Review Article

Exploring pathophysiology of COVID-19 infection: Faux espoir and dormant therapeutic options

Vinod Nikhra*

Published: 05 May, 2020 | Volume 4 - Issue 1 | Pages: 034-040

COVID-19 virus structural components: The 2019-nCoV, also called SARS-CoV-2, was first reported in Wuhan, China in December 2019. The disease was named Coronavirus Disease 2019 (COVID-19) and the virus responsible for it as the COVID-19 virus, respectively, by WHO. The 2019-nCoV has a round, elliptic or pleomorphic form with a diameter of 60–140 nm. It has single-stranded RNA genome containing 29891 nucleotides, a lipid shell, and spike, envelope, membrane and hemagglutinin-esterase (HE) proteins.

Steps in progression of COVID-19 illness: Once inside the airways, the S protein on the viral surface recognizes and mediates the attachment to host ACE-2 receptors and gains access to endoplasmic reticulum. The HE protein facilitates the S protein-mediated cell entry and virus spread through the mucosa, helping the virus to attack the ACE2-bearing cells lining the airways and infecting upper as well as lower respiratory tracts. With the dying cells sloughing down and filling the airways, the virus is carried deeper into the lungs. In addition, the virus is able to infect ACE2-bearing cells in other organs, including the blood vessels, gut and kidneys. With the viral infestation, the activated immune system leads to inflammation, pyrexia and pulmonary edema. The hyperactivated immune response, called cytokine storm in extreme cases, can damage various organs apart from lungs and increases susceptibility to infectious bacteria especially in those suffering from chronic diseases.

The current therapeutics for COVID-19: At present, there is no specific antiviral treatment available for the disease. The milder cases may need no treatment. In moderate to severe cases, the clinical management includes infection prevention and control measures, and symptomatic and supportive care, including supplementary oxygen therapy. In the critically ill patients, mechanical ventilation is required for respiratory failure and hemodynamic support is imperative for managing circulatory failure and septic shock.

Conclusion: Confusion, despair and hopes: There is no vaccine for preexposure prophylaxis or postexposure management. There are no specific approved drugs for the treatment for the disease. A number of drugs approved for other conditions as well as several investigational drugs are being canned and studied in several clinical trials for their likely role in COVID-19 prophylaxis or treatment. The future seems afflicted with dormant therapeutic options as well as faux Espoir or false hopes. As obvious, not all clinical trials will be successful, but having so many efforts in progress, some may succeed and provide a positive solution. Right now, though, confusion and despair prevail.

Read Full Article HTML DOI: 10.29328/journal.ijcv.1001013 Cite this Article Read Full Article PDF


COVID-19; 2019 nCoV; Spike (S) protein; ACE-2; Cytokine storm syndrome; Azithromycin; Chloroquine; Hydroxychloroquine; Remdesivir; COVID-19 vaccine


