2020年 · 第133卷第09期

In December 2019, a cluster of viral pneumonia cases of unknown origin emerged in Wuhan, Hubei Province of China. This emergency has attracted global concern, and the World Health Organization (WHO) declared the outbreak a Public Health Emergency of International Concern. Joint efforts to identify the causative agent were undertaken by multidisciplinary task forces under the organization of the National Health Commission of the People’s Republic of China, and a novel coronavirus, named 2019 novel coronavirus (2019-nCoV) by the WHO, was swiftly identified as the pathogen responsible for this contagious epidemic.

Since early December 2019, the novel coronavirus has caused an outbreak of pneumonia that has claimed over 2000 lives, with more than 77,000 confirmed cases of infection by February 23, 2020 in China.^[1]The World Health Organization (WHO) recently named the disease caused by this new coronavirus as "coronavirus disease 2019 (COVID-19)" . The International Committee on Taxonomy of Viruses (ICTV) has named the new virus "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" .^[2]However, questions have been raised by different academic and professional bodies regarding whether the nomenclature is appropriate. In view of the lack of consensus, theChinese Medical Journalinvited Chinese scientists, epidemiologists, and virologists to submit their comments and provide references for establishing an acceptable nomenclature .

Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel batorigin CoV causing severe and fatal pneumonia in humans.

We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.

Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.

A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak.

Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens.

None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea.

The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.

Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.

Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher’s exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.

Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U= 4.932, P= 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ² = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U= 2.057, P= 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ² = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U= 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U= 1.315, P= 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ² = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P= 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P= 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression.

Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence.

The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed.

In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R² = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t= 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05).

In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks.

The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed.

The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China, respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases.

The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.

Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model.

A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively.

The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhanhu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC₅₀] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10^-4vs. 1.00 ± 0.12, t= 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10^-4vs. 1.00 ± 0.43, t= 3.98, P < 0.05).

Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.

Preeclampsia (PE) is a serious complication that affects maternal and perinatal outcomes. However, the mechanisms have not been fully explained. This study was designed to analyze longitudinal gut microbiota alterations in pregnant women with and without PE in the second (T2) and third trimesters (T3).

In this nested case-control study, which was conducted at Nanjing Maternity and Child Health Care Hospital, fecal samples from 25 PE patients (25 fecal samples obtained in T2 and 15 fecal samples obtained in T3) and 25 matched healthy controls (25 fecal samples obtained in T2 and 22 fecal samples obtained in T3) were collected, and the microbiota were analyzed using 16S rRNA gene sequencing. The diversity and composition of the microbiota of PE cases and controls were compared.

No significant differences in diversity were found between the PE and control groups (P > 0.05). In the control group, from T2 to T3, the relative abundances of Proteobacteria (median [Q1, Q3]: 2.25% [1.24%, 3.30%] vs. 0.64% [0.20%, 1.20%], Z = -3.880, P < 0.05), and Tenericutes (median [Q1, Q3]: 0.12% [0.03%, 3.10%] vs. 0.03% [0.02%, 0.17%], Z= -2.369, P < 0.05) decreased significantly. In the PE group, the relative abundance of Bacteroidetes in T2 was lower than in T3 (median [Q1, Q3]: 18.16% [12.99%, 30.46%] vs. 31.09% [19.89%, 46.06%], Z= -2.417, P < 0.05). In T2, the relative abundances of mircrobiota showed no significant differences between the PE group and the control group. However, in T3, the relative abundance of Firmicutes was significantly lower in the PE group than in the control group (mean ± standard deviation: 60.62% ± 15.17% vs. 75.57% ± 11.53%, t= -3.405, P < 0.05). The relative abundances of Bacteroidetes, Proteobacteria, and Enterobacteriaceae were significantly higher in the PE group than in the control group (median [Q1, Q3]: 31.09% [19.89%, 46.06%] vs. 18.24% [12.90%, 32.04%], Z=-2.537, P < 0.05; 1.52% [1.05%, 2.61%] vs. 0.64% [0.20%, 1.20%], Z=-3.310, P < 0.05; 0.75% [0.20%, 1.00%] vs. 0.01% [0.004%, 0.023%], Z = -4.152, P < 0.05). Linear discriminant analysis combined effect size measurements analysis showed that the relative abundances of the phylum Bacteroidetes, class Bacteroidia and order Bacteroidales were increased in the PE group, while those of the phylum Firmicutes, the class Clostridia, the order Clostridiales, and the genus unidentified Lachnospiraceae were decreased in the PE group; and these differences were identified as taxonomic biomarkers of PE in T3.

