Given the short half-life of anti-SARS-CoV-2 antibody shown by the UK vaccine task force, the protective capacity of the future vaccination may be still elusive. The common but life-threatening complication of COVID-19 is acute respiratory distress syndrome (ARDS). Targeting the virus by itself may not be sufficient since the mammalian pathogen sensor for this virus include TLR7 and RIG-I potentially inducing hyper-inflammation and cell death as evidenced by the pathological findings of COVID-19-associated ARDS such as edema, micro-emboli and infiltrating white blood cells. Although clinical trials are underway for TNFa and IL-6 in the accompanying cytokine storm, the first drug proven to diminish deaths in patients with severe lung complications is dexamethasone, a well-known anti-inflammatory steroid. However, steroids in general have not been routinely recommended in ARDS therapy. We may have no fear of the virus without ARDS. One analogous setting is found in tumor metastasis in the lungs, which is accompanied by sterile pulmonary inflammation induced by cytokine storms.
ARDS is a clinically defined condition with impaired gas exchange, pathological manifestation of which includes alveolar destruction and increased pulmonary vascular permeability. ARDS associated with COVID-19 is caused by inflammation that is induced by both the exogenous virus and endogenous mediators including cytokines. Dead cells can evoke inflammation, which is tightly associated with coagulation. Cytokines such as CCL2, TNFa, IL-6 and S100A8 have been found to be up-regulated in reliable clinical samples of severe COVID-19 as well as metastatic tumor conditions, and therefore the pathogenesis is called cytokine storm. Cytokine storm is an ambiguous term which does not describe any particular set, order, strength, specific producer and responder cells of cytokines in an organized manner. Most of the cytokines are chemokines at the same time capable inducing cell mobilization and vascular permeability, and therefore the levels of inflammation are expected to be high and could be irreversible. Brakes in immunity-associated inflammation are found in Treg and ?d-T cells, both of which are decreased in number in severe COVID-19 cases. In a small number of severe cases, an antibody against IL-6 receptor could be effective to abrogate this hyper-inflammation and resulting lethality. To avoid hyper-inflammation, other types of brakes such as PD-1 might be useful.
This Research Topic aims to highlight insights from shared biological events by COVID-19-associated ARDS and ARDS induced by other biological circumstances. Logical proposals of drugs potentially capable of eliminating the fatal outcome are valuable. We welcome focused submissions of Original Research, Reviews, Mini-Reviews, Opinion, Theory, Hypothesis and Perspective articles focusing on the following mechanisms and phenomena:
(1) Loss of brakes causing super-effects - Treg, ?d-T cells, PD-1
(2) Delayed anti-viral interferon responses - hepatitis type C (HCV) virus
(3) Alterations in signaling - vicious cycles, irreversibility, ADE (antibody-dependent enhancement)
(4) Transition of signaling molecules from un-druggable to druggable targets - endotoxin, CCL2, S100A8.
(5) Cell death signaling - cell debris, alarmins
(6) Inflammation-associated pathological events including VEGF, vascular permeability, coagulation
(7) ARDS - steroid, CCL2, TNFa, S100A8, TLRs, VAERD (vaccine-associated enhanced respiratory disease)
(8) Highly effective inhibitors such as tyrosine kinase inhibitors
Dr. Karin is the founder of Elgia Therapeutics and of the Scientific Advisory Board of the Joint Center For Life Sciences, and receives research support from Merck, Janssen, Gossamer, and Aduro. The other Topic Editors declare no competing interests
Given the short half-life of anti-SARS-CoV-2 antibody shown by the UK vaccine task force, the protective capacity of the future vaccination may be still elusive. The common but life-threatening complication of COVID-19 is acute respiratory distress syndrome (ARDS). Targeting the virus by itself may not be sufficient since the mammalian pathogen sensor for this virus include TLR7 and RIG-I potentially inducing hyper-inflammation and cell death as evidenced by the pathological findings of COVID-19-associated ARDS such as edema, micro-emboli and infiltrating white blood cells. Although clinical trials are underway for TNFa and IL-6 in the accompanying cytokine storm, the first drug proven to diminish deaths in patients with severe lung complications is dexamethasone, a well-known anti-inflammatory steroid. However, steroids in general have not been routinely recommended in ARDS therapy. We may have no fear of the virus without ARDS. One analogous setting is found in tumor metastasis in the lungs, which is accompanied by sterile pulmonary inflammation induced by cytokine storms.
ARDS is a clinically defined condition with impaired gas exchange, pathological manifestation of which includes alveolar destruction and increased pulmonary vascular permeability. ARDS associated with COVID-19 is caused by inflammation that is induced by both the exogenous virus and endogenous mediators including cytokines. Dead cells can evoke inflammation, which is tightly associated with coagulation. Cytokines such as CCL2, TNFa, IL-6 and S100A8 have been found to be up-regulated in reliable clinical samples of severe COVID-19 as well as metastatic tumor conditions, and therefore the pathogenesis is called cytokine storm. Cytokine storm is an ambiguous term which does not describe any particular set, order, strength, specific producer and responder cells of cytokines in an organized manner. Most of the cytokines are chemokines at the same time capable inducing cell mobilization and vascular permeability, and therefore the levels of inflammation are expected to be high and could be irreversible. Brakes in immunity-associated inflammation are found in Treg and ?d-T cells, both of which are decreased in number in severe COVID-19 cases. In a small number of severe cases, an antibody against IL-6 receptor could be effective to abrogate this hyper-inflammation and resulting lethality. To avoid hyper-inflammation, other types of brakes such as PD-1 might be useful.
This Research Topic aims to highlight insights from shared biological events by COVID-19-associated ARDS and ARDS induced by other biological circumstances. Logical proposals of drugs potentially capable of eliminating the fatal outcome are valuable. We welcome focused submissions of Original Research, Reviews, Mini-Reviews, Opinion, Theory, Hypothesis and Perspective articles focusing on the following mechanisms and phenomena:
(1) Loss of brakes causing super-effects - Treg, ?d-T cells, PD-1
(2) Delayed anti-viral interferon responses - hepatitis type C (HCV) virus
(3) Alterations in signaling - vicious cycles, irreversibility, ADE (antibody-dependent enhancement)
(4) Transition of signaling molecules from un-druggable to druggable targets - endotoxin, CCL2, S100A8.
(5) Cell death signaling - cell debris, alarmins
(6) Inflammation-associated pathological events including VEGF, vascular permeability, coagulation
(7) ARDS - steroid, CCL2, TNFa, S100A8, TLRs, VAERD (vaccine-associated enhanced respiratory disease)
(8) Highly effective inhibitors such as tyrosine kinase inhibitors
Dr. Karin is the founder of Elgia Therapeutics and of the Scientific Advisory Board of the Joint Center For Life Sciences, and receives research support from Merck, Janssen, Gossamer, and Aduro. The other Topic Editors declare no competing interests
