Preview

Meditsinskiy sovet = Medical Council

Advanced search

Prerequisites for the creation of an atlas of postcovid inflammation as a way of personalized pharmacotherapy, as well as predicting and preventing organ and systemic dysfunctions

https://doi.org/10.21518/2079-701X-2021-12-72-88

Abstract

SARS-CoV-2 is a novel coronavirus that has been identified as the cause of the 2019 coronavirus infection (COVID-19), which originated at Wuhan city of PRC in late 2019 and widespread worldwide. As the number of patients recovering from COVID-19 continue to grow, it’s very important to understand what health issues they may keep experiencing. COVID-19 is now recognized as an infectious disease that can cause multiple organ diseases of various localization. It is against this background that a new term was introduced: post-acute post-COVID-19 syndrome characterized by several persistent symptoms inherent in the acute phase of the disease, as well as the occurrence of delayed and (or) long-term complications beyond 4 weeks from the onset of the disease. The work reflected in this article revealed a portrait of a patient with post-COVID-19 syndrome, the most common complications of this period, as well as the mechanisms of their development and the resulting metabolic, cellular, tissue disorders leading to the tissue and organ dysfunctions. A comprehensive biochemical and immunological screening was carried out using the example of three clinical cases to identify the most significant disorders in these patients and to correlate with their clinical status over time. In point of fact, such patients were diagnosed with vascular dysfunction factors (development of endothelial dysfunction), metabolic dysfunction factors (metabolic acidosis, mitochondrial dysfunction, carbohydrate metabolism disorder, insulin resistance, altered branched-chain and aromatic amino acid metabolism), neurological disorder factors (neurotoxicity of the resulting metabolites), immunological disorder factors (decreased efficiency of detoxification systems, secondary immunodeficiency, risk of secondary bacterial infection). 

About the Authors

I. V. Kukes
International Association of Clinical Pharmacologists and Pharmacists
Russian Federation

Cand. Sci. (Med.), Clinical Pharmacologist, Immunologist, Head of the Scientific and Clinical Department, 

2, Bldg. 1, Malaya Kalitnikovskaya St., Moscow, 109147



J. M. Salmasi
Pirogov Russian National Research Medical University
Russian Federation

Dr. Sci. (Med.), Professor, Head of the Department of Pathophysiology and Clinical Pathophysiology, Faculty of Medicine,

1, Ostrovityanov St., Moscow, 117997



K. S. Ternovoy
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Cand. Sci. (Med.), Associate Professor of the Department of Traumatology, Orthopedics and Disaster Surgery, 

8, Bldg. 2, Trubetskaya St., Moscow, 119991



A. N. Kazimirskii
Pirogov Russian National Research Medical University
Russian Federation

Dr. Sci. (Biol.), Associate Professor, Leading Researcher, Department of Molecular Technologies,

1, Ostrovityanov St., Moscow, 117997



T. E. Obodzinskaya
ChromsystemsLab LLC
Russian Federation

Medical Director of the Research and Laboratory Complex Chromolab, 

20, Bldg. 2, Nauchnyy proezd, Moscow, 117246



V. G. Lim
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Dr. Sci. (Med.), Professor of the Department of Sports Medicine and Medical Rehabilitation, Clinic of Medical Rehabilitation,
University Clinical Hospital No. 2, 

8, Bldg. 2, Trubetskaya St., Moscow, 119991



P. B. Glagovskiy
ChromsystemsLab LLC
Russian Federation

MBA, Director of the Research and Laboratory Complex Chromolab, 

20, Bldg. 2, Nauchnyy proezd, Moscow, 117246



I. S. Mamedov
ChromsystemsLab LLC
Russian Federation

Cand. Sci. (Med.), General Director of the Research and Laboratory Complex Chromolab, 

20, Bldg. 2, Nauchnyy proezd, Moscow, 117246



G. V. Poryadin
Pirogov Russian National Research Medical University
Russian Federation

Corr. Member RAS, Dr. Sci. (Med.), Professor of the Department of Pathophysiology and Clinical Pathophysiology, Faculty of Medicine,

1, Ostrovityanov St., Moscow, 117997



A. S. Savicheva
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Resident of the Department of Sports Medicine and Medical Rehabilitation,

8, Bldg. 2, Trubetskaya St., Moscow, 119991



E. A. Kukes
Pirogov Russian National Research Medical University
Russian Federation

Researcher, Department of Pathophysiology and Clinical Pathophysiology, Faculty of Medicine, 

1, Ostrovityanov St., Moscow, 117997



M. S. Ptitsyn
ChromsystemsLab LLC
Russian Federation

Manager of Scientific Projects of the Research and Laboratory Complex Chromolab, 

20, Bldg. 2, Nauchnyy proezd, Moscow, 117246



A. D. Andreev
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Student, 

8, Bldg. 2, Trubetskaya  St., Moscow, 119991



References

1. Carfì A., Bernabei R., Landi F. Persistent Symptoms in Patients after Acute COVID-19. JAMA. 2020;324(6):603–605. https://doi.org/10.1001/jama.2020.12603.

