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Open accessJournal ArticleDOI: 10.3390/JCM10050975

Spontaneous Breathing and Evolving Phenotypes of Lung Damage in Patients with COVID-19: Review of Current Evidence and Forecast of a New Scenario.

02 Mar 2021-Journal of Clinical Medicine (MDPI AG)-Vol. 10, Iss: 5, pp 975
Abstract: The mechanisms of acute respiratory failure other than inflammation and complicating the SARS-CoV-2 infection are still far from being fully understood, thus challenging the management of COVID-19 patients in the critical care setting. In this unforeseen scenario, the role of an individual’s excessive spontaneous breathing may acquire critical importance, being one potential and important driver of lung injury and disease progression. The consequences of this acute lung damage may impair lung structure, forecasting the model of a fragile respiratory system. This perspective article aims to analyze the progression of injured lung phenotypes across the SARS-CoV-2 induced respiratory failure, pointing out the role of spontaneous breathing and also tackling the specific respiratory/ventilatory strategy required by the fragile lung type.

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Topics: Lung injury (68%), Respiratory failure (51%), Lung (50%)
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9 results found


Open accessJournal ArticleDOI: 10.1186/S13613-021-00904-7
Liam Weaver1, Anup Das1, Sina Saffaran2, Nadir Yehya3  +6 moreInstitutions (7)
Abstract: There is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e., severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen. Simulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0 ± 0.3 cmH2O at baseline to 33.8 ± 0.4 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2 ± 0.5 cmH2O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7 ± 0.1 cmH2O at baseline to 17.9 ± 0.3 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29 ± 0.006 at baseline to 0.65 ± 0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6 ± 0.1 J/min at baseline to 12.9 ± 0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9 ± 0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7 ± 0.2 cmH2O at baseline to 19.6 ± 0.2 cmH2O at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. Our results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.

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Topics: Lung injury (59%), Mechanical ventilation (51%), Population (50%)

