Tocilizumab use in Kidney Transplant Patients with COVID‐19

Trujillo, Hernando; Caravaca-Fontán, Fernando; Sevillano, Ángel; Gutiérrez, Eduardo; Fernández‐Ruiz, Mario; López‐Medrano, Francisco; Hernández, Ana María del Pilar Martínez; Aguado, José María; Praga, Manuel; Andrés, Amado

doi:10.1111/ctr.14072

Cited by 22 publications

(14 citation statements)

References 19 publications

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“…Other anecdotal evidence exists for tocilizumab use in SOTRs, in addition to antirejection immunosuppression. 144 145 Tocilizumab has also previously been shown to be safe and have activity in PLWH on ART with Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. 146 Ideally, patients with immunosuppressed conditions should not be excluded from COVID-19 clinical trials.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

Goldman

Robinson

Uldrick

et al. 2021

J Immunother Cancer

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SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.

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Section: Discussionmentioning

confidence: 99%

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

Goldman

Robinson

Uldrick

et al. 2021

J Immunother Cancer

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“…In a recent report, including 80 KTRs, tocilizumab efficiently reduced CRP levels and this decrease positively correlated with survival 25 . In another small‐scale, single‐center study, including 10 KT patients with severe COVID‐19, a single dose of tocilizumab (400–600 mg) decreased CRP levels, improved the clinical course, reduced oxygen requirement, and provided hospital discharge in seven patients 26 . In our study, we used tocilizumab in seven patients whose PaO 2 levels were between 50 and 54 mmHg after IVIg treatment.…”

Section: Discussionmentioning

confidence: 90%

COVID‐19 pneumonia in kidney transplant recipients: A promising treatment algorithm in the absence of a disease‐specific drug

Karataş

Tatar

Şimşek

et al. 2021

Journal of Medical Virology

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There is no consensus on the management of coronavirus disease 2019 (COVID‐19) and modification of immunosuppressive therapy in kidney transplant recipients (KTRs). In this study, we examined the clinical outcome of our KTRs with COVID‐19 disease, who were treated with a broad‐spectrum anti‐inflammatory protocol. This protocol is essentially composed of intravenous immunoglobulin +/‐ tocilizumab in KTRs with severe COVID‐19 pneumonia. Among 809 KTRs, 64 patients diagnosed with COVID‐19 disease between April 2020 and February 2021, were evaluated. Twenty‐nine patients with pneumonia confirmed by chest computed tomography (CCT) were hospitalized. The treatment protocol included high‐dose intravenous methylprednisolone, favipiravir, enoxaparin, and empirical antibiotics. Patients with pneumonic involvement of more than 25% on CCT with or without respiratory failure were given a total of 2 g/kg intravenous immunoglobulin (IVIg) therapy. Nonresponders received tocilizumab, an interleukin‐6 receptor antibody. Of the 29 patients with pneumonia, 6 were treated in other hospitals. These six patients did not receive IVIg and 5 of them deceased. In our center, IVIg treatment was applied to 15 of 23 patients. Seven of them required tocilizumab. Respiratory parameters improved significantly in all but one patient after IVIg ± tocilizumab treatment. The mortality rate was 6.6% in patients who received IVIg therapy and 35.7% in those who did not ( p = 0.08). The mortality rate was higher in patients who received treatment in external centers (2.2% vs. 26.3%; p = 0.0073). The treatment of KTRs with severe COVID‐19 pneumonia in organ transplant centers with significant experience yields better results. The administration of broad‐spectrum anti‐inflammatory treatment in this patient group was safe and provided excellent outcomes.

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“…It is effective and safe for treating both paediatric (with two or more years of age) as well as adults. Tocilizumab is being studied for managing ARDS in severe ill patients with COVID-19 alone or in combination with other antiviral therapies like hydroxychloroquine, remdesivir and favipiravir and broad spectrum antibiotics in several clinical trials ( Antwi-Amoabeng et al, 2020 ; Borku Uysal et al, 2020 ; Campochiaro et al, 2020 ; Christou et al, 2020 ; Farooqi et al, 2020 ; Jordan et al, 2020 ; Mazzitelli et al, 2020 ; Moreno-Pérez et al, 2020 ; Quartuccio et al, 2020 ; Toniati et al, 2020 ; Trujillo et al, 2020 ; Wang et al, 2020 ). These clinical studies concluded that intravenous administration of Tocilizumab at a dose of 8mg/kg results in reduced serum IL-6 level and rapid clinical improvement of COVID-19 pneumonia with ARDS ( Toniati et al, 2020 ) in majority of participants.…”

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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Tocilizumab use in Kidney Transplant Patients with COVID‐19

Cited by 22 publications

References 19 publications

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

COVID‐19 pneumonia in kidney transplant recipients: A promising treatment algorithm in the absence of a disease‐specific drug

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

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