Immunopathology of Hyperinflammation in COVID-19.
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ABSTRACT:
SUBMITTER: Gustine JN
PROVIDER: S-EPMC7484812 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk-factor for severe disease. Inflammation is central to the aetiology of both conditions where immune responses influence disease course. Identifying at-risk groups through immuno-inflammatory signatures can direct personalised care and help develop potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leukocyte populations in circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia, of CD8+ lymphocytes, was associated with severe COVID-19 and intensive care admission in non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia of classical monocytes were specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Over-expression of inflammatory markers reminiscent of the type-1 interferon pathway underlaid the immunophenotype associated with T2D. These changes may contribute to severity of COVID-19 in T2D. These findings show characteristics of severe COVID-19 in T2D as well as provide evidence that type-1 interferons may be actionable targets for future studies.
| S-SCDT-EMM-2020-13038 | biostudies-other
Project description:COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.
| S-EPMC7316488 | biostudies-literature
Project description: Not available
| S-EPMC7490488 | biostudies-literature
Project description:we profiled the inflammatory transcriptome of ten COVID-19 skin manifestations from patients with moderate-to-severe disease and compared the resultant signatures with those obtained from skin lesions of patients with cutaneous lupus erythematosus.
2022-01-07 | GSE193068 | GEO
Project description:Rationale: In life-threatening coronavirus disease (COVID-19), corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or an independent immunopathologic process is unknown.Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses and the relationships among viral presence, inflammation, and organ injury.Methods: Tissue was acquired from 11 detailed postmortem examinations. SARS-CoV-2 organotropism was mapped by using multiplex PCR and sequencing, with cellular resolution achieved by in situ viral S (spike) protein detection. Histologic evidence of inflammation was quantified from 37 anatomic sites, and the pulmonary immune response was characterized by using multiplex immunofluorescence.Measurements and Main Results: Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein between or within tissues. An arteritis was identified in the lung, which was further characterized as a monocyte/myeloid-rich vasculitis, and occurred together with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticuloendothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues.Conclusions: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease. Our data highlight novel immunopathologic mechanisms and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma-cell responses as well as promote pathogen tolerance in COVID-19.
| S-EPMC7874430 | biostudies-literature
Project description:Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by significant lung pathology and extrapulmonary complications. Type I interferons (IFNs) play an essential role in the pathogenesis of COVID-19. While rapid induction of type I IFNs limits virus propagation, sustained elevation of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome. Using proteomic data from a lung-on-chip model revealed that, in addition to macrophages, SARS-CoV-2 infection activates cGAS-STING signalling in endothelial cells through mitochondrial DNA release, leading to cell death and type I IFN production.
2022-04-04 | PXD030753 | Pride
Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID-19 cases are characterised by a mild, self-limiting disease course, a considerable subset of patients develop a more severe condition, varying from pneumonia and acute respiratory distress syndrome (ARDS) to multi-organ failure (MOF). Progression of COVID-19 is thought to occur as a result of a complex interplay between multiple pathophysiological mechanisms, all of which may orchestrate SARS-CoV-2 infection and contribute to organ-specific tissue damage. In this respect, dissecting currently available knowledge of COVID-19 immunopathogenesis is crucially important, not only to improve our understanding of its pathophysiology but also to fuel the rationale of both novel and repurposed treatment modalities. Various immune-mediated pathways during SARS-CoV-2 infection are relevant in this context, which relate to innate immunity, adaptive immunity, and autoimmunity. Pathological findings in tissue specimens of patients with COVID-19 provide valuable information with regard to our understanding of pathophysiology as well as the development of evidence-based treatment regimens. This review provides an updated overview of the main pathological changes observed in COVID-19 within the most commonly affected organ systems, with special emphasis on immunopathology. Current management strategies for COVID-19 include supportive care and the use of repurposed or symptomatic drugs, such as dexamethasone, remdesivir, and anticoagulants. Ultimately, prevention is key to combat COVID-19, and this requires appropriate measures to attenuate its spread and, above all, the development and implementation of effective vaccines. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
| S-EPMC8013908 | biostudies-literature
Project description:In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines “cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.
| S-EPMC7195984 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of inducing the activation of NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, a macromolecular structure sensing the danger and amplifying the inflammatory response. The main product processed by NLRP3 inflammasome is interleukin (IL)-1β, responsible for the downstream production of IL-6, which has been recognized as an important mediator in coronavirus disease 2019 (COVID-19). Since colchicine is an anti-inflammatory drug with the ability to block NLRP3 inflammasome oligomerization, this may prevent the release of active IL-1β and block the detrimental effects of downstream cytokines, i.e. IL-6. To date, few randomized clinical trials and many observational studies with colchicine have been conducted, showing interesting signals. As colchicine is a nonspecific inhibitor of the NLRP3 inflammasome, compounds specifically blocking this molecule might provide increased advantages in reducing the inflammatory burden and its related clinical manifestations. This may occur through a selective blockade of different steps preceding NLRP3 inflammasome oligomerization as well as through a reduced release of the main cytokines (IL-1β and IL-18). Since most evidence is based on observational studies, definitive conclusion cannot be drawn and additional studies are needed to confirm preliminary results and further dissect how colchicine and other NLRP3 inhibitors reduce the inflammatory burden and evaluate the timing and duration of treatment.
| S-EPMC8811745 | biostudies-literature
Project description:The clinical manifestation of coronavirus disease 2019 (COVID-19) mainly targets the lung as a primary affected organ, which is also a critical site of immune cell activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, recent reports also suggest the involvement of extrapulmonary tissues in COVID-19 pathology. The interplay of both innate and adaptive immune responses is key to COVID-19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long-term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS-CoV-2, in acute and post-acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID-19.
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