The cytokine storm in COVID-19: Further advances in our understanding the role of specific chemokines involved

Coperchini, Francesca; Chiovato, Luca; Ricci, Gianluca; Croce, Laura; Magri, Flavia; Rotondi, Mario

doi:10.1016/j.cytogfr.2020.12.005

Cited by 107 publications

(106 citation statements)

References 68 publications

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“…CXCL10 was recently identified as the cardinal chemokine playing a crucial role in COVID-19 being a chemoattractant for monocytes/ macrophages, dendritic cells, NK cells, and T cells. Elevated serum levels of CXCL10 were consistently reported in patients with COVID-19, being positively correlated (together with CCL2) with increased disease severity and, more importantly with an increased risk of mortality (11,65,66). High levels of CXCL10 were previously reported to be associated also with the severe acute respiratory syndrome (SARS) disease progression and to the development of ARDS in preclinical models (67,68).…”

Section: The Il-6-cxcl10-macrophages Networkmentioning

confidence: 91%

“…Based on our current knowledge, the balance of the composition of the cytokine/chemokine network characterizing the "cytokine storm" seems to be crucial in the progression of COVID-19 (10,11).…”

Section: Introductionmentioning

confidence: 99%

“…Following the demonstration of the pathological role of the cytokine storm, several studies were designed with the aim of investigating whether specific chemokines could play a role in driving COVID-19 progression. These type of studies were aimed not only at identifying possible targets for treatment of the disease but also at detecting a possible "immune signature" in patients with COVID-19 (11). Indeed, COVID-19 is a very heterogeneous disease, characterized by a clinical course which may range from a rather free of symptoms condition to fatal events.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, COVID-19 is a very heterogeneous disease, characterized by a clinical course which may range from a rather free of symptoms condition to fatal events. Thus, it is evident that the identification of a specific "immune signature" (i.e., high or low concentrations of one or more specific chemokine) of COVID-19 patients would potentially represent a helpful clinical tool for early identification, already in the early stages of the infection, of patients more or less prone to develop a severe clinical condition (11).…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One!

2021

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SARS-COV-2 virus is responsible for the ongoing devastating pandemic. Since the early phase of the pandemic, the “cytokine-storm” appeared a peculiar aspect of SARS-COV-2 infection which, at least in the severe cases, is responsible for respiratory treat damage and subsequent multi-organ failure. The efforts made in the last few months elucidated that the cytokine-storm results from a complex network involving cytokines/chemokines/infiltrating-immune-cells which orchestrate the aberrant immune response in COVID-19. Clinical and experimental studies aimed at depicting a potential “immune signature” of SARS-COV-2, identified three main “actors,” namely the cytokine IL-6, the chemokine CXCL10 and the infiltrating immune cell type macrophages. Although other cytokines, chemokines and infiltrating immune cells are deeply involved and their role should not be neglected, based on currently available data, IL-6, CXCL10, and infiltrating macrophages could be considered prototype factors representing each component of the immune system. It rapidly became clear that a strong and continuous interplay among the three components of the immune response is mandatory in order to produce a severe clinical course of the disease. Indeed, while IL-6, CXCL10 and macrophages alone would not be able to fully drive the onset and maintenance of the cytokine-storm, the establishment of a IL-6/CXCL10/macrophages axis is crucial in driving the sequence of events characterizing this condition. The present review is specifically aimed at overviewing current evidences provided by both in vitro and in vivo studies addressing the issue of the interplay among IL-6, CXCL10 and macrophages in the onset and progression of cytokine storm. SARS-COV-2 infection and the “cytokine storm.”

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Section: The Il-6-cxcl10-macrophages Networkmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One!

2021

Self Cite

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“…Besides the cytokines, several other small chemical molecules or chemokines such as CCL2 (MCP1), CCL3 (MIP1α), CXCL10 (IP-10) have been reported to be higher in the serum of severely ill patients with COVID-19 [ 73 , 74 , 75 , 76 ]. These chemokines may correlate with the increased level of cytokines as they act as chemoattractants for several immune cells and lead to the cytokine storm via modulating the immune response in severe cases [ 75 , 76 , 77 , 78 , 79 ]. For example, Chi et al detected the production of pro-inflammatory chemokines and cytokines in the serum samples of asymptomatic as well as symptomatic patients [ 80 ].…”

Section: Factors Influencing Inflammatory Cytokine Production By Modulation Of the Immune Systemmentioning

confidence: 99%

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

et al. 2021

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The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

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Host Genetic Impact on Infectious Diseases among Different Ethnic Groups

Naidoo,

Arumugam,

Ramsuran

2023

Advanced Genetics

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Infectious diseases such as malaria, tuberculosis (TB), human immunodeficiency virus (HIV), and the coronavirus disease of 2019 (COVID‐19) are problematic globally, with high prevalence particularly in Africa, attributing to most of the death rates. There have been immense efforts toward developing effective preventative and therapeutic strategies for these pathogens globally, however, some remain uncured. Disease susceptibility and progression for malaria, TB, HIV, and COVID‐19 vary among individuals and are attributed to precautionary measures, environment, host, and pathogen genetics. While studying individuals with similar attributes, it is suggested that host genetics contributes to most of an individual's susceptibility to disease. Several host genes are identified to associate with these pathogens. Interestingly, many of these genes and polymorphisms are common across diseases. This paper analyzes genes and genetic variations within host genes associated with HIV, TB, malaria, and COVID‐19 among different ethnic groups. The differences in host–pathogen interaction among these groups, particularly of Caucasian and African descent, and which gene polymorphisms are prevalent in an African population that possesses protection or risk to disease are reviewed. The information in this review could potentially help develop personalized treatment that could effectively combat the high disease burden in Africa.

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The cytokine storm in COVID-19: Further advances in our understanding the role of specific chemokines involved

Cited by 107 publications

References 68 publications

Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One!

Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One!

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Host Genetic Impact on Infectious Diseases among Different Ethnic Groups

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