Down to a T: The Functional Importance of Lymphopenia in Severe COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Shahridan Faiez T
PROVIDER: S-EPMC9875899 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Down to a T: The Functional Importance of Lymphopenia in Severe COVID-19.
Shahridan Faiez Tasnim T Singanayagam Aran A
American journal of respiratory and critical care medicine 20220601 12
Similar Datasets
Project description: Not available
| S-BSST416 | biostudies-other
Project description:ObjectiveClinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19.MethodsComprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking.ResultsThere were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference - 361.06 μL [- 439.18, - 282.95], p < 0.001; I 2 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference - 395.35 μL [- 165.64, - 625.07], p < 0.001; I 2 87%), experienced ARDS (mean difference - 377.56 μL [- 271.89, - 483.22], p < 0.001; I 2 0%), received ICU care (mean difference - 376.53 μL [- 682.84, - 70.22], p = 0.02; I 2 89%), and have severe COVID-19 (mean difference - 353.34 μL [- 250.94, - 455.73], p < 0.001; I 2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I 2 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034).ConclusionThis meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.
| S-EPMC7245646 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-01 | GSE198257 | GEO
Project description:The study aims at investigating the specifical transcriptional signatures of severe COVID-19
2021-01-15 | GSE164805 | GEO
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:Analysis of COVID-19 hospitalized patients, with different kind of symptoms, by human rectal swabs collection and 16S sequencing approach.
2022-09-22 | E-MTAB-12236 | biostudies-arrayexpress
Project description:Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae but little is known about the eventual persistence of this immune alteration. Herein, we evaluated Toll-like receptor-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n=97). In the acute phase, we observed impaired cytokine production by monocytes in the most severe patients. This capacity was globally restored in convalescent patients. Yet, we observed increased responsiveness to TLR1/2 ligation in patients that recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. We identified a specific transcriptomic and epigenomic state in monocytes from acute severe patients that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at AP-1 and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes both during the acute and the convalescent phases in a completely distinct manner. This could have important implications for our understanding of short and long-term COVID19-related morbidity.
2022-04-01 | GSE198256 | GEO
Project description:Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae but little is known about the eventual persistence of this immune alteration. Herein, we evaluated Toll-like receptor-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n=97). In the acute phase, we observed impaired cytokine production by monocytes in the most severe patients. This capacity was globally restored in convalescent patients. Yet, we observed increased responsiveness to TLR1/2 ligation in patients that recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. We identified a specific transcriptomic and epigenomic state in monocytes from acute severe patients that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at AP-1 and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes both during the acute and the convalescent phases in a completely distinct manner. This could have important implications for our understanding of short and long-term COVID19-related morbidity.
2022-04-01 | GSE198255 | GEO
Project description:This submission contains a result of a study of transcriptiomic profiles of blood of COVID-19 patients.
2022-01-10 | GSE185863 | GEO
Project description:Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19-associated respiratory failure. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-associated pneumonia in the native lung. Most importantly, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report results of the first successful lung transplantation procedures in patients with non-resolving COVID-19-associated respiratory failure in the United States. We performed sm-FISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. We used a machine learning approach to project single cell RNA-Seq data from patients with late stage COVID-19 onto a single cell atlas of pulmonary fibrosis, revealing similarities across cell lineages. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.
2020-10-28 | GSE158127 | GEO