Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9535810.26442/20751753.2020.12.200558ArticlesСтатьиReview ArticleNonsteroidal anti-inflammatory drugs and ibuprofen for COVID-19: a systematic reviewПрименение нестероидных противовоспалительных препаратов и ибупрофена при заболевании COVID-19: систематический обзорLeonovaMarina V.ЛеоноваМарина Васильевна

чл.-кор. РАЕН, д-р мед. наук, проф.

anti23@mail.ruAssociation of Clinical PharmacologistsМОО «Ассоциация клинических фармакологов»151220202212VOL 22, NO12 (2020)ТОМ 22, №12 (2020)313628122021Copyright ©; 2020, Consilium MedicumCopyright ©; 2020, ООО "Консилиум Медикум"2020Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95358

COVID-19 pandemic is currently the most pressing public health problem worldwide. Despite growing knowledge about the nature of SARS-CoV-2-assosiated severe acute respiratory syndrome, the treatment options are still poorly defined. The safety of nonsteroidal anti-inflammatory drugs (NSAIDs), in particular ibuprofen, has been questioned without any supporting evidence. This has contributed to a number of observational studies evaluating the effect of ibuprofen on COVID-19 disease outcomes. A search of publications was carried out and a systematic review of 9 studies was presented, pharmacodynamic effects of ibuprofen were considered in terms of the effect on angiotensin-converting enzyme 2 and cyclooxygenase. The studies data have shown no direct interaction between ibuprofen and SARS-CoV-2, no evidence that ibuprofen affects the up-regulation of angiotensin-converting enzyme 2 as a COVID-19 receptor in human studies. Observational studies have not found evidence that ibuprofen, when used chronically before COVID-19 or when acutely used to relieve symptoms of COVID-19, contributes to infection or increases the risk of adverse outcomes (mortality, risk of hospitalization, risk of mechanical ventilation). Subsequently, international regulatory authorities (World Health Organization, European Medical Agency, FDA) concluded that there is no link between the more severe course of COVID-19 and NSAID treatment; paracetamol and other NSAIDs (ibuprofen) are recommended to treat the symptoms of COVID-19; patients on chronic NSAID treatment are warned not to discontinue it, as their condition may worsen.

Пандемия COVID-19 в настоящее время является наиболее острой проблемой здравоохранения в мире. Несмотря на растущие знания о природе тяжелого острого респираторного синдрома, вызванного SARS-CoV-2, варианты лечения по-прежнему плохо определены. Безопасность нестероидных противовоспалительных препаратов (НПВП), в частности ибупрофена, подвергалась сомнению без каких-либо подтверждающих доказательств. Это способствовало проведению ряда наблюдательных исследований по оценке влияния ибупрофена на исходы заболевания COVID-19. Проведен поиск публикаций и представлен систематический обзор 9 исследований, рассмотрены фармакодинамические эффекты ибупрофена в аспекте влияния на ангиотензинпревращающий фермент 2 (АПФ-2) и циклооксигеназу. Результаты исследований показали отсутствие прямого взаимодействия между ибупрофеном и SARS-CoV-2, отсутствие доказательств того, что ибупрофен влияет на up-регуляцию АПФ-2 как рецептора COVID-19 в исследованиях с участием людей. В наблюдательных исследованиях не получили доказательств, что ибупрофен при хроническом применении до заболевания COVID-19 или при остром применении для купирования симптомов COVID-19 способствует инфицированию или увеличивает риск неблагоприятных исходов (смертность, риск госпитализации, риск искусственной вентиляции легких). Впоследствии международные регуляторные органы (Всемирная организация здравоохранения, Европейское медицинское агентство, Управление по контролю пищевых продуктов и лекарств в США) заключили, что нет связи между более тяжелым течением COVID-19 и лечением НПВП; парацетамол и другие НПВП (ибупрофен) рекомендуются для лечения симптомов COVID-19; пациентов, находящихся на хроническом лечении НПВП, предупреждают, чтобы они не прекращали его, так как их состояние может ухудшиться.

