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February 7, 2020
Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China
In December 2019, cases of pneumonia appeared in Wuhan, China. The etiology of these infections was a novel coronavirus (2019-nCoV),1,2 possibly connected to zoonotic or environmental exposure from the seafood market in Wuhan. Human-to-human transmission has accounted for most of the infections, including among health care workers.3,4 The virus has spread to different parts of China and at least 26 other countries.1 A high number of men have been infected, and the reported mortality rate has been approximately 2%, which is lower than that reported from other coronavirus epidemics including severe acute respiratory syndrome (SARS; mortality rate, >40% in patients aged >60 years)5 and Middle East respiratory syndrome (MERS; mortality rate, 30%).6 However, little is known about the clinical manifestations of 2019-nCoV in healthy populations or cases outside Wuhan. We report early clinical features of 13 patients with confirmed 2019-nCoV infection admitted to hospitals in Beijing.
The median age of the patients was 34 years (25th-75th percentile, 34-48 years); 2 patients were children (aged 2 years and 15 years), and 10 (77%) were male. Twelve patients either visited Wuhan, including a family (parents and son), or had family members (grandparents of the 2-year-old child) who visited Wuhan after the onset of the 2019-nCoV epidemic (mean stay, 2.5 days). One patient did not have any known contact with Wuhan.
Twelve patients reported fever (mean, 1.6 days) before hospitalization. Symptoms included cough (46.3%), upper airway congestion (61.5%), myalgia (23.1%), and headache (23.1%) (Table). No patient required respiratory support before being transferred to the specialty hospital after a mean of 2 days. The youngest patient (aged 2 years) had intermittent fever for 1 week and persistent cough for 13 days before 2019-nCoV diagnosis. Levels of inflammatory markers such as C-reactive protein were elevated, and numbers of lymphocytes were marginally elevated (Table).
Four patients had chest radiographs and 9 had computed tomography. Five images did not demonstrate any consolidation or scarring. One chest radiograph demonstrated scattered opacities in the left lower lung; in 6 patients, ground glass opacity was observed in the right or both lungs (Figure). As of February 4, 2020, all the patients recovered, but 12 were still being quarantined in the hospital.
The current coronavirus outbreak in China is the third epidemic caused by coronavirus in the 21st century, already surpassing SARS and MERS in the number of individuals infected.1 The higher number of infections may be attributable to late identification of the etiologic agent and the ability of the host to shed the infection while asymptomatic, rather than to greater infectivity of the virus compared with SARS.3
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Original Investigation
Caring for the Critically Ill Patient
February 7, 2020
This report, to our knowledge, is the largest case series to date of hospitalized patients with NCIP. As of February 3, 2020, of the 138 patients included in this study, 26% required ICU care, 34.1% were discharged, 6 died (4.3%), and 61.6% remain hospitalized. For those who were discharged (n = 47), the hospital stay was 10 days (IQR, 7.0-14.0). The time from onset to dyspnea was 5.0 days, 7.0 days to hospital admission, and 8.0 days to ARDS. Common symptoms at onset of illness were fever, dry cough, myalgia, fatigue, dyspnea, and anorexia. However, a significant proportion of patients presented initially with atypical symptoms, such as diarrhea and nausea. Major complications during hospitalization included ARDS, arrhythmia, and shock. Bilateral distribution of patchy shadows and ground glass opacity was a typical hallmark of CT scan for NCIP. Most critical ill patients were older and had more underlying conditions than patients not admitted to the ICU. Most patients required oxygen therapy and a minority of the patients needed invasive ventilation or even extracorporeal membrane oxygenation.
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China
JAMA. Published online February 7, 2020. doi:10.1001/jama.2020.1585
Key PointsQuestion What are the clinical characteristics of hospitalized patients with 2019 novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) in Wuhan, China?