From T2 to T3, there was an obvious alteration in the gut microbiota. The gut microbiota of PE patients in T3 was significantly different from that of the control group.

The association between dietary sodium intake and blood pressure variability (BPV) in hypertensive patients remains unclear. The objective of this study was to demonstrate whether dietary sodium intake is a predictor of elevated BPV in Chinese patients with hypertension.

A total of 235 patients with essential hypertension were enrolled in the Department of Cardiology, Chinese People’s Liberation Army (PLA) General Hospital in 2018 to 2019, all of whom underwent 24-h ambulatory blood pressure monitoring. BPV was calculated as the standard deviation (SD), coefficient of variation (CV), variation independent of mean (VIM) of blood pressure measurements, respectively, and divided into diurnal systolic BPV (SBPV), diurnal diastolic BPV (DBPV), nocturnal SBPV, and nocturnal DBPV. 24-h urine samples were collected to measure 24-h urine sodium excretion, which represents dietary sodium intake. The relationship between dietary sodium intake and BPV was analyzed by using Spearman correlations and multiple linear regression analysis.

Nocturnal SBPV-SD, CV, VIM, and nocturnal DBPV-SD in the high urine sodium excretion group were significantly higher than those in the medium and low urine sodium excretion groups, whereas diurnal SBPV-SD, CV, VIM, diurnal DBPV-SD, CV, VIM, and nocturnal DBPV-CV, VIM were not. Using the Spearman correlation analysis, we found a linear correlation between 24-h urine sodium excretion and nocturnal SBPV-SD, CV, VIM (SD, r= 0.22, P= 0.001; CV, r= 0.17, P= 0.009; VIM, r= 0.16, P = 0.020), nocturnal DBPV-SD (r = 0.21, P = 0.001), respectively. After further adjusting for confounding factors by multiple linear regression, the positive correlations remained between 24-h urine sodium excretion and nocturnal SBPV-SD, CV, VIM (SD, β= 0.224, P < 0.001; CV, β= 0.211, P= 0.001; VIM, β= 0.213, P= 0.001), nocturnal DBPV (SD, β= 0.215, P= 0.001), respectively.

Dietary sodium intake is associated with nocturnal SBPV in Chinese patients with hypertension.

Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism.

SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.

Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ± 30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ± 46.8 vs. 421.7 ± 48.3 pg/ml; amylase: 2102.3 ± 165.3 vs. 3186.4 ± 245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ± 50.3 vs. 332.4 ± 25.1 Hz; discharge amplitude: 33.4 ± 5.3 vs. 20.5 ± 2.9 μV).

Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus-and α7nAChR-dependent mechanisms.

At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.

The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.

The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.

ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

Since December 2019, multiple cases of novel coronavirus pneumonia (COVID-19) have been identified in Wuhan, Hubei. With the spread of the epidemic, such cases have also been found in other parts of China and other countries. As an acute respiratory infectious disease, COVID-19 has been included in Class B infectious diseases prescribed in the Law of the People’s Republic of China on Prevention and Treatment of Infectious Diseases, and managed as an infectious disease of Class A. By taking a series of preventive control and medical treatment measures, the rise of the epidemic situation in China has been contained to a certain extent, and the epidemic situation has eased in most provinces, but the incidence abroad is on the rise. With increased understanding of the clinical manifestations and pathology of the disease, and the accumulation of experience in diagnosis and treatment, in order to further strengthen the early diagnosis and early treatment of the disease, improve the cure rate, reduce the mortality rate, avoid nosocomial infection as much as possible and pay attention to the spread caused by the imported cases from overseas, we revised theDiagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 6)toDiagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7).

Since December 2019, many patients in Wuhan sustained pneumonia with unknown causes.^[1,2]A part of severe patients developed acute respiratory distress syndrome or septic shock, and even death. On January 7, 2020, Chinese researchers have for the first time detected a new coronavirus. On January 20, 2020, the National Health Commission issued Announcement No. 1 of 2020, which included the new coronavirus pneumonia as a Class B infectious disease, and conducted epidemic prevention and control according to the Class A infectious disease. This new kind of pneumonia has been named coronavirus disease 2019 (COVID-19). The sixth edition of "Diagnosis and Treatment Scheme for New Coronavirus Infected Pneumonia" points out that the main transmission routes include respiratory droplets and close contact transmission. There is a possibility of aerosol transmission in a relatively closed environment with prolonged exposure to high concentrations of aerosol. New coronavirus pneumonia has a certain incubation period.

