Blood transcriptome analysis revealed the crosstalk between severe COVID-19 and systemic lupus erythematosus.
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ABSTRACT:
SUBMITTER: Meng R
PROVIDER: S-EPMC9916182 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
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Blood transcriptome analysis revealed the crosstalk between severe COVID-19 and systemic lupus erythematosus.
Meng Ruogang R Zhang Ning N Yang Feixiang F Xu Zhihao Z Wu Zhengyang Z Du Yinan Y
The Journal of infection 20230210 4
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Project description:Purpose of reviewTo describe the current state of knowledge regarding COVID-19 in patients with systemic lupus erythematosus (SLE). We focus on (i) SARS-CoV-2 vaccination uptake, immunogenicity and safety, and (ii) outcomes of COVID-19 in patients with SLE and pertinent risk factors for adverse sequelae.Recent findingsNotwithstanding the potential concern of patients about possible post-vaccination side-effects, the safety of anti-SARS-CoV-2 vaccines in patients with SLE has been undisputedly confirmed in numerous studies. Humoral immunogenicity is generally attained in SLE, although affected by the use of background immunosuppressive drugs, especially rituximab. The latter has also clearly been implicated with adverse COVID-19 outcomes in SLE, including need for hospitalization, mechanical ventilation and death. Although the wide adoption of vaccination has significantly improved COVID-19 outcomes, patients with SLE continue to pose challenges during the pandemic, mainly owing to administered immunosuppressive medications.
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Project description:BackgroundThe severe coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has resulted in the most devastating pandemic in modern history. Human immunodeficiency virus (HIV) destroys immune system cells and weakens the body's ability to resist daily infections and diseases. Furthermore, HIV-infected individuals had double COVID-19 mortality risk and experienced worse COVID-related outcomes. However, the existing research still lacks the understanding of the molecular mechanism underlying crosstalk between COVID-19 and HIV. The aim of our work was to illustrate blood transcriptome crosstalk between COVID-19 and HIV and to provide potential drugs that might be useful for the treatment of HIV-infected COVID-19 patients.MethodsCOVID-19 datasets (GSE171110 and GSE152418) were downloaded from Gene Expression Omnibus (GEO) database, including 54 whole-blood samples and 33 peripheral blood mononuclear cells samples, respectively. HIV dataset (GSE37250) was also obtained from GEO database, containing 537 whole-blood samples. Next, the "Deseq2" package was used to identify differentially expressed genes (DEGs) between COVID-19 datasets (GSE171110 and GSE152418) and the "limma" package was utilized to identify DEGs between HIV dataset (GSE37250). By intersecting these two DEG sets, we generated common DEGs for further analysis, containing Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional enrichment analysis, protein-protein interaction (PPI) analysis, transcription factor (TF) candidate identification, microRNAs (miRNAs) candidate identification and drug candidate identification.ResultsIn this study, a total of 3213 DEGs were identified from the merged COVID-19 dataset (GSE171110 and GSE152418), and 1718 DEGs were obtained from GSE37250 dataset. Then, we identified 394 common DEGs from the intersection of the DEGs in COVID-19 and HIV datasets. GO and KEGG enrichment analysis indicated that common DEGs were mainly gathered in chromosome-related and cell cycle-related signal pathways. Top ten hub genes (CCNA2, CCNB1, CDC20, TOP2A, AURKB, PLK1, BUB1B, KIF11, DLGAP5, RRM2) were ranked according to their scores, which were screened out using degree algorithm on the basis of common DEGs. Moreover, top ten drug candidates (LUCANTHONE, Dasatinib, etoposide, Enterolactone, troglitazone, testosterone, estradiol, calcitriol, resveratrol, tetradioxin) ranked by their P values were screened out, which maybe be beneficial for the treatment of HIV-infected COVID-19 patients.ConclusionIn this study, we provide potential molecular targets, signaling pathways, small molecular compounds, and promising biomarkers that contribute to worse COVID-19 prognosis in patients with HIV, which might contribute to precise diagnosis and treatment for HIV-infected COVID-19 patients.
