key: cord-261246-m40kwgcg authors: Chen, Nanshan; Zhou, Min; Dong, Xuan; Qu, Jieming; Gong, Fengyun; Han, Yang; Qiu, Yang; Wang, Jingli; Liu, Ying; Wei, Yuan; Xia, Jia'an; Yu, Ting; Zhang, Xinxin; Zhang, Li title: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study date: 2020-01-30 journal: Lancet DOI: 10.1016/s0140-6736(20)30211-7 sha: doc_id: 261246 cord_uid: m40kwgcg BACKGROUND: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. METHODS: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. FINDINGS: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. INTERPRETATION: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. FUNDING: National Key R&D Program of China. Since Dec 8, 2019, several cases of pneumonia of unknown aetiology have been reported in Wuhan, Hubei province, China. [1] [2] [3] Most patients worked at or lived around the local Huanan seafood wholesale market, where live animals were also on sale. In the early stages of this pneumonia, severe acute respiratory infection symptoms occurred, with some patients rapidly dev eloping acute respiratory distress syndrome (ARDS), acute respiratory failure, and other serious complications. On Jan 7, a novel coronavirus was identified by the Chinese Center for Disease Control and Prevention (CDC) from the throat swab sample of a patient, and was subsequently named 2019nCoV by WHO. 4 Coronaviruses can cause multiple system infections in various animals and mainly respiratory tract infections in humans, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). [5] [6] [7] Most patients have mild symptoms and good prognosis. So far, a few patients with 2019nCoV have developed severe pneumonia, pulmonary oedema, ARDS, or mul tiple organ failure and have died. All costs of 2019nCoV treatment are covered by medical insurance in China. At present, information regarding the epidemiology and clinical features of pneumonia caused by 2019nCoV is scarce. [1] [2] [3] In this study, we did a comprehensive exploration of the epidemiology and clinical features of 99 patients with confirmed 2019nCoV pneumonia admitted to Jinyintan Hospital, Wuhan, which admitted the first patients with 2019nCoV to be reported on. For this retrospective, singlecentre study, we recruited patients from Jan 1 to Jan 20, 2020, at Jinyintan Hospital in Wuhan, China. Jinyintan Hospital is a hospital for adults (ie, aged ≥14 years) specialising in infectious diseases. Accord ing to the arrangements put in place by the Chinese Government, adult patients were admitted centrally to the hospital from the whole of Wuhan without selectivity. All patients at Jinyintan Hospital who were diagnosed as having 2019nCoV pneumonia according to WHO interim guidance were enrolled in this study. 4 All the data of included cases have been shared with WHO. The study was approved by Jinyintan Hospital Ethics Committee and written informed consent was obtained from patients involved before enrolment when data were collected retrospectively. We obtained epidemiological, demographic, clinical, laboratory, management, and outcome data from patients' medical records. Clinical outcomes were followed up to Jan 25, 2020. If data were missing from the records or clarification was needed, we obtained data by direct communication with attending doctors and other health care providers. All data were checked by two physicians (XD and YQ). Laboratory confirmation of 2019nCoV was done in four different institutions: the Chinese CDC, the Chinese Academy of Medical Science, Academy of Military Medical Sciences, and Wuhan Institute of Virology, Chinese Academy of Sciences. Throatswab specimens from the upper respiratory tract that were obtained from all patients at admission were maintained in viraltransport medium. 2019nCoV was confirmed by realtime RTPCR using the same protocol described previously. 3 RTPCR detection reagents were provided by the four institutions. Other respiratory viruses including influenza A virus (H1N1, H3N2, H7N9), influenza B virus, respiratory syncytial virus, parainfluenza virus, adenovirus, SARS coronavirus (SARSCoV), and MERS coronavirus (MERSCoV) were also examined with real time RTPCR Sputum or endotracheal aspirates were obtained at admission for identification of possible causative bacteria or fungi. Additionally, all patients were given chest xrays or chest CT. We describe epidemi ological data (ie, shortterm [occasional visits] and longterm [worked at or lived near] exposure to Huanan seafood market); demographics; signs and symptoms on admission; comorbidity; labora tory results; coinfection with other respiratory pathogens; chest radiography and CT findings; treatment received for 2019nCoV; and clinical outcomes. We present continuous measurements as mean (SD) if they are normally distributed or median (IQR) if they are not, and categorical variables as count (%). For laboratory results, we also assessed whether the mea surements were outside the normal range. We used SPSS (version 26.0) for all analyses. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. 