Prospects of Hyaluronidase Therapy in Novel COVID-19 Infection with Damage to Lungs

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

INTRODUCTION: In recent years, the production and regulation of synthesis of hyaluronic acid in COVID-19 has been actively studied. Hyaluronan plays a significant role in development of severe lung damage in COVID-19 and is a potential therapeutic target the action on which will probably improve prognosis for patients with COVID-19.

AIM: To study prospects of using bovhyaluronidaze azoximer in complex treatment of patients with COVID-19 with lung damage at the inpatient stage.

MATERIALS AND METHODS: Thirty five patients (6 men and 29 women) aged 58.9 ± 12.9 years hospitalized with COVID-19 infection, were examined. Capillary blood saturation (SpO2) was 80.1 ± 8.6%, the volume of lung damage in X-ray computed tomography (X-ray CT) was 45.1 ± 19.4% on the right and 40.0 ± 19.5% on the left. All the patients received treatment according to the “Temporary Guidelines: prevention, diagnosis and treatment of novel coronavirus infection. Ver. 14 (27.12.2021)”. Besides, as part of complex treatment for COVID-19, bovhyaluronidaze azoximer was administered intramuscularly on the 21.9 ± 6.8th day of illness with a course of 10 injections (once in 3 days).

RESULTS: In the course of comprehensive treatment including bovhyaluronidaze azoximer, increase in SpO2 was recorded: in 7 patients ― after 1 injection (4.2 ± 1.7%), in 24 ― after 2 injections (5.4 ± 0.6%), another 4 patients did not show any significant increase in SpO2 after the first two injections. Increase in SpO2 after the 1st injection inversely correlated with age (r = -0.34; p < 0.05) and the initial saturation (r = -0.38; p < 0.05). Increase in SpO2 after the second injection correlated with the day of illness on which treatment with bovhyaluronidaze azoximer began (r = -0.36; p < 0.05).

CONCLUSION: Use of bovhyaluronidaze azoximer in complex treatment for COVID-19 with the lung damage at the inpatient stage can be effective in younger patients with more expressed initial reduction of SpO2, and also in case of administration of the drug in the early stages of the disease. The data obtained in the pilot study, dictate the necessity of studying the level of hyaluronic acid in blood of patients with COVID-19 and lung damage and its role in risk stratification of such patients.

About the authors

Aleksandra V. Solov’yeva

Ryazan State Medical University

Author for correspondence.
Email: savva2005@bk.ru
ORCID iD: 0000-0001-7896-6356
SPIN-code: 1943-7765

MD, Dr. Sci. (Med.), Associate Professor

Russian Federation, Ryazan

Ludmila Korshunova

ФГБОУ ВО РязГМУ Минздрава России

Email: post_luda@mail.ru
ORCID iD: 0000-0003-0945-0772
SPIN-code: 4694-3605

доцент, кандидат медицинских наук, доцент кафедры факультетской терапии имени профессора В.Я.Гармаша

главный внештатный специалист-пульмонолог Министерства Здравоохранения Рязанской области

Russian Federation

Ekaterina Shurpo

ФГБОУ ВО РязГМУ Минздрава России
ГБУ РО ГК БСМП

Email: shurpo_87@mail.ru
SPIN-code: 9242-2880
ResearcherId: AAF-6813-2022

кандидат медицинских наук, доцент кафедры факультетской терапии имени профессора В.Я.Гармаша

