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Background: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients' outcome., Methods: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed., Results: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death., Conclusions: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.

Pulmonary fibrosis arises from the repeated epithelial mild injuries and insufficient repair lead to over activation of fibroblasts and excessive deposition of extracellular matrix, which result in a mechanical stretched niche. However, increasing mechanical stress likely exists before the establishment of fibrosis since early micro injuries increase local vascular permeability and prompt cytoskeletal remodeling which alter cellular mechanical forces. It is noteworthy that COVID-19 patients with severe hypoxemia will receive mechanical ventilation as supportive treatment and subsequent pathology studies indicate lung fibrosis pattern. At advanced stages, mechanical stress originates mainly from the stiff matrix since boundaries between stiff and compliant parts of the tissue could generate mechanical stress. Therefore, mechanical stress has a significant role in the whole development process of pulmonary fibrosis. The alveoli are covered by abundant capillaries and function as the main gas exchange unit. Constantly subject to variety of damages, the alveolar epithelium injuries were recently recognized to play a vital role in the onset and development of idiopathic pulmonary fibrosis. In this review, we summarize the literature regarding the effects of mechanical stress on the fundamental cells constituting the alveoli in the process of pulmonary fibrosis, particularly on epithelial cells, capillary endothelial cells, fibroblasts, mast cells, macrophages and stem cells. Finally, we briefly review this issue from a more comprehensive perspective: the metabolic and epigenetic regulation.

Background: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date., Methods: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality., Findings: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4-40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20-2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6-41·5)., Interpretation: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients' outcomes is still poorly understood., Design: Observational, prospective, multicentre study., Setting: Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards., Participants: Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded., Interventions: Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101-200 mm Hg); mild (PaO2/FiO2 201-300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg)., Primary and Secondary Outcome Measures: The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay., Results: 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55-76) years with a PaO2/FiO2 at admission of 262 (140-343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04)., Conclusions: A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality., Trial Registration Number: NCT04307459., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Respiratory failure is the most common cause of death in patients with corona virus disease 2019 (COVID-19). There have been many investigations to determine predictors of bad outcomes in patients with this illness. Liver enzyme elevation has been described in hospitalized patients with severe COVID-19; however, little is known about the significance of liver injury regarding outcomes. We conducted a retrospective chart review of 348 patients admitted with COVID-19 in our quaternary care center. Liver injury on admission was defined based on the laboratory cutoff of aspartate aminotransferase >35 IU/L and/or alanine aminotransferase >52 IU/L. Patients were divided into two cohorts based on the presence or absence of liver injury. These cohorts were compared to assess differences in presentation, complications, and outcomes. The primary outcome was respiratory failure requiring intubation, and the secondary outcome was in-hospital mortality. The presence of new onset liver enzyme elevation on presentation was associated with increased severity of illness, need for mechanical ventilation, and mortality. Presence of liver injury increased the chance of acute hypoxic respiratory failure requiring mechanical ventilation by 1.79 times. The degree and timeline of liver enzyme elevation during hospitalization corresponded with elevations of other inflammatory markers. Conclusion : Liver injury appears to correlate with the inflammatory syndrome caused by COVID-19, with the degree of liver injury corresponding with severity of inflammation. We suggest early and continued monitoring of liver enzymes as they can be useful to identify patients who may need early escalation of care., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO 2 /FiO 2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure ( P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin ( r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials., Competing Interests: Competing interest statement: T.E.M. is a member of the Scientific Advisory Board for Ra Pharmaceutical producing complement inhibitors. All other authors declare no competing interests., (Copyright © 2020 the Author(s). Published by PNAS.)

Study Objective: The goal of this study is to create a predictive, interpretable model of early hospital respiratory failure among emergency department (ED) patients admitted with coronavirus disease 2019 (COVID-19)., Methods: This was an observational, retrospective, cohort study from a 9-ED health system of admitted adult patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) and an oxygen requirement less than or equal to 6 L/min. We sought to predict respiratory failure within 24 hours of admission as defined by oxygen requirement of greater than 10 L/min by low-flow device, high-flow device, noninvasive or invasive ventilation, or death. Predictive models were compared with the Elixhauser Comorbidity Index, quick Sequential [Sepsis-related] Organ Failure Assessment, and the CURB-65 pneumonia severity score., Results: During the study period, from March 1 to April 27, 2020, 1,792 patients were admitted with COVID-19, 620 (35%) of whom had respiratory failure in the ED. Of the remaining 1,172 admitted patients, 144 (12.3%) met the composite endpoint within the first 24 hours of hospitalization. On the independent test cohort, both a novel bedside scoring system, the quick COVID-19 Severity Index (area under receiver operating characteristic curve mean 0.81 [95% confidence interval {CI} 0.73 to 0.89]), and a machine-learning model, the COVID-19 Severity Index (mean 0.76 [95% CI 0.65 to 0.86]), outperformed the Elixhauser mortality index (mean 0.61 [95% CI 0.51 to 0.70]), CURB-65 (0.50 [95% CI 0.40 to 0.60]), and quick Sequential [Sepsis-related] Organ Failure Assessment (0.59 [95% CI 0.50 to 0.68]). A low quick COVID-19 Severity Index score was associated with a less than 5% risk of respiratory decompensation in the validation cohort., Conclusion: A significant proportion of admitted COVID-19 patients progress to respiratory failure within 24 hours of admission. These events are accurately predicted with bedside respiratory examination findings within a simple scoring system., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The role of tracheostomy during the coronavirus disease 2019 (COVID-19) pandemic remains unknown. The goal of this consensus statement is to examine the current evidence for performing tracheostomy in patients with respiratory failure from COVID-19 and offer guidance to physicians on the preparation, timing, and technique while minimizing the risk of infection to health care workers (HCWs)., Methods: A panel including intensivists and interventional pulmonologists from three professional societies representing 13 institutions with experience in managing patients with COVID-19 across a spectrum of health-care environments developed key clinical questions addressing specific topics on tracheostomy in COVID-19. A systematic review of the literature and an established modified Delphi consensus methodology were applied to provide a reliable evidence-based consensus statement and expert panel report., Results: Eight key questions, corresponding to 14 decision points, were rated by the panel. The results were aggregated, resulting in eight main recommendations and five additional remarks intended to guide health-care providers in the decision-making process pertinent to tracheostomy in patients with COVID-19-related respiratory failure., Conclusion: This panel suggests performing tracheostomy in patients expected to require prolonged mechanical ventilation. A specific timing of tracheostomy cannot be recommended. There is no evidence for routine repeat reverse transcription polymerase chain reaction testing in patients with confirmed COVID-19 evaluated for tracheostomy. To reduce the risk of infection in HCWs, we recommend performing the procedure using techniques that minimize aerosolization while wearing enhanced personal protective equipment. The recommendations presented in this statement may change as more experience is gained during this pandemic., (Copyright © 2020. Published by Elsevier Inc.)

We aimed to systematically review the clinical characteristics of coronavirus disease 2019 (COVID-19). Seven databases were searched to collect studies about the clinical characteristics of COVID-19 from January 1, 2020 to February 28, 2020. Then, meta-analysis was performed by using Stata12.0 software. A total of 38 studies involving 3062 COVID-19 patients were included. Meta-analysis showed that a higher proportion of infected patients was male (56.9%). The incidence rate of respiratory failure or acute respiratory distress syndrome was 19.5% and the fatality rate was 5.5%. Fever (80.4%), fatigue (46%), cough (63.1%), and expectoration (41.8%) were the most common clinical manifestations. Other common symptoms included muscle soreness (33%), anorexia (38.8%), chest tightness (35.7%), shortness of breath (35%), dyspnea (33.9%). Minor symptoms included nausea and vomiting (10.2%), diarrhea (12.9%), headache (15.4%), pharyngalgia (13.1%), shivering (10.9%), and abdominal pain (4.4%). The proportion of patients that was asymptomatic was 11.9%. Normal leukocyte counts (69.7%), lymphopenia (56.5%), elevated C-reactive protein levels (73.6%), elevated ESR (65.6%), and oxygenation index decreased (63.6%) were observed in most patients. About 37.2% of patients were found with elevated D-dimer, 25.9% of patients with leukopenia, along with abnormal levels of liver function (29%), and renal function (25.5%). Other findings included leukocytosis (12.6%) and elevated procalcitonin (17.5%). Only 25.8% of patients had lesions involving a single lung and 75.7% of patients had lesions involving bilateral lungs. The most commonly experienced symptoms of COVID-19 patients were fever, fatigue, cough, and expectoration. A relatively small percentage of patients were asymptomatic. Most patients showed normal leucocytes counts, lymphopenia, elevated levels of C-reactive protein and ESR. Bilateral lung involvement was common., (© 2020 Wiley Periodicals LLC.)