  1. Naming the coronavirus disease (COVID-19) and the virus that causes it. 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it
  2. Lu R, Zhao X, Li J, Niu P, Yang B, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395: 565-574. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32007145
  3. Chan JF, Kok KH, Zhu Z, Chu H, To KK, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020; 9: 221-236. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31987001
  4. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015; 1282: 1–23. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25720466
  5. Li Q, Guan X, Wu P, Wang X, Zhou L, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020; 382: 1199-1207. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31995857
  6. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. et al. Features, Evaluation and Treatment Coronavirus (COVID-19). StatPearls Publishing LLC. Bookshelf ID: NBK554776. 2020; PMID: 32150360. PubMed: https://www.ncbi.nlm.nih.gov/books/NBK554776/
  7. Porter DL, Maloney DG. Cytokine release syndrome (CRS). UpToDate. 2020. Retrieved from https://www.uptodate.com/contents/cytokine-release-syndrome-crs?
  8. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Resp Med. Corres. 2020. https://www.ncbi.nlm.nih.gov/pubmed/32353251 PubMed:
  9. Angeletti S, Benvenuto D, Bianchi M, Giovanetti M, Pascarella S, et al. COVID-2019: The role of the nsp2 and nsp3 in its pathogenesis. J Med Virol. 2020.
  10. Lei J, Kusov Y, Hilgenfeld R. Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein. Antiviral Res. 2018; 149: 58-74. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29128390
  11. Tai W, He L, Zhang X, Pu J, Voronin D, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol. 2020. https://www.ncbi.nlm.nih.gov/pubmed/32203189
  12. Xu X, Chen P, Wang J, Feng J, Zhou H, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modelling of its spike protein for risk of human transmission. Sci China Life Sci. 2020; 63: 457-460. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32009228
  13. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020; 92: 418-423. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31967327
  14. Kuba K, Imai Y, Rao S, Gao H, Guo F, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2020; 11: 875-879. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16007097
  15. Xu H, Zhong L, Deng J, Peng J, Dan H, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020; 12: 8.
  16. In the author’s opinion – inferring on the available findings and research data.
  17. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, et al. A novel coronavirus from patients with pneumonia in China. N Engl J Med. 2019. https://www.nejm.org/doi/full/10.1056/NEJMoa2001017
  18. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y,et al. Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. 2020.
  19. Cao Y, Li L, Feng Z, Wan S, Huang P, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020; 6: 11. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32133153
  20. Guan WJ, Ni Z, Hu Y, Liang W, Ou C, et al. Clinical characteristics of 2019 novel coronavirus infection in China. N England J of Med. www.medrxiv.org/content/10.1101/2020.02.06.20020974v1
  21. Huang C, Wang Y, Li X, Ren 4, Zhao J, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395: 497-506. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31986264
  22. In the author’s opinion – inferring on the available findings and research data.
  23. Anosmia, hyposmia and dysgeusia in the absence of other relevant disease should alert to the possibility of COVID-19 infection and warrant consideration for testing. American Academy of Otolaryngology-Head and Neck Surgery – position statement.
  24. Tian Y, Rong L, Nian W, He Y. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020; 51: 843-851. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32222988
  25. Wu Z, McGoogan JM. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32091533
  26. Lianhan S, Jianping Z, Yi H, Du Ronghui, Bin C. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet. 2020.
  27. Baden LR, Rubin EJ. Covid-19 - The Search for Effective Therapy. 2020. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32187463
  28. Cao B, Wang Y, Wen D, Liu W, Wang J, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32187464
  29. Huang J. Efficacy of Chloroquine and Lopinavir/ Ritonavir in mild/general novel coronavirus (CoVID-19) infections: a prospective, open-label, multicenter randomized controlled clinical study. 2020. http://www.chictr.org.cn/showproj.aspx?proj=49263
  30. https://www.the-scientist.com/news-opinion/flu-and-anti-hiv-drugs-show-efficacy-against-coronavirus-67052
  31. Chen C, Zhang Y, Huang J, Yin P, Cheng Z, et al. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. 2020. www.medrxiv.org/content/10.1101/2020.03.17.20037432v1
  32. precisionvaccinations.com/avigan-favipiravir-t-705-broad-spectrum-inhibitor-viral-rna-polymerase
  33. Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Götte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem. 2020; 295: 4773-4779. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32094225
  34. Wang M, Cao R, Zhang L, Yang X, Liu J, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30: 269-271. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32020029
  35. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020; 105949. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32205204
  36. Liu J, Cao R, Xu M, Wang X, Zhang H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020; 6: 16. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32194981
  37. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D, et al. Chloroquine and hydroxychloroquine as available weapons to Figureht COVID-19. Int J Antimicrob Agents. 2020; 105932. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32145363
  38. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005; 2: 69. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16115318
  39. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020; 14: 72-73. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32074550
  40. Yao X, Ye F, Zhang M, Cui C, Huang B, et al. in vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; pii: ciaa237. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32150618
  41. Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. in vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004; 323: 264-268. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15351731
  42. Yao X, Ye F, Zhang M, Cui C, Huang B, et al. in vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; pii: ciaa237. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32150618
  43. Information on registered clinical trials for COVID-19 in the United States is available at: https://clinicaltrials.gov/external icon
  44. Duan K, Liu B, Li C, Zhang H, Yu T, et al. The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study. 2020.
  45. https://www.boston.com/news/health/2020/03/24/when-might-experimental-drugs-to-treat-covid-19-be-ready
  46. Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrobial Chemotherapy. 2020; dkaa114.
  47. cnbc.com/2020/03/17/hopes-of-a-coronavirus-vaccine-mount-as-three-key-biotech-players-make-progress.html


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