Early evidence of pronounced brain involvement in fatal COVID-19 outcomes.
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ABSTRACT:
SUBMITTER: von Weyhern CH
PROVIDER: S-EPMC7272176 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Early evidence of pronounced brain involvement in fatal COVID-19 outcomes.
von Weyhern Claus Hann CH Kaufmann Ines I Neff Frauke F Kremer Marcus M
Lancet (London, England) 20200604 10241
Similar Datasets
Project description:Single-cell RNA-sequencing reveals a shift from focused IFN alpha-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 – a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
2021-06-18 | GSE178404 | GEO
Project description:IntroductionCoronavirus disease 2019 (COVID-19) has become the worst catastrophe of the twenty-first century and has led to the death of more than 6.9 million individuals across the globe. Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between baseline and early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood.MethodsHere, we conducted a time series cross-sectional study aimed at assessing different measured parameters and socio-demographic factors that are associated with disease severity and the outcome of the disease in 268 PCR-confirmed COVID-19 Patients.ResultsWe found COVID-19 patients who died had a median age of 61 years (IQR, 50 y - 70 y), which is significantly higher (p < 0.05) compared to those who survived and had a median age of 54 years (IQR, 42y - 65y). The median RBC count of COVID-19 survivors was 4.9 × 106/μL (IQR 4.3 × 106/μL - 5.2 × 106/μL) which is higher (p < 0.05) compared to those who died 4.4 × 106/μL (3.82 × 106/μL - 5.02 × 106/μL). Similarly, COVID-19 survivors had significantly (p < 0.05) higher lymphocyte and monocyte percentages compared to those who died. One important result we found was that COVID-19 patients who presented with severe/critical cases at the time of first admission but managed to survive had a lower percentage of neutrophil, neutrophil to lymphocyte ratio, higher lymphocyte and monocyte percentages, and RBC count compared to those who died.ConclusionTo conclude here, we showed that simple laboratory parameters can be used to predict severity and outcome in COVID-19 patients. As these parameters are simple, inexpensive, and radially available in most resource-limited countries, they can be extrapolated to future viral epidemics or pandemics to allocate resources to particular patients.
| S-EPMC10751315 | biostudies-literature
Project description:Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocytosis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely impeding the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune signature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found monocyte and neutro-phil immune suppression loss associated with fatal clinical outcome in severe patients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allele, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of my-eloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.
2021-01-27 | GSE157344 | GEO
Project description:Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.
2021-05-03 | GSE155897 | GEO
Project description:The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), p = 0.001; HR = 15.65 (95% CI = 2.43-100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p < 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.
| S-EPMC7355571 | biostudies-literature
Project description:Cardiac microthrombi have been variably identified at autopsy of Covid-19 decedents. Little is known about the morphologic and molecular changes associated with cardiac microthrombi and whether predictive biomarkers exist. We sought to determine the prevalence, pathogenesis, and biomarker risk factors of Covid-19-associated cardiac microthrombi. In addition to histology and immunohistochemical analyses, we investigated right verticles from 8 Covid-19 decedents via single nuclei RNA sequencing for cell-type specific transcriptional differences between hearts with and without microthrombi, as well as between Covid-19 decedents and publicly available non-Covid-19 donor controls.
2021-12-28 | GSE185457 | GEO
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
2022-02-01 | E-MTAB-10129 | biostudies-arrayexpress
Project description:The blood of pregnant women affected by severe COVD-19 shows profound changes in immune cells. On the contrary, their placentas are relatively protected from severe perturbations.
2025-03-28 | GSE249139 | GEO
Project description:The current outbreak of coronavirus disease 2019 (COVID-19) has affected people around the world. Typically, COVID-19 originates in the lung, but lately it can extend to other organs and lead to tissue injury and multiorgan failure in severe patients, such as acute respiratory distress syndrome (ARDS), kidney failure and sepsis or systemic inflammation. Given that COVID-19 has been detected in a range of other organs, the COVID-19-associated disease is an alert of aberrant activation of host immune response which drives un-controlled inflammation that affects multiple organs. Complement is a vital component of innate immunity where it forms the first line of defense against potentially harmful microbes, but its role in COVID-19 is still not clear. Notably, the abnormal activation and continuous deposits of complement components were identified in the pre-clinical samples from COVID-19 patients, which have been confirmed in animal models. Recent evidence has revealed that the administration of complement inhibitors leads to relieve inflammatory response in ARDS. Hence, we speculate that the targeting complement system could be a potential treatment option for organ damage in COVID-19 patients.
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Project description:The aim of this study is to investigate clinical characteristics and fatal outcomes of hypertension as well as the role of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) use in patients with severe coronavirus disease 2019 (COVID-19). A total of 220 (female: 51.8%) patients with severe COVID-19 were included. The mean age of included patients was 59.5 years and 70 (31.8%) patients had a history of hypertension. There were 23 patients (32.9%) receiving ACEI/ARB therapy. Patients with hypertension were older and had more comorbidities, and were more likely to suffer from severe inflammatory response and acute cardiac injury. Moreover, patients with hypertension were associated with significantly higher risk of in-hospital mortality than patients without hypertension. After adjustment of potential confounders, the independent correlation was still observed. In addition, ACEI/ARB users were associated with lower level of high-sensitivity cardiac troponin I and creatinine kinase-myocardial band, and lower risk of acute cardiac injury than ACEI/ARB non-users. In conclusion, patients with hypertension were more likely to suffer from severe inflammatory response, acute cardiac injury and had high risk of in-hospital mortality in severe COVID-19. The use of ACEI/ARB may protect patients with COVID-19 from acute cardiac injury.
| S-EPMC7762496 | biostudies-literature