Objective: This study aims to describe the clinical characteristics and predictors of mechanical ventilation of adult inpatients with COVID-19 in a single center., Methods: A retrospective cohort study was performed and included adult inpatients hospitalized from March 17th to May 3rd, 2020, who were diagnosed with SARS-CoV-2 infection. Clinical and demographic characteristics were extracted from electronic medical records., Results: Overall, 88 consecutive patients were included in this study. The median age of the patients was 63 years (IQR 49 - 71); 59 (67%) were male, 65 (86%) had a college degree and 67 (76%) had at least one comorbidity. Twenty-nine (33%) patients were admitted to the intensive care unit, 18 (20%) patients needed mechanical ventilation, and 9 (10.2%) died during hospitalization. The median length of stay in the intensive care unit and the median duration of mechanical ventilation was 23 and 29.5 days, respectively. An age ≥ 65 years was an independent risk factor for mechanical ventilation (OR 8.4 95%CI 1.3 - 55.6 p = 0.02)., Conclusion: Our findings describe the first wave of Brazilian patients hospitalized for COVID-19. Age was the strongest predictor of respiratory insufficiency and the need for mechanical ventilation in our population.

A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can vary from asymptomatic to severe symptoms. It can lead to respiratory failure and acute respiratory distress syndrome requiring intubation and mechanical ventilation. Triaging patients is key to prevent spread, conserving medical resources, and providing appropriate care. The treatment of these patients remains supportive. Respiratory failure due to the virus should be managed by providing supplemental oxygen and early intubation. Some patients develop acute respiratory distress syndrome and refractory hypoxemia. In this article, we review the 2 phenotypes of respiratory failure, mechanical ventilation and the management of refractory hypoxemia.

Pulmonary complications are the most common clinical manifestations of coronavirus disease (COVID-19). From recent clinical observation, two phenotypes have emerged: a low elastance or L-type and a high elastance or H-type. Clinical presentation, pathophysiology, pulmonary mechanics, radiological and ultrasound findings of these two phenotypes are different. Consequently, the therapeutic approach also varies between the two. We propose a management algorithm that combines the respiratory rate and oxygenation index with bedside lung ultrasound examination and monitoring that could help determine earlier the requirement for intubation and other surveillance of COVID-19 patients with respiratory failure.

We report the case of an 18-month-old infant with severe serotype 3 adenovirus pneumonia, exceptionally associated with hemophagocytic syndrome. Treatment included cidofovir and mechanical ventilation for 13 days. The child developed chronic respiratory insufficiency due to bronchiectasis and bronchiolitis obliterans., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

The ongoing COVID-19 pandemic has placed pressure on health care systems and intensive care unit capacity worldwide. Respiratory insufficiency is the most common reason for hospital admission in patients with COVID-19. The most severe form of respiratory failure is acute respiratory distress syndrome (ARDS), which is associated with significant morbidity and mortality. Patients with ARDS are often treated with invasive mechanical ventilation according to established evidence-based and guideline recommended management strategies. With growing strain on critical care capacity, clinicians from diverse backgrounds, including cardiovascular specialists, might be required to help care for the growing number of patients with severe respiratory failure and ARDS. The aim of this article is to outline the fundamentals of ARDS diagnosis and management, including mechanical ventilation, for the nonintensivist. In the absence of mechanical ventilation trials specifically in patients with COVID-19-associated ARDS, the information presented is on the basis of general ARDS trials., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation., Hypothesis: The primary hypothesis is that canakiumab will shorten time to recovery., Methods: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin and C-reactive protein (CRP). The primary endpoint is defined as the time in days from randomization to either an improvement of two points on a seven category ordinal scale or discharge from the hospital, whichever occurs first up to 14 days postrandomization. The secondary endpoint is mortality at day 28. A total of 45 patients will be enrolled with an anticipated 5 month follow up period., Results: Baseline characteristics for the first 20 randomized patients reveal a predominantly male (75%), elderly population (median 67 years) with a high prevalence of hypertension (80%) and hyperlipidemia (75%). CRPs have been markedly elevated (median 16.2 mg/dL) with modest elevations in high-sensitivity troponin T (median 21 ng/L), in keeping with the concept of enrolling patients with early myocardial injury., Conclusions: The three C study will provide insights regarding whether IL-1β inhibition may improve outcomes in patients with SARS-CoV2 associated myocardial injury and increased inflammation., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: Specific comorbidities and old age create a greater vulnerability to severe Coronavirus Disease 19 (COVID-19). While obesity seems to aggravate the course of disease, the actual impact of the BMI and the cutoff which increases illness severity are still under investigation. The aim of the study was to analyze whether the BMI represented a risk factor for respiratory failure, admission to the intensive care unit (ICU) and death., Research Design and Methods: A retrospective cohort study of 482 consecutive COVID-19 patients hospitalised between March 1 and April 20, 2020. Logistic regression analysis and Cox proportion Hazard models including demographic characteristics and comorbidities were carried out to predict the endpoints within 30 days from the onset of symptoms., Results: Of 482 patients, 104 (21.6%) had a BMI ≥ 30 kg/m2. At logistic regression analysis, a BMI between 30 and 34.9 kg/m2 significantly increased the risk of respiratory failure (OR: 2.32; 95% CI: 1.31-4.09, P = 0.004) and admission to the ICU (OR: 4.96; 95% CI: 2.53-9.74, P < 0.001). A significantly higher risk of death was observed in patients with a BMI ≥ 35 kg/m2 (OR: 12.1; 95% CI: 3.25-45.1, P < 0.001)., Conclusions: Obesity is a strong, independent risk factor for respiratory failure, admission to the ICU and death among COVID-19 patients. A BMI ≥ 30 kg/m2 identifies a population of patients at high risk for severe illness, whereas a BMI ≥ 35 kg/m2 dramatically increases the risk of death.

COVID-19 patients admitted to the Intensive Care Unit may develop painful range of motion restrictions of the large joints due to heterotopic ossifications. Here we describe two patients who developed restricted and painful passive and active mobility of the hips, shoulders and elbows after mechanical ventilation because of respiratory failure due to COVID-19 pneumonia. Conventional radiography showed extensive heterotopic ossifications. Retrospectively, alkaline phosphatase levels were elevated. It is likely that local and systemic factors contribute to the development of heterotopic ossifications. Early diagnosis is important to provide complementary non-pharmacological interventions (gentle passive mobilization) and medication (non-steroidal anti-inflammatory drugs, such as indomethacin). If pain and limited joint mobility remain present, surgical removal of ectopic bone could be considered. Future trials are needed to systematically map the prevalence of heterotopic ossifications in COVID-19 patients who were admitted to the Intensive Care Unit, andto evaluate whether prophylactic treatment with non-steroidal anti-inflammatory drug is of relevance.

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.

In coronavirus disease 2019 (COVID-19), higher morbidity and mortality are associated with age, male gender, and comorbidities, such as chronic lung diseases, cardiovascular pathologies, hypertension, kidney diseases, diabetes mellitus, and obesity. All of the above conditions are characterized by increased sympathetic discharge, which may exert significant detrimental effects on COVID-19 patients, through actions on the lungs, heart, blood vessels, kidneys, metabolism, and/or immune system. Furthermore, COVID-19 may also increase sympathetic discharge, through changes in blood gases (chronic intermittent hypoxia, hyperpnea), angiotensin-converting enzyme (ACE)1/ACE2 imbalance, immune/inflammatory factors, or emotional distress. Nevertheless, the potential role of the sympathetic nervous system has not yet been considered in the pathophysiology of COVID-19. In our opinion, sympathetic overactivation could represent a so-far undervalued mechanism for a vicious circle between COVID-19 and comorbidities., (© 2020 Federation of European Biochemical Societies.)

