Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study

Giudice, Valentina; Pagliano, Pasquale; Vatrella, Alessandro; Masullo, Alfonso; Poto, S; Polverino, Benedetto; Gammaldi, Renato; Maglio, Angelantonio; Sellitto, Carmine; Vitale, Carolina; Serio, Bianca; Cuffa, Bianca; Borrelli, Anna; Vecchione, Carmine; Filippelli, Amelia; Selleri, Carmine

doi:10.3389/fphar.2020.00857

Cited by 116 publications

(130 citation statements)

References 23 publications

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“…Eculizumab binds C5, inhibiting the terminal complement complex, and has been shown to be effective in treating COVID-19 in several case reports. [36][37][38] Although we did not measure complement levels in our cohort, as serum samples were not preserved, we noticed ghost cells in several cases, which suggest complement activation on red blood cells. 39 A nanobody, caplacizumab, that inhibits the binding of VWF to gp-1b on platelets has been shown effective to treat TMAs.…”

Section: Discussionmentioning

confidence: 99%

Evidence for secondary thrombotic microangiopathy in COVID-19

Sweeney

Barouqa

Krause

et al. 2020

Preprint

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The causes of coagulopathy associated with COVID-19 disease are poorly understood. We aimed to investigate the relationship between markers of endothelial activation, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with equal distribution of survivors and non-survivors. Patients who died had significantly lower ADAMTS13 activity, significantly higher LDH, schistocytes and von Willebrand Factor levels compared to patients discharged alive. Only 30% of patients with an initial ADAMTS13 activity <43% survived vs. 60% with ADAMTS13 >43% who survived. In conclusion, COVID-19 may manifest as a TMA-like illness in a subset of hospitalized patients. Presence of schistocytes on admission may warrant a work-up for TMA. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of TMA treatments in COVID-19.

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Section: Discussionmentioning

confidence: 99%

Evidence for secondary thrombotic microangiopathy in COVID-19

Sweeney

Barouqa

Krause

et al. 2020

Preprint

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“…Recent findings are optimistic, but data validation by robust scientific evidence has been hampered by the small sample size in most case reports and studies on the use of mAbs blocking other immune mediators, such as IL-1b, GM-CSF, and complement protein C5 (238,(248)(249)(250). However, seeking to verify the effectiveness of using mAbs blocking inflammatory mediators, dozens of clinical trials are currently underway.…”

Section: Antibody-based Therapymentioning

confidence: 99%

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

et al. 2020

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Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs. The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.

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“…Based on the hypothesis that viral infections activate coagulation and complement cascades, triggering ARDS, antiCD5-a complement monoclonal antibody eculizumab, was combined with a JAK1/2 inhibitor, ruxolitinib in 17 patients and the combination demonstrated significant clinical benefit [ 63 ].…”

Section: Introductionmentioning

confidence: 99%

Emerging treatment strategies for COVID-19 infection

Gavriatopoulou

Ntanasis‐Stathopoulos

et al. 2020

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The new type of coronavirus (COVID-19), SARS-CoV-2 originated from Wuhan, China and has led to a worldwide pandemic. COVID-19 is a novel emerging infectious disease caused by SARS-CoV-2 characterized as atypical pneumonia. As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. The typical manifestations of COVID-19 include fever, sore throat, fatigue, cough, and dyspnoea combined with recent exposure. Most of the patients with COVID-19 have mild or moderate disease, however up to 5–10% present with severe and even life-threatening disease course. The mortality rates are approximately 2%. Therefore, there is an urgent need for effective and specific antiviral treatment. Currently, supportive care measures such as ventilation oxygenation and fluid management remain the standard of care. Several clinical trials are currently trying to identify the most potent drug or combination against the disease, and it is strongly recommended to enroll patients into ongoing trials. Antivirals can be proven as safe and effective only in the context of randomized clinical trials. Currently several agents such as chloroquine, hydroxychloroquine, favipiravir, monoclonal antibodies, antisense RNA, corticosteroids, convalescent plasma and vaccines are being evaluated. The large numbers of therapeutic interventions aim to define the most efficacious regimen. The aim of this article is to describe the treatment strategies that have been used for COVID-19 patients and review all the available literature.

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Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study

Cited by 116 publications

References 23 publications

Evidence for secondary thrombotic microangiopathy in COVID-19

Evidence for secondary thrombotic microangiopathy in COVID-19

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

Emerging treatment strategies for COVID-19 infection

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