Pathogenesis and Management of COVID-19

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Abstract

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.

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Most cited references 211

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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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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary 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.)

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Hernan Flores-Rozas: Role: Academic Editor

Journal

Journal ID (nlm-ta): J Xenobiot

Journal ID (iso-abbrev): J Xenobiot

Journal ID (publisher-id): jox

Title: Journal of Xenobiotics

Publisher: MDPI

ISSN (Print): 2039-4705

ISSN (Electronic): 2039-4713

Publication date (Electronic): 21 May 2021

Publication date Collection: June 2021

Volume: 11

Issue: 2

Pages: 77-93

Affiliations

[1 ]Hala Alfarouk Cancer Center, Department of Evolutionary Pharmacology and Tumor Metabolism, Khartoum 11123, Sudan; derma55@ 123456yahoo.com

[2 ]Research Center, Zamzam University College, Khartoum 11123, Sudan; rector@ 123456zamzam.edu.sd

[3 ]Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, Medina 42353, Saudi Arabia; shoufie@ 123456taibahu.edu.sa

[4 ]College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; samahmed@ 123456sharjah.ac.ae

[5 ]Pharmacology Department, Faculty of Medicine, Fayoum University, Fayoum 63514, Egypt; mfs01@ 123456fayoum.edu.eg

[6 ]Department of Oesphogastric and General Surgery, University Hospitals of Leicester, Leicester LE5 4PW, UK; Ahmed.ahmed@ 123456doctors.org.uk

[7 ]Pharmacy Practice Research Unit, Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; ssalqahtani@ 123456jazanu.edu.sa

[8 ]Department of Medical Laboratories Sciences, College of Applied Medical Sciences, Najran University, Najran 66446, Saudi Arabia; asmezher@ 123456nu.edu.sa

[9 ]Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia; amsfr@ 123456kku.edu.sa

[10 ]Department of Preventive Dental Sciences, Ibn Sina National College, Jeddah 22421, Saudi Arabia; amramadan@ 123456ibnsina.edu.sa

[11 ]Department of Surgery, Faculty of Medicine Al-Neelain University, Khartoum 11111, Sudan

[12 ]Faculty of Pharmacy, University of Khartoum, P. O. Box 321, Khartoum 11111, Sudan; Heyam57@ 123456hotmail.com

[13 ]Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan; mibrahim@ 123456iend.org

[14 ]Scientific Direction, Foltra Medical Centre, 15886 Teo, Spain; jesus.devesa@ 123456usc.es

[15 ]Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy; rosaangela.cardone@ 123456uniba.it (R.A.C.); stephanjoel.reshkin@ 123456uniba.it (S.J.R.)

[16 ]Assistance Publique des Hôpitaux de Paris, 75003 Paris, France; dr.Laurentschwartz@ 123456gmail.com

Author notes

[* ]Correspondence: Alfarouk@ 123456hala-alfarouk.org ; Tel.: +249-912-148-466

Author information

Khalid O. Alfarouk https://orcid.org/0000-0001-8656-6117

Ali M. Alqahtani https://orcid.org/0000-0002-2240-4757

Heyam S. Ali https://orcid.org/0000-0002-4441-0525

Jesus Devesa https://orcid.org/0000-0002-4153-2543

Rosa A. Cardone https://orcid.org/0000-0002-2011-9135

Stephan J. Reshkin https://orcid.org/0000-0001-9757-5908

Article

Publisher ID: jox-11-00006

DOI: 10.3390/jox11020006

PMC ID: 8163157

PubMed ID: 34063739

SO-VID: a95888dc-4cfb-4bc1-bdd0-c81b68fc22de

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

Pathogenesis and Management of COVID-19

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Novel Coronavirus Disease COVID-19

Most cited references 211

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

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

A Novel Coronavirus from Patients with Pneumonia in China, 2019

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