Similar Datasets
Project description:SARS-CoV-2 infection can cause persistent respiratory sequelae, as seen in long COVID. However, the underlying mechanisms remain unclear. To investigate pulmonary cellular and transcriptomic changes mediated by SARS-CoV-2 and influenza infection, we characterized the SARS-CoV-2-infected K18-hACE2 (K18) mice and compared their lung recovery with a mouse-adapted influenza model and verified the finding in SARS-CoV-2-infected nonhuman primates and in fatal human COVID-19 cases. K18-hACE2 mice infected with a sub-lethal dose of SARS-CoV-2 lost body weight from 1 - 8 days post-infection (DPI), and then gradually returned to baseline weight between 8 -13 DPI. Infected mice showed patchy pneumonia associated with histiocytic inflammation, collagen deposition, and increased pulmonary interferon and inflammatory response signature gene changes at 21 and 45 DPI. Transcriptomic analyses revealed that compared to influenza-infected mice, SARS-CoV-2-infected mice had reduced interferon-gamma/alpha responses at 4 DPI and failed to induce keratin 5 (Krt5) at 6 DPI in lung, a marker of nascent pulmonary progenitor cells. They also showed reduced activation of epithelial-to-mesenchymal transition and apical junction pathways compared to influenza (Flu)-infected mice. Histologically, influenza- but not SARS-CoV-2- infected mice showed extensive Krt5+ “pods” structure co-stained with stem cell markers Trp63/ NGFR proliferated in the pulmonary consolidation area at both 7 and 14 DPI, with regression at 21 DPI. These Krt5+ “pods” and proliferative stem cells were not observed in SARS-CoV-2 infection in the lungs of humans or nonhuman primates. These results suggest that SARS-CoV-2 infection fails to induce nascent Krt5+ cell proliferation in consolidated regions, leading to incomplete repair of the injured lung which may underlie the persistent clinical symptoms of long COVID.
2023-12-02 | GSE248775 | GEO
Project description:SARS-CoV-2 infection can cause persistent respiratory sequelae, as seen in long COVID. However, the underlying mechanisms remain unclear. To investigate pulmonary cellular and transcriptomic changes mediated by SARS-CoV-2 and influenza infection, we characterized the SARS-CoV-2-infected K18-hACE2 (K18) mice and compared their lung recovery with a mouse-adapted influenza model and verified the finding in SARS-CoV-2-infected nonhuman primates and in fatal human COVID-19 cases. K18-hACE2 mice infected with a sub-lethal dose of SARS-CoV-2 lost body weight from 1 - 8 days post-infection (DPI), and then gradually returned to baseline weight between 8 -13 DPI. Infected mice showed patchy pneumonia associated with histiocytic inflammation, collagen deposition, and increased pulmonary interferon and inflammatory response signature gene changes at 21 and 45 DPI. Transcriptomic analyses revealed that compared to influenza-infected mice, SARS-CoV-2-infected mice had reduced interferon-gamma/alpha responses at 4 DPI and failed to induce keratin 5 (Krt5) at 6 DPI in lung, a marker of nascent pulmonary progenitor cells. They also showed reduced activation of epithelial-to-mesenchymal transition and apical junction pathways compared to influenza (Flu)-infected mice. Histologically, influenza- but not SARS-CoV-2- infected mice showed extensive Krt5+ “pods” structure co-stained with stem cell markers Trp63/ NGFR proliferated in the pulmonary consolidation area at both 7 and 14 DPI, with regression at 21 DPI. These Krt5+ “pods” and proliferative stem cells were not observed in SARS-CoV-2 infection in the lungs of humans or nonhuman primates. These results suggest that SARS-CoV-2 infection fails to induce nascent Krt5+ cell proliferation in consolidated regions, leading to incomplete repair of the injured lung which may underlie the persistent clinical symptoms of long COVID.
2023-12-02 | GSE248773 | GEO
Project description:COVID-19 and influenza infections mediate distinct pulmonary cellular and transcriptomic changes
| PRJNA1045987 | ENA
Project description:COVID-19 and influenza infections mediate distinct pulmonary cellular and transcriptomic changes [RNA-seq]
| PRJNA1045984 | ENA
Project description:COVID-19 and influenza infections mediate distinct pulmonary cellular and transcriptomic changes [scRNA-Seq]
| PRJNA1045991 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-05 | GSE237180 | GEO
Project description:Dexamethasone is the standard of care for critically ill patients with COVID-19, but its immunological effects in this setting and the mechanisms by which it decreases mortality are not understood. We performed bulk and single-cell RNA sequencing of the lower respiratory tract and blood, and plasma cytokine profiling to study the effect of dexamethasone on systemic and pulmonary immune cells. We find signatures of decreased viral injury, antigen presentation, and T cell recruitment in patients treated with dexamethasone. We identify compartment- and cell- specific differences in the effect of dexamethasone in patients with severe COVID that are reproducible in publicly available datasets. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
2024-05-05 | GSE237109 | GEO
Project description:Dexamethasone is the standard of care for critically ill patients with COVID-19, but its immunological effects in this setting and the mechanisms by which it decreases mortality are not understood. We performed bulk and single-cell RNA sequencing of the lower respiratory tract and blood, and plasma cytokine profiling to study the effect of dexamethasone on systemic and pulmonary immune cells. We find signatures of decreased viral injury, antigen presentation, and T cell recruitment in patients treated with dexamethasone. We identify compartment- and cell- specific differences in the effect of dexamethasone in patients with severe COVID that are reproducible in publicly available datasets. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
2024-05-05 | GSE236030 | GEO
Project description:To rapidly prognosticate and generate hypotheses on pathogenesis, leukocyte multi-cellularity was evaluated in SARS-CoV-2 infected patients treated in India or the United States (152 individuals, 384 temporal observations). Within hospital (<90-day) death or discharge were retrospectively predicted based on the admission complete blood cell counts (CBC). Two methods were applied: (i) a "reductionist" one, which analyzes each cell type separately, and (ii) a "non-reductionist" method, which estimates multi-cellularity. The second approach uses a proprietary software package that detects distinct data patterns generated by complex and hypothetical indicators and reveals each data pattern's immunological content and associated outcome(s). In the Indian population, the analysis of isolated cell types did not separate survivors from non-survivors. In contrast, multi-cellular data patterns differentiated six groups of patients, including, in two groups, 95.5% of all survivors. Some data structures revealed one data point-wide line of observations, which informed at a personalized level and identified 97.8% of all non-survivors. Discovery was also fostered: some non-survivors were characterized by low monocyte/lymphocyte ratio levels. When both populations were analyzed with the non-reductionist method, they displayed results that suggested survivors and non-survivors differed immunologically as early as hospitalization day 1.
| S-EPMC8913044 | biostudies-literature
Project description:Influenza A infection is a serious threat to human and animal health. Many of the biological mechanisms of the host-pathogen-interactions are still not well understood and reliable biomarkers indicating the course of the disease are missing. The mouse is a valuable model system enabling us to study the local inflammatory host response and the influence on blood parameters under controlled circumstances. Here, we compared the lung and peripheral changes after PR8 (H1N1) influenza A virus infection in C57BL/6J and DBA/2J mice using virus variants of different pathogenicity resulting in non-lethal and lethal disease. We monitored hematological and immunological parameters revealing that the granulocyte to lymphocyte ratio in the blood represents an early indicator of severe disease progression already two days after influenza A infection in mice. These findings might be relevant to optimize early diagnostic options of severe influenza disease and to monitor successful therapeutic treatment in humans.
| S-EPMC4110021 | biostudies-literature