COVID-19

== Research ==
{{Further|COVID-19 drug development}}

International research on vaccines and medicines in COVID{{nbhyph}}19 is underway by government organisations, academic groups, and industry researchers.<ref name="dhama">{{#invoke:cite journal || vauthors = Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP, Chaicumpa W  | title = COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics | journal = Human Vaccines & Immunotherapeutics | volume = 16 | issue = 6 | pages = 1232–1238 | date = June 2020 | pmid = 32186952 | pmc = 7103671 | doi = 10.1080/21645515.2020.1735227 | title-link = doi | doi-access = free }}</ref><ref name="zhang2020">{{#invoke:cite journal || vauthors = Zhang L, Liu Y | title = Potential interventions for novel coronavirus in China: A systematic review | journal = Journal of Medical Virology | volume = 92 | issue = 5 | pages = 479–490 | date = May 2020 | pmid = 32052466 | pmc = 7166986 | doi = 10.1002/jmv.25707 }}</ref> The CDC has classified it to require a [[BSL3]] grade laboratory.<ref name=inlbg>{{#invoke:Cite web||title=Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19) |url=https://www.cdc.gov/coronavirus/2019-ncov/lab/lab-biosafety-guidelines.html |website=Coronavirus Disease 2019 (COVID-19) Lab Biosafety Guidelines |date=11 February 2020 |publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) |access-date=1 April 2020}}</ref> There has been a great deal of COVID‑19 research, involving accelerated research processes and publishing shortcuts to meet the global demand.<ref name="Aristovnik et al. 2020">{{#invoke:cite journal||vauthors=Aristovnik A, Ravšelj D, Umek L|date=November 2020|title=A Bibliometric Analysis of COVID-19 across Science and Social Science Research Landscape|journal=Sustainability|volume=12|issue=21|pages=9132|doi=10.3390/su12219132|doi-access=free | title-link = doi }}</ref>

{{As of|2020|December}}, hundreds of [[clinical trial]]s have been undertaken, with research happening on every continent except [[COVID-19 pandemic in Antarctica|Antarctica]].<ref>{{#invoke:cite journal || vauthors = Kupferschmidt K |title=First-of-its-kind African trial tests common drugs to prevent severe COVID-19 |journal=[[Science (journal)|Science]] |date=3 December 2020 |doi=10.1126/science.abf9987 |doi-access=free | title-link=doi |url=https://www.science.org/content/article/first-its-kind-african-trial-tests-common-drugs-prevent-severe-covid-19 |access-date=8 March 2022 }}</ref> {{As of|2020|November}}, more than 200 possible treatments have been studied in humans.<ref>{{#invoke:Cite magazine || vauthors = Reardon S |date= November 2020|title=For COVID Drugs, Months of Frantic Development Lead to Few Outright Successes|url=https://www.scientificamerican.com/article/for-covid-drugs-months-of-frantic-development-lead-to-few-outright-successes/|access-date=10 December 2020|magazine=[[Scientific American]] }}</ref>