COVID-19COVID-19non-steroidal anti-inflammatory drugsibuprofenobservational studiesmortalityнестероидные противовоспалительные препаратыибупрофеннаблюдательные исследованиясмертностьDay M. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists. BMJ 2020; 368: m1086. DOI: 10.1136/bmj.m1086Zhang H, Penninger JM, Li Y et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020; 46 (4): 586-90. DOI: 10.1007/s00134-020-05985-9Smart L, Fawkes N, Goggin P et al. A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality. Inflammopharmacology 2020; 28 (5): 1141-52. DOI: 10.1007/s10787-020-00745-zHoffmann M, Kleine-Weber H, Schroeder S et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020; 181 (2): 271-80. DOI: 10.1016/j.cell.2020.02.052Walls AC, Park YJ, Tortorici MA et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020; 181 (2): 281-92. DOI: 10.1016/j.cell.2020.02.058Levy BD, Clish CB, Schmidt B et al. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2001; 2 (7): 612-9. DOI: 10.1038/89759Qiao W, Wang C, Chen B et al. Ibuprofen attenuates cardiac fibrosis in streptozotocin-induced diabetic rats. Cardiology 2015; 131 (2): 97-106. DOI: 10.1159/000375362Bancos S, Bernard MP, Topham DJ, Phipps RP. Ibuprofen and other widely used non-steroidal antiinflammatory drugs inhibit antibody production in human cells. Cell Immunol 2009; 258 (1): 18-28. DOI: 10.1016/j.cellimm.2009.03.007Graham NM, Burrell CJ, Douglas RM et al. Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers. J Infect Dis 1990; 162 (6): 1277-82. DOI: 10.1093/infdis/162.6.1277Bruce E, Barlow-Pay F, Short R et al. Prior routine use of non-steroidal anti-inflammatory drugs (NSAIDs) and important outcomes in hospitalised patients with COVID-19. J Clin Med 2020; 9 (8): 2586. DOI: 10.3390/jcm9082586Imam Z, Odish F, Gill I et al. Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States. J Intern Med 2020; 288 (4): 469-76. DOI: 10.1111/joim.13119Jeong HE, Lee H, Shin HJ et al. Association between NSAIDs use and adverse clinical outcomes among adults hospitalized with COVID-19 in South Korea: A nationwide study. Clin Infect Dis 2020; ciaa1056. DOI: 10.1093/cid/ciaa1056Lund LC, Kristensen KB, Reilev M et al. Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study. PLoS Med 2020; 17 (9): e1003308. DOI: 10.1371/journal.pmed.1003308Rentsch CT, Kidwai-Khan F, Tate JP et al. Covid-19 testing, hospital admission, and iIntensive care among 2.026.227 United States veterans aged 54-75 years. medRxiv 2020; 2020.04.09.20059964. DOI: 10.1101/2020.04.09.20059964Rinott E, Kozer E, Shapira Y et al. Ibuprofen use and clinical outcomes in COVID-19 patients. Clin Microbiol Infect 2020; 26 (9): 1259.e5-7. DOI: 10.1016/j.cmi.2020.06.003Abu Esba LC, Alqahtani RA, Thomas A et al. Ibuprofen and NSAID use in COVID-19 infected patients Is not associated with worse outcomes: a prospective cohort study. Infect Dis Ther 2020; 116. DOI: 10.1007/s40121-020-00363-wCastro VM, Ross RA, McBride SM, Perlis RH. Identifying common pharmacotherapies associated with reduced COVID19 morbidity using electronic health records. medRxiv preprint April 2020. DOI: 10.1101/2020.04.11.20061994Castro VM, Ross RA, McBride SM, Perlis RH. Identifying common pharmacotherapies associated with reduced COVID19 morbidity using electronic health records. medRxiv 2020: 2020.04.11.20061994. DOI: 10.1101/2020.04.11.20061994Updated: WHO Now Doesn’t Recommend Avoiding Ibuprofen For COVID-19 Symptoms. https://www.sciencealert.com/whorecommends-to-avoid-taking-ibuprofen-for-covid-19-symptomsTorjesen I. Covid-19: ibuprofen can be used for symptoms, says UK agency, but reasons for change in advice are unclear. BMJ 2020; 369: m1555. DOI: 10.1136/bmj.m1555Capuano A, Scaglione F, Berrino L et al. Official statement of the section of Clinical Pharmacology of Italian Society of Pharmacology on Nonsteroidal anti-infammatory drugs (NSAIDs) and the increased risk of complications during infections with commentary. Pharmadvances 2020; 2 (1): 610. http://www.pharmadvances.com/official-statement-of-the-section-of-clinical-pharmacology-of-italian-society-of-pharmacology-on-non-steroidal-anti-inflammatory-drugs-nsaids-and-the-increased-risk-of-complications-during-infection-2/Zolk O, Hafner S, Schmidt CQ et al. COVID-19 pandemic and therapy with ibuprofen or renin-angiotensin system blockers: no need for interruptions or changes in ongoing chronic treatments. Na-unyn Schmiedebergs Arch Pharmacol 2020; 393 (7): 1131-5. DOI: 10.1007/s00210-020-01890-6EMA gives advice on the use of non-steroidal antiinflammatories for COVID-19. EMA/136850/2020. March 2020. https://www.ema.europa.eu/en/documents/press-release/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19_en.pdf