2. Tenforde M.W., Kim S.S., Lindsell C.J., Billig Rose E., Shapiro N.I., Files D.C. et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network – United States, March-June 2020. MMWR Morb Mortal Wkly Rep. 2020;69(30):993–998. https://doi.org/10.15585/mmwr.mm6930e1.

3. Huang C., Huang L., Wang Y., Li X., Ren L., Gu X. et al. 6-Month Consequences of COVID-19 in Patients Discharged from Hospital: A Cohort Study. Lancet. 2021;397(10270):220–232. https://doi.org/10.1016/S0140-6736(20)32656-8.

4. McElvaney O.J., McEvoy N.L., McElvaney O.F., Carroll T.P., Murphy M.P., Dunlea D.M. et al. Characterization of the Inflammatory Response to Severe COVID-19 Illness. Am J Respir Crit Care Med. 2020;202(6):812–821. https://doi.org/10.1164/rccm.202005-1583OC.

5. Sungnak W., Huang N., Bécavin C., Berg M., Queen R., Litvinukova M. et al. SARS-CoV-2 Entry Factors Are Highly Expressed in Nasal Epithelial Cells together with Innate Immune Genes. Nat Med. 2020;26(5):681–687. https://doi.org/10.1038/s41591-020-0868-6.

6. Tang N., Li D., Wang X., Sun Z. Abnormal Coagulation Parameters Are Associated with Poor Prognosis in Patients with Novel Coronavirus Pneumonia. J Thromb Haemost. 2020;18(4):844–847. https://doi.org/10.1111/jth.14768.

7. Nalbandian A., Sehgal K., Gupta A., Madhavan M.V., McGroder C., Stevens J.S. et al. Post-Acute COVID-19 Syndrome. Nat Med. 2021;27(4):601–615. https://doi.org/10.1038/s41591-021-01283-z.

8. Ayres J.S. A Metabolic Handbook for the COVID-19 Pandemic. Nat Metab. 2020;2(7):572–585. https://doi.org/10.1038/s42255-020-0237-2.

9. Sanchez E.L., Lagunoff M. Viral Activation of Cellular Metabolism. Virology. 2015;479-480:609–618. https://doi.org/10.1016/j.virol.2015.02.038.

10. González Plaza J.J., Hulak N., Kausova G., Zhumadilov Z., Akilzhanova A. Role of Metabolism during Viral Infections, and Crosstalk with the Innate Immune System. Intractable Rare Dis Res. 2016;5(2):90–96. https://doi.org/10.5582/irdr.2016.01008.

11. Moreno-Altamirano M.M.B., Kolstoe S.E., Sánchez-García F.J. Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses. Front Cell Infect Microbiol. 2019;9:95. https://doi.org/10.3389/fcimb.2019.00095.

12. Melkonian E.A., Schury M.P. Biochemistry, Anaerobic Glycolysis. Treasure Island (FL): StatPearls Publishing; 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK546695/.

13. Adeva-Andany M., López-Ojén M., Funcasta-Calderón R., AmeneirosRodríguez E., Donapetry-García C., Vila-Altesor M., Rodríguez-Seijas J. Comprehensive Review on Lactate Metabolism in Human Health. Mitochondrion. 2014;17:76–100. https://doi.org/10.1016/j.mito.2014.05.007.

14. Ikawa M., Okazawa H., Yoneda M. Molecular Imaging for Mitochondrial Metabolism and Oxidative Stress in Mitochondrial Diseases and Neurodegenerative Disorders. Biochim Biophys Acta Gen Subj. 2021;1865(3):129832. https://doi.org/10.1016/j.bbagen.2020.129832.

15. Guillemin G.J. Quinolinic Acid: Neurotoxicity. FEBS J. 2012;279(8):1355. https://doi.org/10.1111/j.1742-4658.2012.08493.x.

16. Ritter J.B., Wahl A.S., Freund S., Genzel Y., Reichl U. Metabolic Effects of Influenza Virus Infection in Cultured Animal Cells: Intra- and Extracellular Metabolite Profiling. BMC Syst Biol. 2010;4:61. https://doi.org/10.1186/1752-0509-4-61.

