The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved