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Journal Article

Clinical interventions for severe and critical COVID-19: What are the options

15 May 2020-American Journal of Translational Research (Am J Transl Res)-Vol. 12, Iss: 5, pp 2110-2117
TL;DR: The current study reviewed published evidence of clinical interventions of severe and critical COVID-19 to provide an up-to-date reference for further clinical treatment.
Abstract: The coronavirus disease 2019 (COVID-19) has been ongoing outbreak and declared as a global public health emergency by the World Health Organization. Severe and critical COVID-19 has high fatality rate due to complications like acute respiratory distress syndrome, acute respiratory failure or multiple organ failure. So far, there have been mounting research on the epidemiological and clinical characteristics of COVID-19. However, the information regarding treatment of severe and critical COVID-19 is limited. The current study reviewed published evidence of clinical interventions of severe and critical COVID-19, aiming to provide an up-to-date reference for further clinical treatment.
Citations
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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
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.

4,408 citations

Journal ArticleDOI
TL;DR: This article summarizes agents with potential efficacy against SARS-CoV-2 and indicates some promising results have been achieved thus far.
Abstract: The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.

1,069 citations

Journal ArticleDOI
TL;DR: The new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease is reviewed, and its clinical features are summarised.
Abstract: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.

585 citations

Posted Content
TL;DR: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization, and the patients with male sex, anorexia and no fever on admission predicted poor efficacy.
Abstract: South Australia is presently in the throes of major changes to its regulatory system governing land use, development of land and the development of planning policy against which development assessment decisions are to be made. Eventually the planning and development control system established under the Development Act 1993 (SA) will be replaced by a new system implemented by the Planning, Development and Infrastructure Act 2016 (SA) (the new Act).

568 citations

Journal ArticleDOI
12 May 2020-JAMA
TL;DR: There is concern that the use of ACEIs and ARBs will increase expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation, and there has been a growing concern that this association with hypertension is confounded by treatment with specific antihypertensive medications.
Abstract: Coronavirus disease 2019 (COVID-19) is a current pandemic infection caused by a positive-sense RNA virus named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The particularly infectious capacity of the virus, along with mortality rates ranging from 1% to above 5%, has raised concerns across the globe.1 Older patients with comorbid conditions including pulmonary disease, cardiac disease, kidney disease, diabetes, and hypertension have been associated with even higher mortality rates, suggesting particularly susceptible populations. The increased mortality and morbidity of COVID-19 in patients with hypertension is an association that has been observed in a number of initial epidemiological studies outlining the characteristics of the COVID-19 epidemic in China. Wu et al2 found hypertension to have a hazard ratio of 1.70 for death and 1.82 for acute respiratory distress syndrome in 201 patients with COVID-19. Zhou et al3 found hypertension to have a hazard ratio of 3.05 for in-hospital mortality in 191 patients with COVID-19. Neither of these studies2,3 adjusted for confounding variables and thus it remains unclear if this association is related to the pathogenesis of hypertension or another associated comorbidity or treatment. There has been a growing concern that this association with hypertension is confounded by treatment with specific antihypertensive medications: angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). The link with ACEIs and ARBs is because of the known association between angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2. ACE2 has been shown4 to be a co-receptor for viral entry for SARSCoV-2 with increasing evidence that it has a protracted role in the pathogenesis of COVID-19. ACE2 has a broad expression pattern in the human body with strong expression noted in the gastrointestinal system, heart, and kidney with more recent data identifying expression of ACE2 in type II alveolar cells in the lungs. The concern that ACEIs and ARBs affect the severity and mortality of COVID-19 is 2-fold. One suggestion is that ACEIs could directly inhibit ACE2; however, ACE2 functions as a carboxypeptidase and is not inhibited by clinically prescribed ACEIs.5 In addition, there is concern that the use of ACEIs and ARBs will increase expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation. There has been considerable evidence in animal models as well as some evidence in humans showing increased expression of ACE2 in the heart, brain, and even in urine after treatment with ARBs; however, there is limited evidence showing changes in serum or pulmonary ACE2 levels. More relevant, the signif icance of ACE2 expression on COVID-19 pathogenesis and mortality is not specifically known. ACE2 primarily acts to counterbalance the effect of ACE. As ACE generates angiotensin II from angiotensin I, ACE2 generates angiotensin (1-7) from angiotensin II which, after binding to the Mas receptor broadly, shifts the balance from vasoconstriction with angiotensin II to vasodilation with Mas receptor activation in the effected vascular bed. The role this vasodilatory effect has in the pathogenesis of COVID-19 is unclear but some animal data suggest a link. ACE2 and angiotensin (1-7) have been found to be protective in a number of different lung injury models. In an acid lung injury model in mice, ACE2 downregulation by SARS-CoV, the SARS virus responsible for the SARS outbreak in 2003, worsened lung injury that was improved by treatment with ARB. This suggested SARS-CoV exacerbates lung injury by decreasing ACE2 that is reversed by ARB treatment.6 Although these preclinical data suggest that increasing ACE2 expression can attenuate SARS-CoV-2–induced lung injury, there is no direct clinical evidence that has proven ACE2 to be an effective treatment for viral-induced lung injury. Of note, a preliminary trial of ACE2 infusion in 10 patients with acute respiratory distress syndrome was completed in humans but was not powered to show efficacy on pulmonary function.7 There is even less evidence to demonstrate that treatment with ACEIs or ARBs can decrease severity of pulmonary injury by SARS-CoV-2, though preclinical data suggest a potential mechanism of benefit. Despite the lack of evidence, there have been advocates for both the use and cessation of ACEIs, ARBs, or both during the treatment for COVID-19 in patients with hypertension. This has prompted some individuals to solicit changes in their hypertensive medications and growing uncertainty from physicians on what should be done. Changes in antihypertensive medications would require patients to visit their pharmacy and possibly obtain blood work, which would increase their exposure and risk of infection. Antihypertensive medication changes between classes additionally require frequent dose adjustment and management of adverse effects and increases the risk of medical errors. In response, the Council on Hypertension of the European Society of Cardiology made the following statement, “The Council on Hypertension strongly recommends that physicians and patients should continue treatment with their usual anti-hypertensive VIEWPOINT

374 citations

References
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Journal ArticleDOI
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.

36,578 citations


Additional excerpts

  • ...ECMO has been applied in severe COVID-19 patients in China according to several studies, however, these studies didn’t report the outcomes of these patients [11, 20, 23, 28]....

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  • ...COVID-19 patients have higher levels of inflammatory markers according to their laboratory tests [11, 23], and the treatment of cytokine storm is an important element for rescuing severe patients....

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  • ...tients are prone to a variety of complications, including ARDS, acute heart injury, impaired renal function, abnormal liver function and secondary infection [19, 20, 23, 24]....

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Journal ArticleDOI
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

21,455 citations

Journal ArticleDOI
TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.

20,189 citations

Journal ArticleDOI
03 Feb 2020-Nature
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Abstract: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV. Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

16,857 citations


Additional excerpts

  • ...Several basic research studies have revealed that angiotensin-converting enzyme 2 (ACE2) has a protracted role in the pathogenesis of COVID-19 as it is a critical receptor for viral entry [21]....

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Journal ArticleDOI
17 Mar 2020-JAMA
TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
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%.

16,635 citations