Findings In this single-center case series involving 138 patients with NCIP, 26% of patients required admission to the intensive care unit and 4.3% died. Presumed human-to-human hospital-associated transmission of 2019-nCoV was suspected in 41% of patients.
Meaning In this case series in Wuhan, China, NCIP was frequently associated with presumed hospital-related transmission, 26% of patients required intensive care unit treatment, and mortality was 4.3%.
Abstract
Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
Objective To describe the epidemiological and clinical characteristics of NCIP.
Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.
Exposures Documented NCIP.
Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.
Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men.
Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]).
Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%).
Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).
Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
Introduction
In December 2019, a cluster of acute respiratory illness, now known as novel coronavirus–infected pneumonia (NCIP), occurred in Wuhan, Hubei Province, China.1-5 The disease has rapidly spread from Wuhan to other areas. As of January 31, 2020, a total of 9692 NCIP cases in China have been confirmed. Internationally, cases have been reported in 24 countries and 5 continents.6 On January 3, 2020, the 2019 novel coronavirus (2019-nCoV) was identified in samples of bronchoalveolar lavage fluid from a patient in Wuhan and was confirmed as the cause of the NCIP.7 Full-genome sequencing and phylogenic analysis indicated that 2019-nCoV is a distinct clade from the betacoronaviruses associated with human severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).7 The 2019-nCoV has features typical of the coronavirus family and was classified in the betacoronavirus 2b lineage. The 2019-nCoV has close similarity to bat coronaviruses, and it has been postulated that bats are the primary source. While the origin of the 2019-nCoV is still being investigated, current evidence suggests spread to humans occurred via transmission from wild animals illegally sold in the Huanan Seafood Wholesale Market.8
Huang et al9 first reported 41 cases of NCIP in which most patients had a history of exposure to Huanan Seafood Wholesale Market. Patients’ clinical manifestations included fever, nonproductive cough, dyspnea, myalgia, fatigue, normal or decreased leukocyte counts, and radiographic evidence of pneumonia. Organ dysfunction (eg, shock, acute respiratory distress syndrome [ARDS], acute cardiac injury, and acute kidney injury) and death can occur in severe cases.9 Subsequently, Chen et al8 reported findings from 99 cases of NCIP from the same hospital and the results suggested that the 2019-nCoV infection clustered within groups of humans in close contact, was more likely to affect older men with comorbidities, and could result in ARDS. However, the difference in clinical characteristics between severe and nonsevere cases was not reported. Case reports confirmed human-to-human transmission of NCIP.10,11 At present, there are no effective therapies or vaccines for NCIP. The objective of this case series was to describe the clinical characteristics of 138 hospitalized patients with NCIP and to compare severe cases who received intensive care unit (ICU) care with nonsevere cases who did not receive ICU care.
Discussion
This report, to our knowledge, is the largest case series to date of hospitalized patients with NCIP. As of February 3, 2020, of the 138 patients included in this study, 26% required ICU care, 34.1% were discharged, 6 died (4.3%), and 61.6% remain hospitalized. For those who were discharged (n = 47), the hospital stay was 10 days (IQR, 7.0-14.0). The time from onset to dyspnea was 5.0 days, 7.0 days to hospital admission, and 8.0 days to ARDS. Common symptoms at onset of illness were fever, dry cough, myalgia, fatigue, dyspnea, and anorexia. However, a significant proportion of patients presented initially with atypical symptoms, such as diarrhea and nausea. Major complications during hospitalization included ARDS, arrhythmia, and shock. Bilateral distribution of patchy shadows and ground glass opacity was a typical hallmark of CT scan for NCIP. Most critical ill patients were older and had more underlying conditions than patients not admitted to the ICU. Most patients required oxygen therapy and a minority of the patients needed invasive ventilation or even extracorporeal membrane oxygenation.
