medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-8-19-27medsovet-6847Research ArticleАКТУАЛЬНЫЕ ВОПРОСЫ ОТОРИНОЛАРИНГОЛОГИИTOPICAL ISSUES OF OTORHINOLARYNGOLOGYОценка эффективности и безопасности применения гипертонического раствора 7% с гиалуроновой кислотой у пациентов с COVID-19 на амбулаторном этапеEvaluation of the efficacy and safety of the 7% hypertonic solution with hyaluronic acid in patients with COVID-19 in the outpatient phasehttps://orcid.org/0000-0002-6298-4186АникинГ. С.AnikinG. S.

Аникин Георгий Станиславович, к.м.н., доцент; врач-клинический фармаколог

119991, Москва, ул. Трубецкая, д. 8, стр. 2

129090, Москва, Грохольский переулок, д. 31

George S. Anikin, Cand. Sci. (Med.); Doctor – Clinical Pharmacologist

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

31, Grokholskiy Lane, Moscow, 129090

medi321@mail.ruhttps://orcid.org/0000-0002-5158-8903СтожковаИ. В.StozhkovaI. V.

Стожкова Ирина Владимировна, аспирант

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Irina V. Stozhkova, Postgraduate Student

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

IStozhkova@bk.ruhttps://orcid.org/0000-0002-9215-9339ШароноваС. С.SharonovaS. S.

Шаронова Светлана Сергеевна, аспирант

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Svetlana S. Sharonova, Postgraduate Student

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

lana.sh917@gmail.comhttps://orcid.org/0000-0001-7723-8701КурдюковаЕ. В.KurdyukovaE. V.

Курдюкова Екатерина Витальевна, студент

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Ekaterina V. Kurdyukova, Student

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

katrin_45_34@mail.ruПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет); Поликлиника №3 Управления делами Президента Российской ФедерацииРоссияSechenov First Moscow State Medical University (Sechenov University); Clinic No. 3 of the Presidential Administration of the Russian FederationRussian FederationПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian Federation202213052022081927Copyright © Аникин Г.С., Стожкова И.В., Шаронова С.С., Курдюкова Е.В., 20222022Аникин Г.С., Стожкова И.В., Шаронова С.С., Курдюкова Е.В.Anikin G.S., Stozhkova I.V., Sharonova S.S., Kurdyukova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6847Введение

Введение. С 2020 г. пандемия, вызванная вирусом SARS-CoV-2, представляет собой серьезную угрозу для систем здравоохранения во многих странах мира. Поиск недорогих и доступных, эффективных и безопасных лекарственных средств, которые могут способствовать быстрому выздоровлению и снизить риск тяжелого течения COVID-19, является важной задачей для системы здравоохранения любой страны. Давно известно, что 7%-й гипертонический раствор натрия хлорида обладает неспецифическими противовирусными, антибактериальными и противогрибковыми свойс твами. Исследования 2020 г. показывают эффективность гипертонических растворов NaCl в блокировании репликации SARS-CoV-2 в клетках Vero. Эти данные свидетельствуют о том, что гипертонический раствор можно использовать в качестве профилактики и комплексного лечения пациентов с COVID-19.

Цель исследования

Цель исследования. Изучить эффективность и безопасность гипертонического раствора с гиалуроновой кислотой у пациентов, находящихся на амбулаторном лечении с легкой и среднетяжелой формой COVID-19.

Материалы и методы

Материалы и методы. Проведено открытое проспективное исследование применения гипертонического раствора 7% (ГР 7%) с гиалуроновой кислотой (ГК) (Ингасалин® форте 7%) у амбулаторных пациентов с подтвержденной инфекцией SARS-CoV-2, имеющих 1 и более факторов риска тяжелого течения заболевания. Пациенты были разделены на 2 группы по 30 человек в каждой. Основная группа получала в дополнение к стандартной терапии (в соответствии с действующими на момент обращения временными рекомендациями, версия 14 от 27.12.21) ингаляции ГР 7% с ГК утром и вечером в течение 10 дней, больные контрольной группы получали стандартную терапию в соответствии с временными рекомендациями.