=== Transmission and prevention research ===
{{Further|COVID-19 vaccine}}

[[Modeling and simulation|Modelling]] research has been conducted with several objectives, including predictions of the dynamics of transmission,<ref>{{#invoke:cite journal || vauthors = Kucharski AJ, Russell TW, Diamond C, Liu Y, Edmunds J, Funk S, Eggo RM  | title = Early dynamics of transmission and control of COVID-19: a mathematical modelling study | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 5 | pages = 553–558 | date = May 2020 | pmid = 32171059 | pmc = 7158569 | doi = 10.1016/S1473-3099(20)30144-4 | doi-access = free | title-link = doi }}</ref> diagnosis and prognosis of infection,<ref>{{#invoke:cite journal||date=3 February 2021|title=Update to living systematic review on prediction models for diagnosis and prognosis of covid-19|url=https://pubmed.ncbi.nlm.nih.gov/33536183|journal=BMJ (Clinical Research Ed.)|volume=372|pages=n236|doi=10.1136/bmj.n236|issn=1756-1833|pmid=33536183|s2cid=231775762}}</ref> estimation of the impact of interventions,<ref>{{#invoke:cite journal || vauthors = Giordano G, Blanchini F, Bruno R, Colaneri P, Di Filippo A, Di Matteo A, Colaneri M  | title = Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy | journal = Nature Medicine | volume = 26 | issue = 6 | pages = 855–860 | date = June 2020 | pmid = 32322102 | pmc = 7175834 | doi = 10.1038/s41591-020-0883-7|arxiv=2003.09861 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Prem K, Liu Y, Russell TW, Kucharski AJ, Eggo RM, Davies N, Jit M, Klepac P  | title = The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study | journal = The Lancet. Public Health | volume = 5 | issue = 5 | pages = e261–e270 | date = May 2020 | pmid = 32220655 | pmc = 7158905 | doi = 10.1016/S2468-2667(20)30073-6 | doi-access = free | title-link = doi }}</ref> or allocation of resources.<ref>{{#invoke:cite journal || vauthors = Emanuel EJ, Persad G, Upshur R, Thome B, Parker M, Glickman A, Zhang C, Boyle C, Smith M, Phillips JP  | title = Fair Allocation of Scarce Medical Resources in the Time of Covid-19 | journal = The New England Journal of Medicine | volume = 382 | issue = 21 | pages = 2049–2055 | date = May 2020 | pmid = 32202722 | doi = 10.1056/NEJMsb2005114 | doi-access = free | title-link = doi }}</ref> Modelling studies are mostly based on [[compartmental models in epidemiology]],<ref>{{#invoke:cite journal ||doi=10.1098/rspa.1927.0118 |volume=115 |issue=772 |pages=700–721 |title=A contribution to the mathematical theory of epidemics |journal=Proceedings of the Royal Society of London. Series A, Containing Papers of a Mathematical and Physical Character |year=1927 |bibcode=1927RSPSA.115..700K |doi-access=free | title-link = doi | vauthors = Kermack WO, McKendrick AG }}</ref> estimating the number of infected people over time under given conditions. Several other types of models have been developed and used during the COVID{{nbhyph}}19 pandemic including [[computational fluid dynamics]] models to study the flow physics of COVID{{nbhyph}}19,<ref>{{#invoke:cite journal ||doi=10.1017/jfm.2020.330 |volume=894 |pages=–2 | vauthors = Mittal R, Ni R, Seo JH |title=The flow physics of COVID-19 |journal=Journal of Fluid Mechanics |year=2020 |arxiv=2004.09354 |bibcode=2020JFM...894F...2M |doi-access=free | title-link = doi }}</ref> retrofits of crowd movement models to study occupant exposure,<ref>{{#invoke:cite journal || vauthors = Ronchi E, Lovreglio R | title = EXPOSED: An occupant exposure model for confined spaces to retrofit crowd models during a pandemic | journal = Safety Science | volume = 130 | pages = 104834 | date = October 2020 | pmid = 32834509 | pmc = 7373681 | doi = 10.1016/j.ssci.2020.104834 | arxiv = 2005.04007 | doi-access = free | title-link = doi }}</ref> mobility-data based models to investigate transmission,<ref>{{#invoke:cite journal || vauthors = Badr HS, Du H, Marshall M, Dong E, Squire MM, Gardner LM | title = Association between mobility patterns and COVID-19 transmission in the USA: a mathematical modelling study | journal = The Lancet Infectious Diseases | volume = 20 | issue = 11 | pages = 1247–1254 | date = November 2020 | pmid = 32621869 | pmc = 7329287 | doi = 10.1016/S1473-3099(20)30553-3 | doi-access = free | title-link = doi }}</ref> or the use of [[macroeconomic]] models to assess the economic impact of the pandemic.<ref>{{#invoke:cite journal || vauthors = McKibbin W, Roshen F | title = The global macroeconomic impacts of COVID-19: Seven scenarios |journal=CAMA Working Paper |year=2020 |doi=10.2139/ssrn.3547729 |s2cid=216307705 |url= https://cama.crawford.anu.edu.au/sites/default/files/publication/cama_crawford_anu_edu_au/2020-03/19_2020_mckibbin_fernando_0.pdf }}</ref>

