304:
2338:
Zhang, Jingjing; Velez, Juan Carlos Q.; Shaefi, Shahzad; Parikh, Chirag R.; Charytan, David M.; Athavale, Ambarish M.; Friedman, Allon N.; Redfern, Roberta E.; Short, Samuel A. P.; Correa, Simon; Pokharel, Kapil K.; Admon, Andrew J.; Donnelly, John P.; Gershengorn, Hayley B.; Douin, David J.; Semler, Matthew W.; Hernán, Miguel A.; Leaf, David E.; STOP-COVID Investigators (20 October 2020).
463:
Early recognition of a cytokine storm in COVID-19 patients is crucial to ensure the best outcome for recovery, allowing treatment with a variety of biological agents that target the cytokines to reduce their levels. Meta-analysis suggests clear patterns distinguishing patients with or without severe
2337:
Gupta, Shruti; Wang, Wei; Hayek, Salim S.; Chan, Lili; Mathews, Kusum S.; Melamed, Michal L.; Brenner, Samantha K.; Leonberg-Yoo, Amanda; Schenck, Edward J.; Radbel, Jared; Reiser, Jochen; Bansal, Anip; Srivastava, Anand; Zhou, Yan; Finkel, Diana; Green, Adam; Mallappallil, Mary; Faugno, Anthony J.;
1076:
Caterino, Marianna, Michele
Costanzo, Roberta Fedele, Armando Cevenini, Monica Gelzo, Alessandro Di Minno, Immacolata Andolfo et al. "The serum metabolome of moderate and severe COVID-19 patients reflects possible liver alterations involving carbon and nitrogen metabolism." International journal of
519:
found that mice producing an early strong interferon response to SARS-CoV-2 were likely to live, but in other cases the disease progressed to a highly morbid overactive immune system. The high mortality rate of COVID-19 in older populations has been attributed to the impact of age on interferon
2065:
Melo, Ana Karla G.; Milby, Keilla M.; Caparroz, Ana Luiza M. A.; Pinto, Ana
Carolina P. N.; Santos, Rodolfo R. P.; Rocha, Aline P.; Ferreira, Gilda A.; Souza, Viviane A.; Valadares, Lilian D. A.; Vieira, Rejane M. R. A.; Pileggi, Gecilmara S.; Trevisani, VirgĂnia F. M. (29 June 2021).
455:
ARDS was shown to be the cause of mortality in 70% of COVID-19 deaths. A cytokine plasma level analysis showed that in cases of severe SARS-CoV-2 infection, the levels of many interleukins and cytokines are highly elevated, indicating evidence of a cytokine storm. Additionally,
223:) is a potent inhibitor of proinflammatory cytokines. Low blood plasma levels of trigonelline (one of the metabolites of vitamin B3) have been suggested for the prognosis of SARS-CoV-2 death (which is thought to be due to the inflammatory phase and cytokine storm).
523:
Short-term use of dexamethasone, a synthetic corticosteroid, has been demonstrated to reduce the severity of inflammation and lung damage induced by a cytokine storm by inhibiting the severe cytokine storm or the hyperinflammatory phase in patients with COVID-19.
367:
of deceased COVID-19 patients were analyzed. Out of 184 protein markers, 20 markers were raised significantly in COVID-19 deceased patients. A group of markers showed over-stimulation of the immune system, including
508:(IL-6). Ferritin and IL-6 are considered to be possible immunological biomarkers for severe and fatal cases of COVID-19. Ferritin and C-reactive protein may be possible screening tools for early diagnosis of
527:
Clinical trials continue to identify causes of cytokine storms in COVID-19 cases. One such cause is the delayed Type I interferon response that leads to accumulation of pathogenic
260:, which killed an estimated 50 million people worldwide. In this case, a healthy immune system may have been a liability rather than an asset. Preliminary research results from
249:, a condition in which the role of excessive and self-perpetuating cytokine release had already been under discussion for many years. The term next appeared in a discussion of
303:
2266:
Hermine, Olivier; Mariette, Xavier; Tharaux, Pierre-Louis; Resche-Rigon, Matthieu; Porcher, Raphaël; Ravaud, Philippe; CORIMUNO-19 Collaborative Group (20 October 2020).
1180:
1063:
992:
515:
Due to the increased levels of cytokines and interferons in patients with severe COVID-19, both have been investigated as potential targets for SARS-CoV-2 therapy. An
347:(ARDS), which has a high mortality rate in COVID-19 patients. SARS-CoV-2 activates the immune system resulting in a release of a large number of cytokines, including
2323:
109:
295:, a company conducting trials for pharmaceutical companies claimed that theralizumab could cause a cytokine storm—the dangerous reaction the men experienced.