Результаты и обсуждение

Результаты и обсуждение. У пациентов основной группы, получавших ГР 7% с ГК, уже на 5-й день терапии статистически значимо уменьшилась одышка и нормализовались показатели сатурации по сравнению с пациентами контрольной группы. В основной группе был госпитализирован 1 пациент, в контрольной – 4 пациента. Побочных эффектов, связанных с приемом ГР 7% с ГК, отмечено не было. Также не наблюдалось развитие кашля или его усиление на фоне ингаляций у пациентов основной группы.

Заключение

Заключение. Целесообразно применение ГР 7% с ГК у пациентов, находящихся на амбулаторном лечении с легкой и среднетяжелой формой COVID-19 и имеющих один и более факторов риска тяжелого течения заболевания в составе комплексной терапии.

Introduction

Introduction. Since 2020, the pandemic caused by the SARS-CoV-2 virus poses a serious threat to health systems in many countries around the world. Finding inexpensive and affordable, effective and safe medications that can promote rapid recovery and reduce the risk of a severe course of COVID-19 is an important challenge for the health care system of any country. It has long been known that 7% hypertonic sodium chloride solution has nonspecific antiviral, antibacterial and antifungal properties. A 2020 study shows the effectiveness of hypertonic NaCl solutions in blocking SARS-CoV-2 replication in Vero cells. These data suggest that hypertonic solutions can be used as a prophylactic and alternative comprehensive treatment for patients with COVID-19.

Aim

Aim. We study the efficacy and safety of hypertonic solution with hyaluronic acid in patients undergoing outpatient treatment with mild to moderate COVID-19.

Materials and methods

Materials and methods. We conducted an open prospective study of the use of hyaluronic acid (HA) solution 7% (Ingasalin® forte 7%) in outpatients with confirmed SARS-CoV-2 infection who had 1 or more risk factors for a severe course of the disease. Patients were divided into 2 groups of 30 patients each. The main group received, in addition to standard therapy (according to the interim guidelines in effect at the time of treatment, version 14 dated 12/27/21), inhalation of 7% HG with HA in the morning and evening for 10 days; patients in the control group received standard therapy according to the interim guidelines.

Results and discussion

Results and discussion. Patients of the study group who received hyaluronic acid solution 7%  had statistically significant decrease of dyspnea and normalization of saturation values already on the 5th day of therapy compared to patients of the control group. One patient in the study group was hospitalized, and 4 patients in the control group were hospitalized. There were no side effects associated with the administration of hyaluronic acid solution 7%. Also, there was no development of cough or its intensification against the background of inhalation in patients of the main group.

Conclusion

Conclusion. It is reasonable to use hyaluronic acid solution 7% in outpatients with mild to moderate COVID-19 and with one or more risk factors of severe disease course as part of complex therapy.