17. Heaton N.S., Perera R., Berger K.L., Khadka S., Lacount D.J., Kuhn R.J., Randall G. Dengue Virus Nonstructural Protein 3 Redistributes Fatty Acid Synthase to Sites of Viral Replication and Increases Cellular Fatty Acid Synthesis. Proc Natl Acad Sci U S A. 2010;107(40):17345–17350. https://doi.org/10.1073/pnas.1010811107.

18. DeBerardinis R.J., Lum J.J., Hatzivassiliou G., Thompson C.B. The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation. Cell Metab. 2008;7(1):11–20. https://doi.org/10.1016/j.cmet.2007.10.002.

19. Zhang B., Zhou X., Zhu C., Song Y., Feng F., Qiu Y. et al. Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients with COVID-19. Front Mol Biosci. 2020;7:157. https://doi.org/10.3389/fmolb.2020.00157.

20. Song C.Y., Xu J., He J.Q., Lu Y.Q. COVID-19 Early Warning Score: A MultiParameter Screening Tool to Identify Highly Suspected Patients. medRxiv. 2020.03.05.20031906. https://doi.org/10.1101/2020.03.05.20031906.

21. Ali R.A., Gandhi A.A., Meng H., Yalavarthi S., Vreede A.P., Estes S.K. et al. Adenosine Receptor Agonism Protects against NETosis and Thrombosis in Antiphospholipid Syndrome. Nat Commun. 2019;10(1):1916. https://doi. org/10.1038/s41467-019-09801-x.

22. Meng H., Yalavarthi S., Kanthi Y., Mazza L.F., Elfline M.A., Luke C.E. et al. In Vivo Role of Neutrophil Extracellular Traps in Antiphospholipid Antibody-Mediated Venous Thrombosis. Arthritis Rheumatol. 2017;69(3):655–667. https://doi.org/10.1002/art.39938.

23. Yadav V., Chi L., Zhao R., Tourdot B.E., Yalavarthi S., Jacobs B.N. et al. Ectonucleotidase tri(di)phosphohydrolase-1 (ENTPD-1) Disrupts Inflammasome/Interleukin 1β-driven Venous Thrombosis. J Clin Invest. 2019;129(7):2872–2877. https://doi.org/10.1172/JCI124804.

24. Iba T., Levy J.H., Raj A., Warkentin T.E. Advance in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation. J Clin Med. 2019;8(5):728. https://doi.org/10.3390/jcm8050728.

25. Ward P.A., Fattahi F. New Strategies for Treatment of Infectious Sepsis. J Leukoc Biol. 2019;106(1):187–192. https://doi.org/10.1002/jlb.4mir1118-425r.

26. Potey P.M., Rossi A.G., Lucas C.D., Dorward D.A. Neutrophils in the Initiation and Resolution of Acute Pulmonary Inflammation: Understanding Biological Function and Therapeutic Potential. J Pathol. 2019;247(5):672– 685. https://doi.org/10.1002/path.5221.

27. Frantzeskaki F., Armaganidis A., Orfanos S.E. Immunothrombosis in Acute Respiratory Distress Syndrome: Cross Talks between Inflammation and Coagulation. Respiration. 2017;93(3):212–225. https://doi.org/10.1159/000453002.

28. Twaddell S.H., Baines K.J., Grainge C., Gibson P.G. The Emerging Role of Neutrophil Extracellular Traps in Respiratory Disease. Chest. 2019;156(4):774–782. https://doi.org/10.1016/j.chest.2019.06.012.

29. Porto B.N., Stein R.T. Neutrophil Extracellular Traps in Pulmonary Diseases: Too Much of a Good Thing? Front Immunol. 2016;7:311. https://doi. org/10.3389/fimmu.2016.00311.

30. Zuo Y., Yalavarthi S., Shi H., Gockman K., Zuo M., Madison J.A. et al. Neutrophil Extracellular Traps in COVID-19. JCI Insight. 2020;5(11):e138999. https://doi.org/10.1172/jci.insight.138999.

31. Liberale L., Holy E.W., Akhmedov A., Bonetti N.R., Nietlispach F., Matter C.M. et al. Interleukin-1β Mediates Arterial Thrombus Formation via NETAssociated Tissue Factor. J Clin Med. 2019;8(12):2072. https://doi.org/10.3390/jcm8122072.

32. Meher A.K., Spinosa M., Davis J.P., Pope N., Laubach V.E., Su G. et al. Novel Role of IL (Interleukin)-1β in Neutrophil Extracellular Trap Formation and Abdominal Aortic Aneurysms. Arterioscler Thromb Vasc Biol. 2018;38(4):843–853. https://doi.org/10.1161/ATVBAHA.117.309897.