=== Treatment-related research ===
{{Main|COVID-19 drug repurposing research}}
[[File:Fmolb-07-585899-g001.jpg|thumb|Seven possible drug targets in viral replication process and drugs]]

Repurposed [[antiviral drug]]s make up most of the research into COVID‑19 treatments.<ref name="milken">{{#invoke:Cite web||date=21 April 2020|title=COVID-19 treatment and vaccine tracker|url=https://milkeninstitute.org/sites/default/files/2020-04/Covid19%20Tracker%20NEW4-21-20-2.pdf|access-date=21 April 2020|publisher=Milken Institute }}</ref><ref name="koch">{{#invoke:Cite web|| vauthors = Koch S, Pong W |date=13 March 2020|title=First up for COVID-19: nearly 30 clinical readouts before end of April|url=https://www.biocentury.com/article/304658|access-date=1 April 2020|publisher=BioCentury Inc.}}</ref> Other candidates in trials include [[vasodilator]]s, [[corticosteroid]]s, immune therapies, [[lipoic acid]], [[bevacizumab]], and [[recombinant DNA|recombinant]] angiotensin-converting enzyme 2.<ref name="koch" />

In March 2020, the [[World Health Organization]] (WHO) initiated the [[Solidarity trial]] to assess the treatment effects of some promising drugs: an [[experimental drug]] called remdesivir; [[Antimalarial medication|anti-malarial]] drugs chloroquine and hydroxychloroquine; two [[Anti-HIV medications|anti-HIV drugs]], [[lopinavir/ritonavir]]; and [[interferon-beta]].<ref name="kai">{{#invoke:cite journal|| vauthors = Kupferschmidt K, Cohen J |date=March 2020|title=WHO launches global megatrial of the four most promising coronavirus treatments|journal=Science|doi=10.1126/science.abb8497|doi-access = free | title-link = doi }}</ref><ref>{{#invoke:Cite web||url=https://news.un.org/en/story/2020/03/1059722|title=UN health chief announces global 'solidarity trial' to jumpstart search for COVID-19 treatment|date=18 March 2020|website=UN News|access-date=23 March 2020|archive-url=https://web.archive.org/web/20200323101633/https://news.un.org/en/story/2020/03/1059722|archive-date=23 March 2020|url-status=live}}</ref> More than 300 active clinical trials are underway as of April 2020.<ref name="Sanders202022" />

Research on the antimalarial drugs [[hydroxychloroquine]] and [[chloroquine]] showed that they were ineffective at best,<ref name="20200526nytimes">{{#invoke:Cite web||date=26 May 2020|title=Citing safety concerns, the W.H.O. paused tests of a drug Trump said he had taken|url=https://www.nytimes.com/2020/05/26/world/coronavirus-news.html |archive-url=https://web.archive.org/web/20200526041004/https://www.nytimes.com/2020/05/26/world/coronavirus-news.html |archive-date=26 May 2020 |url-access=subscription |url-status=live|work=The New York Times}}</ref><ref>{{citation-attribution|1={{#invoke:cite press release||title=Hydroxychloroquine does not benefit adults hospitalized with COVID-19|website=National Institutes of Health (NIH)|date=9 November 2020|url=https://www.nih.gov/news-events/news-releases/hydroxychloroquine-does-not-benefit-adults-hospitalized-covid-19|access-date=9 November 2020}} }}</ref> and that they may reduce the antiviral activity of remdesivir.<ref>{{citation-attribution|1={{#invoke:cite press release||title=Coronavirus (COVID-19) Update: FDA Warns of Newly Discovered Potential Drug Interaction That May Reduce Effectiveness of a COVID-19 Treatment Authorized for Emergency Use|website=U.S. [[Food and Drug Administration]] (FDA)|date=15 June 2020|url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-warns-newly-discovered-potential-drug-interaction-may-reduce|access-date=15 June 2020}} }}</ref> {{As of|2020|May|alt=By May 2020}}, France, Italy, and Belgium had banned the use of hydroxychloroquine as a COVID‑19 treatment.<ref>{{#invoke:Cite web||date=27 May 2020|title=France bans use of hydroxychloroquine, drug touted by Trump, in coronavirus patients|url=https://www.cbsnews.com/news/france-bans-use-of-hydroxychloroquine-drug-touted-by-trump-to-treat-coronavirus/|publisher=CBS News}}</ref>