452:
organs. The higher mortality has been linked to the effects of ARDS aggravation and the tissue damage that can result in organ-failure and/or death.
1291:
Ferrara JL, Abhyankar S, Gilliland DG (February 1993). "Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1".
509:
1320:"Interleukin-1 is a critical effector molecule during cytokine dysregulation in graft versus host disease to minor histocompatibility antigens1"
1838:"Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option?"
574:"Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: Could nicotine be a therapeutic option?"
355:
and cause a migration of fluid and blood cells into the alveoli leading to such consequent symptoms as dyspnea and respiratory failure. In an
460:
of patients with COVID-19 has shown a large accumulation of inflammatory cells in lung tissues including macrophages and T-helper cells.
2268:"Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial"
344:
90:
159:
401:
265:
89:. Cytokines are a normal part of the body's immune response to infection, but their sudden release in large quantities may cause
316:
256:
It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the
2068:"Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis"
360:
201:. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset (
198:
170:
105:
101:
1598:
729:
Tisoncik, Jennifer R.; Korth, Marcus J.; Simmons, Cameron P.; Farrar, Jeremy; Martin, Thomas R.; Katze, Michael G. (2012).
1947:
Hojyo, Shintaro; Uchida, Mona; Tanaka, Kumiko; Hasebe, Rie; Tanaka, Yuki; Murakami, Masaaki; Hirano, Toshio (2020-10-01).
623:
Wong, Jonathan P.; Viswanathan, Satya; Wang, Ming; Sun, Lun-Quan; Clark, Graeme C.; D'Elia, Riccardo V. (February 2017).
481:
308:
197:
that may represent a severe episode of cytokine release syndrome or a component of another disease entity, such as
1523:"High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome"
2506:
1738:"Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China"
343:, some doctors have attributed many deaths to cytokine storms. A cytokine storm can cause the severe symptoms of
190:
174:
137:
31:
2340:"Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19"
158:
is a diverse set of conditions that can result in a cytokine storm. Cytokine storm syndromes include familial
1626:
Razaghi, Ali; Szakos, Attila; Alouda, Marwa; Bozóky, Béla; Björnstedt, Mikael; Szekely, Laszlo (2022-11-14).
1131:
Sugimoto J, Romani AM, Valentin-Torres AM, Luciano AA, Ramirez
Kitchen CM, Funderburg N; et al. (2012).
280:
125:
1379:
548:
457:
246:
133:
2183:
2317:
2127:"Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology"
1628:"Proteomic Analysis of Pleural Effusions from COVID-19 Deceased Patients: Enhanced Inflammatory Markers"
1174:
1104:
1057:
986:
485:
377:
352:
288:
162:, Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis, systemic or non-systemic juvenile
2079:
1019:
78:
1384:
2501:
369:
145:
121:
2511:
2188:
1405:
1273:
1133:"Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism"
1089:"Blood Plasma Trigonelline Concentration and the Early Prognosis of Death in SARS-Cov-2 Patients"
489:
242:
2006:
Tang, Yujun; Liu, Jiajia; Zhang, Dingyi; Xu, Zhenghao; Ji, Jinjun; Wen, Chengping (2020-07-10).
1008:"Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation"
2477:
2428:
2410:
2369:
2305:
2287:
2248:
2219:"Dexamethasone to combat cytokine storm in COVID-19: Clinical trials and preliminary evidence"
2193:
2164:
2146:
2107:
2047:
2029:
1988:
1970:
1929:
1875:
1857:
1818:
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1718:
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1579:
1544:
1503:
1454:
1397:
1367:
1349:
1341:
1300:
1265:
1227:
1162:
1045:
974:
925:
894:"Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel"
874:
866:
825:
807:
768:
750:
711:
662:
644:
605:
340:
257:
56:
2467:
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2418:
2400:
2359:
2351:
2295:
2279:
2238:
2230:
2154:
2138:
2097:
2087:
2037:
2019:
1978:
1960:
1919:
1909:
1865:
1849:
1808:
1798:
1757:
1749:
1708:
1698:
1657:
1639:
1571:
1534:
1521:
Mori M, Rothman AL, Kurane I, Montoya JM, Nolte KB, Norman JE, et al. (February 1999).
