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      SARS-CoV-2 and Cardiovascular Complications: from Molecular Mechanisms to Pharmaceutical Management

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      Author(s): a , 1 , b , 1 , c , a , d , a , b , e , *
      Publication date (Electronic):
      Journal: Biochemical Pharmacology
      Publisher: Elsevier Inc.
      Keywords: SARS-CoV-2, COVID-19, Cardiovascular, ACE2, Cytokine storm, ACE, Angiotensin-converting enzyme, Ang, Angiotensin, ARB, Angiotensin receptor blocker, ARDS, Acute respiratory distress syndrome, CAD, Coronary artery disease, COVID-19, Coronavirus disease 2019, CVD, Cardiovascular diseases, DIC, Disseminated intravascular coagulation, ECMO, Extracorporeal membranous oxygenation, HFpEF, Heart failure with preserved ejection fraction, ICU, Intensive care unit, IFN, Interferon, IL, Interleukin, IP-10, Interferon -γ inducible protein 10, MCP-1, monocyte chemoattractant protein 1, MERS, Middle East respiratory syndrome, MOF, Multiple organ failure, NT-proBNP, N-terminal pro-brain natriuretic peptide, RAAS, Renin-angiotensin-aldosteron system, RDRP, RNA-dependent RNA polymerase proteins, ROS, reactive oxygen species, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, TNF, Tumor necrosis factor

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          Abstract

          The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up–to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Fei Zhou, Ting Yu, Ronghui Du … (2020)
            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<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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              Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

              Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
              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.
              Article 0 comments Cited 10784 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jun Ren
                Journal
                Journal ID (nlm-ta): Biochem Pharmacol
                Journal ID (iso-abbrev): Biochem. Pharmacol
                Title: Biochemical Pharmacology
                Publisher: Elsevier Inc.
                ISSN (Print): 0006-2952
                ISSN (Electronic): 1873-2968
                Publication date PMC-release: 21 June 2020
                Publication date (Electronic): 21 June 2020
                Electronic Location Identifier: 114114
                Affiliations
                [a ]Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China
                [b ]School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, WY 82071 USA
                [c ]Department of Emergency, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
                [d ]University of Wyoming at Casper and the Department of Zoology and Physiology, Casper, WY 82601, USA
                [e ]Department of Pathology, University of Washington Seattle, Seattle, WA, USA
                Author notes
                [* ]Corresponding author. ren.jun@ 123456zs-hospital.sh.cn
                [1]

                Equal contribution

                Article
                Publisher ID: S0006-2952(20)30350-6 Publisher ID: 114114
                DOI: 10.1016/j.bcp.2020.114114
                PMC ID: 7306106
                PubMed ID: 32579957
                SO-VID: 3f38c549-50b7-4c5e-b4a5-66892fd622f6
                Copyright © © 2020 Elsevier Inc. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 19 May 2020
                Date revision received : 15 June 2020
                Date accepted : 18 June 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: sars-cov-2,covid-19,cardiovascular,ace2,cytokine storm,ace, angiotensin-converting enzyme,ang, angiotensin,arb, angiotensin receptor blocker,ards, acute respiratory distress syndrome,cad, coronary artery disease,covid-19, coronavirus disease 2019,cvd, cardiovascular diseases,dic, disseminated intravascular coagulation,ecmo, extracorporeal membranous oxygenation,hfpef, heart failure with preserved ejection fraction,icu, intensive care unit,ifn, interferon,il, interleukin,ip-10, interferon -γ inducible protein 10,mcp-1, monocyte chemoattractant protein 1,mers, middle east respiratory syndrome,mof, multiple organ failure,nt-probnp, n-terminal pro-brain natriuretic peptide,raas, renin-angiotensin-aldosteron system,rdrp, rna-dependent rna polymerase proteins,ros, reactive oxygen species,sars-cov-2, severe acute respiratory syndrome coronavirus 2,tnf, tumor necrosis factor
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: sars-cov-2, covid-19, cardiovascular, ace2, cytokine storm, ace, angiotensin-converting enzyme, ang, angiotensin, arb, angiotensin receptor blocker, ards, acute respiratory distress syndrome, cad, coronary artery disease, covid-19, coronavirus disease 2019, cvd, cardiovascular diseases, dic, disseminated intravascular coagulation, ecmo, extracorporeal membranous oxygenation, hfpef, heart failure with preserved ejection fraction, icu, intensive care unit, ifn, interferon, il, interleukin, ip-10, interferon -γ inducible protein 10, mcp-1, monocyte chemoattractant protein 1, mers, middle east respiratory syndrome, mof, multiple organ failure, nt-probnp, n-terminal pro-brain natriuretic peptide, raas, renin-angiotensin-aldosteron system, rdrp, rna-dependent rna polymerase proteins, ros, reactive oxygen species, sars-cov-2, severe acute respiratory syndrome coronavirus 2, tnf, tumor necrosis factor

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