99 patients with 2019nCoV were included in this study, two of whom were husband and wife. In total, 49 (49%) Evidence before this study We searched PubMed on Jan 25, 2020, for articles that describe the epidemiological and clinical characteristics of the 2019 novel coronavirus (2019-nCoV) in Wuhan, China, using the search terms "novel coronavirus" and "pneumonia" with no language or time restrictions. Previously published research discussed the epidemiological and clinical characteristics of severe acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus, and primary study for the evolution of the novel coronavirus from Wuhan. The only report of clinical features of patients infected with 2019-nCoV was published on Jan 24, 2020, with 41 cases included. We have obtained data on 99 patients in Wuhan, China, to further explore the epidemiology and clinical features of 2019-nCoV. This study is, to our knowledge, the largest case series to date of 2019-nCoV infections, with 99 patients who were transferred to Jinyintan Hospital from other hospitals all over Wuhan, and provides further information on the demographic, clinical, epidemiological, and laboratory features of patients. It presents the latest status of 2019-nCoV infection in China and is an extended investigation of the previous report, with 58 extra cases and more details on combined bacterial and fungal infections. In all patients admitted with medical comorbidities of 2019-nCoV, a wide range of clinical manifestations can be seen and are associated with substantial outcomes. The 2019-nCoV infection was of clustering onset, is more likely to affect older men with comorbidities, and could result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. Early identification and timely treatment of critical cases of 2019-nCoV are important. Effective life support and active treatment of complications should be provided to effectively reduce the severity of patients' conditions and prevent the spread of this new coronavirus in China and worldwide. patients were clustered and had a history of exposure to the Huanan seafood market. Among them, there were 47 patients with longterm exposure history, most of whom were salesmen or market managers, and two patients with shortterm exposure history, who were shoppers. None of the patients were medical staff. Most patients were men, with a mean age of 55·5 years (SD 13·1; table 1). 50 (51%) patients had chronic diseases, including cardiovascular and cerebro vascular diseases, endocrine system disease, digestive system disease, respiratory system disease, malignant tumour, and nervous system disease (table 1) . On admission, most patients had fever or cough and a third of patients had shortness of breath (table 2) . Other symptoms included muscle ache, headache, confu sion, chest pain, and diarrhoea (table 2) . Many patients presented with organ function damage, including 17 (17%) with ARDS, eight (8%) with acute respiratory injury, three (3%) with acute renal injury, four (4%) with septic shock, and one (1%) with venti latorassociated pneumonia (table 2) . On admission, leucocytes were below the normal range in nine (9%) patients and above the normal range in 24 (24%) patients ( (table 3) . Platelets were below the normal range in 12 (12%) patients and above the normal range in four (4%). 43 patients had differing degrees of liver function abnormality, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the normal range (table 3) ; one patient had severe liver function damage (ALT 7590 U/L, AST 1445 U/L). Most patients had abnormal myocardial zymogram, which showed the elevation of creatine kinase in 13 (13%) patients and the elevation of lactate dehy drogenase in 75 (76%) patients, one of whom also showed abnormal creatine kinase (6280 U/L) and lactate dehydrogenase (20 740 U/L). Seven (7%) patients had different degrees of renal function damage, with elevated blood urea nitrogen or serum creatinine. Regarding the infection index, procalcitonin was above the normal range in six (6%) patients. Most patients had serum ferritin above the normal range (table 3 ). 73 patients were tested for Creactive protein, most of whom had levels above the normal range (table 3 ). All patients were tested for nine respiratory pathogens and the nucleic acid of influenza viruses A and B. Bacteria and fungi culture were done at the same time. We did not find other respiratory viruses in any of the patients. Acinetobacter baumannii, Klebsiella pneumoniae, and Aspergillus flavus were all cultured in one patient. A baumannii turned out to be highly resistant to antibiotics. One case of fungal infection was diagnosed as Candida glabrata and three cases of fungal infection were diagnosed as Candida albicans. According to chest xray and CT, 74 (75%) patients showed bilateral pneumonia (75%) with just 25 (25%) Procalcitonin (ng/mL; normal range 0·0-5·0) 0·5 (1·1) figure) . Additionally, pneumothorax occurred in one (1%) patient. All patients were treated in isolation. 75 (76%) patients received antiviral treatment, including oseltamivir (75 mg every 12 h, orally), ganciclovir (0·25 g every 12 h, intra venously), and lopinavir and ritonavir tablets (500 mg twice daily, orally). The duration of antiviral treatment was 3-14 days (median 3 days [IQR 3-6]). Most patients were given antibiotic treatment (table 2); 25 (25%) patients were treated with a single antibiotic and 45 (45%) patients were given combination therapy. The antibiotics used generally covered common patho gens and some atypical pathogens; when secondary bacterial infection occurred, medication was admin istered according to the results of bacterial culture and drug sensitivity. The antibiotics used were cephalo sporins, quinolones, carbapenems, tigecycline against methicillinresistant Staphylococcus aureus, linezolid, and antifungal drugs. The duration of antibiotic treatment was 3-17 days (median 5 days [IQR [3] [4] [5] [6] [7] ). 