1493:
1485:
1444:
1436:
1389:
1331:
1257:
1217:
1207:
1152:
1144:
1092:
1035:
1027:
964:
956:
915:
905:
856:
815:
799:
758:
742:
701:
693:
652:
636:
595:
585:
469:
364:
148:
to produce viral nucleic acid, which stimulates the infected cells to release cytokines and
1117:
129:
2387:
Sa Ribero, Margarida; Jouvenet, Nolwenn; Dreux, Marlène; Nisole, Sébastien (2020-07-29).
2083:
1023:
2472:
2447:
2423:
2388:
2300:
2267:
2243:
2218:
2159:
2126:
2102:
2067:
2042:
2007:
1983:
1948:
1924:
1897:
1870:
1837:
1813:
1786:
1762:
1737:
1713:
1686:
1662:
1627:
1498:
1473:
1449:
1424:
1222:
1195:
1157:
1132:
1040:
1007:
969:
944:
920:
893:
820:
787:
763:
730:
706:
681:
657:
624:
600:
573:
449:
385:
2364:
2339:
1785:
Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T (October 2020).
1703:
1575:
2495:
1336:
1319:
960:
505:
497:
409:
405:
348:
2355:
2283:
1409:
1277:
682:"The cytokine storm of severe influenza and development of immunomodulatory therapy"
625:"Current and future developments in the treatment of virus-induced hypercytokinemia"
272:
usually involve cytokine storms as well. Cytokine storm has also been implicated in
544:
516:
417:
373:
328:
284:
250:
213:
82:
2463:
2405:
2092:
287:
becoming critically ill, with multiple organ failure, high fever, and a systemic
1685:
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ (March 2020).
1644:
786:
Song, Peipei; Li, Wei; Xie, Jianqin; Hou, Yanlong; You, Chongge (October 2020).
552:
493:
465:
324:
253:
in 2002. In 2003, it was first used in reference to a reaction to an infection.
117:
2234:
1965:
1853:
1803:
1753:
1031:
590:
229:
decreases inflammatory cytokine production by modulation of the immune system.
2142:
910:
803:
501:
425:
312:
273:
217:
163:
149:
141:
113:
97:
61:
17:
2414:
2291:
2197:
2150:
2033:
2024:
1974:
1914:
1861:
1836:
Farsalinos, Konstantinos; Barbouni, Anastasia; Niaura, Raymond (2020-05-09).
1653:
1345:
1148:
870:
811:
754:
648:
2217:
Sharun, Khan; Tiwari, Ruchi; Dhama, Jaideep; Dhama, Kuldeep (October 2020).
845:"Review: Cytokine Storm Syndrome: Looking Toward the Precision Medicine Era"
536:
226:
202:
166:
2481:
2432:
2373:
2309:
2252:
2168:
2111:
2051:
2008:"Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies"
1992:
1933:
1879:
1822:
1771:
1722:
1671:
1583:
1507:
1489:
1458:
1401:
1269:
1261:
1231:
1166:
1096:
1049:
978:
929:
878:
829:
772:
715:
666:
609:
1548:
1423:
Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, Lei HY (February 2005).
1353:
1304:
746:
640:
535:
is also associated with exacerbated Type I interferons response and worse
540:
528:
473:
445:
194:
86:
1474:"Confronting potential influenza A (H5N1) pandemic with better vaccines"
1393:
1212:
697:
1196:"Magnesium deficiency and increased inflammation: current perspectives"
1006:
Yanez M, Jhanji M, Murphy K, Gower RM, Sajish M, Jabbarzadeh E (2019).
572:
Farsalinos, Konstantinos; Barbouni, Anastasia; Niaura, Raymond (2020).
532:
477:
356:
292:
1440:
861:
844:
264:
also indicated this as the probable reason for many deaths during the
77:, is a pathological reaction in humans and other animals in which the
1087:
Besharati, Mohammad Reza; Izadi, Mohammad; Alireza
Talebpour (2021).
397:
261:
189:
The term "cytokine storm" is often loosely used interchangeably with
178:
1088:
1687:"COVID-19: consider cytokine storm syndromes and immunosuppression"
1539:
1522:
464:
disease. Possible predictors of severe and fatal cases may include
1318:
Abhyankar, Sunil; Gilliland, D. Gary; Ferrara, James L.M. (1993).
441:
433:
421:
393:
389:
332:
320:
2389:"Interplay between SARS-CoV-2 and the type I interferon response"
945:"Nicotinamide is a potent inhibitor of proinflammatory cytokines"
792:
Clinica
Chimica Acta; International Journal of Clinical Chemistry
1562:
The Lancet
Oncology (February 2007). "High stakes, high risks".