Background: Currently, the epidemic of coronavirus disease 2019 (COVID-19) has begun to spread worldwide. We aim to explore reliable evidence for the diagnosis and treatment of the COVID-19 by analyzing all the published studies by Chinese scholars on the clinical and imaging features in novel coronavirus pneumonia caused by SARS-CoV-2., Methods: We searched five medical databases including two Chinese and three English databases for all published articles on COVID-19 since the outbreak. A random-effects model was designed, and the imaging and clinical data from all studies were collected for meta-analysis., Results: Overall, 31 articles and 46 959 patients were included, including 10 English articles and 21 Chinese articles. The results of meta-analysis showed that the most common clinical manifestations were fever (87.3%; 0.838-0.909), cough (58.1%; 0.502-0.660), dyspnea (38.3%; 0.246-0.520), muscle soreness or fatigue (35.5%; 0.253-0.456), and chest distress (31.2%; -0.024 to 0.648). The main imaging findings were bilateral pneumonia (75.7%; 0.639-0.871) and ground-glass opacification (69.9%; 0.602-0.796). Among the patients, the incidence that required intensive care unit (ICU) was (29.3%; 0.190-0.395), the incidence with acute respiratory distress syndrome was (28.8%; 0.147-0.429), the incidence with multiple organ dysfunction syndrome was (8.5%; -0.008 to 0.179), and the case fatality rate of patients with COVID-19 was (6.8%; 0.044-0.093)., Conclusion: COVID-19 is a new clinical infectious disease that mainly causes bilateral pneumonia and lung function deteriorates rapidly. Nearly a third of patients need to be admitted to the ICU, and patients are likely to present respiratory failure or even death., (© 2020 Wiley Periodicals, Inc.)

SARS2-CoV-2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post-mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID-19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS-CoV-2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS-CoV-2 triggers a series of reactions leading to striking vascular alterations., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

SARS-CoV-2 causes a phenotype of pneumonia with diverse manifestation, which is termed as coronavirus disease 2019 (COVID-19). An impressive high transmission rate allows COVID-19 conferring enormous challenge for clinicians worldwide, and developing to a pandemic level. Combined with a series of complications, a part of COVID-19 patients progress into severe cases, which critically contributes to the risk of fatality. To date, coagulopathy has been found as a prominent feature of COVID-19 and severe coagulation dysfunction may be associated with poor prognosis. Coagulopathy in COVID-19 may predispose patients to hypercoagulability-related disorders including thrombosis and even fatal vascular events. Inflammatory storm, uncontrolled inflammation-mediated endothelial injury and renin angiotensin system (RAS) dysregulation are the potential mechanisms. Ongoing efforts made to develop promising therapies provide several potential strategies for hypercoagulability in COVID-19. In this review, we introduce the clinical features of coagulation and the increased vascular thrombotic risk conferred by coagulopathy according to present reports about COVID-19. The potential underlying mechanisms and emerging therapeutic avenues are discussed, emphasizing an urgent need for effective interventions., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products., Source: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology., Principal Findings: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density., Conclusions: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.

SARS-CoV-2 has wreaked havoc globally and has claimed innumerable lives all over the world. Apart from the characteristic respiratory illness, this disease has been associated with florid extrapulmonary manifestations and complications. A 59-year-old female healthcare worker presented with features of acute-onset non-compressive myelopathy with a sensory level at T10 segment along with high-grade fever for 4 days. MRI of dorsal spine was suggestive of myelitis at T7 vertebral level. She was initiated on injectable steroids and did show some initial signs of recovery. A day later, she developed an acute-onset respiratory failure but could not be revived despite our best efforts. Her nasopharyngeal and oropharyngeal swab turned out to be positive for SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR). We hereby report a case of acute transverse myelitis with COVID-19 as a probable aetiology., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND Pneumonia caused by coronavirus originated in Wuhan, China in late 2019 and has spread around the world, becoming a pandemic. Many patients deteriorate rapidly and require intubation and mechanical ventilation, which is causing the collapse of healthcare systems in many countries. Coronavirus infection is associated with extensive lung inflammation and microvascular thrombosis, which can result in hypoxia. It can also cause severe and lasting harm in other organs, including the heart and kidneys. At present, there is no proven and efficacious treatment for this new disease. Consequently, there is a growing tendency to use novel methods. Ozone therapy consists of administration of a mixture of oxygen and ozone (a molecule consisting of 3 oxygen atoms). The potential benefits of this therapy include reduced tissue hypoxia, decreased hypercoagulability, renal and heart protection, modulated immune function, improved phagocytic function, and impaired viral replication. CASE REPORT We report rapidly improved hypoxia with associated decreases in inflammatory markers and D-dimer immediately after 1-4 sessions of oxygen-ozone (O₂-O₃) therapy in 3 patients with COVID-19 pneumonia who presented with respiratory failure. Invasive mechanical ventilation was not required in these 3 patients. All patients were discharged home on days 3-4 after O₂-O₃ therapy. CONCLUSIONS O₂-O₃ therapy appears to be an effective therapy for COVID-19 patients with severe respiratory failure. Large controlled clinical trials are required to study the efficacy and safety of using O₂-O₃ therapy compared with the standard supportive case in patients with COVID-19 in terms of the need for invasive ventilation and length of hospital and intensive care unit stays.