Pneumonia caused by a novel coronavirus known as 2019 novel coronavirus disease (COVID-19)^[1]appeared in Wuhan, China in December 2019, and approximately 15% to 30% of patients developed acute respiratory distress syndrome within a short period of time.^[2,3]To reduce respiratory symptoms and improve prognosis, respiratory support is the most important means of life support,^[1]and non-invasive respiratory support systems,^[2]including various conventional oxygen therapies, non-invasive positive pressure ventilation (NPPV), and high-flow nasal cannula (HFNC), are most commonly used. However, their efficacy and safety remain unclear, and whether they increase the risk of aerosol dispersion and disease transmission is particularly controversial.^[4,5]Given that there are many similarities between COVID-19 pneumonia and severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS),^[6]this study primarily discusses clinical indications and provides details regarding the prevention of nosocomial infections during NPPV and HFNC treatment of COVID-19 pneumonia based on previous clinical data on the use of these two therapies for SARS and MERS and our experience with the treatment of COVID-19 pneumonia.

Emerging infectious diseases represent a serious threat for human public health worldwide.^[1,2]The 2019 novel coronavirus (2019-nCoV) caused a pneumonia outbreak, which is spreading around the country and has affected 32 provinces and regions of China as of January 27, 2020.^[3,4]Countries outside China, including Japan, the United States, Thailand, and South Korea, have also reported cases imported from other countries.^[5]With the joint efforts of Chinese scientists, health workers, and related departments, the pathogen causing this epidemic was quickly identified as a new type of coronavirus, 10 days after the first official report. After confirming the pathogen, specific detection methods were rapidly developed, with improvement in etiological diagnosis. As of January 22, 2020, it has been confirmed that the new coronavirus came from wild bats and belonged to group 2b of the beta coronavirus, which includes severe acute respiratory syndrome-associated coronavirus (SARS-CoV).^[6]Although 2019-nCoV and SARS-CoV belong to the same sub-group of beta coronaviruses, the similarity at the genome level is only 80%,^[7,8]meaning that the new virus is genetically different from SARS-CoV [Supplementary Figure 1A, http://links. lww.com/CM9/A209]. Rapid discovery of the causative agent and development of diagnostic reagents demonstrated that technology has greatly improved in the 17 years since the SARS outbreak. However, no effective anti-viral medication or vaccines are available for this new virus, and many of its aspects remain to be explored. Similar to the SARS outbreak, this outbreak also occurred during the spring festival, the most important of the Chinese traditional festivals, when 3 billion people travel throughout the country.^[9]This unexpectedly provides beneficial conditions for the transmission of this highly infectious disease and correspondingly poses great challenges for the prevention and control of the outbreak.

The 2019 novel coronavirus disease (COVID-19) has spread rapidly across Hubei province and to all regions in China owing to its person-to-person transmission and strong invasiveness targeting the lower respiratory tract.^[1]By the end of February 15, 2020, more than 68,000 cases of COVID-19 pneumonia had been confirmed in China, including over 1600 fatalities.^[2]Most infected patients who developed COVID-19 pneumonia suffered from only mild symptoms and then completely recovered. However, in some patients, the phenotype may rapidly progress to acute respiratory distress syndrome (ARDS) and multiorgan failure. The initial clinical data, collected in Wuhan Jinyintan Hospital, showed that ARDS was reported in 12 (29%) among 41 confirmed patients.^[3]Among the 41 patients, 13 patients received medical care in the intensive care unit (ICU), 4 patients were provided invasive mechanical ventilations, whereas for two patients, extracorporeal membrane oxygenation (ECMO) treatment was applied. Finally, six of the 41 patients died. The clinical data of 99 confirmed patients from the same hospital demonstrated that 17 in 99 patients developed ARDS; among them, three received ECMO treatment, and 11 died.^[4]Another study reported that 22 in 138 cases (16%) developed into ARDS and were admitted into the ICU, of which four received ECMO.^[5]

Coronaviruses have in the past been known to be the etiologic agents of mild upper respiratory infections in humans, similar to the ubiquitous and relatively benign "common cold" -type upper respiratory illnesses induced by the human rhinoviruses in adults and children. Subsequent to the severe acute respiratory syndrome (SARS) outbreak in China 2003, and the Middle East respiratory syndrome (MERS) outbreak in the Middle East in 2012, global concerns regarding the pathogenicity and epidemic/pandemic potential of novel human coronaviruses began to emerge, with some experts predicting that novel coronaviruses could likely again cross the species barrier and present humans with future pandemic-potential infections.^[1]These concerns have proven prescient with the emergence, late in 2019, of the 2019 coronavirus disease (COVID-19) or novel coronavirus pneumonia.

