Sarilumab use in severe SARS-CoV-2 pneumonia

Gremese, Elisa; Cingolani, Antonella; Bosello, Silvia Laura; Alivernini, Stefano; Tolusso, Barbara; Perniola, Simone; Landi, Francesco; Pompili, Maurizio; Murri, Rita; Santoliquido, Angelo; Garcovich, Matteo; Sali, Michela; Pascale, Gennaro De; Gabrielli, Maurizio; Biscetti, Federico; Montalto, Massimo; Tosoni, Alberto; Gambassi, Giovanni; Rapaccini, Gian Ludovico; Iaconelli, Amerigo; Verme, Lorenzo Zileri Del; Petricca, Luca; Fedele, Anna Laura; Lizzio, Marco Maria; Tamburrini, Enrica; Natalello, Gerlando; Gigante, Laura; Bruno, Dario; Verardi, Lucrezia; Taddei, Eleonora; Calabrese, Angelo; Lombardi, Fabrizio; Bernabei, Roberto; Cauda, Roberto; Franceschi, Francesco; Landolfi, Raffaele; Richeldi, Luca; Sanguinetti, Maurizio; Fantoni, Massimo; Antonelli, Massimo; Gasbarrini, Antonio

doi:10.1016/j.eclinm.2020.100553

Cited by 66 publications

(52 citation statements)

References 24 publications

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“…In an early clinical study, siltuximab therapy at the onset of mechanical ventilation was associated with reduced occurrence of respiratory failure and death in severe COVID-19 cases (Gritti et al, 2020). Sarilumab is another IL-6R inhibitor that appears to be a potential therapy against severe COVID-19 (Gremese et al, 2020).…”

Section: Il-6 Inhibitorsmentioning

confidence: 99%

Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies

et al. 2021

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Severe acute respiratory disease coronavirus 2 (SARS-CoV-2, formerly 2019-nCoV) is a novel coronavirus that has rapidly disseminated worldwide, causing the coronavirus disease 2019 (COVID-19) pandemic. As of January 6th, 2021, there were over 86 million global confirmed cases, and the disease has claimed over 1.87 million lives (a ∼2.2% case fatality rate). SARS-CoV-2 is able to infect human cells by binding its spike (S) protein to angiotensin-conversing enzyme 2 (ACE2), which is expressed abundantly in several cell types and tissues. ACE2 has extensive biological activities as a component of the renin-angiotensin-aldosterone system (RAAS) and plays a pivotal role as counter-regulator of angiotensin II (Ang II) activity by converting the latter to Ang (1-7). Virion binding to ACE2 for host cell entry leads to internalization of both via endocytosis, as well as activation of ADAM17/TACE, resulting in downregulation of ACE2 and loss of its protective actions in the lungs and other organs. Although COVID-19 was initially described as a purely respiratory disease, it is now known that infected individuals can rapidly progress to a multiple organ dysfunction syndrome. In fact, all human structures that express ACE2 are susceptible to SARS-CoV-2 infection and/or to the downstream effects of reduced ACE2 levels, namely systemic inflammation and injury. In this review, we aim to summarize the major features of SARS-CoV-2 biology and the current understanding of COVID-19 pathogenesis, as well as its clinical repercussions in the lung, heart, kidney, bowel, liver, and brain. We also highlight potential therapeutic targets and current global efforts to identify safe and effective therapies against this life-threatening condition.

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Section: Il-6 Inhibitorsmentioning

confidence: 99%

Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies

et al. 2021

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“…It was observed that Tocilizumab was associated with a low death rate [ 162 ]. A study in severe COVID-19 pneumonia patients showed that treatment with Sarilumab exhibited promising results [ 163 ].…”

Section: Available Repurposed Drugs Against Covid-19mentioning

confidence: 99%

COVID-19, cytokines, inflammation, and spices: How are they related?

et al. 2021

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Background Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/ ) in the USA is high (1199/million) as compared to countries like India is low (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. Aim To evaluate the literature available on the anti-inflammatory properties of some spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. Method A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19 and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. Key findings The literature search resulted in numerous in vitro , in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. Significance As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm.

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“…It shares the same mode of action as the previously described tocilizumab but binds the IL-6 receptor with higher affinity [ 86 ]. Gremese et al showed a trend of sarilumab to improve the clinical outcome in severe cases of COVID-19, compared to SOC-treated patients, albeit with only 53 participants in the study [ 87 ]. This result was supported by other early studies with limited patients numbers, which suggested that sarilumab-mediated IL-6 reduction correlated with faster recovery [ 88 , 89 , 90 ].…”

Section: Clinical-stage Therapeuticsmentioning

confidence: 99%

Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

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et al. 2021

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The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and involvement of specific chemokines is undoubtedly crucial for the development and progression of COVID-19. Cytokine storm and the often-resulting cytokine release syndrome (CRS) are pathophysiological hallmarks in COVID-19 infections related to its most severe and fatal cases. In this hyperinflammatory event, chemokines and other cytokines are highly upregulated and are therefore not fulfilling their beneficial function in the host response anymore but causing harmful effects. Here, we present the recent views on the involvement of chemokines and selected cytokines in COVID-19 and the therapeutics currently in clinical development targeting or interfering with them, discussing their potentials in the treatment of COVID-19 infections.

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Sarilumab use in severe SARS-CoV-2 pneumonia

Cited by 66 publications

References 24 publications

Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies

Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies

COVID-19, cytokines, inflammation, and spices: How are they related?

Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

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