Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality

Zhang, Chi; Zhao, Weihong; Li, Jiawen; Zhao, Hong; Wang, Gui Qiang

doi:10.1016/j.ijantimicag.2020.105954

Cited by 1,687 publications

(1,827 citation statements)

References 51 publications

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“…Although COVID-19 pathogenesis is still unclear, some patients with a severe disease have laboratory evidence of a systemic inflammation similar to cytokine release syndrome (CRS) [11,12]. CRS is characterized by a sharp increase of a large number of proinflammatory cytokines, among which IL-6 plays a pivotal role [11][12][13]. Therefore, blocking the IL-6 pathway might reduce the vigorous inflammatory response in COVID-19 [11].…”

Section: Introductionmentioning

confidence: 99%

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Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE)

et al. 2020

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Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective analysis of patients treated with TCZ matched using propensity score to patients treated with Standard Of Care (SOC) was conducted. Setting: The study was conducted at IRCCS Policlinico San Matteo Hospital, Pavia, Italy, from March 14, 2020 to March 27, 2020. Participants: Patients with a confirmed diagnosis of COVID-19 hospitalized in our institution at the time of TCZ availability. Interventions: TCZ was administered to 21 patients. The first administration was 8 mg/kg (up to a maximum 800 mg per dose) of Tocilizumab intravenously, repeated after 12 h if no side effects were reported after the first dose. Main Outcomes and Measures: ICU admission and 7-day mortality rate. Secondary outcomes included clinical and laboratory data. Results: There were 112 patients evaluated (82 were male and 30 were female, with a median age of 63.55 years). Using propensity scores, the 21 patients who received TCZ were matched to 21 patients who received SOC (a combination of hydroxychloroquine, azithromycin and prophylactic dose of low weight heparin). No adverse event was detected following TCZ administration. This study found that treatment with TCZ did not significantly affect ICU admission (OR 0.11; 95% CI between 0.00 and 3.38; p = 0.22) or 7-day mortality rate (OR 0.78; 95% CI between 0.06 and 9.34; p = 0.84) when compared with SOC. Analysis of laboratory measures showed significant interactions between time and treatment regarding C-Reactive Protein (CRP), alanine aminotransferase (ALT), platelets and international normalized ratio (INR) levels. Variation in lymphocytes count was observed over time, irrespective of treatment. Conclusions: TCZ administration did not reduce ICU admission or

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Section: Introductionmentioning

confidence: 99%

“…CRS is characterized by a sharp increase of a large number of proinflammatory cytokines, among which IL-6 plays a pivotal role [11][12][13]. Therefore, blocking the IL-6 pathway might reduce the vigorous inflammatory response in COVID-19 [11].…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE)

et al. 2020

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“…In some case series, anti-IL6 therapy was successful in stabilizing the alveolar capillary membrane, reducing alveolar wall edema, and preventing/reversing ARDS [41][42][43][44], shortening the intensive care unit stay [45,46]. The currently available reagents that can neutralize IL-6 activity are the humanized monoclonal antibody (mAb) Tocilizumab, and the fully human mAb Sarilumab.…”

Section: Immunological Rationale For Targeting the Immune System To Fmentioning

confidence: 99%

SARS-CoV-2 Inflammatory Syndrome. Clinical Features and Rationale for Immunological Treatment

Prete

Favoino

Catacchio

et al. 2020

IJMS

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The current pandemic coronavirus, SARS-CoV-2, is a global health emergency because of its highly contagious nature, the great number of patients requiring intensive care therapy, and the high fatality rate. In the absence of specific antiviral drugs, passive prophylaxis, or a vaccine, the treatment aim in these patients is to prevent the potent virus-induced inflammatory stimuli from leading to the acute respiratory distress syndrome (ARDS), which has a severe prognosis. Here, the mechanism of action and the rationale for employing immunological strategies, which range from traditional chemically synthesized drugs, anti-cytokine antibodies, human immunoglobulin for intravenous use, to vaccines, are reviewed.

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“…Indeed, understanding the biological mechanisms that are the basis of the higher susceptibility to death in elderly people may be important to plan preventive and therapeutic strategies in the current pandemic, as well as for the future emergence of similar pandemic viruses for which vaccines are unavailable. Blocker of IL-6R, IL-6 is among the most common SASP factor [28,29] Hydroxychloroquine and azithromycin Clinical Trial (NCT04322396) and other pilot studies…”

Section: Introductionmentioning

confidence: 99%

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

Malavolta

Giacconi

Brunetti

et al. 2020

Cells

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The higher death rate caused by COVID-19 in older people, especially those with comorbidities, is a challenge for biomedical aging research. Here we explore the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, may drive the deleterious consequences of the infection. Data shows that other RNA viruses, such as influenza virus, can display enhanced replication efficiency in senescent cells, suggesting that the accumulation of senescent cells with aging and age-related diseases may play a role in this phenomenon. However, at present, we are completely unaware of the response to SARS-CoV and SARS-COV-2 occurring in senescent cells. We deem that this is a priority area of research because it could lead to the development of several therapeutic strategies based on senotherapeutics or prevent unsuccessful attempts. Two of these senotherapeutics, azithromycin and ruxolitinib, are currently undergoing testing for their efficacy in treating COVID-19. The potential of these strategies is not only for ameliorating the consequences of the current emergence of SARS-CoV-2, but also for the future emergence of new viruses or mutated ones for which we are completely unprepared and for which no vaccines are available.

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Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality

Cited by 1,687 publications

References 51 publications

Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE)

Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE)

SARS-CoV-2 Inflammatory Syndrome. Clinical Features and Rationale for Immunological Treatment

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

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