гипертонический растворгиалуроновая кислотаCOVID-19амбулаторное лечениевируспандемияhypertonic solutionhyaluronic acidCOVID-19outpatient treatmentviruspandemicReferencesTanni S.E., Silvinato A., Floriano I., Bacha H.A., Barbosa A.N., Bernardo W.M. Use of remdesivir in patients with COVID-19: a systematic review and meta-analysis. J Bras Pneumol. 2022;48(1):e20210393. https://doi.org/10.36416/1806-3756/e20210393.Tanni S.E., Silvinato A., Floriano I., Bacha H.A., Barbosa A.N., Bernardo W.M. Use of remdesivir in patients with COVID-19: a systematic review and meta-analysis. J Bras Pneumol. 2022;48(1):e20210393. https://doi.org/10.36416/1806-3756/e20210393.Ceribelli A., Motta F., De Santis M., Ansari A.A., Ridgway W.M., Gershwin M.E., Selmi C. Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy. J Autoimmun. 2020;109:102442. https://doi.org/10.1016/j.jaut.2020.102442.Ceribelli A., Motta F., De Santis M., Ansari A.A., Ridgway W.M., Gershwin M.E., Selmi C. Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy. J Autoimmun. 2020;109:102442. https://doi.org/10.1016/j.jaut.2020.102442.Castro- Conde A.B., Mouriño V.M.L., Falque I.S., Castro J.L. COVID 19 and the new challenges in health management: The pilot experience of the Internal Medicine Department of a Regional hospital. J Healthc Qual Res. 2021;36(1):54–55. https://doi.org/10.1016/j.jhqr.2020.11.001.Castro- Conde A.B., Mouriño V.M.L., Falque I.S., Castro J.L. COVID 19 and the new challenges in health management: The pilot experience of the Internal Medicine Department of a Regional hospital. J Healthc Qual Res. 2021;36(1):54–55. https://doi.org/10.1016/j.jhqr.2020.11.001.Blumenthal D., Fowler E.J., Abrams M., Collins S.R. Covid-19 – Implications for the Health Care System. N Engl J Med. 2020;383(15):1483–1488. https://doi.org/10.1056/NEJMsb2021088.Blumenthal D., Fowler E.J., Abrams M., Collins S.R. Covid-19 – Implications for the Health Care System. N Engl J Med. 2020;383(15):1483–1488. https://doi.org/10.1056/NEJMsb2021088.Michon A.-L., Jumas- Bilak E., Chiron R., Lamy B., Marchandin H. Advances toward the Elucidation of Hypertonic Saline Effects on Pseudomonas aeruginosa from Cystic Fibrosis Patients. PLoS ONE. 2014;9(2):e90164. https://doi.org/10.1371/journal.pone.0090164.Michon A.-L., Jumas- Bilak E., Chiron R., Lamy B., Marchandin H. Advances toward the Elucidation of Hypertonic Saline Effects on Pseudomonas aeruginosa from Cystic Fibrosis Patients. PLoS ONE. 2014;9(2):e90164. https://doi.org/10.1371/journal.pone.0090164.Thorarinsdottir H.R., Kander T., Holmberg A., Petronis S., Klarin B. Biofilm formation on three different endotracheal tubes: a prospective clinical trial. Crit Care. 2020;24(1):382. https://doi.org/10.1186/s13054-020-03092-1.Thorarinsdottir H.R., Kander T., Holmberg A., Petronis S., Klarin B. Biofilm formation on three different endotracheal tubes: a prospective clinical trial. Crit Care. 2020;24(1):382. https://doi.org/10.1186/s13054-020-03092-1.Wang S.-H., Lin H.-L., Chen C.-S. Antimicrobial effect of hypertonic saline on sputum and biofilm in endotracheal tube. European Respiratory Journal. 2020;56:2337. https://doi.org/10.1183/13993003.congress-2020.2337.Wang S.-H., Lin H.-L., Chen C.-S. Antimicrobial effect of hypertonic saline on sputum and biofilm in endotracheal tube. European Respiratory Journal. 2020;56:2337. https://doi.org/10.1183/13993003.congress-2020.2337.Lin H.-L., Chiu L.-C., Wan G.-H., Huang C.-C., Lee Z.-T., Lin Y.