заместитель главного врача по клинико-диагностической работе ГБУ РО ГК БСМП

Russian Federation

Anastasia Namestnikova

ГБУ РО ГК БСМП, Рязань, Россия

Email: asik1402@yandex.ru
ResearcherId: AAЕ-9185-2022

врач-терапевт отделения № 5 для взрослого населения с коронавирусной инфекцией

References

  1. Ng CK, Chan JWM, Kwan TL, et al. Six month radiological and physiological outcomes in severe acute respiratory syndrome (SARS) survivors. Thorax. 2004;59(10):889–91. doi: 10.1136/thx.2004.023762
  2. Xie L, Liu Y, Fan B, et al. Dynamic changes of serum SARS-coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge. Respiratory Research. 2005;6(1):5. doi: 10.1186/1465-9921-6-5
  3. Das KM, Lee EY, Singh R, et al. Follow-up chest radiographic findings in patients with MERS-CoV after recovery. Indian Journal of Radiology & Imaging. 2017;27(3):342–9. doi: 10.4103/ijri.IJRI_469_16
  4. Zhang P, Li J, Liu H, et al. Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study. Bone Research. 2020;8:8. doi: 10.1038/s41413-020-0084-5
  5. Ojo AS, Balogun SA, Williams OT, et al. Pulmonary Fibrosis in COVID-19 Survivors: Predictive Factors and Risk Reduction Strategies. Pulmonary Medicine. 2020;2020:6175964. doi: 10.1155/2020/6175964
  6. Zumla A, Hui DS, Azhar EI, et al. Reducing mortality from 2019-nCoV: hostdirected therapies should be an option. Lancet. 2020;395(10224):e35–6. doi: 10.1016/S0140-6736(20)30305-6
  7. Vasarmidi E, Tsitoura E, Spandidos DA, et al. Pulmonary fibrosis in the aftermath of the COVID-19 era (Review). Experimental and Therapeutic Medicine. 2020;20(3):2557–60. doi: 10.3892/etm.2020.8980
  8. Tale S, Ghosh S, Meitei SP, et al. Post COVID-19 pneumonia pulmonary fibrosis. QJM. 2020;113(11):837–8. doi: 10.1093/qjmed/hcaa255
  9. Kligerman SJ, Franks TJ, Galvin JR. From the radiologic pathology archives: organization and fibrosis as a response to lung injury in diffuse alveolar damage, organizing pneumonia, and acute fibrinous and organizing pneumonia. Radiographics. 2013;33(7):1951–75. doi: 10.1148/rg.337130057
  10. George PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. The Lancet. Respiratory Medicine. 2020;8(8):807–15. doi: 10.1016/S2213-2600(20)30225-3
  11. Han X, Fan Y, Alwalid O, et al. Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia. Radiology. 2021;299(1):E177–86. doi: 10.1148/radiol.2021203153
  12. Wong K–T, Antonio GE, Hui DSC, et al. Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period. Journal of Computer Assisted Tomography. 2004;28(6):790–5. doi: 10.1097/00004728-200411000-00010
  13. Liu C, Ye L, Xia R, et al. Chest Computed Tomography and Clinical Follow-Up of Discharged Patients with COVID-19 in Wenzhou City, Zhejiang, China. Annals of the American Thoracic Society. 2020;17(10):1231–7. doi: 10.1513/AnnalsATS.202004-324OC
  14. Ding M, Zhang Q, Li Q, et al. Correlation analysis of the severity and clinical prognosis of 32 cases of patients with COVID-19. Respiratory Medicine. 2020;167:105981. doi: 10.1016/j.rmed.2020.105981
  15. Hellman U, Karlsson MG, Engström–Laurent A, et al. Presence of hyaluronan in lung alveoli in severe Covid-19: An opening for new treatment options? The Journal of Biological Chemistry. 2020;295(45):15418–22. doi: 10.1074/jbc.AC120.015967
  16. Queisser KA, Mellema RA, Middleton EA, et al. COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction. JCI Insight. 2021;6(17):e147472. doi: 10.1172/jci.insight.147472
  17. Ontong P, Prachayasittikul V. Unraveled roles of hyaluronan in severe COVID-19. EXCLI Journal. 2021;20:117–25. doi: 10.17179/excli2020-3215
  18. Hällgren R, Samuelsson T, Laurent TC, et al. Accumulation of hyaluronan (hyaluronic acid) in the lung in adult respiratory distress syndrome. The American Review of Respiratory Disease. 1989;139(3):682–7. doi: 10.1164/ajrccm/139.3.682
  19. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet. Respiratory Medicine. 2020;8(4):420–2. doi: 10.1016/S2213-2600(20)30076-X
  20. Bell TJ, Brand OJ, Morgan DJ, et al. Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis. Matrix Biology. 2019;80:14–28. doi: 10.1016/j.matbio.2018.06.006
  21. Shi Y, Wang Y, Shao C, et al. COVID-19 infection: the perspectives on immune responses. Cell Death and Differentiation. 2020;27(5):1451–4. doi: 10.1038/s41418-020-0530-3
  22. McKallip RJ, Ban H, Uchakina ON. Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation. Inflammation. 2015;38(3):1250–9. doi: 10.1007/s10753-014-0092-y
  23. Nekrasov AV, Ivanova AS, Puchkova NG. Longidaza ― sovremennyj podhod v lechenii zabolevanij, soprovozhdayushchihsya giperplaziej soedinitel'noj tkani. Signatura. 2006;(1):43–52. (In Russ).
  24. Chernyavskaya OA, Osipov AV. Pathogenetic bases of the use of antifibrotic therapy with Bovhyaluronidazum azoximerum in patients with new coronavirus infection COVID-19. Medical Council. 2021;(12):154–60. (In Russ). doi: 10.21518/2079-701X-2021-12-154-160
  25. Vremennyye metodicheskiye rekomendatsii: profilaktika, diagnostika i lecheniye novoy koronavirusnoy infektsii (COVID-19). Versiya 14 (27.12.2021). Available at: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/059/041/original/%D0%92%D0%9C%D0%A0_COVID-19_V14_27-12-2021.pdf. Accessed: 2022 February 20. (In Russ).
  26. Kotova NV, Polyanskiy AV. Chto delat’ s patsiyentom, perenesshim COVID-pnevmoniyu? Opyt klinicheskogo ispol’zovaniya bovgialuronidazy azoksimer (longidazy) dlya profilaktiki i lecheniya post-kovidnogo fibroza legkikh. Glavnyy Vrach Yuga Rossii. 2021;(4):11–2. (In Russ).
  27. Zabozlaev F.G., Kravchenko E.V., Gallyamova A.R., et al. Pulmonary pathology of the new coronavirus disease (COVID-19). The preliminary analysis of post-mortem findings. Journal of Clinical Practice. 2020;11(2):21–37. (In Russ). doi: 10.17816/clinpract34849