Aim: Previous studies have suggested a more frequent and severe course of novel coronavirus SARS-CoV-2 infection in cancer patients undergoing active oncologic treatment. Our aim was to describe the characteristics of the disease in this population and to determine predictive factors for poor outcome in terms of severe respiratory distress (acute respiratory distress syndrome [ARDS]) or death., Patients and Methods: Patients consecutively admitted for SARS-CoV-2 infection were prospectively collected, and retrospective statistical analysis was performed. Univariate and multivariate analyses were performed to assess potential factors for poor outcomes defined as ARDS or death., Results: Sixty-three patients were analysed, and 34 of them developed respiratory failure (70% as ARDS). Lymphocytes/mm3 (412 versus 686; p = 0.001), serum albumin (2.84 versus 3.1); lactate dehydrogenase (LDH) (670 versus 359; p < 0.001) and C-reactive protein (CRP) levels (25.8 versus 9.9; p < 0.001) discriminate those that developed respiratory failure. Mortality rate was 25%, significantly higher among ARDS, neutropenic patients (p = 0.01) and in those with bilateral infiltrates (44% versus 0%; p < 0.001). Multivariate logistic analyses model confirmed the predictive value of severe neutropenia (odds ratio [OR] 16.54; 95% confidence interval [CI] 1.43-190.9, p 0.025), bilateral infiltrates (OR 32.83, CI 95% 3.51-307, p 0.002) and tumour lung involvement (OR 4.34, CI 95% 1.2-14.95, p 0.02)., Conclusion: Cancer patients under active treatment admitted for SARS-CoV-2 infection have worse outcomes in terms of mortality and respiratory failure rates compared with COVID-19 global population. Lymphopenia, LDH, CRP and albumin discriminate illness severity, whereas neutropenia, bilateral infiltrates and tumour pulmonary involvement are predictive of higher mortality., Competing Interests: Conflict of interest statement None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflammatory state. The cytokinic storm, thromboinflammation and pulmonary tropism are the bedrock of tissue lesions responsible for acute respiratory failure and for prolonged infection that may lead to multiple organ failure and death. The thrombogenicity of this infectious disease is illustrated by the high frequency of thromboembolic events observed even in Covid-19 patients treated with anticoagulation. Increased D-Dimers, a biomarker reflecting activation of hemostasis and fibrinolysis, and low platelet count (thrombocytopenia) are associated with higher mortality in Covid-19 patients. In this review, we will summarize our current knowledge on the thromboembolic manifestations, the disturbed hemostatic parameters, and the thromboinflammatory conditions associated to Covid-19 and we will discuss the modalities of anticoagulant treatment or other potential antithrombotic options., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice., Methods: This is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020., Results: Length of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p<0.001). Symptoms of fever, fatigue and diarrhoea were seen in 76%, 43% and 23% of patients, respectively. There were four rheumatic patients who experienced a flare of rheumatic disease during hospital stay, with symptoms of muscle aches, back pain, joint pain or rash. While lymphocytopaenia was seen in 57% of rheumatic patients, only one patient (5%) presented with leucopenia in rheumatic cases. Rheumatic patients presented with similar radiological features of ground-glass opacity and consolidation. Patients with pre-existing interstitial lung disease showed massive fibrous stripes and crazy-paving signs at an early stage. Five rheumatic cases used hydroxychloroquine before the diagnosis of COVID-19 and none progressed to critically ill stage., Conclusions: Respiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered., Trial Registration Number: ChiCTR2000030795., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND As the severe acute respiratory syndrome coronavirus 2 (SARS CoV2) spreads around the world infecting people of all ages, clinicians and researchers are working to gather data on the presentation of coronavirus disease (COVID-19). Further study is necessary to better diagnose and treat COVID-19 patients. CASE REPORT We describe the case of an 8-year-old boy admitted with status epilepticus, who also tested positive for COVID-19, while afebrile, with no initial respiratory symptoms. Benzodiazepines were given per treatment guidelines, abating the seizure activity. He subsequently developed respiratory distress and desaturation requiring temporary emergent intubation. All clinical symptoms resolved within a few hours. Results of a computed tomography (CT) scan of the brain were within normal limits. Results of a 24-h electroencephalogram (EEG) were abnormal, indicative of diffuse cerebral dysfunction. As a result of intubation and findings of bilateral infiltrates on chest x-ray, a COVID-19 test was administered and the result was positive. CONCLUSIONS For proper diagnosis and treatment, patients and clinicians should be aware that COVID-19 may not present in the typical fashion of respiratory distress and fever. The present case suggests a rare neurological presentation of COVID-19.