In June, initial results from the randomised [[RECOVERY Trial]] in the United Kingdom showed that dexamethasone reduced mortality by one third for people who are critically ill on ventilators and one fifth for those receiving supplemental oxygen.<ref>{{#invoke:cite news || vauthors = Boseley S |title=Recovery trial for Covid-19 treatments: what we know so far |url= https://www.theguardian.com/world/2020/jun/16/recovery-trial-for-covid-19-treatments-what-we-know-so-far |access-date=21 June 2020 |work=[[The Guardian]] |date=16 June 202}}</ref> Because this is a well-tested and widely available treatment, it was welcomed by the WHO, which is in the process of updating treatment guidelines to include dexamethasone and other steroids.<ref>{{#invoke:cite press release ||title=WHO welcomes preliminary results about dexamethasone use in treating critically ill COVID-19 patients |url=https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients |website=[[World Health Organization]] (WHO) |access-date=21 June 2020 |date=16 June 2020}}</ref><ref>{{#invoke:Cite press release||title=Q&A: Dexamethasone and COVID-19|url=https://www.who.int/news-room/q-a-detail/q-a-dexamethasone-and-covid-19|access-date=12 July 2020|website=[[World Health Organization]] (WHO)}}</ref> Based on those preliminary results, dexamethasone treatment has been recommended by the NIH for patients with COVID‑19 who are mechanically ventilated or who require supplemental oxygen but not in patients with COVID‑19 who do not require supplemental oxygen.<ref>{{#invoke:Cite web||title=Corticosteroids|url=https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/|access-date=12 July 2020|website=COVID-19 Treatment Guidelines|publisher=National Institutes of Health}}</ref>

In September 2020, the WHO released updated guidance on using corticosteroids for COVID‑19.<ref name="WHO guidance">{{#invoke:cite report || vauthors=((World Health Organization)) | year=2020 | title=Corticosteroids for COVID-19: living guidance, 2 September 2020 | author-link=World Health Organization | id=WHO/2019-nCoV/Corticosteroids/2020.1 | hdl=10665/334125 | hdl-access=free }}</ref><ref>{{#invoke:Cite web|| title=WHO updates clinical care guidance with corticosteroid recommendations | publisher=[[World Health Organization]] (WHO) | url=https://www.who.int/news-room/feature-stories/detail/who-updates-clinical-care-guidance-with-corticosteroid-recommendations | access-date=25 January 2022}}</ref> The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID‑19 (strong recommendation, based on moderate certainty evidence).<ref name="WHO guidance" /> The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID‑19 (conditional recommendation, based on low certainty evidence).<ref name="WHO guidance" /> The updated guidance was based on a meta-analysis of clinical trials of critically ill COVID‑19 patients.<ref>{{#invoke:cite journal || vauthors = Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LC, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JP, Horby P, Jüni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Møller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC  | title = Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis | journal = JAMA | volume = 324 | issue = 13 | pages = 1330–1341 | date = October 2020 | pmid = 32876694 | pmc = 7489434 | doi = 10.1001/jama.2020.17023 | collaboration = The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group | s2cid = 221467783 | doi-access = free | title-link = doi }}</ref><ref>{{#invoke:cite journal || vauthors = Prescott HC, Rice TW | title = Corticosteroids in COVID-19 ARDS: Evidence and Hope During the Pandemic | journal = JAMA | volume = 324 | issue = 13 | pages = 1292–1295 | date = October 2020 | pmid = 32876693 | doi = 10.1001/jama.2020.16747 | s2cid = 221468015 | doi-access = free | title-link = doi }}</ref>