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. The degree of severity of lung tissue damage of the studied patients (n = 35) on admission according to the results of X-ray computed tomography of lungs. Note: CT — the degree of lung damage according to the results of X-ray computed tomography.

Download (25KB)
Indexing metadata
3. Fig. 2. The incidence (%) of comorbid pathology in the study patients (n = 35). Notes: АH ― arterial hypertension, Ob-1 ― 1 degree obesity, DM GCS ― diabetes mellitus associated with glucocorticosteroid intake, Оb-2 ― 2 degree obesity, DM ― diabetes mellitus, CHD ― coronary heart disease, EA ― exertion angina, BA ― bronchial asthma, ACVE ― acute cerebrovascular event, PICS ― postinfarction cardiosclerosis.

Download (25KB)
Indexing metadata
4. Fig. 3. Dynamics of changes of the results of X-ray computed tomography of lungs of patient R., 61 years old, with COVID-19, in the course of complex treatment including bovhyaluronidase azoximer: in the hospital on admission (18th day of illness, before start of therapy with bovhyaluronidase azoximer) (A), 27th day of illness (10th day of treatment with bovhyaluronidase azoximer) (B).

Download (58KB)
Indexing metadata

Copyright (c) 2022 Solov’yeva A.V., Korshunova L., Shurpo E., Namestnikova A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies