SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

doi:10.1016/j.fct.2020.111769

Review

. 2020 Dec:146:111769.

doi: 10.1016/j.fct.2020.111769. Epub 2020 Sep 30.

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

Aristides Tsatsakis¹, Daniela Calina², Luca Falzone³, Dimitrios Petrakis⁴, Radu Mitrut⁵, Vasileios Siokas⁶, Manuela Pennisi⁷, Giuseppe Lanza⁸, Massimo Libra⁹, Sotirios G Doukas¹⁰, Panagiotis G Doukas¹¹, Leena Kavali¹², Amar Bukhari¹³, Chiranjeevi Gadiparthi¹⁴, Dimitra P Vageli¹⁵, Diamantis P Kofteridis¹⁶, Demetrios A Spandidos¹⁷, Monica M B Paoliello¹⁸, Michael Aschner¹⁹, Anca Oana Docea²⁰

Affiliations

¹ Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece; I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146, Moscow, Russia. Electronic address: tsatsaka@uoc.gr.
² Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. Electronic address: calinadaniela@gmail.com.
³ Epidemiology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", 80131, Naples, Italy. Electronic address: l.falzone@istitutotumori.na.it.
⁴ Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece. Electronic address: dimitriospetrakis@hotmail.com.
⁵ Department of Cardiology, University and Emergency Hospital, 050098, Bucharest, Romania. Electronic address: radumitrut@yahoo.co.uk.
⁶ Department of Neurology, University of Thessaly, University Hospital of Larissa, 41221, Larissa, Greece. Electronic address: bill_s1983@hotmail.com.
⁷ Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy. Electronic address: manuela.pennisi@unict.it.
⁸ Department of Surgery and Medical-Surgical Specialties, University of Catania, 95123, Catania, Italy; Department of Neurology IC, Oasi Research Institute-IRCCS, 94018, Troina, Italy. Electronic address: giuseppe.lanza1@unict.it.
⁹ Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy; Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123, Catania, Italy. Electronic address: m.libra@unict.it.
¹⁰ Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece; Department of Internal Medicine, Saint Peter's University Hospital, 254 Easton Ave, New Brunswick, NJ, 08901, USA. Electronic address: sotirios.doukas.mail@gmail.com.
¹¹ University of Pavol Josef Safarik University, Faculty of Medicine, Kosice, Slovakia. Electronic address: panagiotis.doukas.mail@gmail.com.
¹² Department of Internal Medicine, Saint Peter's University Hospital, 254 Easton Ave, New Brunswick, NJ, 08901, USA. Electronic address: leena.kavali@gmail.com.
¹³ Department of Medicine, Division of Pulmonary and Critical Care 240 Easton Ave, Adult Ambulatory at Cares Building 4th Floor, New Brunswick, NJ, 08901, USA. Electronic address: ABukhari@saintpetersuh.com.
¹⁴ Division of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter's University Hospital, New Brunswick, NJ, USA. Electronic address: cgadiparthi@saintpetersuh.com.
¹⁵ Department of Surgery, The Yale Larynx Laboratory, New Haven, CT, 06510, USA. Electronic address: dimitra.vangeli@yale.edu.
¹⁶ Department of Internal Medicine, University Hospital of Heraklion, 71110, Heraklion, Crete, Greece. Electronic address: kofteridisd@hotmail.com.
¹⁷ Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, 71003, Greece. Electronic address: spandidos@spandidos.gr.
¹⁸ Department of Molecular Pharmacology, Albert Eisntein College of Medicine, 1300 Morris Park Avenue Bronx, NY, 10461, USA. Electronic address: monibas2@gmail.com.
¹⁹ I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146, Moscow, Russia; Department of Molecular Pharmacology, Albert Eisntein College of Medicine, 1300 Morris Park Avenue Bronx, NY, 10461, USA. Electronic address: michael.aschner@einsteinmed.org.
²⁰ Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. Electronic address: daoana00@gmail.com.

PMID: 32979398
PMCID: PMC7833750
DOI: 10.1016/j.fct.2020.111769

Review

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

Aristides Tsatsakis et al. Food Chem Toxicol. 2020 Dec.

. 2020 Dec:146:111769.

doi: 10.1016/j.fct.2020.111769. Epub 2020 Sep 30.