The data in this study suggest rapid person-to-person transmission of 2019-nCoV may have occurred. The main reason is derived from the estimation of the basic reproductive number (R0) based on a previous study.15 R0 indicates how contagious an infectious disease is. As an infection spreads to new people, it reproduces itself; R0 indicates the average number of additional individuals that one affected case infects during the course of their illness and specifically applies to a population of people who were previously free of infection and have not been vaccinated. Based on the report, R0 from nCoV is 2.2, which estimated that, on average, each patient has been spreading infection to 2.2 other people.15 One reason for the rapid spread may be related to the atypical symptoms in the early stage in some patients infected with nCoV.
A recent study showed that nCoV was detected in stool samples of patients with abdominal symptoms.16 However, it is difficult to differentiate and screen patients with atypical symptoms. Nevertheless, the rapid human-to-human transmission among close contacts is an important feature in nCoV pneumonia.10,11,15
The patients admitted to the ICU were older and had a greater number of comorbid conditions than those not admitted to the ICU. This suggests that age and comorbidity may be risk factors for poor outcome. However, there was no difference in the proportion of men and women between ICU patients and non-ICU patients. These data differ from the recent report that showed 2019-nCoV infection is more likely to affect males.8 The possible explanation is that the nCoV infection in patients in the previous report was related to exposure associated with the Huanan Seafood Wholesale Market, and most of the affected patients were male workers. Compared with symptoms in non-ICU patients, symptoms were more common in critically ill patients, including dyspnea, abdominal pain, and anorexia. The onset of symptoms may help physicians identify the patients with poor prognosis. In this cohort, the overall rates of severe hypoxia and invasive ventilation were higher than those in the previous study,9 likely because the cases in the previous study were from the early epidemic stage of the NCIP, and the current cases are from the stage of outbreak.
The most common laboratory abnormalities observed in this study were depressed total lymphocytes, prolonged prothrombin time, and elevated lactate dehydrogenase. Compared with non-ICU patients, patients who received ICU care had numerous laboratory abnormalities. These abnormalities suggest that 2019-nCoV infection may be associated with cellular immune deficiency, coagulation activation, myocardia injury, hepatic injury, and kidney injury. These laboratory abnormalities are similar to those previously observed in patients with MERS-CoV and SARS-CoV infection.
The dynamic profile of laboratory findings was tracked in 33 patients with NCIP (5 nonsurvivors and 28 survivors). In the nonsurvivors, the neutrophil count, D-dimer, blood urea, and creatinine levels continued to increase, and the lymphocyte counts continued to decrease until death occurred. Neutrophilia may be related to cytokine storm induced by virus invasion, coagulation activation could have been related to sustained inflammatory response, and acute kidney injury could have been related to direct effects of the virus, hypoxia, and shock. The 3 pathologic mechanisms may be associated with the death of patients with NCIP.
Until now, no specific treatment has been recommended for coronavirus infection except for meticulous supportive care.17 Currently, the approach to this disease is to control the source of infection; use of personal protection precaution to reduce the risk of transmission; and early diagnosis, isolation, and supportive treatments for affected patients. Antibacterial agents are ineffective. In addition, no antiviral agents have been found to provide benefit for treating SARS and MERS. All of the patients in this study received antibacterial agents, 90% received antiviral therapy, and 45% received methylprednisolone. The dose of oseltamivir and methylprednisolone varied depending on disease severity. However, no effective outcomes were observed.
This study has several limitations. First, respiratory tract specimens were used to diagnose NCIP through RT-PCR. The serum of patients was not obtained to evaluate the viremia. The viral load is a potentially useful marker associated with disease severity of coronavirus infection, and this should be determined in NCIP. Second, hospital-related transmission/infection could not be definitively proven but was suspected and presumed based on timing and patterns of exposure to infected patients and subsequent development of infection. Third, among the 138 cases, most patients are still hospitalized at the time of manuscript submission. Therefore, it is difficult to assess risk factors for poor outcome, and continued observations of the natural history of the disease are needed.
Conclusions
In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
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发表于 2020-2-11 15:28