19 (19%) patients were also treated with methylpred nisolone sodium succinate, methylprednisolone, and dexametha sone for 3-15 days (median 5 [3] [4] [5] [6] [7] ). 13 patients used noninvasive ventilator mechanical ventilation for 4-22 days (median 9 days [IQR 7-19]). Four patients used an invasive ventilator to assist ventilation for 3-20 days (median 17 [12] [13] [14] [15] [16] [17] [18] [19] ). The ventilator adopted PSIMV mode, the inhaled oxygen concentration was 35-100%, and the positive end expiratory pressure was 6-12 cm H 2 O. All four patients were still using ventilators at data cutoff. Moreover, nine (9%) patients received continuous blood purifi cation due to renal failure and three (3%) patients were treated with extracorporeal membrane oxygenation (ECMO; table 2). By the end of Jan 25, 31 (31%) patients had been discharged and 11 (11%) patients had died; all other patients were still in hospital (table 1). The first two deaths were a 61yearold man (patient 1) and a 69yearold man (patient 2). They had no previous chronic underlying disease but had a long history of smoking. Patient 1 was transferred to Jinyintan Hospital and diagnosed with severe pneumonia and ARDS. He was immediately admitted to the intensive care unit (ICU) and given an intubated ventilatorassisted breathing therapy. Later, the patient, having developed severe res piratory failure, heart failure, and sepsis, experienced a sudden cardiac arrest on the 11th day of admission and was declared dead. Patient 2 had severe pneumonia and ARDS after admission. The patient was transferred to the ICU and given ventilatorassisted breathing, and received anti infection and ECMO treatment after admission. The patient's hypoxaemia remained unresolved. On the ninth day of admission, the patient died of severe pneumonia, septic shock, and respiratory failure. The intervals 1 (1A) . The brightness of both lungs was diffusely decreased, showing a large area of patchy shadow with uneven density. Tracheal intubation was seen in the trachea and the heart shadow outline was not clear. The catheter shadow was seen from the right axilla to the mediastinum. Bilateral diaphragmatic surface and costal diaphragmatic angle were not clear, and chest x-ray on Jan 2 showed worse status (1B). Case 2: chest x-ray obtained on Jan 6 (2A). The brightness of both lungs was decreased and multiple patchy shadows were observed; edges were blurred, and large ground-glass opacity and condensation shadows were mainly on the lower right lobe. Tracheal intubation could be seen in the trachea. Heart shadow roughly presents in the normal range. On the left side, the diaphragmatic surface is not clearly displayed. The right side of the diaphragmatic surface was light and smooth and rib phrenic angle was less sharp. Chest x-ray on Jan 10 showed worse status (2B). Case 3: chest CT obtained on Jan 1 (3A) showed mass shadows of high density in both lungs. Bright bronchogram is seen in the lung tissue area of the lesion, which is also called bronchoinflation sign. Chest CT on Jan 15 showed improved status (3B). between the onset of symptoms and the use of ventilator assisted breathing in the two patients were 3 days and 10 days, respectively. The course of the disease and lung lesions progressed rapidly in both patients, with both developing multiple organ failure in a short time. The deaths of these two patients were consistent with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. 8 Of the remaining nine patients who died, eight patients had lymphopenia, seven had bilateral pneumonia, five were older than 60 years, three had hypertension, and one was a heavy smoker. This is an extended descriptive study on the epidemiology and clinical characteristics of the 2019nCoV, including data on 99 patients who were transferred to Jinyintan Hospital from other hospitals across Wuhan. It presents the latest status of the 2019nCoV infection in China and adds details on combined bacterial and fungal infections. Human coronavirus is one of the main pathogens of respiratory infection. The two highly pathogenic viruses, SARSCoV and MERSCoV, cause severe res piratory syndrome in humans and four other human corona viruses (HCoVOC43, HCoV229E, HCoVNL63, HCoVHKU1) induce mild upper respiratory disease. The major SARSCoV outbreak involving 8422 patients occurred during 2002-03 and spread to 29 countries globally. 9,10 MERSCoV emerged in Middle Eastern countries in 2012 but was imported into China. 11, 12 The sequence of 2019nCoV is relatively different from the six other coronavirus subtypes but can be classified as betacoronavirus. SARSCoV and MERSCoV can be transmitted directly to humans from civets and dromedary camels, respectively, and both viruses origi nate in bats, but the origin of 2019nCoV needs further investigation. [13] [14] [15] 2019nCoV also has enveloped virions that measure approximately 50-200 nm in diameter with a single positivesense RNA genome. 16 Clubshaped glycoprotein spikes in the envelope give the virus a crownlike or coronal appearance. Transmission rates are unknown for 2019nCoV; however, there is evidence of humantohuman transmission. None of the 99 patients we examined were medical staff, but 15 medical workers have been reported with 2019nCoV infection, 14 of whom are assumed to have been infected by the same patient. 17 The mortality of SARSCoV has been reported as more than 10% and MERSCoV at more than 35%. 5, 18 At data cutoff for this study, mortality of the 99 included patients infected by 2019nCoV was 11%, resembling that in a previous study. 