Neopterin Predicts Disease Severity in Hospitalized Patients With COVID-19.
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ABSTRACT:
SUBMITTER: Bellmann-Weiler R
PROVIDER: S-EPMC7665702 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T cell response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor Beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to the severity of the disease course. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 785 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 140 SARS-CoV-2 specific TRB sequences belonging to 119 clusters in our COVID-19 patients. Next, we investigated 92 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences towards the nonstructural proteins (NSPs) of ORF1a/b of the SARS-CoV-2 genome was observed in clusters with critical disease course when compared to COVID-19 clusters with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from nonstructural proteins of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.
2021-07-07 | GSE161810 | GEO
Project description:ObjectivesAngiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells. Here we investigated circulating ACE2 activity to predict the severity and mortality of COVID-19.MethodsSerum ACE2 activity was measured in COVID-19 (110 critically ill and 66 severely ill subjects at hospital admission and 106 follow-up samples) and in 32 non-COVID-19 severe sepsis patients. Associations between ACE2, inflammation-dependent biomarkers, pre-existing comorbidities, and clinical outcomes were studied.ResultsInitial ACE2 activity was significantly higher in critically ill COVID-19 patients (54.4 [36.7-90.8] mU/L) than in severe COVID-19 (34.5 [25.2-48.7] mU/L; P<0.0001) and non-COVID-19 sepsis patients (40.9 [21.4-65.7] mU/L; P=0.0260) regardless of comorbidities. Circulating ACE2 activity correlated with inflammatory biomarkers and was further elevated during the hospital stay in critically ill patients. Based on ROC-curve analysis and logistic regression test, baseline ACE2 independently indicated the severity of COVID-19 with an AUC value of 0.701 (95% CI [0.621-0.781], P<0.0001). Furthermore, non-survivors showed higher serum ACE2 activity vs. survivors at hospital admission (P<0.0001). Finally, high ACE2 activity (≥45.4 mU/L) predicted a higher risk (65 vs. 37%) for 30-day mortality (Log-Rank P<0.0001).ConclusionsSerum ACE2 activity correlates with COVID-19 severity and predicts mortality.
| S-EPMC8613979 | biostudies-literature
Project description:Mechanisms of neutrophil involvement in severe COVID-19 remain incompletely understood. Here we collect longitudinal blood samples from 306 hospitalized COVID-19+ patients and 86 controls, and perform bulk RNA-sequencing of enriched neutrophils, plasma proteomics, and high-throughput antibody profiling to investigate relationships between neutrophil states and disease severity. We identify dynamic switches between 6 distinct neutrophil subtypes. At days 3 and 7 post-hospitalization, patients with severe disease display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while patients with resolving disease show a neutrophil progenitor-like signature. Humoral responses are identified as potential drivers of neutrophil effector functions, with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirm that while patient-derived IgG antibodies induce phagocytosis in healthy donor neutrophils, IgA antibodies predominantly induce neutrophil cell death. Overall, our study demonstrates a dysregulated myelopoietic response in severe COVID-19 and a potential role for IgA-dominant responses contributing to mortality.
2022-08-28 | GSE212041 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-07-19 | GSE236017 | GEO
Project description:BackgroundData from the 2009 influenza pandemic suggested asthma might protect from severe disease in hospitalized patients. Asthma does not appear to increase risk for hospitalization or mortality with COVID-19.ObjectiveThis study was undertaken to see if atopy actually protected those hospitalized with COVID-19.MethodsRetrospective chart review on all patients testing positive for SARS-CoV-2 over 2 months at a major adult and pediatric tertiary referral center hospital. Charts were evaluated for history of atopic disease, as were the need for ICU admission, requirement for supplemental oxygen and/or intubation, and in hospital mortality.ResultsNo significant differences in outcomes for patients (n = 275) based on atopic disease were noted: ICU admission, 43% versus 44.7% (atopic versus no atopic disease, respectively; p = 0.84); supplemental oxygen use, 79.1% versus 73.6% (p = 0.36); intubation rate, 35.8% versus 36.5% (p = 0.92); and mortality rate, 13.4% versus 20.7% (p = 0.19). More patients with atopic disease had COPD listed as a diagnosis in their chart (38.8% versus 17.3%, p < 0.001). COPD was associated with an increased rate of ICU admission (aOR = 2.22 (1.15, 4.30) p = 0.02) and intubation (aOR = 2.05 (1.07, 3.92) p = 0.03). After adjusting for COPD, patients with atopic disease had a trend for reduced mortality (aOR 0.55 (0.23, 1.28), p = 0.16), but those with asthma did not (p > 0.2).ConclusionSeverity of COVID-19 in hospitalized patients does not differ based on atopic status. However, adjusting for presence of COPD led to a suggestion of possible reduced severity in patients with atopy but not asthma.
