Volume 133 · Issue 09 · 2020

2019年12月，中国湖北省武汉市出现群组不明原因病毒性肺炎病例。这一突发事件引起全球关注，世界卫生组织（世卫组织）宣布此次疫情为国际关注的突发公共卫生事件。在国家卫生健康委员会的组织下，多学科工作组共同努力确定病原体，并迅速确定了一种被世卫组织命名为2019新型冠状病毒（2019新型冠状病毒）的新型冠状病毒是此次传染性流行病的病原体。

自2019年12月初以来，新型冠状病毒引发了肺炎疫情，夺去了2000多人的生命，截至2020年2月23日，中国已有超过77,000例确诊感染病例。^[1]世界卫生组织（WHO）日前将这种新型冠状病毒引起的疾病命名为“冠状病毒疾病2019（COVID-19）”。国际病毒分类委员会（ICTV）已将这种新病毒命名为“严重急性呼吸综合征冠状病毒2（新型冠状病毒）”。^[2]然而，不同的学术和专业团体对该术语是否适当提出了问题。鉴于缺乏共识，中华医学杂志邀请中国科学家、流行病学家和病毒学家提交他们的意见，为建立可接受的命名法提供参考。

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.

自2019年12月以来，湖北省武汉市发现多例新型冠状病毒肺炎（COVID-19）病例。随着疫情蔓延，我国其他地区和其他国家也发现了此类病例。新冠肺炎作为一种急性呼吸道传染病，已被纳入《中华人民共和国传染病防治法》规定的乙类传染病，按甲类传染病管理。通过采取一系列防控和医疗救治措施，国内疫情上升势头得到一定遏制，大部分省份疫情有所缓解，但境外发病呈上升趋势。随着对本病临床表现和病理认识的增加，以及诊疗经验的积累，为进一步加强本病的早诊早治，提高治愈率，降低病死率，尽可能避免院内感染并注意境外输入病例引起的传播，我们修订了新型冠状病毒肺炎病诊疗方案（试行第六版）到新型冠状病毒肺炎病诊疗方案（试行第7版）.

2019年12月以来，武汉多名患者持续感染不明原因肺炎。^[1,2]一部分重症患者发生急性呼吸窘迫综合征或感染性休克，甚至死亡。2020年1月7日，中国研究人员首次检测到一种新型冠状病毒。2020年1月20日，国家卫健委发布2020年第1号公告，将新型冠状病毒肺炎纳入乙类传染病，按照甲类传染病进行疫情防控。这种新型肺炎被命名为冠状病毒疾病2019（新冠肺炎）。第六版《新型冠状病毒感染的肺炎诊疗方案》指出，主要传播途径包括呼吸道飞沫和密切接触传播。在长期暴露于高浓度气溶胶的相对封闭的环境中，存在气溶胶传播的可能性。新冠肺炎有一定的潜伏期。

由一种被称为2019新型冠状病毒病（COVID-19）的新型冠状病毒引起的肺炎^[1]2019年12月在中国武汉出现，约15%~30%的患者在短时间内出现急性呼吸窘迫综合征。^[2,3]为减轻呼吸道症状和改善预后，呼吸支持是最重要的生命支持手段，^[1]和无创呼吸支持系统，^[2]包括各种常规氧疗，最常用的是无创正压通气（NPPV）和高流量鼻插管（HFNC）。然而，它们的疗效和安全性仍不清楚，它们是否会增加气溶胶扩散和疾病传播的风险尤其有争议。^[4,5]鉴于新冠肺炎与严重急性呼吸综合征（SARS）、中东呼吸综合征（MERS）有诸多相似之处，^[6]本研究主要讨论临床适应症，并根据既往使用这两种疗法治疗SARS和MERS的临床数据以及我们治疗新冠肺炎的经验，提供了有关NPPV和HFNC治疗新冠肺炎期间预防医院感染的详细信息。

新出现的传染病对全球人类公共健康构成严重威胁。^[1,2]2019年新型冠状病毒（2019新型冠状病毒）引发肺炎疫情，疫情正在全国蔓延，截至2020年1月27日，已影响中国32个省区。^[3,4]中国以外的国家，包括日本、美国、泰国、韩国也报告了从其他国家输入的病例。^[5]在中国科学家、卫生工作者、相关部门的共同努力下，引发此次疫情的病原体很快被确定为新型冠状病毒，距离首次正式报告已过去10天。在确认病原体后，特异性检测方法迅速发展，病原学诊断有所提高。截至2020年1月22日，已确认新型冠状病毒来自野生蝙蝠，属于β冠状病毒的2b组，其中包括严重急性呼吸综合征相关冠状病毒（SARS-CoV）。^[6]虽然2019新型冠状病毒和SARS-CoV属于β冠状病毒的同一亚组，但在基因组水平上的相似性仅为80%，^[7,8]这意味着这种新病毒在基因上不同于SARS-CoV【补充图1A，http：//links.lww.com/CM9/A209】。病原体的快速发现和诊断试剂的开发表明，自SARS爆发以来的17年里，技术已经有了很大的进步。然而，目前还没有针对这种新病毒的有效抗病毒药物或疫苗，其许多方面仍有待探索。与SARS疫情类似，这次疫情也发生在中国传统节日中最重要的春节期间，全国有30亿人出行。^[9]这出乎意料地为这种高传染性疾病的传播提供了有利条件，也相应地对疫情的防控提出了巨大挑战。