COVID-19 is an emerging disease that can manifest itself as asymptomatic or mild respiratory tract infection in the majority of individuals, but in some, it can progress into severe pneumonia and acute respiratory distress syndrome (ARDS). Inflammation is known to play a crucial role in the pathogenesis of severe infections and ARDS and evidence is emerging that the IL-1/IL-6 pathway is highly upregulated in patients with severe disease. These findings open new avenues for host-directed therapies in patients with symptomatic SARS-CoV-2 infection and might in addition to antiviral treatment be enough to curb the currently unacceptably high morbidity and mortality associated with COVID-19.

Background: COVID-19 pneumonia can result in severe hypoxaemic respiratory failure that requires intensive medical care. We wished to describe COVID-19 intensive care patients who were treated with and without invasive ventilatory support., Material and Method: The material was retrieved from the local quality register and comprises data on patients with COVID-19 admitted to the intensive care department at Oslo University Hospital Ullevål from 5 March-28 May 2020. The patients were categorised in three groups on the basis of the treatment they received for respiratory failure (oxygen alone, supplemental non-invasive ventilation (NIV), and intubation/ventilator) and described using descriptive statistics., Results: Of 165 hospitalised COVID-19 patients, a total of 26 (16 %) were treated in our intensive care department. Four of them had do-not-resuscitate-orders and were excluded. The 22 patients included in this study had an average age of 56 years (range 25 to 78 years); 17 (77 %) were men. Eleven patients received ventilator treatment, seven oxygen by mask, and four supplemental NIV. In the ventilator group, as of 28 May 2020 two had died, and the remainder had been discharged alive from the intensive care department, with one remaining hospitalised on a ward. All patients treated with oxygen and NIV were alive and had been discharged from hospital., Interpretation: For many patients with COVID-19 respiratory failure and need for intensive care, increased oxygen and NIV are sufficient, but the need for intubation must be continuously assessed. More than 90 % of actively treated intensive care patients survived.

Objective: A novel coronavirus emerged this year as a cause of viral pneumonia. The main characteristics of the virus are rapid transmission, high contagion capacity and potential severity. The objective of this case series study is to describe the clinical characteristics of patients with confirmed coronavirus disease (COVID-19) admitted to different intensive care units in Argentina for mechanical ventilation., Methods: A descriptive, prospective, multicenter case series study was conducted between April 1 and May 8, 2020. Data from patients older than 18 years who were admitted to the intensive care unit for mechanical ventilation for acute respiratory failure with a positive diagnosis of COVID-19 were included., Results: The variables for 47 patients from 31 intensive care units were recorded: 78.7% were men (median age of 61 years), with a SAPS II score of 43 and a Charlson index score of 3. The initial ventilatory mode was volume control - continuous mandatory ventilation with a tidal volume less than 8mL/kg in 100% of cases, with a median positive end-expiratory pressure of 10.5cmH2O. At the end of the study, 29 patients died, 8 were discharged, and 10 remained hospitalized. The SAPS II score was higher among patients who died (p = 0.046). Charlson comorbidity index was associated with higher mortality (OR = 2.27, 95% CI 1.13 - 4.55, p = 0.02)., Conclusion: Patients with COVID-19 and on mechanical ventilation in this series presented clinical variables similar to those described to date in other international reports. Our findings provide data that may predict outcomes.

Respiratory failure is the most worrisome problem of COVID-19. Patients may develop severe pneumonia requiring invasive mechanical ventilation and a significant proportion of them dies. It has been suggested that brainstem might play a role in severe respiratory failure of COVID-19 patients. We described three COVID-19 patients in ICU at Federico II Hospital in Naples that, although had recovered from pneumonia, could not be weaned from invasive mechanical ventilation. Our clinical evaluation was consistent with an involvement of the brainstem and especially of respiratory centre thus possibly explaining the weaning failure in patients that were awake and had recovered from lung involvement. Our data, though limited, indicate that brainstem involvement may play a role in respiratory failure and perhaps in the high death rate of COVID-19 patients. Moreover, the weaning failure from mechanical ventilation due to central respiratory drive depression might underlie the unusual long stay in ICU reported for COVID-19 patients.