5 Citations


Open accessJournal ArticleDOI: 10.1164/RCCM.202104-1029LE
Abstract: A great debate has started as to whether acute respiratory failure (ARF) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease [COVID-19]) should be classified as a classic form of acute respiratory distress syndrome (ARDS) or a subtype of lung injury with different pathophysiological characteristics (1) and mechanisms of progression (2). The magnitude of inspiratory effort correlated with the need to switch to invasive ventilation in patients without COVID-19 suggest that selfinflicted lung injury could play a role (3). We aimed to describe and compare the inspiratory effort (primary outcome) and the breathing pattern of spontaneously breathing patients with ARF due to COVID-19 and historically matched patients without COVID-19, either type a candidate for noninvasive mechanical ventilation (NIV). Patients with COVID-19 were treated at the Respiratory Intensive Care Unit and the Intensive Care Unit of the University Hospital of Modena (fromAugust 1, 2020, toMarch 15, 2021) and 1:1 propensity matched (by PaO2/FIO2 ratio, age, bodymass index, and Sequential Organ Failure Assessment score) with non–COVID-19 patients extracted from our dataset (period 2016 to 2021). The logit of the score was taken with a caliper of 0.2 to maximize the number of patients without compromising the match. All patients were in a similar phase from onset of ARF, unable to maintain SaO2. 92% despite optimized high-flow oxygen, and thus were candidates to receive NIV according to local protocol. The study was conducted in accordance with the local “AVEN Ethics Committee” approval (protocol 4485/CE) and represents a report of ancillary data of a registered protocol (www. clinicaltrials.gov [NCT03826797]). On admission, demographics, clinical characteristics and severity, respiratory function, and peripheral blood lactate and D-dimer concentrations were recorded. A nasogastric tube with pressure transducer and monitoring system (NutriVent and OptiVentTM, SIDAM,Mirandola-I) to record swings in esophageal pressure (Pes) and dynamic transpulmonary pressure (PL) was placed as previously described (3). For recording, we always referred to DPes and DPL from the end-expiratory level, calculated as recommended (4). Expiratory tidal volume (VTE) was obtained by numerical integration of the flow signal and adjusted to the predicted body weight (in kilograms). The VTE/DPL ratio was measured as a surrogate for lung compliance (“dynamic compliance”). A simplified surrogate of mechanical power (“dynamic mechanical power”) was calculated as 0.0983RR 3VTE3 (DPL1 positive end-expiratory pressure), where RR represents respiratory rate (5). Measures were recorded for patients of both groups under standardized conditions with unassisted breathing (5 min long) and then 2 hours after starting NIV (Engstr€ omCarestation [GE Healthcare]). Pressure support was started at 10 cmH2O and then adjusted according to Carteaux and colleagues (6) to target a peripheral oxygen saturation as measured by pulse oximetry.92% with a delivered FIO2, 0.7. Endotracheal intubation rate and 28-day death rate were recorded. The Student’s t test assessed the between-group difference when data were distributed normally; otherwise, the Mann-WhitneyU test was used. A comparison between dichotomous variables was performed with the x test or Fisher exact test. ANOVAwas used to test as an interaction for whether the change in physiological variables 2 hours after NIV was different between groups. Table 1 shows the characteristics of patients at admission and the clinical outcomes. Compared with the non–COVID-19 group, patients with COVID-19 before NIV showed lower values of inspiratory effort as assessed byDPes (Figure 1). Shown are baseline values of lung mechanics, RR, V_ E, VTE, and dynamic mechanical power at baseline and 2 hours after NIV are resumed (Table 1). The COVID-19 group showed lower values of RR (P, 0.001), VTE (P=0.003), V_ E (P, 0.001), and dynamic mechanical power (P, 0.001) and higher dynamic compliance (P, 0.001) compared with the non–COVID-19 group. After NIV, a reduction inDPes and RR and an increase in dynamicmechanical power was reported for both groups, whereas no change was noted in either dynamic compliance or VTE. Despite there being no group interactions or changes in the physiological variables after NIV,DPL showed a significant increase in the COVID-19 group. In this group, the baseline value of dynamic mechanical power was considerably lower than in the non–COVID-19 group (27 vs. 95 J/min, P, 0.0001) and was significantly increased following NIV. This may suggest an unfavorable interaction between kinetic energy transferred from the respiratory muscles and the NIV to the lungs of these patients, at least early. Nevertheless, the absolute value of dynamic mechanical power was lower in patients with COVID-19 than in non–COVID-19 patients. To our knowledge, this is the first report assessing inspiratory effort and respiratory mechanics in spontaneously breathing patients with COVID-19 developing ARF. At their early onset of ARF, these patients showed different mechanical characteristics and breathing patterns when compared with non–COVID-19 patients. It has been speculated that the progression across COVID-19may be triggered by excessive inspiratory drive activation (7).We have previously found that patients withmoderate to severe ARDS exhibited very high inspiratory effort—even early during NIV—which was associated with unfavorable outcomes (3). Because themean arterial pHwas 7.48 in both groups, patients with COVID-19 also appeared to have a (relatively) high respiratory drive. However, the inspiratory effort of patients with COVID-19 was lower than in non–COVID-19 patients, thus suggesting amismatch between lungmechanics and hypoxia, at variance with the typical form of ARDS. Indeed, a different lungmorphology, as compared with ARDS, might explain this: the This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern.

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Topics: Breathing (57%)

2 Citations


Open accessPosted ContentDOI: 10.1101/2021.03.17.21253788
Liam Weaver1, Anup Das1, Sina Saffaran2, Nadir Yehya3  +7 moreInstitutions (7)
17 Mar 2021-medRxiv
Abstract: BackgroundThere is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e. severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen. ResultsSimulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0{+/-}0.3 cmH2O at baseline to 33.8{+/-}0.4 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2{+/-}0.5 cmH2O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7{+/-}0.1 cmH2O at baseline to 17.9{+/-}0.3 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2{+/-}0.3 cmH2O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29{+/-}0.006 at baseline to 0.65{+/-}0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6{+/-}0.1 J/min at baseline to 12.9{+/-}0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9{+/-}0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7{+/-}0.2 cmH2O at baseline to 19.6{+/-}0.2 at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9{+/-}0.3 cmH2O at 10 ml/kg/30 breaths/min. ConclusionsOur results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.

