Non-antiviral Agents for Treatment of COVID-19 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 5207

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Guest Editor
Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan
Interests: bioactive peptide; adrenomedullin; inflammatory bowel disease; COVID-19; hypertension
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Special Issue Information

Dear Colleagues,

The novel coronavirus disease (COVID-19) continues to affect millions around the world, with no end in sight. A significant number of patients with COVID-19 who experienced exacerbated symptoms have died. Thus, saving the lives of patients with severe COVID-19 is currently of the highest importance. While antiviral agents, including those currently under development, are effective in the early phase of the disease, they are not effective in the late and advanced phases of COVID-19. Alternative approaches are required for these cases, including modulators for cytokines, inflammation inhibitors, and protective agents for tissue injury. This Special Issue aims to publish original research papers and/or relevant reviews of the most recent literature on the beneficial effects of non-antiviral agents for the treatment of moderate-to-severe COVID-19.

Dr. Toshihiro Kita
Guest Editor

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Keywords

  • COVID-19
  • antiviral agents
  • cytokines
  • tissue-protective factors
  • moderate-to-severe pneumonia

Published Papers (2 papers)

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Review

21 pages, 1353 KiB  
Review
Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review
by Cristian-Mihail Niculae, Adriana Hristea and Ruxandra Moroti
Biomedicines 2023, 11(3), 929; https://doi.org/10.3390/biomedicines11030929 - 16 Mar 2023
Cited by 3 | Viewed by 3300
Abstract
COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the [...] Read more.
COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation–endotheliopathy–thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways. Full article
(This article belongs to the Special Issue Non-antiviral Agents for Treatment of COVID-19 2.0)
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30 pages, 882 KiB  
Review
From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?
by Goran Rondovic, Dragan Djordjevic, Ivo Udovicic, Ivan Stanojevic, Snjezana Zeba, Tanja Abazovic, Danilo Vojvodic, Dzihan Abazovic, Wasim Khan and Maja Surbatovic
Biomedicines 2022, 10(10), 2620; https://doi.org/10.3390/biomedicines10102620 - 18 Oct 2022
Cited by 5 | Viewed by 1615
Abstract
Complex immune response to infection has been highlighted, more than ever, during the COVID-19 pandemic. This review explores the immunomodulatory treatment of moderate-to-severe forms of this viral sepsis in the context of specific immunopathogenesis. Our objective is to analyze in detail the existing [...] Read more.
Complex immune response to infection has been highlighted, more than ever, during the COVID-19 pandemic. This review explores the immunomodulatory treatment of moderate-to-severe forms of this viral sepsis in the context of specific immunopathogenesis. Our objective is to analyze in detail the existing strategies for the use of immunomodulators in COVID-19. Immunomodulating therapy is very challenging; there are still underpowered or, in other ways, insufficient studies with inconclusive or conflicting results regarding a rationale for adding a second immunomodulatory drug to dexamethasone. Bearing in mind that a “cytokine storm” is not present in the majority of COVID-19 patients, it is to be expected that the path to the adequate choice of a second immunomodulatory drug is paved with uncertainty. Anakinra, a recombinant human IL-1 receptor antagonist, is a good choice in this setting. Yet, the latest update of the COVID-19 Treatment Guidelines Panel (31 May 2022) claims that there is insufficient evidence to recommend either for or against the use of anakinra for the treatment of COVID-19. EMA’s human medicines committee recommended extending the indication of anakinra to include treatment of COVID-19 in adult patients only recently (17 December 2021). It is obvious that this is still a work in progress, with few ongoing clinical trials. With over 6 million deaths from COVID-19, this is the right time to speed up this process. Our conclusion is that, during the course of COVID-19, the immune response is changing from the early phase to the late phase in individual patients, so immunomodulating therapy should be guided by individual responses at different time points. Full article
(This article belongs to the Special Issue Non-antiviral Agents for Treatment of COVID-19 2.0)
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