COVID 19: in the eye of the cytokine storm

Liuzzo, Giovanna; Patrono, Carlo

doi:10.1093/eurheartj/ehaa1005

Cited by 18 publications

(13 citation statements)

References 7 publications

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“…The term cytokine storm was first used in an influenza infection model to describe the pro-inflammatory nature of cytokine overproduction in a short time and is associated with uncontrolled pro-inflammatory responses and significant immunopathology [ 92 ]. Development of a cytokine storm with attendant pulmonary damage has subsequently been reported in other viral, bacterial, and fungal infections and more recently, in COVID-19 [ 93 , 94 ]. Our Luminex and Metascape results clearly demonstrate that the inflammatory pathway takes the lead in pathology of infected M1 -/- mice.…”

Section: Discussionmentioning

confidence: 99%

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Jaggi

Matundan

et al. 2021

PLoS Pathog

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Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also showed that HSV-1 infectivity in the presence and absence of M2-macrophages was similar to wild-type (WT) control mice. However, it is not clear whether the absence of M1 macrophages plays a role in protection and disease in HSV-1 infected mice. To explore the role of M1 macrophages in HSV-1 infection, we used mice lacking M1 activation (M1-/- mice). Our results showed that macrophages from M1-/- mice were more susceptible to HSV-1 infection in vitro than were macrophages from WT mice. M1-/- mice were highly susceptible to ocular infection with virulent HSV-1 strain McKrae, while WT mice were refractory to infection. In addition, M1-/- mice had higher virus titers in the eye than did WT mice. Adoptive transfer of M1 macrophages from WT mice to M1-/- mice reduced death and rescued virus replication in the eye of infected mice. Infection of M1-/- mice with avirulent HSV-1 strain KOS also increased ocular virus replication and eye disease but did not affect latency-reactivation seen in WT control mice. Severity of virus replication and eye disease correlated with significantly higher inflammatory responses leading to a cytokine storm in the eyes of M1-/- infected mice that was not seen in WT mice. Thus, for the first time, our study illustrates the importance of M1 macrophages specifically in primary HSV-1 infection, eye disease, and survival but not in latency-reactivation.

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Section: Discussionmentioning

confidence: 99%

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Jaggi

Matundan

et al. 2021

PLoS Pathog

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“…Furthermore, the abundant presence of the ACE2 receptor in lung alveolar epithelial cells promotes the binding of SARS-CoV-2 spike-S-glycoprotein, thus, accelerating viral infection. Critically ill COVID-19 patient data showed the increased levels, to name a few, of IL-2, IL-6, IL-7, IL-10, monocyte chemoattractant protein-1 (MCP-1), and TNF-α ( 10 , 11 ). MSCs have specific properties to endow them attractive candidates for the therapeutic use of autoimmune inflammatory and tissue damage repairing or tissue homeostasis maintaining.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Human Umbilical Cord Mesenchymal Stem Cells as a Therapeutic Intervention for a Critically Ill COVID-19 Patient

Zhang

Huang

et al. 2021

Front. Med.

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Here we report a critically ill patient who was cured of SARS-CoV-2 infection in Changsha, China. A 66-year-old Chinese woman, with no significant past medical history, developed severe pneumonia-like symptoms and later diagnosed as severe COVID-19 pneumonia. Within 2 months of hospitalization, the patient deteriorated to ARDS including pulmonary edema and SIRS with septic shock. When treatment schemes such as antibiotics plus corticosteroids showed diminished therapeutic value, hUCMSC therapy was compassionately prescribed under the patient's consent of participation. After treatment, there was significant improvement in disease inflammation-related indicators such as IL-4, IL-6, and IL-10. Eventually, it confirmed the therapeutic value that hUCMSCs could dampen the cytokine storm in the critically ill COVID-19 patient and modulated the NK cells. In the continued hUCMSC treatment, gratifying results were achieved in the follow-up of the patient. The data we acquired anticipate a significant therapeutic value of MSC treatment in severe and critically ill patients with COVID-19, while further studies are needed.

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“…Approximately 80% of severe and moderate COVID-19 cases are accompanied by the development of CSS due to excessive immune activation [ 55 , 56 , 57 , 58 , 59 ]. It is associated with a systemic release of cytokines [ 60 , 61 ], causing multiorgan failure resulting in decreased patient survival [ 62 , 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Cytokine Profiling of Patients with COVID-19 Receiving Tocilizumab Therapy

Lebedeva

Molodtsov

Anisimova

et al. 2022

IJMS

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Coronavirus disease 2019 (COVID-19) is characterized by immune activation in response to viral spread, in severe cases leading to the development of cytokine storm syndrome (CSS) and increased mortality. Despite its importance in prognosis, the pathophysiological mechanisms of CSS in COVID-19 remain to be defined. Towards this goal, we analyzed cytokine profiles and their interrelation in regard to anti-cytokine treatment with tocilizumab in 98 hospitalized patients with COVID-19. We performed a multiplex measurement of 41 circulating cytokines in the plasma of patients on admission and 3–5 days after, during the follow-up. Then we analyzed the patient groups separated in two ways: according to the clusterization of their blood cytokines and based on the administration of tocilizumab therapy. Patients with and without CSS formed distinct clusters according to their cytokine concentration changes. However, the tocilizumab therapy, administered based on the standard clinical and laboratory criteria, did not fully correspond to those clusters of CSS. Furthermore, among all cytokines, IL-6, IL-1RA, IL-10, and G-CSF demonstrated the most prominent differences between patients with and without clinical endpoints, while only IL-1RA was prognostically significant in both groups of patients with and without tocilizumab therapy, decreasing in the former and increasing in the latter during the follow-up period. Thus, CSS in COVID-19, characterized by a correlated release of multiple cytokines, does not fully correspond to the standard parameters of disease severity. Analysis of the cytokine signature, including the IL-1RA level in addition to standard clinical and laboratory parameters may be useful to define the onset of a cytokine storm in COVID-19 as well as the indications for anti-cytokine therapy.

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COVID 19: in the eye of the cytokine storm

Cited by 18 publications

References 7 publications

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Case Report: Human Umbilical Cord Mesenchymal Stem Cells as a Therapeutic Intervention for a Critically Ill COVID-19 Patient

Comprehensive Cytokine Profiling of Patients with COVID-19 Receiving Tocilizumab Therapy

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