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Topics: Lung injury (57%), Respiratory system (51%), Population (50%)

1 Citations


Open accessJournal ArticleDOI: 10.1016/J.BJA.2021.09.031
Abstract: Background Prone positioning in non-intubated spontaneously breathing patients is becoming widely applied in practice alongside noninvasive respiratory support. This systematic review and meta-analysis evaluates the effect, timing, and populations that might benefit from awake proning regarding oxygenation, mortality, and tracheal intubation compared with supine position in hypoxaemic acute respiratory failure. Methods We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, and BMJ Best Practice until August 2021 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42021250322). Studies included comprise least-wise 20 adult patients with hypoxaemic respiratory failure secondary to acute respiratory distress syndrome or coronavirus disease (COVID-19). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and study quality was assessed using the Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool. Results Fourteen studies fulfilled the selection criteria and 2352 patients were included; of those patients, 99% (n=2332/2352) had COVID-19. Amongst 1041 (44%) patients who were placed in the prone position, 1021 were SARS-CoV-2 positive. The meta-analysis revealed significant improvement in the PaO2/FiO2 ratio (mean difference –23.10; 95% confidence interval [CI]: –34.80 to 11.39; P=0.0001; I2=26%) after prone positioning. In patients with COVID-19, lower mortality was found in the group placed in the prone position (150/771 prone vs 391/1457 supine; odds ratio [OR] 0.51; 95% CI: 0.32–0.80; P=0.003; I2=48%), but the tracheal intubation rate was unchanged (284/824 prone vs 616/1271 supine; OR 0.72; 95% CI: 0.43–1.22; P=0.220; I2=75%). Overall proning was tolerated for a median of 4 h (inter-quartile range: 2–16). Conclusions Prone positioning can improve oxygenation amongst non-intubated patients with acute hypoxaemic respiratory failure when applied for at least 4 h over repeated daily episodes. Awake proning appears safe, but the effect on tracheal intubation rate and survival remains uncertain.

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Topics: Prone position (60%), Supine position (57%), Respiratory failure (54%) ... read more

Book ChapterDOI: 10.1007/978-3-030-87234-2_35
Amogh Hiremath1, Lei Yuan2, Rakesh Shiradkar1, Kaustav Bera1  +11 moreInstitutions (4)
27 Sep 2021-
Abstract: Although, recently convolutional neural networks (CNNs) based prognostic models have been developed for COVID-19 severity prediction, most of these studies have analyzed characteristics of lung infiltrates (ground-glass opacities and consolidations) on chest radiographs or CT. However, none of the studies have explored the possible lung deformations due to the disease. Our hypothesis is that more severe disease results in more pronounced deformation. The key contributions of this work are three-fold: (1) A new lung deformation based biomarker analyzing regions of differential distensions between COVID-19 patients with mild and severe disease. (2) Integrating 3D-CNN characterization of lung deformation regions and lung infiltrates on lung CT into a novel framework (LuMiRa) for prognosticating COVID-19 severity. (3) Validating LuMiRa on one of the largest multi-institutional cohort till date (N = 948 patients). We found that majority of the shape deformations were observed in the mediastinal surface of both the lungs and in left interior lobe. On a testing cohort based on two institutions, Av (N = 419) and Bv (N = 113), LuMiRa yielded an area under the receiver operating characteristic curve (AUC) of 0.89 and 0.77 respectively showing significant improvement over a 3D-CNN trained over just lung infiltrates (AUC = 0.85 (p < 0.001), AUC = 0.75 (p = 0.01)). Additionally, LuMiRa performed significantly better than machine learning models trained on clinical and radiomic features (0.82, 0.78 and 0.72, 0.72 on Av and Bv respectively).

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84 results found


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30183-5
Chaolin Huang1, Yeming Wang2, Xingwang Li3, Lili Ren4  +25 moreInstitutions (8)
24 Jan 2020-The Lancet
Abstract: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.

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26,390 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2002032
Wei-jie Guan1, Zhengyi Ni1, Yu Hu1, Wenhua Liang1  +33 moreInstitutions (1)
Abstract: Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of...

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16,855 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30566-3
Fei Zhou1, Ting Yu, Ronghui Du, Guohui Fan2  +16 moreInstitutions (5)
28 Mar 2020-The Lancet
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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Topics: Cohort study (56%), Retrospective cohort study (56%), Odds ratio (53%) ... read more

15,279 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.1585
Dawei Wang1, Bo Hu1, Chang Hu1, Fangfang Zhu1  +10 moreInstitutions (1)
17 Mar 2020-JAMA
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%.

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Topics: Interquartile range (51%)

13,270 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30211-7
Nanshan Chen1, Min Zhou2, Xuan Dong1, Jie-Ming Qu2  +10 moreInstitutions (3)
30 Jan 2020-The Lancet
Abstract: 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. 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.

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12,381 Citations