Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage.
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ABSTRACT:
SUBMITTER: Chen YM
PROVIDER: S-EPMC7737620 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mortality rate is high with COVID-19. Multiple organ damage is a common and lethal complication of the severe COVID-19 patients. Of 198 recruited participants, 65 patients (32.8 %) had coagulopathy. In this retrospective study, we analyzed the association of coagulopathy with organ dysfunction in hospitalized COVID-19 patients. The incidence of coagulopathy was associated with increased odds of acute liver injury, renal dysfunction and acute respiratory distress syndrome (ARDS) by multivariable regression. Overall mortality was 65 % for the patients with coagulopathy and 3.76 % for the patients without coagulopathy. History of hypertension, leukocytosis and elevated CRP concentrations were associated with higher odds of coagulopathy. Patients with coagulopathy had similar levels of hepatic and renal functional enzymes prior to the onset of coagulopathy as the patients without coagulopathy, suggesting that coagulopathy is an association of the progression of multi-organ dysfunction in COVID-19. Plasma IL-6 was higher in patients with coagulopathy than controls, but it's not a risk factor for organ dysfunction by logistic regression. The present study shows that coagulopathy, overt DIC and non-overt DIC, associates with organ dysfunction and higher mortality rate in COVID-19. Thus, anticoagulant therapy may prevent organ dysfunction and increase survival rate in COVID-19.
| S-EPMC7868640 | biostudies-literature
Project description:Multi-omics single-cell profiling of surface proteins, gene expression and lymphocyte immune receptors from hospitalised COVID-19 patient peripheral blood immune cells and healthy controls donors. Identification of the coordinated immune cell compositional and state changes in response to SARS-CoV-2 infection or LPS challenge, compared to healthy control immune cells.
2021-03-17 | E-MTAB-10026 | biostudies-arrayexpress
Project description:Abstract Background: The development of severe coronavirus disease 2019 (COVID-19) is associated with systemic hyperinflammation, which drives multi-organ failure and death. Disease deterioration tends to occur when the virus is receding; however, whether other factors besides viral products are involved in the inflammatory cascade remains unclear. Methods: Twenty-eight COVID-19 patients with laboratory-confirmed SARS-CoV-2 infection hospitalized at the Fifth Medical Center of Chinese PLA General Hospital from January 23 to February 20, 2020 and nine healthy donors during the same period were recruited in the study. COVID-19 patients were grouped as mild, moderate, severe based on disease severity. Plasma damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), calprotectin (S100A8/A9), surfactant protein A (SP-A), cold-inducible RNA-binding protein (CIRBP), and Histone H4 were detected by ELISA assay, and analyzed in combination with clinical data. Plasma cytokines, chemokines and lymphocytes were determined by flow cytometry. Results: Plasma levels of HMGB1 (38292.3 ± 4564.4 vs. 32686.3 ± 3678.1, P = 0.002), S100A8/A9 (1490.8 ± 819.3 vs. 742.2 ± 300.8, P = 0.015), and SP-A (6713.6 ± 1708.7 vs. 5296.3 ± 1240.4, P = 0.048) were increased in COVID-19 patients compared to healthy donors, while CIRBP (57.4 ± 30.7 vs. 111.9 ± 55.2, P = 0.004) levels decreased. Five DAMPs did not vary among mild, moderate, and severe patients. Moreover, SP-A levels correlated positively with inflammatory cytokines and negatively with time elapsed after symptom onset, whereas CIRBP showed an opposite pattern. Conclusions: These findings suggest SP-A may involve in the inflammation of COVID-19, while CIRBP likely plays a protective role. Therefore, DAMPs represent a potential target in the prevention or treatment of COVID-19.