The epidemiological history of some patients infected with novel coronavirus (2019-nCoV) is unclear, and the incubation period of the virus can last for 2 weeks, even longer. During the period of latent infection or the period of incubation following infection, the disease may be infectious. As in cases of influenza, some patients develop only upper respiratory tract infection, whereas others with a severe form of the disease develop pneumonia. Patients may not have fever, mild cough, or apparent respiratory symptoms, and headache or gastrointestinal symptoms may be present. Some patients show insidious onset and slow progression, and do not appear to be sick. Thus, they may not receive attention or be identified. Some patients with severe disease or critical illness may present with moderate-to-low-grade fever, but apparent fever may also be absent.

Since December 2019, the outbreak of infection caused by 2019 novel coronavirus (2019-nCoV) has become a major public health emergency worldwide. Approximately 40% of the confirmed cases of 2019-nCoV infection (judged by positivity of viral RNA testing) were initially asymptomatic but later developed overt clinical symptoms of coronavirus disease-2019 (COVID-19).^[1]A presumed asymptomatic carrier of 2019-nCoV was also reported.^[2]But her infection of 2019-nCoV was not fully confirmed. As far as we know, confirmed 2019-nCoV carriers but without overt clinical symptoms have been not yet reported.

Inflammatory demyelinating diseases (IDD) of the central nervous system (CNS) occur throughout the world and are the leading cause of nontraumatic neurological disability in young adults.^[1]Early diagnosis of IDD allows prompt immunotherapies that minimize relapse, disabilities and mortality.^[2]Multiple sclerosis (MS) is the most frequent IDD in adults. The histological characteristics of chronic MS lesions are well known to neuropathologists; however, diagnosing an inflammatory demyelinating process in biopsy may be challenging since the specimens are frequently small and often represent only parts of a larger lesion.^[3]Furthermore, the histopathological hallmarks of acute MS differ fundamentally from the well-known characteristics of chronic demyelinated plaques observed in autopsies.^[3]Kuhlmannet al^[4]recently proposed a new histological classification system for MS lesions. Whether this new classification system corresponds to clinical manifestations and thus reflects the temporal multiplicity of MS and whether it can be applied to all IDD cases remain to be further studied.

The World Health Organization has recently declared the 2019-novel coronavirus (2019-nCoV) a global public health emergency. Huanget al^[1]reported acute kidney injury (AKI) in 7% of the 41 patients infected with 2019-nCoV, this value was even higher (up to 31%) among intensive-care patients. Furthermore, Liet al^[2]reported that plasma creatinine levels increased in 11 of 59 patients with 2019-nCoV infection, suggesting that kidney function was probably impaired when the disease progressed. Guanet al^[3]reported that plasma creatinine level increased in 4.3% of severely diseased patients. 2019-nCoV is a highly contagious pathogen that predominantly causes pneumonic symptoms. Although respiratory failure has been associated with the highest mortality, the lung was not the only organ involved. Hoffmannet al^[4]reported that 2019-nCoV and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) share a common receptor angiotensin-converting enzyme 2 (ACE2) that is required to enter target cells, and cellular protease transmembrane protease serine 2 (TMPRSS2) can cleave and activate the spike protein of 2019-nCoV for membrane fusion. We investigated whether ACE2 and TMPRSS2 were expressed in kidney cells using precisiontechnology single-cell RNA sequencing.

To the Editor:At the end of 2019, an outbreak of novel coronavirus disease 2019 (COVID-19), caused by 2019-nCov, causing widespread novel coronavirus disease. This outbreak of COVID-19 occurred during the period of the 2020 Spring Festival in China, a period known for massive population movements within China. This has resulted in large numbers of infected patients as a consequence of multiple human contact episodes in individual travelers.