Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study

Carvalho et al., medRxiv, doi:10.1101/2020.07.13.20149328, Jul 2020
Mortality -166% improvement lower risk ← → higher risk Tocilizumab  Carvalho et al.  LATE TREATMENT Is late treatment with tocilizumab beneficial for COVID-19? Retrospective 53 patients in Brazil (March - May 2020) Higher mortality with tocilizumab (not stat. sig., p=0.3) c19early.org Carvalho et al., medRxiv, July 2020 0 0.5 1 1.5 2+ RR
Retrospective 53 critically ill COVID-19 patients showing no difference in mortality, need for renal replacement therapy, use of antibiotics, or positive cultures with tocilizumab treatment.
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risk of death, 165.6% higher, RR 2.66, p = 0.30, treatment 5 of 29 (17.2%), control 4 of 24 (16.7%), odds ratio converted to relative risk.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Carvalho et al., 15 Jul 2020, retrospective, Brazil, preprint, 6 authors, study period 21 March, 2020 - 31 May, 2020. Contact: torcortes@yahoo.com.br.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 Brazil United Kingdom Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Brazil favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 Brazil United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria Brazil favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study
MD, MSc Victor C P Carvalho, MD Ricardo Turon, MD, MSc Bruno Gonçalves, MD Victor Fraga Ceotto, MD Pedro Kurtz, MD Cássia Righy
doi:10.1101/2020.07.13.20149328
Objectives: Critically ill patients with COVID-19 may suffer from a cytokine release syndrome (CRS) characterized by remarkably high levels of interleukin 6 (IL-6). We assessed the effects of tocilizumab, an IL-6 receptor antagonist, on intra-hospital mortality and development of positive cultures in patients with COVID-19 admitted to the ICU. Design: Patients with COVID 19 admitted in the ICU who were treated with tocilizumab plus standard care were enrolled and compared to controls. Setting COVID-19 severe disease Patients Patients with severe COVID-19 disease admitted in the ICU. Interventions Tocilizumab 400 mg IV two doses. Standard and intensive medical care as per institutional clinical protocol. Measures and Main Results Main outcome: 1) intra-hospital mortality; Secondary Outcomes: 1) the need for renal replacement therapy, 2) use of antibiotics and positive culture, and 3) inflammatory and oxygenation markers. There was no difference in mortality, need for renal replacement therapy, use of antibiotics or positive cultures between the two groups. The use of corticosteroids was more frequent in the treatment group. Levels of C-reactive protein (CRP) and WBC (white blood cells) counts declined significantly faster in the treatment group. Oxygenation markers rose significantly higher in patients in the tocilizumab group as compared to controls. .
Conclusions The improvement in oxygenation and inflammatory markers with no increase secondary infections or intra-hospital mortality suggests that tocilizumab could be an option for patients with progressive COVID-19 after initiation of systemic corticosteroids.
References
Guaraldi, Meschiari, Cozzi-Lepri, Tocilizumab in patients with severe COVID-19: a retrospective cohort study, Lancet Rheumatol
Horby, Lim, Emberson, Mafham, Bell et al., Effect of Dexamethasone in Hospitalized Patients with COVID-19
Kewan, Covut, Mj, Rose, Gopalakrishna et al., Tocilizumab for treatment of patients with severe COVID-19: A retrospective cohort study
Klopfenstein, Zayet, Lohse, Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients, Med Mal Infect
Liu, Li, Zhou, Guan, Xiang, Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?, J Autoimmun
Sun, Wang, Cai, Cytokine storm intervention in the early stages of COVID-19 pneumonia, Cytokine Growth Factor Rev
Toniati, Piva, Cattalini, Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy, Autoimmun Rev
Wang, Liu, Wu, The Definition and Risks of Cytokine Release Syndrome in 11 COVID-19-Affected Critically Ill Patients with Pneumonia: Analysis of Disease Characteristics, J Infect Dis
Who, Coronavirus disease (COVID-19): Situation Report -168
Xu, Han, Li, Effective treatment of severe COVID-19 patients with tocilizumab, Proc Natl Acad Sci U S A
DOI record: { "DOI": "10.1101/2020.07.13.20149328", "URL": "http://dx.doi.org/10.1101/2020.07.13.20149328", "abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>Critically ill patients with COVID-19 may suffer from a cytokine release syndrome (CRS) characterized by remarkably high levels of interleukin 6 (IL-6). We assessed the effects of tocilizumab, an IL-6 receptor antagonist, on intra-hospital mortality and development of positive cultures in patients with COVID-19 admitted to the ICU.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Patients with COVID 19 admitted in the ICU who were treated with tocilizumab plus standard care were enrolled and compared to controls.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>COVID-19 severe disease</jats:p></jats:sec><jats:sec><jats:title>Patients</jats:title><jats:p>Patients with severe COVID-19 disease admitted in the ICU.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>Tocilizumab 400 mg IV two doses. Standard and intensive medical care as per institutional clinical protocol.</jats:p></jats:sec><jats:sec><jats:title>Measures and Main Results</jats:title><jats:p>Main outcome: 1) intra-hospital mortality; Secondary Outcomes: 1) the need for renal replacement therapy, 2) use of antibiotics and positive culture, and 3) inflammatory and oxygenation markers. There was no difference in mortality, need for renal replacement therapy, use of antibiotics or positive cultures between the two groups. The use of corticosteroids was more frequent in the treatment group. Levels of C-reactive protein (CRP) and WBC (white blood cells) counts declined significantly faster in the treatment group. Oxygenation markers rose significantly higher in patients in the tocilizumab group as compared to controls.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Tocilizumab was associated with rapid improvement in oxygenation and a faster decrease of CRP and WBC counts in patients with COVID-19 and should be evaluated as rescue therapy for patients with progressive disease</jats:p></jats:sec>", "accepted": { "date-parts": [ [ 2020, 7, 15 ] ] }, "author": [ { "affiliation": [], "family": "Carvalho", "given": "Victor", "sequence": "first" }, { "affiliation": [], "family": "Turon", "given": "Ricardo", "sequence": "additional" }, { "affiliation": [], "family": "Gonçalves", "given": "Bruno", "sequence": "additional" }, { "affiliation": [], "family": "Ceotto", "given": "Victor Fraga", "sequence": "additional" }, { "affiliation": [], "family": "Kurtz", "given": "Pedro", "sequence": "additional" }, { "affiliation": [], "family": "Righy", "given": "Cássia", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 7, 15 ] ], "date-time": "2020-07-15T17:45:38Z", "timestamp": 1594835138000 }, "deposited": { "date-parts": [ [ 2021, 1, 12 ] ], "date-time": "2021-01-12T23:45:26Z", "timestamp": 1610495126000 }, "group-title": "Intensive Care and Critical Care Medicine", "indexed": { "date-parts": [ [ 2024, 7, 18 ] ], "date-time": "2024-07-18T00:51:23Z", "timestamp": 1721263883676 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 10, "issued": { "date-parts": [ [ 2020, 7, 15 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2020.07.13.20149328", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2020, 7, 15 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2020, 7, 15 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "key": "2021011105050527000_2020.07.13.20149328v1.1", "unstructured": "WHO. 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Late treatment
is less effective
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