Promising Therapy for Heart Failure in Patients with Severe COVID-19: Calming the Cytokine Storm

Xiang, Peng; Wang, Yani; Xi, Xiangwen; Jia, Ying; Tian, Jiangtian; Yu, Bo; Tian, Jing

doi:10.1007/s10557-020-07120-8

Cited by 26 publications

(16 citation statements)

References 158 publications

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“…Moreover, the presumptive assumptions of the causative reason for multiple organ damage and mortality during SARS-CoV-2 infection have been closely linked to cytokine storm. Recently, Peng et al (2021) also suggested that the cytokine storm plays a crucial role in the progression of SARS-CoV-2 infection and could be a major reason for multiple organ damage and an increased fatality rate in immunocompromised patients [28].…”

Section: Cytokinesand Chemokines Associated With Cytokine Stormmentioning

confidence: 99%

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

et al. 2021

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.

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Section: Cytokinesand Chemokines Associated With Cytokine Stormmentioning

confidence: 99%

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

et al. 2021

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“…IL-1, TNF-α, and IL-6 have been consistently reported as being central to cytokine storm regulation. A treatment algorithm based on effective inhibition of pro-inflammatory cytokines could be crucial for improving patient outcomes [ 32 ]; for example, Anakinra, a recombinant humanized IL-1 receptor antagonist, has been effectively used to treat MAS [ 33 ]. Recent data have indicated that IL-6 holds a key role in cytokine storm pathophysiology and lung tissue damage, probably by inducing MMP-9 expression in macrophages via Cox-2-dependent and -independent mechanisms [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Method for the Production of an Autologous Anti-Inflammatory and Anti-Catabolic Product (Cytorich) from Human Blood: A Prospective Treatment for the COVID-19-Induced Cytokine Storm

Brokhman¹,

Watkin²,

Bacher³

et al. 2021

Med Sci Monit

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Background Autologous blood-derived products can target specific inflammatory molecular pathways and have potentially beneficial therapeutic effects on inflammatory pathologies. The purpose of this study was to assess in vitro the anti-inflammatory and anti-catabolic potential of an autologous blood product as a possible treatment for COVID-19-induced cytokine storm. Material/Methods Blood samples from healthy donors and donors who had recovered from COVID-19 were incubated using different techniques and analyzed for the presence of anti-inflammatory, anti-catabolic, regenerative, pro-inflammatory, and procatabolic molecules. Results The highest concentrations of therapeutic molecules for targeting inflammatory pathways were found in the blood that had been incubated for 24 h at 37°C, whereas a significant increase was observed after 6 h of incubation in blood from COVID-19-recovered donors. Beneficially, the 6-h incubation process did not downregulate anti-COVID-19 immunoglobulin G concentrations. Unfortunately, increases in matrix metalloproteinase 9, tumor necrosis factor α, and interleukin-1 were detected in the product after incubation; however, these increases could be blocked by adding citric acid, with no effect on the concentration of the target therapeutic molecules. Our data allow for safer and more effective future treatments. Conclusions An autologous blood-derived product containing anti-inflammatory and anti-catabolic molecules, which we term Cytorich, has a promising therapeutic role in the treatment of a virus-induced cytokine storm, including that associated with COVID-19.

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“…The cytokine storm has a devastating consequence on immune dysregulation in patients ( Fajgenbaum and June 2020 ; Mehta et al, 2020 ). This condition can cause organ failure and increase the fatality rate ( Peng et al, 2021 ). However, several immunotherapeutic molecules are repurposed to treat the cytokine storm among COVID-19 patients.…”

Section: Lessons Learned From Immunotherapeutic Molecules Developmentmentioning

confidence: 99%

The Drug Repurposing for COVID-19 Clinical Trials Provide Very Effective Therapeutic Combinations: Lessons Learned From Major Clinical Studies

et al. 2021

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SARS-CoV-2 has spread across the globe in no time. In the beginning, people suffered due to the absence of efficacious drugs required to treat severely ill patients. Nevertheless, still, there are no established therapeutic molecules against the SARS-CoV-2. Therefore, repurposing of the drugs started against SARS-CoV-2, due to which several drugs were approved for the treatment of COVID-19 patients. This paper reviewed the treatment regime for COVID-19 through drug repurposing from December 8, 2019 (the day when WHO recognized COVID-19 as a pandemic) until today. We have reviewed all the clinical trials from RECOVERY trials, ACTT-1 and ACTT-2 study group, and other major clinical trial platforms published in highly reputed journals such as NEJM, Lancet, etc. In addition to single-molecule therapy, several combination therapies were also evaluated to understand the treatment of COVID-19 from these significant clinical trials. To date, several lessons have been learned on the therapeutic outcomes for COVID-19. The paper also outlines the experiences gained during the repurposing of therapeutic molecules (hydroxychloroquine, ritonavir/ lopinavir, favipiravir, remdesivir, ivermectin, dexamethasone, camostatmesylate, and heparin), immunotherapeutic molecules (tocilizumab, mavrilimumab, baricitinib, and interferons), combination therapy, and convalescent plasma therapy to treat COVID-19 patients. We summarized that anti-viral therapeutic (remdesivir) and immunotherapeutic (tocilizumab, dexamethasone, and baricitinib) therapy showed some beneficial outcomes. Until March 2021, 4952 clinical trials have been registered in ClinicalTrials.gov toward the drug and vaccine development for COVID-19. More than 100 countries have participated in contributing to these clinical trials. Other than the registered clinical trials (medium to large-size), several small-size clinical trials have also been conducted from time to time to evaluate the treatment of COVID-19. Four molecules showed beneficial therapeutic to treat COVID-19 patients. The short-term repurposing of the existing drug may provide a successful outcome for COVID-19 patients. Therefore, more clinical trials can be initiated using potential anti-viral molecules by evaluating in different phases of clinical trials.

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Promising Therapy for Heart Failure in Patients with Severe COVID-19: Calming the Cytokine Storm

Cited by 26 publications

References 158 publications

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

A Novel Method for the Production of an Autologous Anti-Inflammatory and Anti-Catabolic Product (Cytorich) from Human Blood: A Prospective Treatment for the COVID-19-Induced Cytokine Storm

The Drug Repurposing for COVID-19 Clinical Trials Provide Very Effective Therapeutic Combinations: Lessons Learned From Major Clinical Studies

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