Successful Treatment of Severe COVID-19 Pneumonia With Clazakizumab in a Heart Transplant Recipient: A Case Report

Vaidya, Gaurang; Czer, L.; Kobashigawa, J.A.; Kittleson, M.; Patel, Jignesh; Chang, D.; Kransdorf, E.; Shikhare, Anuja; Tran, Hai; Vo, Ashley; Ammerman, Noriko; Huang, Edmund; Zabner, Rachel; Jordan, Stanley C.

doi:10.1016/j.transproceed.2020.06.003

Cited by 39 publications

(30 citation statements)

References 9 publications

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“…Although not yet approved by Food and Drug Administration (FDA), clazakizumab (a monoclonal antibody against human IL-6) may be helpful in inhibiting the cytokine storms, and related clinical trials are underway worldwide (86). It is also reported that patients with rapidly progressing COVID-19 respiratory failure requiring ventilatory support may benefit from treatment with siltuximab (IL-6 monoclonal antibody) because of reduced mortality and cytokine-driven hyperinflammation (NCT04322188) (66).…”

Section: Blocking Of Il-6/il-6rmentioning

confidence: 99%

Controlling Cytokine Storm Is Vital in COVID-19

et al. 2020

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Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people’s health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.

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Section: Blocking Of Il-6/il-6rmentioning

confidence: 99%

Controlling Cytokine Storm Is Vital in COVID-19

et al. 2020

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“…Although not yet FDA approved, It is primarily registered for phase II clinical trials for the treatment of kidney transplant recipients with late antibody-mediated rejection. Clinical trials of clazakizumab for treating critical cases of COVID-19 are under investigation ( Vaidya et al, 2020 ). Olocizumab is also an investigational monoclonal antibody against IL-6.…”

Section: Discussionmentioning

confidence: 99%

Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19

Patel

Saxena

Mehta

2021

Heliyon

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Clinical studies have identified a cytokine storm in the third stage of disease progression in critical ill patients with coronavirus disease 2019 . Hence, effectively suppressing the uncontrolled immune response of the host towards the invaded viruses in a cytokine storm is a critical step to prevent the deterioration of patient conditions and decrease the rate of mortality. Therapeutic monoclonal antibodies (mAbs) are found to be effective for the management of acute respiratory distress syndrome in patients with COVID-19. In this review, we compiled all therapeutic mAbs targeting cytokine storm, which are in clinical trials for its repurposing in the management of COVID-19. Compilation of clinical trial data indicated that therapeutic monoclonal antibodies targeting interleukins (IL-6, IL-1ra, IL-8, IL-1β, IL-17A, IL-33), interferon-gamma, tumor necrosis factor-alpha, Pselectin, connective tissue growth factor, plasma kallikrein, tumor necrosis factor superfamily 14, granulocyte macrophage colony stimulating factor, colony stimulating factor 1 receptor, C-C chemokine receptor type 5, cluster of differentiation 14 and 147, vascular endothelial growth factor, programmed cell death protein-1, Angiopoietin -2, human factor XIIa, complementary protein 5, natural killer cell receptor G2A, human epidermal growth factor receptor 2, immunoglobulin-like transcript 7 receptor, complement component fragment 5a receptor and viral attachment to the human cell were under investigation for management of severely ill patients with COVID-19. Among these, about 65 clinical trials are targeting IL-6 inhibition as the most promising one and Tocilizumab, an IL-6 inhibitor is considered to be the potential candidate to treat cytokine storm associated with the COVID-19. OverviewCoronavirus disease 2019 (COVID-19) is the infectious disease, which affects primarily the lungs, caused by newly identified coronavirus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patient infected with SARS-CoV-2 was initially discovered at Wuhan, China in December 2019 and is still spreading across the globe (Singhal, 2020). The COVID-19 outbreak was declared as pandemic on March 11, 2020 by the world health organization (WHO) (Coperchini et al., 2020). By September 9, 2020 the number of deaths raised to 896K amongst 27.5 million confirmed cases of COVID-19. The majority of the patients infected with SARS-CoV-2 in this COVID-19 pandemic are clinically asymptomatic or develop mild clinical manifestations like cough, mild fever, or muscle soreness. However, nearly 10-20% of patients (especially geriatric and patients with other co-morbidity) will develop pneumonia and acute respiratory distress syndrome (ARDS) (Soy et al., 2020). This COVID-19 pandemic created global crises of both public health as well as economic and thus emerged the need for rapid development of vaccines and therapeutic countermeasures (Sempowski et al., 2020). One approach for finding appropriate therapeutics for treating COVID-19 is rapid repurposing of existin...

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“…At present, randomized placebo-controlled clinical investigations are examining the efficiency of clazakizumab in the treatment of SARS-CoV-2 pneumonia affected patients at Cedars Sinai Medical Center and NYU Langone Medical Center [123,124]. Clazakizumab has some negative impacts, which are dose dependent including mild infections, increasing the level of aminotransferase and cholesterol, decreasing platelet and neutrophil counts [125]. Clazakizumab might be a safe choice for monitoring the characteristics of cytokine storm for serious COVID-19 pneumonia patients, including transplant recipients, but further clinical investigations must be conducted for the accuracy and efficacy [125].…”

Section: Clazakizumabmentioning

confidence: 99%