COVID-19

==== Cytokine storm ====
[[File:Fimmu-11-01648-g003.jpg|thumb|Various therapeutic strategies for targeting cytokine storm|right]]

A [[cytokine storm]] can be a complication in the later stages of severe COVID‑19. A cytokine storm is a potentially deadly immune reaction where a large amount of pro-inflammatory cytokines and [[chemokine]]s are released too quickly. A cytokine storm can lead to ARDS and multiple organ failure.<ref>{{#invoke:cite journal || vauthors = Li X, Geng M, Peng Y, Meng L, Lu S | title = Molecular immune pathogenesis and diagnosis of COVID-19 | journal = Journal of Pharmaceutical Analysis | volume = 10 | issue = 2 | pages = 102–108 | date = April 2020 | pmid = 32282863 | pmc = 7104082 | doi = 10.1016/j.jpha.2020.03.001 }}</ref> Data collected from Jin Yin-tan Hospital in Wuhan, China indicates that patients who had more severe responses to COVID‑19 had greater amounts of pro-inflammatory cytokines and chemokines in their system than patients who had milder responses. These high levels of pro-inflammatory cytokines and chemokines indicate presence of a cytokine storm.<ref>{{#invoke:cite journal || vauthors = Zhao Z, Wei Y, Tao C | title = An enlightening role for cytokine storm in coronavirus infection | journal = Clinical Immunology | volume = 222 | pages = 108615 | date = January 2021 | pmid = 33203513 | pmc = 7583583 | doi = 10.1016/j.clim.2020.108615 }}</ref>

[[Tocilizumab]] has been included in treatment guidelines by China's [[National Health Commission]] after a small study was completed.<ref name="tocil-1">{{#invoke:cite news ||vauthors = Liu R, Miller J |url = https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-of-roche-arthritis-drug-for-coronavirus-patients-idUSKBN20R0LF |title=China approves use of Roche drug in battle against coronavirus complications |date=3 March 2020 |work=[[Reuters]] |access-date=14 March 2020 |archive-url=https://web.archive.org/web/20200312204625/https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-of-roche-arthritis-drug-for-coronavirus-patients-idUSKBN20R0LF |archive-date=12 March 2020 |url-status=live}}</ref><ref name="tocil-2">{{#invoke:cite journal ||vauthors = Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H |title = Effective treatment of severe COVID-19 patients with tocilizumab |journal = Proceedings of the National Academy of Sciences of the United States of America |volume = 117 |issue = 20 |pages = 10970–10975 |date = May 2020 |pmid = 32350134 |pmc = 7245089 |doi = 10.1073/pnas.2005615117 |doi-access = free |title-link = doi |bibcode = 2020PNAS..11710970X }}</ref> It is undergoing a [[Phase IIb|Phase{{spaces}}II]] non-randomised trial at the national level in Italy after showing positive results in people with severe disease.<ref>{{#invoke:Cite web||vauthors = Ovadia D, Agenzia Z |title=COVID-19 – Italy launches an independent trial on tocilizumab |url=https://www.univadis.co.uk/viewarticle/covid-19-italy-launches-an-independent-trial-on-tocilizumab-715741 |website=Univadis from Medscape |publisher=Aptus Health |access-date=22 April 2020}}</ref><ref>{{#invoke:Cite web||title=Tocilizumab in COVID-19 Pneumonia (TOCIVID-19) (TOCIVID-19) |url=https://clinicaltrials.gov/ct2/show/NCT04317092 |website=clinicaltrials.gov |access-date=22 April 2020}}</ref> Combined with a serum ferritin blood test to identify a cytokine storm (also called cytokine storm syndrome, not to be confused with cytokine release syndrome), it is meant to counter such developments, which are thought to be the cause of death in some affected people.<ref name="tocil-5,6,8">Various sources:
* {{#invoke:Cite web||url=https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-deaths-china-treatment-cytokine-storm-syndrome|title=How doctors can potentially significantly reduce the number of deaths from Covid-19|work=[[Vox (website)|Vox]]|access-date=14 March 2020|date=12 March 2020|archive-url=https://web.archive.org/web/20200319155218/https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-deaths-china-treatment-cytokine-storm-syndrome|archive-date=19 March 2020|url-status=live}}
* {{#invoke:cite journal || vauthors = Ruan Q, Yang K, Wang W, Jiang L, Song J | title = Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China | journal = Intensive Care Medicine | volume = 46 | issue = 5 | pages = 846–848 | date = May 2020 | pmid = 32125452 | pmc = 7080116 | doi = 10.1007/s00134-020-05991-x | ref = none }}
* {{#invoke:cite journal || vauthors = Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ | title = COVID-19: consider cytokine storm syndromes and immunosuppression | journal = Lancet | volume = 395 | issue = 10229 | pages = 1033–1034 | date = March 2020 | pmid = 32192578 | pmc = 7270045 | doi = 10.1016/S0140-6736(20)30628-0 | ref = none | title-link = doi | doi-access = free }}</ref> The [[interleukin-6 receptor]] (IL-6R) [[receptor antagonist|antagonist]] was approved by the FDA to undergo a Phase{{spaces}}III clinical trial assessing its effectiveness on COVID‑19 based on retrospective case studies for the treatment of steroid-refractory cytokine release syndrome induced by a different cause, [[Chimeric antigen receptor T cell|CAR T cell]] [[Gene therapy|therapy]], in 2017.<ref name="CancerNetworkTocilizumabTrial">{{#invoke:Cite web|| vauthors = Slater H |title=FDA Approves Phase III Clinical Trial of Tocilizumab for COVID-19 Pneumonia |url=https://www.cancernetwork.com/news/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia |website=cancernetwork.com |date=26 March 2020 |publisher=Cancer Network |access-date=22 April 2020}}</ref> There is no randomised, controlled evidence that tocilizumab is an efficacious treatment for CRS. Prophylactic tocilizumab has been shown to increase serum IL-6 levels by saturating the IL-6R, driving IL-6 across the [[blood–brain barrier]], and exacerbating [[neurotoxicity]] while having no effect on the incidence of CRS.<ref>{{#invoke:cite journal ||vauthors=Locke FL, Neelapu SS, Bartlett NL, Lekakis LJ, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Reagan PM, Bot A, Rossi JM, Sherman M, Navale L, Jiang Y, Aycock JS, Elias M, Wiezorek JS, Go WY, Miklos DB |title=Preliminary Results of Prophylactic Tocilizumab after Axicabtageneciloleucel (axi-cel; KTE-C19) Treatment for Patients with Refractory, Aggressive Non-Hodgkin Lymphoma (NHL) |journal=Blood |year=2017 |volume=130 |issue=Supplement 1 |pages=1547 |doi=10.1182/blood.V130.Suppl_1.1547.1547 |s2cid=155698207 |url=https://ashpublications.org/blood/article/130/Supplement%201/1547/79746}}</ref>

[[Lenzilumab]], an anti-GM-CSF [[monoclonal antibody]], is protective in murine models for CAR T cell-induced CRS and neurotoxicity and is a viable therapeutic option due to the observed increase of pathogenic GM-CSF secreting T{{spaces}}cells in hospitalised patients with COVID‑19.<ref>{{#invoke:cite journal || vauthors = Sterner RM, Sakemura R, Cox MJ, Yang N, Khadka RH, Forsman CL, Hansen MJ, Jin F, Ayasoufi K, Hefazi M, Schick KJ, Walters DK, Ahmed O, Chappell D, Sahmoud T, Durrant C, Nevala WK, Patnaik MM, Pease LR, Hedin KE, Kay NE, Johnson AJ, Kenderian SS  | title = GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR T cell function in xenografts | journal = Blood | volume = 133 | issue = 7 | pages = 697–709 | date = February 2019 | pmid = 30463995 | pmc = 6376281 | doi = 10.1182/blood-2018-10-881722 }}</ref>