| S-EPMC8057315 | biostudies-literature
Project description:BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) blunts the broad inflammatory response induced by damage-associated molecular patterns via binding to extracellular high mobility group box 1 and heat shock proteins, as well as regulating the downstream Siglec10-Src homology 2 domain-containing phosphatase 1 pathway. A recent randomized phase III trial evaluating CD24Fc for patients with severe COVID-19 (SAC-COVID; NCT04317040) demonstrated encouraging clinical efficacy.MethodsUsing a systems analytical approach, we studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial to discern the impact of CD24Fc treatment on immune homeostasis. We performed high dimensional spectral flow cytometry and measured the levels of a broad array of cytokines and chemokines to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19.ResultsTwenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found that patients with severe COVID-19 had systemic hyper-activation of multiple cellular compartments, including CD8+ T cells, CD4+ T cells, and CD56+ natural killer cells. Treatment with CD24Fc blunted this systemic inflammation, inducing a return to homeostasis in NK and T cells without compromising the anti-Spike protein antibody response. CD24Fc significantly attenuated the systemic cytokine response and diminished the cytokine coexpression and network connectivity linked with COVID-19 severity and pathogenesis.ConclusionsOur data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.
| S-EPMC8744064 | biostudies-literature
Project description:SARS-CoV-2 causes COVID-19 through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns (DAMPs) and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) is able to blunt the broad inflammatory response induced by DAMPs in multiple models. A recent randomized phase III trial evaluating the impact of CD24Fc in patients with severe COVID-19 demonstrated encouraging clinical efficacy. We studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial (NCT04317040) collected before and after treatment with CD24Fc or placebo. We performed high dimensional spectral flow cytometry analysis of peripheral blood mononuclear cells and measured the levels of a broad array of cytokines and chemokines. A systems analytical approach was used to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found systemic hyper-activation of multiple cellular compartments in the placebo group, including CD8+ T cells, CD4+ T cells, and CD56+ NK cells. By contrast, CD24Fc-treated patients demonstrated blunted systemic inflammation, with a return to homeostasis in both NK and T cells within days without compromising the ability of patients to mount an effective anti-Spike protein antibody response. A single dose of CD24Fc significantly attenuated induction of the systemic cytokine response, including expression of IL-10 and IL-15, and diminished the coexpression and network connectivity among extensive circulating inflammatory cytokines, the parameters associated with COVID-19 disease severity. Our data demonstrates that CD24Fc treatment rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19. NIH.
| S-EPMC8404902 | biostudies-literature
Project description:The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.
| S-EPMC7794601 | biostudies-literature
Project description: Not available
| S-BSST416 | biostudies-other
Project description:As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.
| S-EPMC8616204 | biostudies-literature
Project description:BackgroundMajor organ complications have been reported in patients hospitalised for COVID-19; most studies lacked controls.ObjectiveExamine major organ damage postdischarge among adults hospitalised for COVID-19 versus non-COVID-19 controls.Data sourcesMEDLINE, Embase and Cochrane Library from 1 January 2020 to 19 May 2021.Study eligibility criteriaEnglish language studies of adults discharged from hospital for COVID-19; reporting major organ damage. Single review of abstracts; independent dual review of full text.Study appraisal and synthesis methodsStudy quality was assessed using the Joanna Briggs Institute Appraisal Checklist for Cohort Studies. Outcome data were not pooled due to heterogeneity in populations, study designs and outcome assessment methods; findings are narratively synthesised.ResultsOf 124 studies in a full evidence report, 9 included non-COVID controls and are described here. Four of the nine (three USA, one UK) used large administrative databases. Four of the remaining five studies enrolled <600 COVID-19 patients. Mean or median age ranged from 49 to 70 years with 46%-94% male and 48%-78% White race; 10%-40% had been in intensive care units. Follow-up ranged from 4 weeks to 22 weeks postdischarge. Four used hospitalised controls, three non-hospitalised controls and two were unclear. Studies used various definitions of, and methods to assess, major organ damage outcomes. While the magnitude of effect differed across studies, incident cardiac, pulmonary, liver, acute and chronic kidney, stroke, diabetes, and coagulation disorders were consistently greater in adults hospitalised for COVID-19 compared with non-COVID-19 controls.LimitationsApplicability to subgroups (age, gender, COVID-19 severity, treatment, vaccination status) and non-hospitalised patients is unknown.Conclusions and implications of key findingsPostacute COVID-19 major organ damage is common and likely higher than controls. However, there is substantial uncertainty. More consistent reporting of clinical outcomes and pre-COVID health status along with careful selection of control groups are needed to address evidence gaps.Prospero registration numberCRD42020204788.
| S-EPMC9412042 | biostudies-literature
Project description:The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19.
| S-EPMC7484812 | biostudies-literature