33. Josefs T., Barrett T.J., Brown E.J., Quezada A., Wu X., Voisin M. et al. Neutrophil Extracellular Traps Promote Macrophage Inflammation and Impair Atherosclerosis Resolution in Diabetic Mice. JCI Insight. 2020;5(7):e134796. https://doi.org/10.1172/jci.insight.134796.

34. Lachowicz-Scroggins M.E., Dunican E.M., Charbit A.R., Raymond W., Looney M.R., Peters M.C. et al. Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma. Am J Respir Crit Care Med. 2019;199(9):1076–1085. https://doi.org/10.1164/rccm.201810-1869OC.

35. Merza M., Hartman H., Rahman M., Hwaiz R., Zhang E., Renström E. et al. Neutrophil Extracellular Traps Induce Trypsin Activation, Inflammation, and Tissue Damage in Mice With Severe Acute Pancreatitis. Gastroenterology. 2015;149(7):1920.e8–1931.e8. https://doi.org/10.1053/j.gastro.2015.08.026.

36. Ridker P.M. From C-Reactive Protein to Interleukin-6 to Interleukin-1: Moving Upstream To Identify Novel Targets for Atheroprotection. Circ Res. 2016;118(1):145–156. https://doi.org/10.1161/CIRCRESAHA.115.306656.

37. Poryadin G.V., Salmasi J.M., Kukes I.V., Kazimirsky A.N., Danilov An.B., Lazareva N.B., Danilov A.B. Modern Knowledge of Inflammatory Diseases of Various Localization and Etiology: New Possibilities of Pharmacotherapy. Farmateka. 2020;27(14):37–46. (In Russ.) https://doi.org/10.18565/pharmateca.2020.14.37-46.

38. Poryadin G.V., Salmasi J.M., Kazimirsky A.N. Mechanisms of Benzydamine Action against Local Inflammatory Process. Meditsinskiy sovet = Medical Council. 2018;(21):78–86. (In Russ.) https://doi.org/10.21518/2079-701X-2018-21-78-86.

39. Salmasi J.M., Kazimirsky A.N., Antonova E.A., Poryadin G.V. Evaluation of Influence Several Drugs with Local Antimicrobial Activity against Local Immunity Cells. Meditsinskiy sovet = Medical Council. 2019;(8):76–82. (In Russ.) https://doi.org/10.21518/2079-701X-2019-8-76-82.

40. Lardy H.A. The Role of Tryptophan Metabolites in Regulating Gluconeogenesis. Am J Clin Nutr. 1971;24(7):764–765. https://doi.org/10.1093/ajcn/24.7.764.

41. Quagliariello E., Papa S., Saccone C., Alifano A. Effect of 3-Hydroxyanthranilic Acid on the Mitochondrial Respiratory System. Biochem J. 1964;91(1):137–146. https://doi.org/10.1042/bj0910137.

42. Kotake Y., Ueda T., Mori T., Igaki S., Hattori M. Abnormal Tryptophan Metabolism and Experimental Diabetes by Xanthurenic Acid (XA). Acta Vitaminol Enzymol. 1975;29(1–6):236–269. Available at: https://pubmed.ncbi.nlm.nih.gov/1244098/.

43. Buczko P., Stokowska W., Górska M., Kucharewicz I., Pawlak D., Buczko W. Tryptophan Metabolites via Kynurenine Pathway in Saliva of Diabetic Patients. Dent Med Probl. 2006;43(1):21–25. Available at: https://www.dbc.wroc.pl/Content/1892/DMP_2006431021_Bucz.pdf.

44. Fernstrom J.D. Effects on the Diet on Brain Neurotransmitters. Metabolism. 1977;26(2):207–223. https://doi.org/10.1016/0026-0495(77)90057-9.

45. Myint K., Jacobs K., Myint A.M., Lam S.K., Henden L., Hoe S.Z., Guillemin G.J. Effects of Stress Associated with Academic Examination on the Kynurenine Pathway Profile in Healthy Students. PLoS ONE. 2021;16(6):e0252668. https://doi.org/10.1371/journal.pone.0252668.

46. Okuda S., Nishiyama N., Saito H., Katsuki H. 3-Hydroxykynurenine, An Endogenous Oxidative Stress Generator, Causes Neuronal Cell Death with Apoptotic Features and Region selectivity. J Neurochem. 1998;70(1):299– 307. https://doi.org/10.1046/j.1471-4159.1998.70010299.x.

