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Table of Contents
EDITORIAL
Year : 2021  |  Volume : 11  |  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


1 Department of Emergency Medicine, Nazareth Hospital, Philadelphia, PA, USA
2 Department of Internal Medicine, Nazareth Hospital, Philadelphia, PA, USA

Date of Submission17-Jun-2021
Date of Acceptance17-Jun-2021
Date of Web Publication29-Jun-2021

Correspondence Address:
Dr. Andrew C Miller
Department of Emergency Medicine, Nazareth Hospital, 2601 Holme Avenue, 3,rd Floor, Marian Building, Philadelphia, PA 19152
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijciis.ijciis_52_21

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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.[1]

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.[2] 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.[3],[4] 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).[2] 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.[2] All distinct lymphocyte subsets (NK cells, B cells, and T cells) may be affected by this innate overactivation.[2] 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].[5],[6],[7] Two prospective studies were excluded for being single-arm without a control arm.[8],[9] 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.[5]
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.



 
   References Top

1.
Finelli L, Gupta V, Petigara T, Yu K, Bauer KA, Puzniak LA. Mortality among US patients hospitalized with SARS-CoV-2 infection in 2020. JAMA Netw Open 2021;4:e216556.  Back to cited text no. 1
    
2.
Verhoef PA, Kannan S, Sturgill JL, Tucker EW, Morris PE, Miller AC, et al. Severe acute respiratory syndrome-associated coronavirus 2 infection and organ dysfunction in the ICU: Opportunities for translational research. Crit Care Explor 2021;3:e0374.  Back to cited text no. 2
    
3.
Miller AC, Ghadermarzi S, Venkatachalam S. What's new in critical illness and injury science? Convalescent plasma for COVID-19 patients with severe or critical illness. Int J Crit Illn Inj Sci 2021;11:1-3.  Back to cited text no. 3
  [Full text]  
4.
Miller AC, Venkatachalam S. What's new in critical illness and injury science? Intravenous immunoglobulin for COVID-19 with severe or critical illness. Int J Crit Illn Inj Sci 2020;10:159-62.  Back to cited text no. 4
  [Full text]  
5.
Rosas IO, Bräu N, Waters M, Go R, Hunter BD, Bhagani S, et al. Tocilizumab in Hospitalized Patients with COVID-19 Pneumonia. medRxiv 2020. Available from: https://www.medrxiv.org/content/10.1101/2020.08.27.20183442 v2. [Last accessed on 2020 Jun 16].  Back to cited text no. 5
    
6.
Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in Patients Hospitalized with Covid-19 pneumonia. N Engl J Med 2021;384:20-30.  Back to cited text no. 6
    
7.
Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020;383:2333-44.  Back to cited text no. 7
    
8.
Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, et al. 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 2020;19:102568.  Back to cited text no. 8
    
9.
Perrone F, Piccirillo MC, Ascierto PA, Salvarani C, Parrella RMarata AM. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. J Transl Med 2020;18:405.  Back to cited text no. 9
    



 
 
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