Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC133610.15690/vramn1336INFECTIOUS DISEASES: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ИНФЕКЦИОННЫХ БОЛЕЗНЕЙResearch ArticleCOVID-19, septic shock and syndrome of disseminated intravascular coagulation syndrome. Part 2COVID-19, септический шок и синдром диссеминированного внутрисосудистого свертывания крови. Часть 2https://orcid.org/0000-0001-8404-10425930-0859BitsadzeVictoria O.БицадзеВиктория Омаровна
Russian Federation

MD, PhD, Professor

д.м.н., профессор

vikabits@mail.ruhttps://orcid.org/0000-0002-0725-96868225-4976KhizroevaJamilya Kh.ХизроеваДжамиля Хизриевна
Russian Federation

MD, PhD, Professor

д.м.н., профессор

jamatotu@gmail.comhttps://orcid.org/0000-0001-7415-46337538-2966MakatsariyaAlexander D.МакацарияАлександр Давидович
Russian Federation

MD, PhD, Professor

д.м.н., академик РАН

gemostasis@mail.ruhttps://orcid.org/0000-0001-7441-27787423-8944SlukhanchukEkaterina V.СлуханчукЕкатерина Викторовна
Russian Federation

MD, PhD, Assistant Professor

к.м.н., доцент

beloborodova@rambler.ruhttps://orcid.org/0000-0002-3628-0804TretyakovaMaria V.ТретьяковаМария Владимировна
Russian Federation

MD, PhD, Assistant Professor

к.м.н., доцент

tretyakova777@yandex.ruhttps://orcid.org/0000-0002-5525-4353RizzoGiuseppeРиццоДжузеппе
Russian Federation

MD, PhD, Professor

д.м.н., профессор

giuseppe.rizzo@uniroma2.ithttps://orcid.org/0000-0002-9899-9910GrisJean-ChristopheГриcЖан-Кристоф
France

MD, PhD, Professor

д.м.н., профессор

jean.christophe.gris@chu-nimes.frhttps://orcid.org/0000-0002-9576-1368ElalamyIsmailЭлаламиИсмаил
France

MD, PhD, Professor

д.м.н., профессор

ismail.elalamy@aphp.frhttps://orcid.org/0000-0003-2976-7128SerovVladimir N.СеровВладимир Николаевич
Russian Federation

MD, PhD, Professor

д.м.н., академик РАН

v_serov@oparina4.ruhttps://orcid.org/0000-0002-9783-1796ShkodaAndrei S.ШкодаАндрей Сергеевич
Russian Federation

MD, PhD

д.м.н.

67gkb@mail.ruhttps://orcid.org/0000-0002-4564-84399084-7676SamburovaNatalia V.СамбуроваНаталья Викторовна
Russian Federation

MD, PhD, Assistant Professor

к.м.н., доцент

nsamburova@bk.ruThe First I.M. Sechenov Moscow State Medical University (Sechenov University)Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)Petrovsky National Research Center of SurgeryРоссийский научный центр хирургии им. акад. Б.В. ПетровскогоMedical Center LLCООО «Лечебный Центр»University of Roma Tor VergataРимский Университет Тор ВергатаUniversity MontpellierУниверситет МонпельеMedicine Sorbonne University, University Hospital TenonМедицинский Университет Сорбонна, Университетский Госпиталь ТенонNational Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. KulakovНаучный центр акушерства, гинекологии и перинатологии им. академика В.И. КулаковаLA Vorokhobov City Clinical Hospital 67Городская клиническая больница № 67 им. Л.А. Ворохобова30042020310820207532142251404202029042020Copyright ©; 2020, "Paediatrician" Publishers LLCCopyright ©; 2020, Издательство "Педиатръ"2020"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/article/view/1336

The article discusses the issues of hemostatic system disorders in patients with COVID-19. Strengthening the coagulopathy characteristic of DIC-syndrome, is a key sign of deterioration and an unfavorable prognosis in COVID-19 patients. Data obtained by Chinese colleagues demonstrates that a significantly increased level of D-dimer is one of the predictors of death. The article also highlights the preliminary recommendations of the International society of Thrombosis and Hemostasis (ISTH, 2020) to identify markers such as D-dimer, prothrombin time and platelet count as significant predictive markers in severe COVID-19 patients. The necessity of anticoagulant therapy in hospitalized patients is justified. The article discusses the features of sepsis in pregnant women. Data from a meta-analysis of 19 studies evaluating pregnancy complications and outcomes in patients with various coronavirus infections are presented. Despite the complicated course of pregnancy, there were no cases of vertical transmission of viral infection. In the pathogenesis of severe COVID-19 complications with the formation of severe acute respiratory distress syndrome, multi-organ dysfunction, super inflammation and cytokine storm play a leading role. In connection with viral sepsis, the article discusses the role of hemophagocytic lymphohistiocytosis as a hyperinflammatory syndrome characterized by fulminant and fatal hypercytokinemia with multiple organ failure, the role of hyperferritinemia in predicting the outcomes of severe sepsis. Groups of patients at high risk of death are discussed, as well as the need for anticoagulant and anti-cytokine therapy in patients with COVID-19.

