Kazan medical journalKazan medical journal0368-48142587-9359Eco-Vector7966810.17816/KMJ2021-934Research ArticleJustification of treatment and possible outcomes of severe COVID-19KhamitovR Frhamitov@mail.ruhttps://orcid.org/0000-0001-8821-0421AndreichevaE Nelena_andre@mail.ruhttps://orcid.org/0000-0002-5382-5095HairullinaA Radelyminsafy@gmail.comhttps://orcid.org/0000-0002-7832-2267MingaleevaG Fm.gulnaz.f@mail.ruhttps://orcid.org/0000-0002-3760-062XKazan State Medical UniversityBoard of Public Health of Kazan City1312202110269349390709202124112021Copyright © 2021, Eco-Vector2021<p>The role of hyaluronic acid in the pathogenesis of acute respiratory distress syndrome, including those associated with severe COVID-19, is known. Pro-inflammatory cytokines (interleukin-1, tumor necrosis factor) are strong inducers of hyaluronic acid synthase (HAS2) in CD31+ endothelial cells, EpCAM+ cells of the alveolar epithelium of the lungs and fibroblasts. Hyaluronic acid can absorb water in quantities significantly exceeding its own molecular weight. Reducing the presence or inhibiting of hyaluronic acid synthesis is of great importance for facilitating the breathing of COVID-19 patients. Hyaluronidase-based preparations can reduce the accumulation of hyaluronic acid and promote pulmonary alveoli cleansing. Respiratory viral infections, including pandemic strains of coronaviruses, especially in severe cases with acute respiratory distress syndrome, can be complicated by the development of pulmonary fibrosis. It has been shown that changes in X-ray Computed Tomography findings characteristic of fibrosis in the first year after COVID-19 can significantly regress. A clinical case from the practice of treating a patient with a severe course of COVID-19, significant cardiovascular comorbidity, grade 2 obesity, which was regarded as significant risk factors for an unfavorable outcome, is presented. The patient with signs of progressive respiratory failure was admitted to the intensive care unit. Pulse therapy with glucocorticosteroids and anticoagulants was started. Deterioration of the condition is regarded as the beginning of acute respiratory distress syndrome, which complicated the cytokine storm induced by the coronavirus. The patient was taken for high-flow oxygenation. An anti-cytokine therapy was prescribed. Reduction of inflammatory markers was obtained, but severe respiratory failure persisted. The bovgialuronidase azoximer was included in the treatment. The patient's condition began to stabilize then she was discharged in stable condition without oxygen support. The available data on the negative role of hyaluronic acid in the pathogenesis of acute respiratory distress syndrome in patients with COVID-19, as well as the need to reduce the likelihood of developing residual fibrous changes in the lungs in patients who have undergone acute respiratory distress syndrome, suggest the need for further studies of domestic azoximer bovgialuronidase properties in the treatment of severe forms of COVID-19.</p>COVID-19pulmonary outcomestreatmentCOVID-19лёгочные исходылечение[Coronavirus in Russia. The number of cases in cities and regions of the Russian Federation. Statistics. https://infotables.ru/meditsina/1198-koronavirus-v-¬rosii (access date: 29.07.2021). (In Russ.)][Hellman U., Karlsson M.G., Engström-Laurent A., Cajander S., Dorofte L., Ahlm C., Laurent C., Blomberg A. Presence of hyaluronan in lung alveoli in severe COVID-19: An opening for new treatment options? J. Biol. Chem. 2020; 295 (45): 15 418–15 422. DOI: 10.1074/jbc.AC120.015967.][Ontong P., Prachayasittikul V. Unraveled roles of hya¬luronan in severe COVID-19. EXCLI J. 2021; 20: 117–125. DOI: 10.17179/excli2020-3215.][Shi Y., Wang Y., Shao C., Huang J., Gan J., Huang X., Bucci E., Piacentini M., Ippolito G., Melino G. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020; 27 (5): 1451–1454. DOI: 10.1038/s41418-020-0530-3.][Li Y., Wu J., Wang S., Li X., Zhou J., Huang B., Luo D., Cao Q., Chen Y., Chen S., Ma L., Peng L., Pan H., Travis W.D., Nie X. Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China. Histopatho¬logy. 2021; 78: 542–555. DOI: 10.1111/his.14249.][Oronsky B., Larson C., Hammond T.C., Oronsky A., Kesari S., Lybeck M., Reid T.R. A review of persistent post-COVID syndrome (PPCS). Clin. Rev. Allergy Immunol. 2021. DOI: 10.1007/s12016-021-08848-3.][Zhang P., Li J., Liu H., Han N., Ju J., Kou Y., Chen L., Jiang M., Pan F., Zheng Y., Gao Z., Jiang B. 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 Res. 2020; 8: 34. DOI: 10.1038/s41413-020-00113-1.][John A.E., Joseph C., Jenkins G., Tatler A.L. COVID-19 and pulmonary fibrosis: A potential role for lung epithelial cells and fibroblasts. Immunol. Rev. 2021; 302: 228–240. DOI: 10.1111/imr.12977.][Zhang C., Wu Z., Li J.W., Tan K., Yang W., Zhao H., Wang G.Q. Discharge may not be the end of treatment: Pay attention to pulmonary fibrosis caused by severe COVID-19. J. Med. Virol. 2021; 93 (3): 1378–1386. DOI: 10.1002/jmv.26634.][Jie Z., He H., Xi H., Zhi Z. Expert recommendations for the diagnosis and treatment of interstitial lung disease caused by novel coronavirus pneumonia. Chinese Research Hospital Association; Respiratory Council. 2020; 43 (10): 827–833. DOI: 10.3760/cma.j.cn112147-20200326-00419.][Vidal. Directory of medicines. Longidaza, instructions for use. https://www.vidal.ru/drugs/longidaze__31621 (access date: 29.07.2021). (In Russ.)][Kotova N.V., Polyanskij A.V. What should I do with a patient who has suffered from COVID-pneumonia? Experience of clinical use of bovgialuronidaz azoksimer (longidase) for the prevention and treatment of post-covid pneumofibrosis of the lungs. Glavnyy vrach Yuga Rossii. 2021; (4): 11–12. (In Russ.)]