In September 2020, the [[European Medicines Agency]] (EMA) endorsed the use of dexamethasone in adults and adolescents from twelve years of age and weighing at least {{convert|40|kg}} who require supplemental oxygen therapy.<ref name="EMA PR">{{#invoke:cite press release || title=EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation | website=[[European Medicines Agency]] (EMA) | date=18 September 2020 | url=https://www.ema.europa.eu/en/news/ema-endorses-use-dexamethasone-covid-19-patients-oxygen-mechanical-ventilation | access-date=21 September 2020}} Text was copied from this source which is European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{#invoke:cite report ||url=https://www.ema.europa.eu/en/documents/other/dexamethasone-covid19-article-53-procedure-assessment-report_en.pdf |title=Dexamethasone in hospitalised patients with COVID-19 |publisher=European Medicines Agency |date=17 September 2020}}</ref> Dexamethasone can be taken [[Oral administration|by mouth]] or given as an injection or [[Intravenous|infusion (drip) into a vein]].<ref name="EMA PR" />

In November 2020, the US [[Food and Drug Administration]] (FDA) issued an emergency use authorisation for the investigational monoclonal antibody therapy [[bamlanivimab]] for the treatment of mild-to-moderate COVID‑19.<ref name="FDA bamlanivimab EUA">{{citation-attribution|1={{#invoke:cite press release || title=Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibody for Treatment of COVID-19 | website=U.S. [[Food and Drug Administration]] (FDA) | date=9 November 2020 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibody-treatment-covid-19 | access-date=9 November 2020}} }}</ref> Bamlanivimab is authorised for people with positive results of direct SARS-CoV-2 viral testing who are twelve years of age and older weighing at least {{convert|40|kg}}, and who are at high risk for progressing to severe COVID‑19 or hospitalisation.<ref name="FDA bamlanivimab EUA" /> This includes those who are 65 years of age or older, or who have chronic medical conditions.<ref name="FDA bamlanivimab EUA" />

In February 2021, the FDA issued an emergency use authorisation (EUA) for bamlanivimab and [[etesevimab]] administered together for the treatment of mild to moderate COVID‑19 in people twelve years of age or older weighing at least {{convert|40|kg|lb}} who test positive for SARS‑CoV‑2 and who are at high risk for progressing to severe COVID‑19. The authorised use includes treatment for those who are 65 years of age or older or who have certain chronic medical conditions.<ref name="FDA PR 20210209">{{citation-attribution|1={{#invoke:cite press release||title=FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19|website=U.S. [[Food and Drug Administration]] (FDA)|date=10 February 2021|url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19-0|access-date=9 February 2021}} }}</ref>

In April 2021, the FDA revoked the emergency use authorisation (EUA) that allowed for the investigational monoclonal antibody therapy bamlanivimab, when administered alone, to be used for the treatment of mild-to-moderate COVID‑19 in adults and certain paediatric patients.<ref name="FDA PR 20210416">{{citation-attribution|1={{#invoke:cite press release || title=Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab | website=U.S. [[Food and Drug Administration]] (FDA) | date=16 April 2021 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-monoclonal-antibody-bamlanivimab | access-date=16 April 2021}} }}</ref>

==== 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>

==== Passive antibodies ====
[[File:Ppat.1008735.g002.png|thumb|Overview of the application and use of [[convalescent plasma]] therapy]]

Transferring purified and concentrated [[Immunoglobulin therapy|antibodies]] produced by the immune systems of those who have recovered from COVID‑19 to people who need them is being investigated as a non-vaccine method of [[Passive immunity|passive immunisation]].<ref name="pmid-32167489">{{#invoke:cite journal || vauthors = Casadevall A, Pirofski LA | title = The convalescent sera option for containing COVID-19 | journal = The Journal of Clinical Investigation | volume = 130 | issue = 4 | pages = 1545–1548 | date = April 2020 | pmid = 32167489 | pmc = 7108922 | doi = 10.1172/JCI138003 }}</ref><ref name=":0">{{#invoke:Cite journal ||last1=Iannizzi |first1=Claire |last2=Chai |first2=Khai Li |last3=Piechotta |first3=Vanessa |last4=Valk |first4=Sarah J. |last5=Kimber |first5=Catherine |last6=Monsef |first6=Ina |last7=Wood |first7=Erica M. |last8=Lamikanra |first8=Abigail A. |last9=Roberts |first9=David J. |last10=McQuilten |first10=Zoe |last11=So-Osman |first11=Cynthia |last12=Jindal |first12=Aikaj |last13=Cryns |first13=Nora |last14=Estcourt |first14=Lise J. |last15=Kreuzberger |first15=Nina |date=2023-05-10 |title=Convalescent plasma for people with COVID-19: a living systematic review |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=5 |pages=CD013600 |doi=10.1002/14651858.CD013600.pub6 |issn=1469-493X |pmc=10171886 |pmid=37162745 |pmc-embargo-date=May 10, 2024 }}</ref> [[Neutralisation (immunology)|Viral neutralisation]] is the anticipated [[mechanism of action]] by which passive antibody therapy can mediate defence against SARS-CoV-2. The spike protein of SARS-CoV-2 is the primary target for neutralising antibodies.<ref name="Ho-2020">{{#invoke:cite journal || vauthors = Ho M | title = Perspectives on the development of neutralizing antibodies against SARS-CoV-2 | journal = Antibody Therapeutics | volume = 3 | issue = 2 | pages = 109–114 | date = April 2020 | pmid = 32566896 | pmc = 7291920 | doi = 10.1093/abt/tbaa009 | title-link = doi | doi-access = free }}</ref> As of 8{{spaces}}August 2020, eight neutralising antibodies targeting the spike protein of SARS-CoV-2 have entered clinical studies.<ref>{{#invoke:cite journal || vauthors = Yang L, Liu W, Yu X, Wu M, Reichert JM, Ho M | title = COVID-19 antibody therapeutics tracker: a global online database of antibody therapeutics for the prevention and treatment of COVID-19 | journal = Antibody Therapeutics | volume = 3 | issue = 3 | pages = 205–212 | date = July 2020 | pmid = 33215063 | pmc = 7454247 | doi = 10.1093/abt/tbaa020 }}</ref> It has been proposed that selection of broad-neutralising antibodies against SARS-CoV-2 and SARS-CoV might be useful for treating not only COVID‑19 but also future SARS-related CoV infections.<ref name="Ho-2020" /> Other mechanisms, however, such as [[antibody-dependent cellular cytotoxicity|antibody-dependant cellular cytotoxicity]] or [[phagocytosis]], may be possible.<ref name="pmid-32167489" /> Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development.<ref name="pmid-32167489" />

The use of passive antibodies to treat people with active COVID{{nbhyph}}19 is also being studied. This involves the production of [[convalescent serum]], which consists of the liquid portion of the blood from people who recovered from the infection and contains antibodies specific to this virus, which is then administered to active patients.<ref name="pmid-32167489" /> This strategy was tried for SARS with inconclusive results.<ref name="pmid-32167489" /> An updated Cochrane review in May 2023 found high certainty evidence that, for the treatment of people with moderate to severe COVID‑19, convalescent plasma did not reduce mortality or bring about symptom improvement.<ref name=":0" /> There continues to be uncertainty about the safety of convalescent plasma administration to people with COVID‑19 and differing outcomes measured in different studies limits their use in determining efficacy.<ref name=":0" />