| S-EPMC9650272 | biostudies-literature
Project description:BackgroundThe extensive spread of coronavirus disease 2019 (COVID-19) has led to a rapid increase in global mortality. Preeclampsia is a commonly observed pregnancy ailment characterized by high maternal morbidity and mortality rates, in addition to the restriction of fetal growth within the uterine environment. Pregnant individuals afflicted with vascular disorders, including preeclampsia, exhibit an increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection via mechanisms that have not been fully delineated. Additionally, the intricate molecular mechanisms underlying preeclampsia and COVID-19 have not been fully elucidated. This study aimed to discern commonalities in gene expression, regulators, and pathways shared between COVID-19 and preeclampsia. The objective was to uncover potential insights that could contribute to novel treatment strategies for both COVID-19 and preeclampsia.MethodTranscriptomic datasets for COVID-19 peripheral blood (GSE152418) and preeclampsia blood (GSE48424) were initially sourced from the Gene Expression Omnibus (GEO) database. Subsequent to that, we conducted a subanalysis by selecting females from the GSE152418 dataset and employed the "Deseq2" package to identify genes that exhibited differential expression. Simultaneously, the "limma" package was applied to identify differentially expressed genes (DEGs) in the preeclampsia dataset (GSE48424). Following that, an intersection analysis was conducted to identify the common DEGs obtained from both the COVID-19 and preeclampsia datasets. The identified shared DEGs were subsequently utilized for functional enrichment analysis, transcription factor (TF) and microRNAs (miRNA) prediction, pathway analysis, and identification of potential candidate drugs. Finally, to validate the bioinformatics findings, we collected peripheral blood mononuclear cell (PBMC) samples from healthy individuals, COVID-19 patients, and Preeclampsia patients. The abundance of the top 10 Hub genes in both diseases was assessed using real-time quantitative polymerase chain reaction (RT-qPCR).ResultA total of 355 overlapping DEGs were identified in both preeclampsia and COVID-19 datasets. Subsequent ontological analysis, encompassing Gene Ontology (GO) functional assessment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, revealed a significant association between the two conditions. Protein-protein interactions (PPIs) were constructed using the STRING database. Additionally, the top 10 hub genes (MRPL11, MRPS12, UQCRH, ATP5I, UQCRQ, ATP5D, COX6B1, ATP5O, ATP5H, NDUFA6) were selected based on their ranking scores using the degree algorithm, which considered the shared DEGs. Moreover, transcription factor-gene interactions, protein-drug interactions, co-regulatory networks of DEGs and miRNAs, and protein-drug interactions involving the shared DEGs were also identified in the datasets. Finally, RT-PCR results confirmed that 10 hub genes do exhibit distinct expression profiles in the two diseases.ConclusionThis study successfully identified overlapping DEGs, functional pathways, and regulatory elements between COVID-19 and preeclampsia. The findings provide valuable insights into the shared molecular mechanisms and potential therapeutic targets for both diseases. The validation through RT-qPCR further supports the distinct expression profiles of the identified hub genes in COVID-19 and preeclampsia, emphasizing their potential roles as biomarkers or therapeutic targets in these conditions.
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Project description:BackgroundPatients with chronic diseases are potential candidates for inadequate follow-up of drug therapy, tending to incur damage to the intended results. This deserves greater attention in the pandemic period, as they are in the considered risk group.MethodsWe aim to assess Treatment Adherence Measure and analyze associations with characteristics related to the patient, treatment, disease, health professionals and service, and sociodemographic issues in patients with Systemic Lupus Erythematosus (SLE). W conducted a cross-sectional study with a sample of 116 participants, whose data were collected through individual interviews and review of medical records, during the first months of the COVID-19 pandemic in Brazil. Adherence was measured using the Treatment Adherence Measure, and associations were evidenced through described and inferential statistics.ResultsThe percentage of adherent patients was 55.2%. An association was found between MTA (Medication Treatment Adherence) and physical exercise practice (p = 0.032), and difficulties with treatment (p = 0.002). Conclusion: Participants who did not practice physical exercise were 3.71 times more likely to not adhere to the treatment. Individuals who identified difficulties in the treatment were 3.43 times more likely to not adhere to the treatment; we believe that the pandemic may have influenced this result. More targeted studies are needed to measure the impact on MTA in these patients.
| S-EPMC8792910 | biostudies-literature
Project description:ObjectiveEmerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown.MethodsIn this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method.ResultsThe results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found.ConclusionThe findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.
| S-EPMC10232808 | biostudies-literature
Project description:The experiment consists of 31 Systemic Lupus Erythematosus patient blood samples and 29 healthy donor blood samples.
2018-03-21 | GSE112087 | GEO
Project description:COVID-19 vaccination has been shown to be safe in patients with systemic lupus erythematosus (SLE), but data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking. We investigated COVID-19 vaccination-related AEs in pregnant SLE patients from the COVAD study, a global esurvey involving 157 collaborators from 106 countries. A total of 9201 complete responses were extracted. Among 6787 (73.8%) women, we identified 70 (1.1%) who were exposed to at least one COVID-19 vaccine dose during pregnancy, 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women. Health-related quality of life and physical function was recorded using PROMIS. Age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs or change in the status of their autoimmune disease. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved after a median of 3 (IQR: 2.5-5.0) days. All patients reported good to excellent health status. No adverse pregnancy outcomes were reported. Importantly, none of the patients reported thrombotic events post-vaccination, which provides reassurance in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or the antiphospholipid syndrome, a considerable portion of SLE patients. Our findings provide reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and high-risk pregnancies due to their background autoimmune disease. The risk/benefit ratio of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.
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Project description:The SARS-CoV-2 novel coronavirus has caused the COVID-19 pandemic with over 35 million cases and over a million deaths worldwide as of early October 2020. The populations most affected are the elderly and especially those with underlying comorbidities. In terms of race and ethnicity, black and hispanic populations are affected at disproportionately higher rates. Individuals with underlying conditions that cause an immune-compromised state are considered vulnerable to this infection. The immune response is an important determinant in viral infections including coronaviruses, not only in the antiviral defense but also in the disease progression, severity, and clinical outcomes of COVID-19. Systemic lupus erythematosus is a chronic autoimmune disease which also disproportionately afflicts black and hispanic populations. In lupus patients, an aberrant immune response is characterized by the presence of circulating autoantibodies, lymphopenia, aberrant T cells, and proinflammatory cytokines along with defective regulatory mechanisms, leading to immune-mediated damage to tissues. Lupus patients are often treated with immune-suppressants and therefore are immune-compromised and more susceptible to infections and may be vulnerable to coronavirus infection. While the anti-viral immune response is important to protect from coronavirus infection, an uncontrolled proinflammatory cytokine response can lead to cytokine storm which causes damage to the lungs and other organs, causing significant morbidity and mortality. Better understanding of the underlying immune response and therapeutic strategies in lupus and COVID-19 is important to guide management of this deadly infectious disease in the context of lupus and vice-versa.
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