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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Clinical Characteristics of Coronavirus Disease 2019 in China.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.

Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/2763184/jamainternal_wu_2020_oi_200022.pdf

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1–3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies. High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS-CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.

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Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.

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%.

https://jamanetwork.com/journals/jama/articlepdf/2761044/jama_wang_2020_oi_200019.pdf

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.

In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. A period of 7–13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.

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Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China.

Rationale: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease.

Objectives: To study the epidemiology, clinical features and outcomes of patients with COVID-19.

Methods: we performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital. 

Measurements and Main Results: The median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%.

Conclusions: The COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes. 

Keywords: coronavirus disease 2019; clinical features; outcomes; severe patients

https://medrxiv.org/content/10.1101/2020.03.02.20030452v1.full.pdf

Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China

INTRODUCTION: Coronavirus disease-2019 (COVID-19) outbreak has spread around the world. However, the dynamic course of critically ill COVID-19 has not been described thoroughly. PATIENTS AND METHODS: We retrospectively analyzed 195 critically ill COVID-19 patients in Hubei province, China, between January 5, 2020 and April 3, 2020. Epidemiologic data, clinical features, treatments, and outcomes were collected and analyzed. RESULTS: Most critically ill patients were older with higher Acute Physiology and Chronic Health Evaluation II scores. After critical illness onset, a total of 181 (92.8%) patients received ventilation support, of which 84 (43.1%) received noninvasive and 97 (49.7%) received invasive mechanic ventilation (IMV). Among the 97 patients with IMV, 28 (28.9%) received prone ventilation, 57 (58.8%) received neuromuscular blocked therapy, and 22 (11.3%) received tracheostomy due to prolonged ventilator use. Early hypoxemia, subsequent hypercapnia, pulmonary hypertension, and finally pulmonary fibrosis were notable in the clinical course of acute respiratory distress syndrome (ARDS). Eighty-nine (45.6%) patients presented with shock. Acute kidney injury (29.7%) and secondary infection (28.2%) were also notable. The overall mortality of critically ill patients at day 28 was 42.1%. Intensive care unit (ICU) mortality was around 33%, as 16 patients died prior to ICU admission. A low PaO2/FiO2 ratio was an independent risk factor for death. High viral load was observed in most non-survivors. CONCLUSION: ARDS and shock were notable in the critical illness of COVID-19. Ventilation support and hemodynamic support were the cornerstones for critical care. High viral load was associated with death of critically ill COVID-19 patients.

Clinical Course of 195 Critically Ill COVID-19 Patients: A Retrospective Multicenter Study.


 Importance: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outbreak in China is now a global issue. There is only a limited understanding of the clinical characteristics of patients with SARS-CoV-2 infections is available.Objective:To describe the characteristics, management strategies, and outcomes of critically ill patients with SARS-CoV-2 infection.Design, Setting, and Patients: This is aretrospective, multi-center case series of 50 critically ill patients with confirmed SARS-CoV-2 infection who were admitted at Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital in Wuhan, China, from January 8 to February 9, 2020.Exposures:Documented Corona Virus Disease, 2019 (COVID-19).Main Outcome Measures: Demographic, clinical, laboratory, imaging data were collected along with management strategies, complications and outcomes of enrolled individuals. Results Fifty critically ill patients with SARS-CoV-2 infections were enrolled. Their median age was 62 (range, 29-92) [IQR,49.5-69.0] years, 68% were male, and 28 (56%) patients had comorbidities, the most common being hypertension. In this cohort, 20(40%) patients survived ,16(32%) patients died, and the rest remained hospitalized. The invasive mechanical ventilator was used in 36(72%) patients with 15(30%) of them requiring prone positioning, and 17(34%) switched to ECMO. The compliance scores of lungs (Cstat)on the day of ICU admission among survivors were higher than those in non-survivors [42.0(18.0-47.0), vs. 19.5(14.0-24.2), p=0.038].The blood IL-6 levels and neutrophils counts at the first day of ICU admission were significantly higher in non-survivors compared to survivors [123.7(85.3-228.8), vs. 20.2(6.8-67.2) ng/ml, p=0.025 for IL-6, and 20.2(6.8-67.2) vs. 4.01(1.99-7.05) × 10⁹/L, p=0.02 for neutrophils counts].The heart rates, PaCO2, lung injury scale (LIS), and positive end-expiratory pressure levels were constantly higher for 10 days in non-survivors than those who survived (p<0.05). The frequency of vasopressor uses and neuromuscular blockers was higher in non-survivors from day 1 to day 10 compared to survivors (p<0.05). In the whole cohort, the most common complications were ARDS (97%), shock (44%), arrhythmia (38%), acute cardiac injury (26%), and acute kidney injury (22%). A secondary bacterial infection was noted in 17(34%) patients. Univariate analysis indicated that lower lung complianceand higher neutrophil counts at the day of ICU admission were related to higher mortality (p-0.03, and 0.04, respectively)ConclusionWe demonstrated that SARS-CoV-2 infection-related critical illness predominantly affected old individuals with comorbidities and characterized by severe hypoxemic respiratory failure, often requiring prolonged mechanical ventilation and rescue therapies. Low lung compliance and persistently elevated PaCO2 indicated poor outcomes.

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Chang Hu

Papers

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.

Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China.

Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China

Clinical Course of 195 Critically Ill COVID-19 Patients: A Retrospective Multicenter Study.

Clinical features of critically ill patients with COVID-19 infection in China