=== Bioethics ===
Since the outbreak of the COVID‑19 pandemic, scholars have explored the [[bioethics]], [[normative economics]], and [[political theories]] of [[healthcare policy|healthcare policies]] related to the public health crisis.<ref>{{#invoke:cite journal || vauthors = Maccaro A, Piaggio D, Pagliara S, Pecchia L | title = The role of ethics in science: a systematic literature review from the first wave of COVID-19 | journal = Health and Technology | volume = 11 | issue = 5 | pages = 1063–1071 | date = June 2021 | pmid = 34104626 | pmc = 8175060 | doi = 10.1007/s12553-021-00570-6|issn=2190-7188 }}</ref> Academics have pointed to the moral distress of healthcare workers, ethics of distributing scarce healthcare resources such as ventilators,<ref>{{#invoke:cite journal || vauthors = McGuire AL, Aulisio MP, Davis FD, Erwin C, Harter TD, Jagsi R, Klitzman R, Macauley R, Racine E, Wolf SM, Wynia M, Wolpe PR  | title = Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force | journal = The American Journal of Bioethics | volume = 20 | issue = 7 | pages = 15–27 | date = July 2020 | pmid = 32511078 | doi = 10.1080/15265161.2020.1764138 | s2cid = 219552665 }}</ref> and the global justice of vaccine diplomacies.{{citation needed|date=November 2021}} The socio-economic inequalities between genders,<ref>{{#invoke:cite journal || vauthors = Wenham C, Smith J, Morgan R | title = COVID-19: the gendered impacts of the outbreak | journal = Lancet | volume = 395 | issue = 10227 | pages = 846–848 | date = March 2020 | pmid = 32151325 | pmc = 7124625 | doi = 10.1016/S0140-6736(20)30526-2 }}</ref> races,<ref>{{#invoke:cite journal || vauthors = Tolchin B, Hull SC, Kraschel K | title = Triage and justice in an unjust pandemic: ethical allocation of scarce medical resources in the setting of racial and socioeconomic disparities | journal = Journal of Medical Ethics | volume = 47 | issue = 3 | pages = 200–202 | date = October 2020 | pmid = 33067315 | doi = 10.1136/medethics-2020-106457 | s2cid = 223558059 }}</ref> groups with disabilities,<ref>{{#invoke:cite journal || vauthors = Sabatello M, Burke TB, McDonald KE, Appelbaum PS | title = Disability, Ethics, and Health Care in the COVID-19 Pandemic | journal = American Journal of Public Health | volume = 110 | issue = 10 | pages = 1523–1527 | date = October 2020 | pmid = 32816541 | pmc = 7483109 | doi = 10.2105/AJPH.2020.305837 }}</ref> communities,<ref>{{#invoke:cite journal || vauthors = Chin T, Kahn R, Li R, Chen JT, Krieger N, Buckee CO, Balsari S, Kiang MV  | title = US-county level variation in intersecting individual, household and community characteristics relevant to COVID-19 and planning an equitable response: a cross-sectional analysis | journal = BMJ Open | volume = 10 | issue = 9 | pages = e039886 | date = September 2020 | pmid = 32873684 | pmc = 7467554 | doi = 10.1136/bmjopen-2020-039886 }}</ref> regions, countries,<ref>{{#invoke:cite journal || vauthors = Elgar FJ, Stefaniak A, Wohl MJ | title = The trouble with trust: Time-series analysis of social capital, income inequality, and COVID-19 deaths in 84 countries | journal = Social Science & Medicine | volume = 263 | pages = 113365 | date = October 2020 | pmid = 32981770 | pmc = 7492158 | doi = 10.1016/j.socscimed.2020.113365 }}</ref> and continents have also drawn attention in academia and the general public.