Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors

Gedda, Mallikarjuna Rao; Danaher, Patrick; Shao, Lipei; Ongkeko, Martin; Chen, Leonard; Dinh, Anh; Sall, Mame Thioye; Reddy, Opal L.; Bailey, Christina; Wahba, Amy; Dzekunova, Inna; Somerville, Robert; Giorgi, Valeria De; Jin, Ping; West, Kamille A.; Panch, Sandhya R.; Stroncek, David F.

doi:10.1186/s12967-022-03751-7

Cited by 6 publications

(3 citation statements)

References 73 publications

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“…Such observations further suggest the involvement of epigenetic regulatory mechanisms in COVID-19 [ 90 ]. MCP-1, a pro-inflammatory chemokine well-known to be increased in COVID-19 patients [ 91 , 92 , 93 , 94 , 95 ], was also found to be increased in SARS-CoV-2-exposed HBMEC conditioned media, as detected by mini-proteome assays. Accordingly, recent findings from our group show that both delta and D614G Spike1 proteins are capable of inducing MCP-1 release from HBMECs (Stangis and Toborek et al, unpublished data).…”

Section: Discussionmentioning

confidence: 95%

Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling

Motta

Torices

Rosa

et al. 2023

Viruses

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Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood–brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.

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Section: Discussionmentioning

confidence: 95%

Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling

Motta

Torices

Rosa

et al. 2023

Viruses

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“…Our data indicate that until receiving the booster vaccine dose, humoral responses were stronger in those individuals with a previous infection with SARS-CoV-2. On the other hand, early T-cell responses after the two first doses were dampened in COVID-19-recovered individuals, which might be associated with the generation of immunomodulatory T regulatory cells (5) and/or T-cell exhaustion due to SARS-CoV-2 infection, as described elsewhere (31)(32)(33). Nevertheless, T-cellmediated responses were comparable in both naïve and recovered participants following 7 months after the second vaccine jab.…”

Section: Discussionmentioning

confidence: 73%

mRNA-1273 boost after BNT162b2 vaccination generates comparable SARS-CoV-2-specific functional responses in naïve and COVID-19-recovered individuals

et al. 2023

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IntroductionCOVID-19 vaccines based on mRNA have represented a revolution in the biomedical research field. The initial two-dose vaccination schedule generates potent humoral and cellular responses, with a massive protective effect against severe COVID-19 and death. Months after this vaccination, levels of antibodies against SARS-CoV-2 waned, and this promoted the recommendation of a third vaccination dose.MethodsWe have performed an integral and longitudinal study of the immunological responses triggered by the booster mRNA-1273 vaccination, in a cohort of health workers previously vaccinated with two doses of the BNT162b2 vaccine at University Hospital La Paz located in Madrid, Spain. Circulating humoral responses and SARS-CoV-2-specific cellular reactions, after ex vivo restimulation of both T and B cells (cytokines production, proliferation, class switching), have been analyzed. Importantly, all along these studies, the analyses have been performed comparing naïve and subjects recovered from COVID-19, addressing the influence of a previous infection by SARS-CoV-2. Furthermore, as the injection of the third vaccination dose was contemporary to the rise of the Omicron BA.1 variant of concern, T- and B-cell-mediated cellular responses have been comparatively analyzed in response to this variant.ResultsAll these analyses indicated that differential responses to vaccination due to a previous SARS-CoV-2 infection were balanced following the boost. The increase in circulating humoral responses due to this booster dropped after 6 months, whereas T-cell-mediated responses were more stable along the time. Finally, all the analyzed immunological features were dampened in response to the Omicron variant of concern, particularly late after the booster vaccination.ConclusionThis work represents a follow-up longitudinal study for almost 1.5 years, analyzing in an integral manner the immunological responses triggered by the prime-boost mRNA-based vaccination schedule against COVID-19.

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“…The dataset GSE211378 investigated the cellular immune response in people who had recovered from SARS-CoV-2 infection. 13 The dataset consists of mRNA expression profiles that were generated using the GPL32571 nCounter Host Response Panel v1.0 platform. The dataset contains 304 whole blood samples from 264 COVID convalescent donors and 40 from healthy donors.…”

Section: Methodsmentioning

confidence: 99%

Integrated Transcriptomics and Network Analysis of Potential Mechanisms and Health Effects of Convalescent COVID-19 Patients

Chujan,

Nakareangrit,

Suriyo

et al. 2023

Bioinform Biol Insights

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Coronaviral disease 2019 (COVID-19) is a recent pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there are still cases of COVID-19 around the world that can develop into persistent symptoms after discharge. The constellation of symptoms, termed long COVID, persists for months and can lead to various diseases such as lung inflammation and cardiovascular disease, which may lead to considerable financial burden and possible risk to human health. Moreover, the molecular mechanisms underlying the post-pandemic syndrome of COVID-19 remain unclear. In this study, we aimed to explore the molecular mechanism, disease association, and possible health risks in convalescent COVID-19 patients. Gene expression data from a human convalescent COVID-19 data set was compared with a data set from healthy normal individuals in order to identify differentially expressed genes (DEGs). To determine biological function and potential pathway alterations, the GO and KEGG databases were used to analyze the DEGs. Disease association, tissue, and organ-specific analyses were used to identify possible health effects. A total of 250 DEGs were identified between healthy and convalescent COVID-19 subjects. The biological function alterations identified revealed cytokine interactions and increased inflammation through NF-κB1, RELA, JUN, STAT3, and SP1. Interestingly, the most significant pathways were cytokine-cytokine receptor interaction, altered lipid metabolism, and atherosclerosis that play a crucial role in convalescent COVID-19. In addition, we also found pneumonitis, dermatitis, and autoimmune diseases. Based on our study, convalescent COVID-19 is associated with inflammation in a variety of organs that could lead to autoimmune and inflammatory diseases, as well as atherosclerosis. These findings are a first step toward fully exploring the disease mechanisms in depth to understand the relationship between post-COVID-19 infection and potential health risks. This is necessary for the development of appropriate strategies for the prevention and treatment of long COVID.

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Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors

Cited by 6 publications

References 73 publications

Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling

Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling

mRNA-1273 boost after BNT162b2 vaccination generates comparable SARS-CoV-2-specific functional responses in naïve and COVID-19-recovered individuals

Integrated Transcriptomics and Network Analysis of Potential Mechanisms and Health Effects of Convalescent COVID-19 Patients

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