Background: Coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available., Objective: We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation., Methods: Patients with COVID-19 who were hospitalized from February 29 to April 9, 2020, were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n = 40) followed by a temporally separated validation cohort (n = 49)., Results: We identified markers of inflammation, lactate dehydrogenase, and creatinine as the variables most predictive of respiratory failure in the evaluation cohort. Maximal IL-6 level before intubation showed the strongest association with the need for mechanical ventilation, followed by maximal CRP level. The respective AUC values for IL-6 and CRP levels in the evaluation cohort were 0.97 and 0.86, and they were similar in the validation cohort (0.90 and 0.83, respectively). The calculated optimal cutoff values during the course of disease from the evaluation cohort (IL-6 level > 80 pg/mL and CRP level > 97 mg/L) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure., Conclusion: The maximal level of IL-6, followed by CRP level, was highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP level to guide escalation of treatment in patients with COVID-19-related hyperinflammatory syndrome., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Singapore was one of the first countries affected by the coronavirus disease 2019 (COVID-19) pandemic but has been able to prevent its healthcare system and intensive care units (ICU) from being overwhelmed. We describe the clinical features, management and outcomes of COVID-19 patients with respiratory failure admitted to our ICU., Materials and Methods: A case series of COVID-19 patients admitted to our ICU for respiratory failure from 7 February, with data censoring at 30 June 2020, was performed from a review of medical records., Results: Twenty-two COVID-19 patients were admitted to our ICU for respiratory failure. The median age was 54.5 years (IQR 30-45.5), 72.7% were male and had at least one comorbidity. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 2.5 (IQR 1.25-7) and 10 (8.25-12) respectively. Thirteen patients required invasive mechanical ventilation (IMV) and had a median PaO2/FiO2 ratio of 194 mmHg (IQR 173-213) after intubation. The 28-day survival was 100%, with 2 patients demising subsequently. The overall ICU mortality rate was 9.1% at the time of data censoring. In IMV survivors, length of IMV and ICU stay were 11 days (IQR 9-17.75) and 16 days (IQR 12-32) respectively., Conclusion: Low COVID-19 ICU mortality was observed in our "pandemic-ready" ICU. This was achieved by having adequate surge capacity to facilitate early ICU admission and IMV, lung protective ventilation, and slow weaning. Being able to maintain clinical standards and evidence-based practices without having to resort to rationing contributed to better outcomes.

Objective: We aim to summarize reliable evidence of evidence-based medicine for the treatment and prevention of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by analyzing all the published studies on the clinical characteristics of patients with SARS-CoV-2., Methods: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of SARS-CoV-2 infection were collected for meta-analysis., Results: Ten studies were included in Meta-analysis, including a total number of 50466 patients with SARS-CoV-2 infection. Meta-analysis shows that, among these patients, the incidence of fever was 0.891 (95% CI: 0.818, 0.945), the incidence of cough was 0.722 (95% CI: 0.657, 0.782), and the incidence of muscle soreness or fatigue was 0.425 (95% CI: 0.213, 0.652). The incidence of acute respiratory distress syndrome (ARDS) was 0.148 (95% CI: 0.046, 0.296), the incidence of abnormal chest computer tomography (CT) was 0.966 (95% CI: 0.921, 0.993), the percentage of severe cases in all infected cases was 0.181 (95% CI: 0.127, 0.243), and the case fatality rate of patients with SARS-CoV-2 infection was 0.043 (95% CI: 0.027, 0.061)., Conclusion: Fever and cough are the most common symptoms in patients with SARS-CoV-2 infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare. The case fatality rate of patients with SARS-CoV-2 infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This meta-analysis also has limitations, so the conclusions of this Meta-analysis still need to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size., (© 2020 Wiley Periodicals, Inc.)

Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic coronavirus named SARS-CoV-2 (previously known as 2019-nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS-CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical symptoms similar to those reported for SARS-CoV and MERS-CoV. The most characteristic symptom of patients with COVID-19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID-19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS-CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse-connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS-CoV and SARS-CoV2, it remains to make clear whether the potential invasion of SARS-CoV2 is partially responsible for the acute respiratory failure of patients with COVID-19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS-CoV-2-induced respiratory failure., (© 2020 Wiley Periodicals, Inc.)