В статье рассматриваются вопросы нарушения системы гемостаза у пациентов с COVID-19. Нарастание коагулопатии, характерной для диссеминированного внутрисосудистого свертывания крови (ДВС-синдрома), ― ключевой признак ухудшения состояния и неблагоприятного прогноза у пациентов с COVID-19. Приводятся данные, полученные китайскими коллегами, согласно которым значительно повышенный уровень D-димера является одним из предикторов смерти. Также освещены предварительные рекомендации Международного общества тромбоза и гемостаза (International Society on Thrombosis and Haemostasis, ISTH, 2020) по определению таких маркеров, как D-димер, протромбиновое время и количество тромбоцитов, в качестве значимых прогностических маркеров у тяжелых больных COVID-19. Обосновывается необходимость антикоагулянтной терапии у госпитализированных больных. В статье обсуждаются особенности сепсиса у беременных. Приводятся данные метаанализа 19 исследований, посвященных оценке осложнений и исходов беременности у пациенток с различными коронавирусными инфекциями. Несмотря на осложненное течение беременности, не отмечено ни одного случая вертикальной передачи вирусной инфекции. В патогенезе тяжелых осложнений COVID-19 с формированием тяжелого острого респираторного дистресс-синдрома, полиорганной дисфункции ведущую роль играют супервоспаление и цитокиновый шторм. В статье в связи с вирусным сепсисом обсуждается роль гемофагоцитарного лимфогистиоцитоза как гипервоспалительного синдрома, характеризуемого фульминантной и фатальной гиперцитокинемией с полиорганной недостаточностью, роль гиперферритинемии в прогнозировании исходов тяжелого сепсиса. Обсуждаются группы пациентов высокого риска развития летальных исходов, а также необходимость антикоагулянтной и антицитокиновой терапии у больных COVID-19.