2019年新型冠状病毒病（COVID-19）由于其人际传播和针对下呼吸道的强侵袭性，已在湖北省和全国所有地区迅速传播。^[1]截至2020年2月15日，中国已确诊超过68,000例COVID-19肺炎病例，包括超过1,600例死亡病例。^[2]大多数感染新冠肺炎的患者只有轻微症状，然后完全康复。然而，在一些患者中，该表型可能会迅速进展为急性呼吸窘迫综合征（ARDS）和多器官衰竭。在武汉金银潭医院收集的初步临床数据显示，在41名确诊患者中，有12名（29%）报告了ARDS。^[3]在41例患者中，13例患者在重症监护室（ICU）接受医疗护理，4例患者接受有创机械通气，而2例患者接受体外膜肺氧合（ECMO）治疗。最终，41名患者中有6名死亡。来自同一医院的99名确诊患者的临床数据显示，99名患者中有17名发生ARDS；其中3例接受ECMO治疗，11例死亡。^[4]另一项研究报告，138例中有22例（16%）发展为ARDS并入住ICU，其中4例接受了ECMO。^[5]

过去已知冠状病毒是人类轻度上呼吸道感染的病原体，类似于成人和儿童中由人鼻病毒诱导的普遍存在且相对良性的“普通感冒”型上呼吸道疾病。继2003年在中国爆发严重急性呼吸综合征（SARS）和2012年在中东爆发中东呼吸综合征（MERS）后，全球开始关注新型人类冠状病毒的致病性和流行性/大流行潜力，一些专家预测新型冠状病毒可能再次跨越物种障碍，并为人类带来未来大流行潜力的感染。^[1]随着2019年底2019冠状病毒病（新冠肺炎）或新型冠状病毒肺炎的出现，这些担忧被证明是有先见之明的。

部分感染新型冠状病毒（2019新型冠状病毒）患者流行病学史不清楚，病毒潜伏期可长达2周，甚至更长。在潜伏感染期间或感染后的潜伏期，疾病可能具有传染性。与流感病例一样，一些患者仅发展为上呼吸道感染，而其他患有严重疾病的患者发展为肺炎。患者可无发热、轻度咳嗽或明显呼吸道症状，可有头痛或胃肠道症状。部分患者表现为起病隐匿，进展缓慢，并不表现为患病。因此，他们可能不会受到关注或被识别。部分重症或危重症患者可表现为中低热，但也可无明显发热。

自2019年12月以来，2019新型冠状病毒（2019新型冠状病毒）感染疫情已成为全球重大突发公共卫生事件。约40%的2019新型冠状病毒感染确诊病例（通过病毒RNA检测阳性判断）最初无症状，但后来出现了冠状病毒疾病-2019（新冠肺炎）的明显临床症状。^[1]还报告了一名推定的无症状2019新型冠状病毒病毒携带者。^[2]但她感染2019新型冠状病毒病毒的情况尚未得到完全证实。据我们所知，确诊但没有明显临床症状的2019新型冠状病毒携带者尚未报告。

中枢神经系统（CNS）的炎性脱髓鞘疾病（IDD）在世界各地都有发生，是年轻人非创伤性神经残疾的主要原因。^[1]碘缺乏病的早期诊断允许及时的免疫治疗，最大限度地减少复发、残疾和死亡率。^[2]多发性硬化（MS）是成人中最常见的IDD。慢性MS病变的组织学特征是神经病理学家熟知的；然而，在活检中诊断炎性脱髓鞘过程可能具有挑战性，因为标本通常很小，并且通常仅代表较大病变的一部分。^[3]此外，急性MS的组织病理学特征与尸检中观察到的慢性脱髓鞘斑块的众所周知的特征根本不同。^[3]库尔曼等人^[4]最近提出了一种新的MS病变组织学分类系统。这种新的分类系统是否与临床表现相对应，从而反映了MS的时间多样性，以及它是否可以应用于所有IDD病例，仍有待进一步研究。

世界卫生组织最近宣布2019-新型冠状病毒（2019新型冠状病毒）为全球突发公共卫生事件。黄等人^[1]在41名感染2019新型冠状病毒病毒的患者中，有7%报告了急性肾损伤（AKI），在重症监护患者中，这一值甚至更高（高达31%）。此外，李等人^[2]报道59例2019新型冠状病毒感染患者中有11例血浆肌酐水平升高，提示疾病进展时肾功能可能受损。关等人^[3]据报道，4.3%的重症患者血浆肌酐水平升高。2019新型冠状病毒病是一种高度传染性的病原体，主要引起肺炎症状。尽管呼吸衰竭与最高死亡率相关，但肺并不是唯一涉及的器官。霍夫曼等人^[4]报道称，2019新型冠状病毒和严重急性呼吸综合征相关冠状病毒（SARS-CoV）共享一种进入靶细胞所需的共同受体血管紧张素转换酶2（ACE2），而细胞蛋白酶跨膜蛋白酶丝氨酸2（TMPRSS2）可以切割并激活2019新型冠状病毒的刺突蛋白进行膜融合。我们使用precisiontechnology单细胞RNA测序研究了ACE2和TMPRSS2是否在肾细胞中表达。

致编辑：2019年底，由2019新型冠状病毒引起的2019年新型冠状病毒病（COVID-19）爆发，导致广泛的新型冠状病毒病。此次新冠肺炎疫情发生在中国2020年春节期间，这是一个以中国境内大规模人口流动而闻名的时期。这导致了大量受感染的患者，这是个别旅行者中多次与人接触的结果。