47. Abbasi F., Asagmi T., Cooke J.P., Lamendola C., McLaughlin T., Reaven G.M. et al. Plasma Concentrations of Asymmetric Dimethylarginine Are Increased in Patients with Type 2 Diabetes Mellitus. Am J Cardiol. 2001;88(10):1201–1203. https://doi.org/10.1016/s0002-9149(01)02063-x.

48. Lin K.Y., Ito A., Asagami T., Tsao P.S., Adimoolam S., Kimoto M. et al. Impaired Nitric Oxide Synthase Pathway in Diabetes Mellitus: Role of Asymmetric Dimethylarginine and Dimethylarginine Dimethylaminohydrolase. Circulation. 2002;106(8):987–992. https://doi.org/10.1161/01.cir.0000027109.14149.67.

49. Toutouzas K., Riga M., Stefanadi E., Stefanadis C. Asymmetric Dimethylarginine (ADMA) and Other Endogenous Nitric Oxide Synthase (NOS) Inhibitors as an Important Cause of Vascular Insulin Resistance. Horm Metab Res. 2008;40(9):655–659. https://doi.org/10.1055/s-0028-1083814.

50. Riccioni G., Scotti L., D’Orazio N., Gallina S., Speziale G., Speranza L., Bucciarelli T. ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association. Int J Mol Sci. 2014;15(4):6391–6398. https://doi.org/10.3390/ijms15046391.

51. Zsuga J., Torok J., Magyar M.T., Valikovics A., Gesztelyi R., Kéki S. et al. Serum Asymmetric Dimethylarginine Negatively Correlates with IntimaMedia Thickness in Early-Onset Atherosclerosis. Cerebrovasc Dis. 2007;23(5–6):388–394. https://doi.org/10.1159/000101461.

52. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagel A.S. et al. Endothelial Cell Infection and Endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5.

53. Goeijenbier M., van Wissen M., van de Weg C., Jong E., Gerdes V.E., Meijers J.C. et al. Review: Viral Infections and Mechanisms of Thrombosis and Bleeding. J Med Virol. 2012;84(10):1680–1696. https://doi.org/10.1002/jmv.23354.

54. Steinberg B.A., Zhao X., Heidenreich P.A., Peterson E.D., Bhatt D.L. et al. Trends in Patients Hospitalized with Heart Failure and Preserved Left Ventricular Ejection Fraction: Prevalence, Therapies, and Outcomes. Circulation. 2012;126(1):65–75. https://doi.org/10.1161/CIRCULATIONAHA.111.080770.

55. Wong R.S., Wu A., To K.F., Lee N., Lam C.W., Wong C.K. et al. Haematological Manifestations in Patients with Severe Acute Respiratory Syndrome: Retrospective Analysis. BMJ. 2003;326(7403):1358–1362. https://doi.org/10.1136/bmj.326.7403.1358.

56. Gavriilaki E., Brodsky R.A. Severe COVID-19 Infection and Thrombotic Microangiopathy: Success Does Not Come Easily. Br J Haematol. 2020;189(6):e227–e230. https://doi.org/10.1111/bjh.16783.

57. DeKosky B.J. A Molecular Trap against COVID-19. Science. 2020;369(6508):1167–1168. https://doi.org/10.1126/science.abe0010.

58. Wijeratne T., Gillard Crewther S., Sales C., Karimi L. COVID19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception-A Systematic Review. Front Neurol. 2021;11:607221. https://doi.org/10.3389/fneur.2020.607221.

59. Mir R., Kelly S.M., Xiao Y., Moore A., Clark C.H., Clementel E. et al. Organ at Risk Delineation for Radiation Therapy Clinical Trials: Global Harmonization Group Consensus Guidelines. Radiother Oncol. 2020;150:30–39. https://doi.org/10.1016/j.radonc.2020.05.038.

60. Gąsecka A., Borovac J.A., Guerreiro R.A., Giustozzi M., Parker W., Caldeira D., Chiva-Blanch G. Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment. Cardiovasc Drugs Ther. 2021;35(2):215–229. https://doi.org/10.1007/s10557-020-07084-9.


Review

For citations:


Kukes IV, Salmasi JM, Ternovoy KS, Kazimirskii AN, Obodzinskaya TE, Lim VG, Glagovskiy PB, Mamedov IS, Poryadin GV, Savicheva AS, Kukes EA, Ptitsyn MS, Andreev AD. Prerequisites for the creation of an atlas of postcovid inflammation as a way of personalized pharmacotherapy, as well as predicting and preventing organ and systemic dysfunctions. Meditsinskiy sovet = Medical Council. 2021;(12):72-88. (In Russ.) https://doi.org/10.21518/2079-701X-2021-12-72-88

Views: 1138


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)