|Year : 2021 | Volume
| Issue : 2 | Page : 49-50
What's New in Critical Illness and Injury Science? Mortality effects of tocilizumab for patients admitted with COVID-19 pneumonia
Andrew C Miller1, Yannick A D'Silva2, Eric A Gruber1
1 Department of Emergency Medicine, Nazareth Hospital, Philadelphia, PA, USA
2 Department of Internal Medicine, Nazareth Hospital, Philadelphia, PA, USA
|Date of Submission||17-Jun-2021|
|Date of Acceptance||17-Jun-2021|
|Date of Web Publication||29-Jun-2021|
Dr. Andrew C Miller
Department of Emergency Medicine, Nazareth Hospital, 2601 Holme Avenue, 3,rd Floor, Marian Building, Philadelphia, PA 19152
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Miller AC, D'Silva YA, Gruber EA. What's New in Critical Illness and Injury Science? Mortality effects of tocilizumab for patients admitted with COVID-19 pneumonia. Int J Crit Illn Inj Sci 2021;11:49-50
|How to cite this URL:|
Miller AC, D'Silva YA, Gruber EA. What's New in Critical Illness and Injury Science? Mortality effects of tocilizumab for patients admitted with COVID-19 pneumonia. Int J Crit Illn Inj Sci [serial online] 2021 [cited 2021 Aug 3];11:49-50. Available from: https://www.ijciis.org/text.asp?2021/11/2/49/319781
Since emerging in December 2019, the coronavirus disease-2019 (COVID-19) pandemic caused by the beta-coronavirus severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) virus has resulted in over 177 million cases worldwide and over 3.82 million deaths (as of 16 June, 2021). Roughly 20% of patients require hospitalization, with an associated mortality of 11% among admitted patients in the United States.
Consensus is lacking on how to characterize the severity and nature of the inflammatory response induced by SARS-CoV-2 infection. Several early case studies in COVID-19 reported markedly elevated levels of interleukin (IL)-1 β, IL-6, IL-10, tumor necrosis factor-α, and other mediators, leading many to characterize it as a cytokine storm. However, not every perturbation is maladaptive, distinguishing between appropriate and dysregulated inflammatory responses remains challenging. Most cytokines induce pleiotropic downstream effects with interdependent biological activities, and interactions among these mediators are neither linear nor uniform. The term cytokine storm implies that the elevated cytokine levels are necessarily injurious to host cells, and widespread acceptance of this term fueled the repurposing of many immunotherapy drugs to suppress inflammatory pathways. In recent issues, we have discussed the use of intravenous immunoglobulin and convalescent plasma., The hypoinflammatory subphenotype manifests a disease similar to immunoparalysis in sepsis. In contrast, the hyperinflammatory subphenotype involves elevated levels of IL-6, IL-10, IL-8, and chemokines (e.g., C-X-C motif ligand [CXCL]-8, CXCL1, CXCL10, and C-C motif chemokine ligand-5). Despite these overall patterns, IL-6 levels are orders of magnitude lower in patients with severe or critical COVID-19 disease (median: 26–210 pg/mL) than in patients with non-COVID-19 acute respiratory distress syndrome (median: 578–1618 pg/mL). Elevated IL-6 levels are needed to activate and potentiate the adaptive immune response and promote T-cell regulation. By contrast, excessive IL-6 levels can block lymphopoiesis and induce lymphocyte death. All distinct lymphocyte subsets (NK cells, B cells, and T cells) may be affected by this innate overactivation. The degree of IL-6 elevation has been correlated with adverse outcomes in COVID-19 patients and has led to trials of anti-IL-6 therapy for COVID-19 patients. This editorial focuses on the impact of anti-IL-6 therapy with tocilizumab on mortality in patients admitted with COVID-19 pneumonia.
A listing of randomized controlled trials in adult (age >18 years) patients admitted with COVID-19 pneumonia is presented in [Table 1].,, Two prospective studies were excluded for being single-arm without a control arm., Risk of bias was assessed for each study using the Cochrane Risk of Bias tool, and evidence was graded according to the GRADE rating system.
|Table 1: The characteristics of the included studies assessing anti-interleukin-6 therapy (i.e., tocilizumab) for management of admitted coronavirus disease-2019 patients|
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The results of included studies are summarized in [Table 2]. When compared to usual care (UC) ± placebo, tocilizumab treatment for hospitalized COVID-19 patients showed no statistically significant benefit on 28-day mortality (3 studies, 1070 patients, tocilizumab 93/704 (13.2%) vs. UC 42/353 (11.9%); odds ratio: 1.12 [95% confidence interval: 0.75, 1.67]; evidence certainty by GRADE criteria HIGH). It should be noted that one included study is a preprint.
|Table 2: Impact of anti-interleukin-6 therapy (i.e., Tocilizumab) on mortality in patients hospitalized with coronavirus disease-2019 pneumonia|
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In conclusion, available evidence suggests that tocilizumab treatment for hospitalized COVID-19 pneumonia patients does not improve 28-day mortality. Routine use of tocilizumab to treat hospitalized COVID-19 patients without other indications for its use is not advised. Data as it pertains to patients with critical illness or requiring mechanical ventilation in lacking, and further investigation in this subpopulation is warranted.
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[Table 1], [Table 2]