COVID-19рemophagocytic lymphohistiocytosishyperferritinemiaDIC-syndromeimmunothrombosishyper-inflammationlow-molecular-weight heparinpentoxifyllineanticytokine therapysepsis and pregnancyCOVID-19гемофагоцитарный лимфогистиоцитозгиперферритинемиякоагулопатияДВС-синдромиммунотромбозгипервоспалениенизкомолекулярные гепариныпентоксифиллинантицитокиновая терапиясепсис и беременностьTang 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. doi: 10.1111/jth.14768.Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID‐19. J Thromb Haemost. 2020. Online ahead of print. doi: 10.1111/jth.14810.Lippi G, Plebani M, Henry MB. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta. 2020;506:145−148. doi: 10.1016/j.cca.2020.03.022.Lin G-L, McGinley JP, Drysdale SB, Pollard AJ. Epidemiology and immune pathogenesis of viral sepsis. Front Immunol. 2018;9:2147. doi: 10.3389/fimmu.2018.02147.Hussain NY, Uriel A, Mammen C, Bonington A. Disseminated herpes simplex infection during pregnancy, rare but important to recognise. Qatar Med J. 2014;(1):61–64. doi: 10.5339/qmj.2014.11.Goodman ZD, Ishak KG, Sesterhenn IA. Herpes simplex hepatitis in apparently immunocompetent adults. Am J Clin Pathol. 1986;85(6):694–699. doi: 10.1093/ajcp/85.6.694.Escobar M, Nieto AJ, Loaiza-Osorio S, et al. Pregnant women hospitalized with chikungunya virus infection, Colombia, 2015. Emerg Infect Dis. 2017;23(11):1777–1783. doi: 10.3201/eid2311.170480.Acosta CD, Harrison DA, Rowan K, et al. Maternal morbidity and mortality from severe sepsis: a national cohort study. BMJ Open. 2016;6(8):e012323. doi: 10.1136/bmjopen-2016-012323.Sauerbrei A, Wutzler P. Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections. Med Microbiol Immunol. 2007;196:95–102. doi: 10.1007/s00430-006-0032-z.Acosta CD, Knight M, Lee HC, et al. The continuum of maternal sepsis severity: incidence and risk factors in a population-based cohort study. PLoS ONE. 2013;8:e67175. doi: 10.1371/journal.pone.0067175.GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980−2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1459–1544. doi: 10.1016/s0140-6736(16)31012-1.Acosta CD, Harrison DA, Rowan K, et al. Maternal morbidity and mortality from severe sepsis: a national cohort study. BMJ Open. 2016;6(8):e012323. doi: 10.1136/bmjopen-2016-012323.Mason KL, Aronoff DM. Postpartum group a Streptococcus sepsis and maternal immunology. Am J Reprod Immunol. 2012;67(2):91–100. doi: 10.1111/j.1600-0897.2011.01083.x.Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci. 2011;1221(1):80–87. doi: 10.1111/j.1749-6632.2010.05938.x.Benster B, Wood EJ. Immunoglobulin levels in normal pregnancy and pregnancy complicated by hypertension. J Obstet Gynaecol Br Commonw. 1970;77(6):518–522. doi: 10.1111/j.1471-0528.1970.tb03559.x.Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol. 2010;63(6):425–433. doi: 10.1111/j.1600-0897.2010.00836.x.Di Mascio D, Khalil A, Saccone G, et al. Outcome of Coronavirus spectrum infections (SARS, MERS, COVID -19) during pregnancy: a systematic review and meta-analysis. Online ahead of print. Am J Obstet Gynecol MFM. 2020;100107. doi: 10.1016/j.ajogmf.2020.100107.Ramos-Casals M, Brito-Zeron P, Lopez-Guillermo A, et al. Adult haemophagocytic syndrome. Lancet. 2014;383(9927):1503−1516. doi: 10.1016/S0140-6736(13)61048-X.Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033−1034. doi: 10.1016/S0140-6736(20)30628-0.Shoenfeld Y. Corona (COVID-19) time musings: our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev. 2020;102538. doi: 10.1016/j.autrev.2020.102538.Seguin A, Galicier L, Boutboul D, et al. Pulmonary involvement in patients with hemophagocytic lymphohistiocytosis. Chest. 2016;149(5):1294–1301. doi: 10.1016/j.chest.2015.11.004.Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497−506. doi: 10.1016/S0140-6736(20)30183-5.Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. Online ahead of print. 2020;1−3. doi: 10.1007/s00134-020-05991-x.Nicastri E, Petrosillo N, Bartoli AT, et al. National institute for the infectious diseases “l. spallanzani” irccs. recommendations for COVID-19 clinical management. Inf Diseas Rep. 2020;12(1):8543. doi: 10.4081/idr.2020.8543.Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immun Canc. 2018;6(1):56. doi: 10.1186/s40425-018-0343-9.Eloseily E, Weiser P, Eloseily EM, et al. Benefit of anakinra in treating pediatric secondary hemophagocytic lymphohistiocytosis Arthritis Rheum. 2020;72(2):326−334. doi: 10.1002/art.41103.Honore PM, Hoste E, Molnár Z, et al. Cytokine removal in human septic shock: where are we and where are we going? Ann Intensive Care. 2019;9(1):56. doi: 10.1186/s13613-019-0530-y.Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30304-4.Stebbing J, Phelan A, Griffin I, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020;20(4):400−402. doi: 10.1016/S1473-3099(20)30132-8.Belizna C, Pregnolato F, Abad S, et al. HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome. Autoimmun Rev. 2018;17(12):1153−1168. doi: 10.1016/j.autrev.2018.05.012.Torigoe M, Sakata K, Ishii A, et al. Hydroxychloroquine efficiently suppresses inflammatory responses of human class-switched memory B cells via Toll-like receptor 9 inhibition. Clin Immunol. 2018;195:1−7. doi: 10.1016/j.clim.2018.07.003.Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16. doi: 10.1038/s41421-020-0156-0.Mousavi S, Moradi M, Khorshidahmad T, Motamedi M. Anti-inflammatory effects of heparin and its derivatives: a systematic review. Adv Pharmacol Sci. 2015;2015:507151. doi: 10.1155/2015/507151.Bernard GR, Vincent JL, Laterre PF, et al. Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10):699−709. doi: 10.1056/NEJM200103083441001.Davidson BL, Geerts WH, Lensing AW. Low-dose heparin for severe sepsis. N Engl J Med. 2002;347(13):1036−1037. doi: 10.1056/NEJM200209263471316.Wen WX, Lee SY, Siang R, Ry K. Repurposing pentoxifylline for the treatment of fibrosis: an overview. Adv Ther. 2017;34(6):1245–1269. doi: 10.1007/s12325-017-0547-2.Romanelli RG, Caligiuri A, Carloni V, et al. Effect of pentoxifylline on the degradation of procollagen type I produced by human hepatic stellate cells in response to transforming growth factor‐β1. Br J Pharmacol. 1997;122(6):1047−1054. doi: 10.1038/sj.bjp.0701484.Yamashita CM, Dolgonos L, Zemans RL, et al. Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis. Am J Pathol. 2011;179(4):1733–1745. doi: 10.1016/j.ajpath.2011.06.041.Liu X, Li Z, Liu S, et al. Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction. Med Rxiv. 2020. doi: 10.1101/2020.02.27.20027557.Etulain J, Martinod K, Wong SL, et al. P-selectin promotes neutrophil extracellular trap formation in mice. Blood. 2015;126(2):242–246. doi: 10.1182/blood-2015-01-624023.Inui S, Fujikawa A, Jitsu M, et al. Chest CT findings in cases from the cruise ship “Diamond Princess” with Coronavirus Disease 2019 (COVID-19). Radiology: Cardiothoracic imaging. 2020;2(2):e204002. doi: 10.1148/ryct.2020200110.