-T. et al. Hypertonic saline enhances the efficacy of aerosolized gentamicin against Pseudomonas aeruginosa. Sci Rep. 2020;10(1):4325. https://doi.org/10.1038/s41598-020-61413-4.Lin H.-L., Chiu L.-C., Wan G.-H., Huang C.-C., Lee Z.-T., Lin Y.-T. et al. Hypertonic saline enhances the efficacy of aerosolized gentamicin against Pseudomonas aeruginosa. Sci Rep. 2020;10(1):4325. https://doi.org/10.1038/s41598-020-61413-4.Lin H.-L., Chiang C.-E., Lin M.-C., Kau M.-L., Lin Y.-T., Chen C.-S. Aerosolized Hypertonic Saline Hinders Biofilm Formation to Enhance Antibiotic Susceptibility of Multidrug- Resistant Acinetobacter baumannii. Antibiotics (Basel). 2021;10(9):1115. https://doi.org/10.3390/antibiotics10091115.Lin H.-L., Chiang C.-E., Lin M.-C., Kau M.-L., Lin Y.-T., Chen C.-S. Aerosolized Hypertonic Saline Hinders Biofilm Formation to Enhance Antibiotic Susceptibility of Multidrug- Resistant Acinetobacter baumannii. Antibiotics (Basel). 2021;10(9):1115. https://doi.org/10.3390/antibiotics10091115.Ramalingam S., Cai B., Wong J., Twomey M., Che R., Fu R.M. et al. Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels. Sci Rep. 2018;8(1):13630. https://doi.org/10.1038/s41598-018-31936-y.Ramalingam S., Cai B., Wong J., Twomey M., Che R., Fu R.M. et al. Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels. Sci Rep. 2018;8(1):13630. https://doi.org/10.1038/s41598-018-31936-y.Tatzber F., Resch U., Lindschinger M., Cvirn G., Wonisch W. Improved protection of filtering facepiece through inactivation of pathogens by hypertonic salt solutions – A possible COVID-19 prevention device. Prev Med Rep. 2020;20:101270. https://doi.org/10.1016/j.pmedr.2020.101270.Tatzber F., Resch U., Lindschinger M., Cvirn G., Wonisch W. Improved protection of filtering facepiece through inactivation of pathogens by hypertonic salt solutions – A possible COVID-19 prevention device. Prev Med Rep. 2020;20:101270. https://doi.org/10.1016/j.pmedr.2020.101270.Wark P., McDonald V.M. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2018;9(9):CD001506. https://doi.org/10.1002/14651858.CD001506.pub4.Wark P., McDonald V.M. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2018;9(9):CD001506. https://doi.org/10.1002/14651858.CD001506.pub4.Mogayzel Jr P.J., Naureckas E.T., Robinson K.A., Mueller G., Hadjiliadis D., Hoag J.b. et al. Cystic Fibrosis Pulmonary Guidelines: Chronic Medications for Maintenance of Lung Health. Am J Respir Crit Care Med. 2013;187(7):680–689. https://doi.org/10.1164/rccm.201207-1160OE.Mogayzel Jr P.J., Naureckas E.T., Robinson K.A., Mueller G., Hadjiliadis D., Hoag J.b. et al. Cystic Fibrosis Pulmonary Guidelines: Chronic Medications for Maintenance of Lung Health. Am J Respir Crit Care Med. 2013;187(7):680–689. https://doi.org/10.1164/rccm.201207-1160OE.Reeves E.P., Williamson M., O’Neill S.J., Greally P., McElvaney N.G. Nebulized Hypertonic Saline Decreases IL-8 in Sputum of Patients with Cystic Fibrosis. Am J Respir Crit Care Med. 2011;183(11):1517–1523. https://doi.org/10.1164/rccm.201101-0072OC.Reeves E.P., Williamson M., O’Neill S.J., Greally P., McElvaney N.G. Nebulized Hypertonic Saline Decreases IL-8 in Sputum of Patients with Cystic Fibrosis. Am J Respir Crit Care Med. 2011;183(11):1517–1523. https://doi.org/10.1164/rccm.201101-0072OC.Bergsson G., Reeves E.P., McNally P., Chotirmall S.H., Greene C.M., Greally P. et al. LL-37 Complexation with Glycosaminoglycans in Cystic Fibrosis Lungs Inhibits Antimicrobial Activity, Which Can Be Restored by Hypertonic Saline. J Immunol. 