Type 1 inflammatory endotype relates to low compliance, lung fibrosis, and severe complications in COVID-19

Hasegawa, Toshifumi; Nakagawa, Atsushi; Suzuki, Kazuhisa; Yamashita, Kazuto; Yamashita, Saya; Iwanaga, Niina; Tamada, Eiya; Noda, Kenta; Tomii, Keisuke

doi:10.1016/j.cyto.2021.155618

Cited by 15 publications

(14 citation statements)

References 34 publications

(43 reference statements)

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“…SARS-CoV-2 infection can also precipitate macrophage activation syndrome, which is characterized by increased type II IFN-related responses as well as elevated IL-6, IL-1β, TNF-α, and ferritin levels [21]. Patients with severe COVID-19 typically have increased serum levels of IL-6, IL-8/CXCL8, CXCL9, CXCL10, TNF-α, MCP1/CCL2, RANTES/CCL5, IL-18, and MIP-1α/CCL3, which promote a sustained pro-inflammatory state that may persist for up to 60 days [22,23].…”

Section: Cytokine Responsesmentioning

confidence: 99%

The pathogenesis of coronavirus-19 disease

Yantiss

2022

J Biomed Sci

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Severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) is the causal agent of coronavirus disease-2019 (COVID-19), a systemic illness characterized by variably severe pulmonary symptoms, cardiac conduction abnormalities, diarrhea, and gastrointestinal bleeding, as well as neurologic deficits, renal insufficiency, myalgias, endocrine abnormalities, and other perturbations that reflect widespread microvascular injury and a pro-inflammatory state. The mechanisms underlying the various manifestations of viral infection are incompletely understood but most data suggest that severe COVID-19 results from virus-driven perturbations in the immune system and resultant tissue injury. Aberrant interferon-related responses lead to alterations in cytokine elaboration that deplete resident immune cells while simultaneously recruiting hyperactive macrophages and functionally altered neutrophils, thereby tipping the balance from adaptive immunity to innate immunity. Disproportionate activation of these macrophages and neutrophils further depletes normal activity of B-cells, T-cells, and natural killer (NK) cells. In addition, this pro-inflammatory state stimulates uncontrolled complement activation and development of neutrophil extracellular traps (NETS), both of which promote the coagulation cascade and induce a state of “thrombo-inflammation”. These perturbations have similar manifestations in multiple organ systems, which frequently show pathologic findings related to microvascular injury and thrombosis of large and small vessels. However, the pulmonary findings in patients with severe COVID-19 are generally more pronounced than those of other organs. Not only do they feature inflammatory thromboses and endothelial injury, but much of the parenchymal damage stems from failed maturation of alveolar pneumocytes, interactions between type 2 pneumocytes and non-resident macrophages, and a greater degree of NET formation. The purpose of this review is to discuss the pathogenesis underlying organ damage that can occur in patients with SARS-CoV-2 infection. Understanding these mechanisms of injury is important to development of future therapies for patients with COVID-19, many of which will likely target specific components of the immune system, particularly NET induction, pro-inflammatory cytokines, and subpopulations of immune cells.

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Section: Cytokine Responsesmentioning

confidence: 99%

The pathogenesis of coronavirus-19 disease

Yantiss

2022

J Biomed Sci

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“…Furthermore, a wealth of clinical data determines the positive correlation of heightened IL-18 concentrations with the occurrence of the ARDS, lung fibrosis, and AKI and disease severity, contributing to the early identification of critical COVID-19 patients [ 19 , 140 , 160 , 161 ] (Table 1 ). Concomitantly, some studies identified IL-18, alongside the IL-15 and Gal-9, as an organ-failure-specific immunological marker of the respiratory system [ 161 , 162 ].…”

Section: Il-18 and Covid-19mentioning

confidence: 99%

“…A study done by Singh et al showed sustained high levels of IL-18 consistent with CCR2, CX3CR1, and macrophage inflammatory factors even in the recovery stages of the infection, suggesting IL-18 s’ roles in the compromised immunity of recovered patients [ 173 ]. Likewise, in the recovery period from ARDS, the serum levels of IL-18, CCL3, and CXCL9 were higher in COVID-19 patients with dyspnea or renal failure, representing IL-18 as a reflecting marker of residual inflammation in these patients [ 161 ]. However, prediction analysis of cell-to-cell interactions utilizing data from the scRNA-Seq in a computational approach indicated that, in late recovery stage (LRS) patients, DC-derived IL-18 and TNF TNFSF13 accompanied by T cell-derived IL-2 and IL-4 might promote B cell survival, proliferation, and differentiation, culminating in the production of various SARS-CoV-2-specific Abs [ 83 ].…”

Section: Il-18 and Covid-19mentioning

confidence: 99%

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19

et al. 2022

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A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.

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“…To this regard, elevated MUC1 mucin protein levels were found in airway mucus of critical ill COVID-19 patients [191] as well as interleukins [164] , though no significant differences have been revealed in baseline levels of IL-1β, IL-6, and TNF-α between patients with COVID-19 and critically ill subjects with ARDS [192] . On the contrary, high levels of IL-18 were found in 85% of the COVID-19 patients that had ARDS and 78% of those that developed pulmonary fibrosis [193] . Further, levels of IL-13, one of the major factors implicated in lung fibrosis, have been demonstrated to be elevated in patients with severe COVID-19, underlining its ability in identifying COVID-19 patients who needed of mechanical ventilation [194] .…”

Section: What About the Lung Lesions In Post-covid-19 Patients?mentioning

confidence: 88%