Molecular Aspects of Co-morbidities in COVID-19 Infection

Document Type : CURRENT CONCEPTS REVIEW

Authors

1 1 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 1 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2 Department of Medical Genetics, Faculty of Medicine

Abstract

Coronaviruses are a group of enveloped viruses with single-stranded non-segmented positive-sense RNA genomes. In
December 2019, SARS-CoV-2 appeared in China for the first time and quickly spread throughout the world. Although
certain medications suggested for other afflictions tend to be potentially effective for curing the infection, there is no
approved vaccination or drug available for this virus yet. Comprehension of the disease molecular pathogenesis could
provide useful tools for COVID-19 patients in surveillance, prognosis, treatment, vaccine development and therapeutic
targeting. The present research aims to summarize the association in COVID-19 patients between molecular dimensions
of comorbidities with clinical and preclinical information.
Developing an ACE2 inhibitor could be a possible therapeutic target. Plasmin is another possible candidate both in
diagnosis and treatment areas. All predicted biomarkers must be validated either through randomized clinical trials or
experimental assays before clinical application in patients.
Level of evidence: V

Keywords


1. Huang L, Shi Y, Gong B, Jiang L, Liu X, Yang J, et al. Blood
single cell immune profiling reveals the interferon-
MAPK pathway mediated adaptive immune response
for COVID-19. medRxiv. 2020.
2. Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et
al. A familial cluster of pneumonia associated with the
2019 novel coronavirus indicating person-to-person
transmission: a study of a family cluster. The Lancet.
2020;395(10223):514-23.
3. Tetro JA. Is COVID-19 receiving ADE from
other coronaviruses? Microbes and Infection.
2020;22(2):72-3.
4. Lippi G, Henry BM. Chronic obstructive pulmonary
disease is associated with severe coronavirus disease
2019 (COVID-19). Respiratory Medicine. 2020.
5. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor
recognition by the novel coronavirus from Wuhan:
an analysis based on decade-long structural studies
of SARS coronavirus. Journal of virology. 2020;94(7).
6. Unterholzner L. The interferon response to
intracellular DNA: why so many receptors?
Immunobiology. 2013;218(11):1312-21.
7. Kroczynska B, Mehrotra S, Arslan AD, Kaur S, Platanias
LC. Regulation of interferon-dependent mRNA
translation of target genes. Journal of Interferon &
Cytokine Research. 2014;34(4):289-96.
8. Xiong Y, Liu Y, Cao L, Wang D, Guo M, Jiang A, et al.
Transcriptomic characteristics of bronchoalveolar
lavage fluid and peripheral blood mononuclear cells in
COVID-19 patients. Emerging Microbes & Infections.
2020;9(1):761-70.
9. Kumar S. COVID-19: A drug repurposing and
biomarker identification by using comprehensive
gene-disease associations through protein-protein
interaction network analysis. 2020.
10. Ma RCW, Holt RIG. COVID-19 and diabetes.
Diabetic medicine : a journal of the British Diabetic
Association. 2020 Apr 3. PubMed PMID: 32242990.
Epub 2020/04/04. eng.
11. Fang L, Karakiulakis G, Roth M. Are patients with
hypertension and diabetes mellitus at increased
risk for COVID-19 infection? The Lancet Respiratory
Medicine. 2020;8(4):e21.
12. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS.
Angiotensin-converting enzyme 2 (ACE2) as a SARSCoV-
2 receptor: molecular mechanisms and potential
therapeutic target. Intensive Care Medicine. 2020:1-5.
13. Ray EC, Miller RG, Demko JE, Costacou T, Kinlough CL,
Demko CL, et al. Urinary plasmin (ogen) as a prognostic
factor for hypertension. Kidney international reports.
2018;3(6):1434-42.
14. Fernandez C, Rysä J, Almgren P, Nilsson J, Engström
G, Orho‐Melander M, et al. Plasma levels of the
proprotein convertase furin and incidence of
diabetes and mortality. Journal of internal medicine.
2018;284(4):377-87.
15. Chen X, Hu W, Ling J, Mo P, Zhang Y, Jiang Q, et al.