437:
429:
413:
381:
315:
infection resulting in ARDS related to COVID-19. Abbreviations:
269:
1248:
Clark, Ian A (June 2007). "The advent of the cytokine storm".
283:
in
England resulted in all 6 of the volunteers given the drug
245:
appears to be by James
Ferrara in 1993 during a discussion of
96:
Cytokine storms may be caused by infectious or non-infectious
1425:"An interferon-gamma-related cytokine storm in SARS patients"
680:
Liu, Qiang; Zhou, Yuan-hong; Yang, Zhan-qiu (January 2016).
2446:
Mangalmurti, Nilam; Hunter, Christopher A. (14 July 2020).
892:
Porter D, Frey N, Wood PA, Weng Y, Grupp SA (March 2018).
1949:"How COVID-19 induces cytokine storm with high mortality"
1787:"How covid-19 induces cytokine storm with high mortality"
152:, activating macrophages, dendritic cells, and others.
1736:
Ruan Q, Yang K, Wang W, Jiang L, Song J (March 2020).
2125:
Channappanavar, Rudragouda; Perlman, Stanley (2017).
2184:"How Covid Sends Some Bodies to War With Themselves"
55:
47:
42:
1898:"The COVID-19 Cytokine Storm; What we know so far"
100:, especially viral respiratory infections such as
268:epidemic in 2003. Human deaths from the bird flu
943:Ungerstedt JS, Blömback M, Söderström T (2003).
185:Cytokine storms versus cytokine release syndrome
81:causes an uncontrolled and excessive release of
1370:(May 2005). "Preparing for the next pandemic".
1243:
1241:
843:Behrens, Edward M.; Koretzky, Gary A. (2017).
193:(CRS) but is more precisely a differentiable
8:
1472:Haque A, Hober D, Kasper LH (October 2007).
1179:: CS1 maint: multiple names: authors list (
1062:: CS1 maint: multiple names: authors list (
991:: CS1 maint: multiple names: authors list (
2322:: CS1 maint: numeric names: authors list (
1077:molecular sciences 22, no. 17 (2021): 9548.
1891:
1889:
735:Microbiology and Molecular Biology Reviews
39:
2471:
2448:"Cytokine Storms: Understanding COVID-19"
2422:
2404:
2363:
2299:
2242:
2158:
2101:
2091:
2041:
2023:
1982:
1964:
1923:
1913:
1869:
1812:
1802:
1761:
1712:
1702:
1661:
1643:
1599:"Mystery over drug trial debacle deepens"
1538:
1497:
1448:
1383:
1335:
1221:
1211:
1156:
1039:
968:
919:
909:
860:
819:
762:
705:
656:
599:
589:
555:of cytokine storms in COVID-19 patients.
323:: Chemokine (C–X–C motif) ligand 9, IL:
302:
173:, NLRC4 macrophage activation syndrome,
136:, and non-infectious conditions such as
2182:Velasquez-Manoff, Moises (2020-08-11).
564:
510:systemic inflammatory response syndrome
2315:
1172:
1113:
1102:
1055:
984:
788:"Cytokine storm induced by SARS-CoV-2"
205:) CRS appears to be a cytokine storm.
1621:
1619:
124:. Other causative agents include the
7:
898:Journal of Hematology & Oncology
731:"Into the Eye of the Cytokine Storm"
1372:The New England Journal of Medicine
686:Cellular & Molecular Immunology
345:acute respiratory distress syndrome
319:: Angiotensin-converting enzyme 2,
307:Cytokine release via activation of
1527:The Journal of Infectious Diseases
160:hemophagocytic lymphohistiocytosis
25:
2223:International Journal of Surgery
1337:10.1097/00007890-199312000-00045
961:10.1046/j.1365-2249.2003.02031.x
237:The first reference to the term
27:Frequently fatal immune reaction
2356:10.1001/jamainternmed.2020.6252
2284:10.1001/jamainternmed.2020.6820
1842:Internal and Emergency Medicine
578:Internal and Emergency Medicine
335:and activator of transcription.
199:macrophage activation syndrome
171:macrophage activation syndrome
140:. The viruses can invade lung
1:
1953:Inflammation and Regeneration
1791:Inflammation and Regeneration
1704:10.1016/S0140-6736(20)30628-0
1576:10.1016/S1470-2045(07)70004-9
1250:Immunology & Cell Biology
311:signalling pathway following
274:hantavirus pulmonary syndrome
2464:10.1016/j.immuni.2020.06.017
2406:10.1371/journal.ppat.1008737
2093:10.1371/journal.pone.0253894
1896:Ragad, Dina (16 June 2020).