Authors

Affiliations

¹ Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece; I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146, Moscow, Russia. Electronic address: tsatsaka@uoc.gr.
² Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. Electronic address: calinadaniela@gmail.com.
³ Epidemiology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", 80131, Naples, Italy. Electronic address: l.falzone@istitutotumori.na.it.
⁴ Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece. Electronic address: dimitriospetrakis@hotmail.com.
⁵ Department of Cardiology, University and Emergency Hospital, 050098, Bucharest, Romania. Electronic address: radumitrut@yahoo.co.uk.
⁶ Department of Neurology, University of Thessaly, University Hospital of Larissa, 41221, Larissa, Greece. Electronic address: bill_s1983@hotmail.com.
⁷ Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy. Electronic address: manuela.pennisi@unict.it.
⁸ Department of Surgery and Medical-Surgical Specialties, University of Catania, 95123, Catania, Italy; Department of Neurology IC, Oasi Research Institute-IRCCS, 94018, Troina, Italy. Electronic address: giuseppe.lanza1@unict.it.
⁹ Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy; Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123, Catania, Italy. Electronic address: m.libra@unict.it.
¹⁰ Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece; Department of Internal Medicine, Saint Peter's University Hospital, 254 Easton Ave, New Brunswick, NJ, 08901, USA. Electronic address: sotirios.doukas.mail@gmail.com.
¹¹ University of Pavol Josef Safarik University, Faculty of Medicine, Kosice, Slovakia. Electronic address: panagiotis.doukas.mail@gmail.com.
¹² Department of Internal Medicine, Saint Peter's University Hospital, 254 Easton Ave, New Brunswick, NJ, 08901, USA. Electronic address: leena.kavali@gmail.com.
¹³ Department of Medicine, Division of Pulmonary and Critical Care 240 Easton Ave, Adult Ambulatory at Cares Building 4th Floor, New Brunswick, NJ, 08901, USA. Electronic address: ABukhari@saintpetersuh.com.
¹⁴ Division of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter's University Hospital, New Brunswick, NJ, USA. Electronic address: cgadiparthi@saintpetersuh.com.
¹⁵ Department of Surgery, The Yale Larynx Laboratory, New Haven, CT, 06510, USA. Electronic address: dimitra.vangeli@yale.edu.
¹⁶ Department of Internal Medicine, University Hospital of Heraklion, 71110, Heraklion, Crete, Greece. Electronic address: kofteridisd@hotmail.com.
¹⁷ Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, 71003, Greece. Electronic address: spandidos@spandidos.gr.
¹⁸ Department of Molecular Pharmacology, Albert Eisntein College of Medicine, 1300 Morris Park Avenue Bronx, NY, 10461, USA. Electronic address: monibas2@gmail.com.
¹⁹ I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146, Moscow, Russia; Department of Molecular Pharmacology, Albert Eisntein College of Medicine, 1300 Morris Park Avenue Bronx, NY, 10461, USA. Electronic address: michael.aschner@einsteinmed.org.
²⁰ Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. Electronic address: daoana00@gmail.com.

PMID: 32979398
PMCID: PMC7833750
DOI: 10.1016/j.fct.2020.111769

Abstract

Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients.

Keywords: COVID-19 pandemic; Cancer; Cardiovascular system; Clinical signs; Gastrointestinal system; Neurological system; Pulmonary system; SARS-C0V-2.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
**The main pulmonary clinical manifestations of COVID-19.** Note: IL-12 – interleukin-12; IL-15 - interleukin-15; IL-6- interleukin-6; IL-17A - interleukin-17A; IL-18 - interleukin-18; TNF-α – tumor necrosis factor alpha; IFN-β – interferon beta; IFN-α – interferon alpha; IFN-γ – interferon gamma.

**Fig. 2**
SARS-CoV-2 infection and its association with the cardiovascular system.

**Fig. 3**
COVID-19 neurological manifestations.

**Fig. 4**
**The most prominent renal clinical manifestations in COVID-19.** Note:BUN – blood urea nitrogen; CK- creatine kinase; LDH – lactate dehydrogenase.

See this image and copyright information in PMC

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References

1. Abedi F., Rezaee R., Karimi G. Plausibility of therapeutic effects of rho kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (COVID-19) Pharmacol. Res. 2020;156:104808. - PMC - PubMed
1. Ai T., Yang Z., Hou H., Zhan C., Chen C., Lv W., et al. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020:200642. - PMC - PubMed
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[1] Abedi F., Rezaee R., Karimi G. Plausibility of therapeutic effects of rho kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (COVID-19) Pharmacol. Res. 2020;156:104808. - PMC - PubMed

[2] Abedi F., Rezaee R., Karimi G. Plausibility of therapeutic effects of rho kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (COVID-19) Pharmacol. Res. 2020;156:104808. - PMC - PubMed

[3] Ai T., Yang Z., Hou H., Zhan C., Chen C., Lv W., et al. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020:200642. - PMC - PubMed

[4] Ai T., Yang Z., Hou H., Zhan C., Chen C., Lv W., et al. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020:200642. - PMC - PubMed

[5] Aiello F., Gallo Afflitto G., Mancino R., Li J.-P.O., Cesareo M., Giannini C., et al. Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular tissues and secretions: a systematic review. Eye. 2020;34(7):1206–1211. - PMC - PubMed

[6] Aiello F., Gallo Afflitto G., Mancino R., Li J.-P.O., Cesareo M., Giannini C., et al. Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular tissues and secretions: a systematic review. Eye. 2020;34(7):1206–1211. - PMC - PubMed

[7] Alberti P., Beretta S., Piatti M., Karantzoulis A., Piatti M.L., Santoro P., et al. Guillain-Barré syndrome related to COVID-19 infection. Neurology - Neuroimmunology Neuroinflammation. 2020;7(4):e741. - PMC - PubMed

[8] Alberti P., Beretta S., Piatti M., Karantzoulis A., Piatti M.L., Santoro P., et al. Guillain-Barré syndrome related to COVID-19 infection. Neurology - Neuroimmunology Neuroinflammation. 2020;7(4):e741. - PMC - PubMed

[9] Allegra A., Di Gioacchino M., Tonacci A., Musolino C., Gangemi S. Immunopathology of SARS-CoV-2 infection: immune cells and mediators, prognostic factors, and immune-therapeutic implications. Int. J. Mol. Sci. 2020;21(13):4782. - PMC - PubMed

[10] Allegra A., Di Gioacchino M., Tonacci A., Musolino C., Gangemi S. Immunopathology of SARS-CoV-2 infection: immune cells and mediators, prognostic factors, and immune-therapeutic implications. Int. J. Mol. Sci. 2020;21(13):4782. - PMC - PubMed

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SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

Affiliations

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

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