Off‐label use of tocilizumab in patients with SARS‐CoV‐2 infection

Giambenedetto, Simona Di; Ciccullo, Arturo; Borghetti, Alberto; Gambassi, Giovanni; Landi, Francesco; Visconti, Elena; Verme, Lorenzo Zileri Dal; Bernabei, Roberto; Tamburrini, Enrica; Cauda, Roberto; Gasbarrini, Antonio

doi:10.1002/jmv.25897

Cited by 109 publications

(112 citation statements)

References 6 publications

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“… 22 Our results may suggest that “critically ill” COVID-19 patients should be sub-divided into two sub-cohorts as patients who developed a requirement for advanced oxygen support later in their hospital course (progressive) had a distinct inflammatory biomarker profile than patients who required immediate intubation on hospital admission (severe). Multiple randomized control trials are examining tocilizumab in COVID-19 infection, 23 , 24 , 25 , 26 , 27 and preliminary results from recent phase III studies have been mixed. The COVACTA trial evaluating tocilizumab (F. Hoffmann-La Roche, press release: https://www.roche.com/investors/updates/inv-update-2020-07-29.htm ) and another trial centered on sarilumab (Sanofi-Aventis U.S., press release: https://www.sanofi.com/en/media-room/press-releases/2020/2020-07-02-22-30-00 ) did not meet primary endpoints.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients

Mueller

Tamura

Crowley

et al. 2020

Cell Reports Medicine

110

104

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In this single-center, retrospective cohort analysis of hospitalized coronavirus disease 2019 (COVID-19) patients, we investigate whether inflammatory biomarker levels predict respiratory decline in patients who initially present with stable disease. Examination of C-reactive protein (CRP) trends reveals that a rapid rise in CRP levels precedes respiratory deterioration and intubation, although CRP levels plateau in patients who remain stable. Increasing CRP during the first 48 h of hospitalization is a better predictor (with higher sensitivity) of respiratory decline than initial CRP levels or ROX indices (a physiological score of respiratory function). CRP, the proinflammatory cytokine interleukin-6 (IL-6), and physiological measures of hypoxemic respiratory failure are correlated, which suggests a mechanistic link. Our work shows that rising CRP predicts subsequent respiratory deterioration in COVID-19 and may suggest mechanistic insight and a potential role for targeted immunomodulation in a subset of patients early during hospitalization.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients

Mueller

Tamura

Crowley

et al. 2020

Cell Reports Medicine

110

104

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“…56 Understanding the mechanisms underlying different prognosis in children is essential for designing targeted therapies for COVID-19. targeting the CRS and hyperinflammatory status of lung destruction via anti-IL-6R antibodies, [218][219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234][235][236][237] IL-1R antagonists, [238][239][240] JAK-STAT inhibitors, 241 or inhibition of entrance by anti CD147 antibodies 237 and destruction of the virus via protective antibody delivered with convalescent plasma 51,54,66,133,134,242 (Table 2). Eculizumab targets complement protein C5 preventing activation of complement terminal complex, which was used off label in patients with SARS-CoV-2 infection and severe pneumonia or ARDS and is now evaluated in an ongoing trail (SOLID-C19).…”

Section: Kids Versus Adults: Mechanisms Explaining the Clinical Difmentioning

confidence: 99%

Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

Sokołowska

Łukasik

Agache

et al. 2020

Allergy

156

167

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With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.

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“…Di Giambenedetto et al. highlighted the efficacy of tocilizumab in the treatment of COVID-19 without detected adverse events and suggested that tocilizumab may be an effective and safe treatment of COVID-19 patients with severe pneumonia [ 82 ].…”

Section: Diagnosis Treatment and Preventionmentioning

confidence: 99%

SARS-CoV-2, the other face to SARS-CoV and MERS-CoV: Future predictions

Abdelghany¹,

Ganash²,

Bakri³

et al. 2021

Biomedical Journal

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COVID-19 outbreak is proving to be an unprecedented disaster that lays its dark shadow on global health, economics and personal freedom. SARS and MERS epidemics provide scientific data that is useful in better understanding and resolution of COVID 19. Similarities among SARS-CoV, MERS-CoV and SARS-CoV-2 have been investigated in the light of available data. SARS-CoV, MERS-CoV and SARS-CoV-2 evolved in bats and have positive-sense RNA genomes of 27.9 kb, 30.1 kb and 29.9 kb, respectively. Molecular and serological tools used for diagnosis of SARS and MERS patients resemble COVID-19 diagnostic tools. Stability and longevity data of SARS and MERS epidemics contribute in the current pandemic precaution policies. Trials to produce vaccines for SARS-CoV and MERS-CoV failed, therefore the current review predict that trials for SARS-CoV-2 vaccine production if achieved, will be require more time not only for vaccine production but also to be available for patients, during this time antiviral agents, Convalescent plasma and monoclonal antibodies provide potential tratments for sever patients. The mortality rate caused by the SARS-CoV and MERS-CoV reached 15% and 37%, respectively. The first declarations about mortality rate of SARS-CoV-2 was around 2–4% but now this rate differs globally and reached more than 13% in some countries. A realistic COVID-19 outbreak scenario suggest that the pandemic might last for three years with fluctuation in the number of infected cases, unless a vaccine or antiviral drug is to be discovered.

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Off‐label use of tocilizumab in patients with SARS‐CoV‐2 infection

Cited by 109 publications

References 6 publications

Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients

Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients

Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

SARS-CoV-2, the other face to SARS-CoV and MERS-CoV: Future predictions

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