2009;183(1):543–551. https://doi.org/10.4049/jimmunol.0803959.Bergsson G., Reeves E.P., McNally P., Chotirmall S.H., Greene C.M., Greally P. et al. LL-37 Complexation with Glycosaminoglycans in Cystic Fibrosis Lungs Inhibits Antimicrobial Activity, Which Can Be Restored by Hypertonic Saline. J Immunol. 2009;183(1):543–551. https://doi.org/10.4049/jimmunol.0803959.Buonpensiero P., De Gregorio F., Sepe A., Di Pasqua A., Ferri P., Siano M. et al. Hyaluronic acid improves “pleasantness” and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis. Adv Ther. 2010;27(11):870–878. https://doi.org/10.1007/s12325-010-0076-8.Buonpensiero P., De Gregorio F., Sepe A., Di Pasqua A., Ferri P., Siano M. et al. Hyaluronic acid improves “pleasantness” and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis. Adv Ther. 2010;27(11):870–878. https://doi.org/10.1007/s12325-010-0076-8.Machado R.R.G., Glaser T., Araujo D.B., Petiz L.L., Oliveira D.B.L., Durigon G.S. et al. Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells. ACS Pharmacol Transl Sci. 2021;4(5):1514–1527. https://doi.org/10.1021/acsptsci.1c00080.Machado R.R.G., Glaser T., Araujo D.B., Petiz L.L., Oliveira D.B.L., Durigon G.S. et al. Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells. ACS Pharmacol Transl Sci. 2021;4(5):1514–1527. https://doi.org/10.1021/acsptsci.1c00080.Desai A.D., Boursiquot B.C., Melki L., Wan E.Y. Management of Arrhythmias Associated with COVID-19. Curr Cardiol Rep. 2021;23(1):2. https://doi.org/10.1007/s11886-020-01434-7.Desai A.D., Boursiquot B.C., Melki L., Wan E.Y. Management of Arrhythmias Associated with COVID-19. Curr Cardiol Rep. 2021;23(1):2. https://doi.org/10.1007/s11886-020-01434-7.Huang J., Hume A.J., Abo K.M., Werder R.B., Villacorta- Martin C., Alysandratos K.-D. et al. SARS-CoV-2 Infection of Pluripotent Stem Cell- Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial- Intrinsic Inflammatory Response. Cell Stem Cell. 2020;27(6):962–973.e7. https://doi.org/10.1016/j.stem.2020.09.013.Huang J., Hume A.J., Abo K.M., Werder R.B., Villacorta- Martin C., Alysandratos K.-D. et al. SARS-CoV-2 Infection of Pluripotent Stem Cell- Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial- Intrinsic Inflammatory Response. Cell Stem Cell. 2020;27(6):962–973.e7. https://doi.org/10.1016/j.stem.2020.09.013.Huijghebaert S., Hoste L., Vanham G. Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19. Eur J Clin Pharmacol. 2021;77(9):1275–1293. https://doi.org/10.1007/s00228-021-03102-3.Huijghebaert S., Hoste L., Vanham G. Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19. Eur J Clin Pharmacol. 2021;77(9):1275–1293. https://doi.org/10.1007/s00228-021-03102-3.Mitra S., Schiller D., Anderson C., Gamboni F., D’Alessandro A., Kelher M. et al. Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. PLoS ONE. 2017;12(12):e0189536. https://doi.org/10.1371/journal.pone.0189536.Mitra S., Schiller D., Anderson C., Gamboni F., D’Alessandro A., Kelher M. et al. Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. PLoS ONE. 2017;12(12):e0189536. https://doi.org/10.1371/journal.pone.0189536.Ji H.-L., Song W., Gao Z., Su X.-F., Nie H.-G., Jiang Y. et al. SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms. Am J Physiol Lung Cell Mol Physiol. 2009;296(3):L372–L383. https://doi.org/10.1152/ajplung.90437.2008.Ji H.-L., Song W., Gao Z., Su X.-F., Nie H.-G., Jiang Y. et al. SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms. Am J Physiol Lung Cell Mol Physiol. 