Hypertension and Diabetes Delay the Viral Clearance
in COVID-19 Patients. medRxiv. 2020.
16. South AM, Diz D, Chappell MC. COVID-19, ACE2
and the Cardiovascular Consequences. American
Physiological Society Rockville, MD; 2020.
17. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et
al. Epidemiological and clinical characteristics of
99 cases of 2019 novel coronavirus pneumonia
in Wuhan, China: a descriptive study. The Lancet.
2020;395(10223):507-13.
18. Ji H-L, Zhao R, Matalon S, Matthay MA. Elevated
plasmin (ogen) as a common risk factor for COVID-19
susceptibility. Physiological Reviews. 2020.
19. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah
N, Decroly E. The spike glycoprotein of the new
coronavirus 2019-nCoV contains a furin-like cleavage
site absent in CoV of the same clade. Antiviral
Research. 2020;176:104742.
20. Kam Y-W, Okumura Y, Kido H, Ng LF, Bruzzone R,
Altmeyer R. Cleavage of the SARS coronavirus spike
glycoprotein by airway proteases enhances virus
entry into human bronchial epithelial cells in vitro.
PloS one. 2009;4(11).
21. Zhao R, Ali G, Nie HG, Chang Y, Bhattarai D, Su X, et al.
Plasmin improves oedematous blood‐gas barrier by
cleaving epithelial sodium channels. British Journal of
Pharmacology. 2020.
22. Oxlund CS, Buhl KB, Jacobsen IA, Hansen MR, Gram J,
Henriksen JE, et al. Amiloride lowers blood pressure
and attenuates urine plasminogen activation in
patients with treatment–resistant hypertension.
Journal of the American Society of Hypertension.
2014;8(12):872-81.
23. Kleyman TR, Kashlan OB, Hughey RP. Epithelial Na+
channel regulation by extracellular and intracellular
factors. Annual review of physiology. 2018;80:263-81.
24. Matthay MA, Aldrich JM, Gotts JE. Treatment for severe
acute respiratory distress syndrome from COVID-19.
The Lancet Respiratory Medicine. 2020.
25. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger
N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry
depends on ACE2 and TMPRSS2 and is blocked by a
clinically proven protease inhibitor. Cell. 2020.
26. Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et
al. Cancer patients in SARS-CoV-2 infection: a
nationwide analysis in China. The Lancet Oncology.
2020;21(3):335-7.
27. Di Bona D, Cippitelli M, Fionda C, Cammà C, Licata A,
Santoni A, et al. Oxidative stress inhibits IFN-α-induced
antiviral gene expression by blocking the JAK–STAT
pathway. Journal of hepatology. 2006;45(2):271-9.
28. Tefferi A. Novel mutations and their functional and
clinical relevance in myeloproliferative neoplasms:
JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1.
Leukemia. 2010;24(6):1128.
29. Genovese MC, Kremer J, Zamani O, Ludivico C,
Krogulec M, Xie L, et al. Baricitinib in patients 
with refractory rheumatoid arthritis. N Engl J Med.
2016;374:1243-52.
30. Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O,
Smith D, et al. COVID-19: combining antiviral and
anti-inflammatory treatments. The Lancet Infectious
Diseases. 2020.
31. Favalli EG, Biggioggero M, Maioli G, Caporali R.
Baricitinib for COVID-19: a suitable treatment? The
Lancet Infectious Diseases. 2020.
32. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall
RS, Manson JJ. COVID-19: consider cytokine storm
syndromes and immunosuppression. The Lancet.
2020.
33. Richardson P, Griffin I, Tucker C, Smith D, Oechsle O,
Phelan A, et al. Baricitinib as potential treatment for
2019-nCoV acute respiratory disease. The Lancet.
2020;395(10223):e30-e1.
34. Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-
Martin JF, Cameron CM, et al. Interferon-mediated
immunopathological events are associated with
atypical innate and adaptive immune responses in
patients with severe acute respiratory syndrome.
Journal of virology. 2007;81(16):8692-706.
35. Channappanavar R, Fehr AR, Zheng J, Wohlford-
Lenane C, Abrahante JE, Mack M, et al. IFN-I response
timing relative to virus replication determines MERS
coronavirus infection outcomes. The Journal of
clinical investigation. 2019;129(9).