1478:Emerging Infectious Diseases
849:Arthritis & Rheumatology
2131:Seminars in Immunopathology
1645:10.3390/diagnostics12112789
1429:Journal of Medical Virology
1293:Transplantation Proceedings
85:signaling molecules called
2528:
2235:10.1016/j.ijsu.2020.08.038
1966:10.1186/s41232-020-00146-3
1854:10.1007/s11739-020-02355-7
1804:10.1186/s41232-020-00146-3
1754:10.1007/s00134-020-05991-x
1032:10.1038/s41598-019-46678-8
629:Future Medicinal Chemistry
591:10.1007/s11739-020-02355-7
482:aspartate aminotransferase
29:
2143:10.1007/s00281-017-0629-x
911:10.1186/s13045-018-0571-y
804:10.1016/j.cca.2020.06.017
191:cytokine release syndrome
175:cytokine release syndrome
138:graft-versus-host disease
91:multisystem organ failure
32:Cytokine release syndrome
2025:10.3389/fimmu.2020.01708
1915:10.3389/fimmu.2020.01446
1597:Coghlan A (2006-08-14).
1149:10.4049/jimmunol.1101765
299:Relationship to COVID-19
30:Not to be confused with
2012:Frontiers in Immunology
1742:Intensive Care Medicine
281:Northwick Park Hospital
258:1918 influenza pandemic
156:Cytokine storm syndrome
2344:JAMA Internal Medicine
2272:JAMA Internal Medicine
1490:10.3201/eid1310.061262
1262:10.1038/sj.icb.7100062
1112:Cite journal requires
1097:10.5281/zenodo.5856445
549:cardiovascular disease
512:in cases of COVID-19.
458:postmortem examination
336:
247:graft vs. host disease
747:10.1128/MMBR.05015-11
641:10.4155/fmc-2016-0181
486:lactate dehydrogenase
353:vascular permeability
351:, which can increase
306:
289:inflammatory response
134:group A streptococcus
1697:(10229): 1033–1034.
1564:The Lancet. Oncology
444:indicated damage to
279:In 2006, a study at
146:alveolar macrophages
79:innate immune system
2084:2021PLoSO..1653894M
1394:10.1056/NEJMp058068
1213:10.2147/JIR.S136742
1194:Nielsen FH (2018).
1024:2019NatSR...910219Y
698:10.1038/cmi.2015.74
472:and high levels of
361:Karolinska Hospital
122:parainfluenza virus
2189:The New York Times
1299:(1 Pt 2): 1216–7.
490:C-reactive protein
337:
243:medical literature
126:Epstein-Barr virus
1441:10.1002/jmv.20255
862:10.1002/art.40071
365:pleural effusions
341:COVID-19 pandemic
333:signal transducer
241:in the published
67:
66:
37:Medical condition
16:(Redirected from
2519:
2507:Endocrine system
2486:
2485:
2475:
2443:
2437:
2436:
2426:
2408:
2384:
2378:
2377:
2367:
2334:
2328:
2327:
2321:
2313:
2303:
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2257:
2256:
2246:
2214:
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2207:
2205:
2204:
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2122:
2116:
2115:
2105:
2095:
2062:
2056:
2055:
2045:
2027:
2003:
1997:
1996:
1986:
1968:
1944:
1938:
1937:
1927:
1917:
1893:
1884:
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1873:
1833:
1827:
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1816:
1806:
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1733:
1727:
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1706:
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1542:
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1512:
1511:
1501:
1469:
1463:
1462:
1452:
1420:
1414:
1413:
1387:
1364:
1358:
1357:
1339:
1330:(6): 1518–1522.
1315:
1309:
1308:
1288:
1282:
1281:
1245:
1236:
1235:
1225:
1215:
1191:
1185:
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1128:
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1100:
1084:
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1074:
1068:
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1061:
1053:
1043:
1003:
997:
996:
990:
982:
972:
949:Clin Exp Immunol
940:
934:
933:
923:
913:
889:
883:
882:
864:
855:(6): 1135–1143.
840:
834:
833:
823:
783:
777:
776:
766:
726:
720:
719:
709:
677:
671:
670:
660:
620:
614:
613:
603:
593:
569:
470:thrombocytopenia
83:pro-inflammatory
75:hypercytokinemia
51:hypercytokinemia
40:
21:
2527:
2526:
2522:
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