2009;296(3):L372–L383. https://doi.org/10.1152/ajplung.90437.2008.Berka U., Khan A., Blaas D., Fuchs R. Human Rhinovirus Type 2 Uncoating at the Plasma Membrane Is Not Affected by a pH Gradient but Is Affected by the Membrane Potential. J Virol. 2009;83(8):3778–3787. https://doi.org/10.1128/JVI.01739-08.Berka U., Khan A., Blaas D., Fuchs R. Human Rhinovirus Type 2 Uncoating at the Plasma Membrane Is Not Affected by a pH Gradient but Is Affected by the Membrane Potential. J Virol. 2009;83(8):3778–3787. https://doi.org/10.1128/JVI.01739-08.Hover S., Foster B., Barr J.N., Mankouri J. Viral dependence on cellular ion channels – an emerging anti-viral target? J Gen Virol. 2017;98(3):345–351. https://doi.org/10.1099/jgv.0.000712.Hover S., Foster B., Barr J.N., Mankouri J. Viral dependence on cellular ion channels – an emerging anti-viral target? J Gen Virol. 2017;98(3):345–351. https://doi.org/10.1099/jgv.0.000712.Jayaweera M., Perera H., Gunawardana B., Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environ Res. 2020;188:109819. https://doi.org/10.1016/j.envres.2020.109819.Jayaweera M., Perera H., Gunawardana B., Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environ Res. 2020;188:109819. https://doi.org/10.1016/j.envres.2020.109819.Nadesalingam A., Chen J.H.K., Farahvash A., Khan M.A. Hypertonic Saline Suppresses NADPH Oxidase- Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis. Front Immunol. 2018;9:359. https://doi.org/10.3389/fimmu.2018.00359.Nadesalingam A., Chen J.H.K., Farahvash A., Khan M.A. Hypertonic Saline Suppresses NADPH Oxidase- Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis. Front Immunol. 2018;9:359. https://doi.org/10.3389/fimmu.2018.00359.Zhang W.-C., Du L.-J., Zheng X.-J., Chen X.-Q., Shi C., Chen B.-Y. et al. Elevated sodium chloride drives type I interferon signaling in macrophages and increases antiviral resistance. J Biol Chem. 2018;293(3):1030–1039. https://doi.org/10.1074/jbc.M117.805093.Zhang W.-C., Du L.-J., Zheng X.-J., Chen X.-Q., Shi C., Chen B.-Y. et al. Elevated sodium chloride drives type I interferon signaling in macrophages and increases antiviral resistance. J Biol Chem. 2018;293(3):1030–1039. https://doi.org/10.1074/jbc.M117.805093.Leidy N.K., Rennard S.I., Schmier J., Jones M.K.C., Goldman M. The breathlessness, cough, and sputum scale: the development of empirically based guidelines for interpretation. Chest. 2003;124(6):2182–2191. https://doi.org/10.1378/chest.124.6.2182.Leidy N.K., Rennard S.I., Schmier J., Jones M.K.C., Goldman M. The breathlessness, cough, and sputum scale: the development of empirically based guidelines for interpretation. Chest. 2003;124(6):2182–2191. https://doi.org/10.1378/chest.124.6.2182.Monk P.D., Marsden R.J., Tear V.J., Brookes J., Batten T.N., Mankowski M. et al. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(2):196–206. https://doi.org/10.1016/S2213-2600(20)30511-7.Monk P.D., Marsden R.J., Tear V.J., Brookes J., Batten T.N., Mankowski M. et al. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(2):196–206. https://doi.org/10.1016/S2213-2600(20)30511-7.Gumber K., Pomila. FDA recommended potent drugs against COVID-19: Insight through molecular docking. Mater Today Proc. 2021;45:3328–3335. https://doi.org/10.1016/j.matpr.2020.12.649.Gumber K., Pomila. FDA recommended potent drugs against COVID-19: Insight through molecular docking. Mater Today Proc. 2021;45:3328–3335. https://doi.org/10.1016/j.matpr.2020.12.649.

The authors declare that there are no conflicts of interest present.