Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study

Kewan, Tariq; Covut, Fahrettin; Al-Jaghbeer, Mohammed; Rose, Lori; Gopalakrishna, K. V.; Akbik, Bassel

doi:10.1016/j.eclinm.2020.100418

Cited by 162 publications

(172 citation statements)

References 27 publications

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“…The findings of leukocytosis associated with prolonged hospital admission in sickle cell patient with COVID-19 infection in this study was consistent with the observation of significant correlation between leukocytosis and the severity of COVID 19 infection in a study by Gleng et al in 2020 [31]. It can also be explained by the study of Suwa et al that demonstated that IL-6 induces both neutrophil demargination in the blood vessel and reduction in neutrophil transit time to exit the bone marrow [35].…”

Section: Discussionsupporting

confidence: 92%

“…Also the observation of markedly elevated C-reactive proteins and IL-6 in was identical to the finding by Mehta et al who noticed SARS-COV 2 induces upregulation of pro-inflammatory cytokines such as (IL-1, IL-6 and TNF-α) [30], this finding was also comparable with the study by Zhang et al in 2020 that demonstrated increase in total number of mortality in patients with condition associated with exaggerated release of cytokine known as cytokine release syndrome [10]. This was also in agreement with the study by Kewan et al in 2020 that has shown the efficacy of Tocilizimab (an anti-human IL-6 receptor monoclonal antibody), which inhibits signal transduction through the IL-6 receptor by binding to sIL-6 receptor and mIL-6 receptor [31].…”

Section: Discussionsupporting

confidence: 83%

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Poor Prognostic Factors in Sickle Cell Disease Patients Infected with Covid-19 – Review of Literatures

Abiola¹,

Abdul²,

Muhammad³

2020

AJLM

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Sickle cell disease (SCD) is the co-inheritance of HbS with other abnormal haemoglobin. COVID-19 is a severe acute respiratory distress syndrome caused by coronavirus 2 infections. The immunosuppression and chronic inflammatory states in patients with SCD predispose them to severe form of COVID-19. The few case studies on sickle cell disease patients infected with COVID-19 mostly discuss the pattern of clinical presentations and laboratory changes in patients with SCD infected with COVID-19. This review of literature assesses the prognostic indicators in sickle cell disease patients infected with COVID 19 in three major case series. Some presenting symptoms and signs, presence of comorbidities and certain laboratory parameters were compared with poor outcome of patients. Poor clinical outcomes of patients in this review included: 1. Duration of admission of ≥10 days, 2. A week or more of intensive care unit admission, 3. Death of patient despite intervention while on admission, and 4. Deterioration in the presenting comorbid clinical condition. The presenting symptoms and signs, presence of comorbidities and certain laboratory parameters associated with these poor clinical outcomes were considered as poor prognostic factors. The presence of comorbidities, markedly elevated pro-inflammatory markers such as leukocytosis, IL-6, C-reactive proteins, marked elevated D-Dimer and high serum creatinine are poor prognostic factors in sickle cell disease patients with COVID-19 infection.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 83%

Poor Prognostic Factors in Sickle Cell Disease Patients Infected with Covid-19 – Review of Literatures

Abiola¹,

Abdul²,

Muhammad³

2020

AJLM

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“…[26][27][28] Treatment with IL-6 antagonists improved the survival and shortened the recovery time. [29][30][31][32][33] However, the cell types responsible for increased IL-6 expression in the lung are poorly defined, and understanding the relationship among IL-6 expression, the extent of SARS-CoV-2 infection, and disease severity is incomplete.…”

Section: Introductionmentioning

confidence: 99%

Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19

Silva

Meng

et al. 2020

Preprint

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Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection in patients with Coronavirus Disease 2019 (COVID-19) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage (DAD), excess inflammation, pneumocyte hyperplasia and proliferation, and formation of platelet aggregates or thromboemboli. However, the mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for viral proteins, and lineage cell markers to identify SARS-CoV-2 tropism and to define the lung pathobiology in postmortem tissues from five patients with fatal SARS-CoV-2 infections. Findings The lung parenchyma showed severe DAD with thromboemboli in all cases. SARS-CoV-2 infection was found in an extensive range of cells including alveolar epithelial type II/pneumocyte type II (AT2) cells (HT2-280), ciliated cells (tyr-α-tubulin), goblet cells (MUC5AC), club-like cells (MUC5B) and endothelial cells (CD31 and CD34). Greater than 90% of infiltrating immune cells were positive for viral proteins including macrophages and monocytes (CD68 and CD163), neutrophils (ELA-2), natural killer (NK) cells (CD56), B-cells (CD19 and CD20), and T-cells (CD3ε). Most but not all infected cells were positive for the viral entry receptor angiotensin-converting enzyme-2 (ACE2). The numbers of infected and ACE2-positive cells correlated with the extent of tissue damage. The infected tissues exhibited low numbers of B-cells and abundant CD3ε+ T-cells consisting of mainly T helper cells (CD4), few cytotoxic T cells (CTL, CD8), and no T regulatory cell (FOXP3). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust interleukin-6 (IL-6) expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage. Interpretation In lung tissues from severely affected COVID-19 patients, there is evidence for broad SARS-CoV-2 cell tropisms, activation of immune cells, and clearance of immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation and compromised adaptive immune responses.

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“…There are reports that patients with COVID-19 have elevated levels of acute-phase reactants and inflammatory cytokines leading to cytokine release syndrome (CRS), and tocilizumab is effectively used in in-hospital patients admitted with CRS [134]. Kewan et al (2020), in their retrospective cohort study, analyzed the resulted favorable outcomes in hypoxic COVID-19 patients who were consecutively admitted between March 13, 2020, and April 19, 2020, and treated with a single intravenous infusion of low-dose tocilizumab. By May, an increasing number of studies had reported the use of tocilizumab in treating COVID-19.…”

Section: Drug Therapy In Covid-19mentioning

confidence: 99%

Impact of COVID-19 on the Cardiovascular System: A Review of Available Reports

Soumya

Unni

Raghu

2020

Cardiovasc Drugs Ther

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The recent emergence of the coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China is now a global health emergency. The transmission of SARS-CoV-2 is mainly via human-to-human contact. This virus is expected to be of zoonotic origin and has a high genome identity to that of bat derived SARS-like coronavirus. Various stringent measures have been implemented to lower person-to-person transmission of COVID-19. Particular observations and attempts have been made to reduce transmission in vulnerable populations, including older adults, children, and healthcare providers. This novel CoV enters the cells through the angiotensin-converting enzyme 2 (ACE2) receptor. There is a higher risk of COVID-19 infection among those with preexisting cardiovascular diseases (CVD), and it has been connected with various direct and indirect complications, including myocarditis, acute myocardial injury, venous thromboembolism, and arrhythmias. This article summarizes the various cardiovascular complications and mechanisms responsible for the same with COVID-19 infection. For the benefit of the scientific community and public, the effect of COVID-19 on major vital organs such as the kidneys, liver, and intestines has been briefly discussed. In this review, we also discuss drugs in different stages of clinical trials and their associated complications, as well as the details of vaccines in various stages of development.

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Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study

Cited by 162 publications

References 27 publications

Poor Prognostic Factors in Sickle Cell Disease Patients Infected with Covid-19 – Review of Literatures

Poor Prognostic Factors in Sickle Cell Disease Patients Infected with Covid-19 – Review of Literatures

Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19

Impact of COVID-19 on the Cardiovascular System: A Review of Available Reports

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