| S-EPMC7820556 | biostudies-literature
Project description:BackgroundTreatment decisions for Coronavirus Disease 2019 (COVID-19) depend on disease severity, but the prescribing pattern by severity and drivers of therapeutic choices remain unclear.ObjectivesThe objectives of the study were to evaluate pharmacological treatment patterns by COVID-19 severity and identify the determinants of prescribing for COVID-19.MethodsUsing electronic health record data from a large Massachusetts-based healthcare system, we identified all patients aged ≥ 18 years hospitalized with laboratory-confirmed COVID-19 from 1 March to 24 May, 2020. We defined five levels of COVID-19 severity at hospital admission: (1) hospitalized but not requiring supplemental oxygen; (2-4) hospitalized and requiring oxygen ≤ 2, 3-4, and ≥ 5 L per minute, respectively; and (5) intubated or admitted to an intensive care unit. We assessed the medications used to treat COVID-19 or as supportive care during hospitalization.ResultsAmong 2821 patients hospitalized for COVID-19, we found inpatient mortality increased by severity from 5% for level 1 to 23% for level 5. As compared to patients with severity level 1, those with severity level 5 were 3.53 times (95% confidence interval 2.73-4.57) more likely to receive a medication used to treat COVID-19. Other predictors of treatment were fever, low oxygen saturation, presence of co-morbidities, and elevated inflammatory biomarkers. The use of most COVID-19 relevant medications has dropped substantially while the use of remdesivir and therapeutic anticoagulants has increased over the study period.ConclusionsCareful consideration of disease severity and other determinants of COVID-19 drug use is necessary for appropriate conduct and interpretation of non-randomized studies evaluating outcomes of COVID-19 treatments.
| S-EPMC7643089 | biostudies-literature
Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
2022-03-01 | E-MTAB-10970 | biostudies-arrayexpress
Project description: Not available
| S-BSST1269 | biostudies-other
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a global health emergency. To improve the understanding of the systemic component of SARS-CoV-2, we investigated if viral load dynamics in plasma and respiratory samples are associated with antibody response and severity of coronavirus disease 2019 (COVID-19). SARS-CoV-2 RNA was found in plasma samples from 14 (44%) out of 32 patients. RNAemia was detected in 5 out of 6 fatal cases. Peak IgG values were significantly lower in mild/moderate than in severe (0.6 (interquartile range, IQR, 0.4-3.2) vs. 11.8 (IQR, 9.9-13.0), adjusted p = 0.003) or critical cases (11.29 (IQR, 8.3-12.0), adjusted p = 0.042). IgG titers were significantly associated with virus Ct (Cycle threshold) value in plasma and respiratory specimens ((ß = 0.4, 95% CI (confidence interval, 0.2; 0.5), p < 0.001 and ß = 0.5, 95% CI (0.2; 0.6), p = 0.002). A classification as severe or a critical case was additionally inversely associated with Ct values in plasma in comparison to mild/moderate cases (ß = -3.3, 95% CI (-5.8; 0.8), p = 0.024 and ß = -4.4, 95% CI (-7.2; 1.6), p = 0.007, respectively). Based on the present data, our hypothesis is that the early stage of SARS-CoV-2 infection is characterized by a primary RNAemia, as a potential manifestation of a systemic infection. Additionally, the viral load in plasma seems to be associated with a worse disease outcome.
| S-EPMC7551174 | biostudies-literature
Project description:BackgroundThe immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease.MethodsWe performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients.ResultsHere we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1β, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts.ConclusionsWe identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19.
| S-EPMC9466310 | biostudies-literature