3 However, additional deaths might occur in those still hospitalised. We observed a greater number of men than women in the 99 cases of 2019nCoV infection. MERSCoV and SARSCoV have also been found to infect more males than females. 19, 20 The reduced susceptibility of females to viral infections could be attributed to the protection from X chromosome and sex hormones, which play an important role in innate and adaptive immunity. 21 Additionally, about half of patients infected by 2019nCoV had chronic underlying diseases, mainly cardiovascular and cerebrovascular diseases and diabetes; this is similar to MERSCoV. 19 Our results suggest that 2019nCoV is more likely to infect older adult males with chronic comorbidities as a result of the weaker immune func tions of these patients. [19] [20] [21] [22] Some patients, especially severely ill ones, had co infections of bacteria and fungi. Common bacterial cultures of patients with secondary infections included A baumannii, K pneumoniae, A flavus, C glabrata, and C albicans. 8 The high drug resistance rate of A baumannii can cause difficulties with antiinfective treatment, leading to higher possibility of developing septic shock. 23 For severe mixed infections, in addition to the virulence factors of pathogens, the host's immune status is also one of the important factors. Old age, obesity, and presence of comorbidity might be associated with increased mor tality. 24 When populations with low immune function, such as older people, diabetics, people with HIV infection, people with longterm use of immuno suppressive agents, and pregnant women, are infected with 2019nCoV, prompt administration of antibiotics to prevent infection and strengthening of immune support treatment might reduce complications and mortality. In terms of laboratory tests, the absolute value of lymphocytes in most patients was reduced. This result suggests that 2019nCoV might mainly act on lympho cytes, especially T lymphocytes, as does SARSCoV. Virus particles spread through the respiratory mucosa and infect other cells, induce a cytokine storm in the body, generate a series of immune responses, and cause changes in peripheral white blood cells and immune cells such as lymphocytes. Some patients progressed rapidly with ARDS and septic shock, which was eventually followed by multiple organ failure. Therefore, early identification and timely treatment of critical cases is of crucial importance. Use of intra venous immunoglobulin is recommended to enhance the ability of antiinfection for severely ill patients and steroids (methylprednisolone 1-2 mg/kg per day) are recommended for patients with ARDS, for as short a duration of treatment as possible. Some studies suggest that a substantial decrease in the total number of lymphocytes indicates that coronavirus consumes many immune cells and inhibits the body's cellular immune function. Damage to T lymphocytes might be an important factor leading to exacerbations of patients. 25 The low absolute value of lymphocytes could be used as a reference index in the diagnosis of new coronavirus infections in the clinic. In general, the characteristics of patients who died were in line with the early warning model for predicting mortality in viral pneumonia in our previous study: the MuLBSTA score. 8 The MuLBSTA score system contains six indexes, which are multilobular infiltration, lympho penia, bacterial coinfection, smoking history, hyper tension, and age. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019nCoV infection. This study has several limitations. First, only 99 patients with confirmed 2019nCoV were included; suspected but undiagnosed cases were ruled out in the analyses. It would be better to include as many patients as possible in Wuhan, in other cities in China, and even in other countries to get a more comprehensive understanding of 2019nCoV. Second, more detailed patient information, particularly regarding clinical outcomes, was unavailable at the time of analysis; however, the data in this study permit an early assess ment of the epidemiological and clinical characteristics of 2019nCoV pneumonia in Wuhan, China. In conclusion, the infection of 2019nCoV was of clustering onset, is more likely to infect older men with comorbidities, and can result in severe and even fatal respiratory diseases such as ARDS. Contributors NC, XD, FG, YH, YQ, JW, YL, YW, JX, TY, and LZ collected the epidemiological and clinical data and processed statistical data. NC and MZ drafted the manuscript. JQ and XZ revised the final manuscript. XZ is responsible for summarising all data related to the virus. LZ is responsible for summarising all epidemiological and clinical data. We declare no competing interests. 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Press release From SARS to MERS, thrusting coronaviruses into the spotlight Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERSCoV): a systematic review and metaanalysis Sexbased differences in susceptibility to severe acute respiratory syndrome coronavirus infection Sexual dimorphism in innate immunity Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and softtissue infections Clinical findings in 111 cases of influenza A (H7N9) virus infection Clinical features of three avian influenza H7N9 virusinfected patients in Shanghai Tcell immunity of SARSCoV: implications for vaccine development against MERSCoV This study was funded by the National Key R&D Program of China (number 2017YFC1309700). We thank all patients involved in the study.