Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge

Yan, Jiayi; Wang, Jieying; Ding, Li; Liu, Shang; Zhan, Youqing; Lu, Jiayue; Li, Zhenyuan; Gu, Leyi; Li, Ping; Zhu, Mingli; Gao, Yuan; Gong, Xingrong; Ban, Haiqun; Cai, Hong; Mou, Shan

doi:10.1016/j.clim.2023.109271

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…Diao et al, 2020, showed an obvious dramatic drop and functional exhaustion of CD4+T-lymphocytes 20 followed by increased incidence of co-infection by other pathogens. 21,22 Consumption and exhaustion of CD4+ and CD8+ T cells might lead to aggravated inflammatory response, as well as cytokine storm production with eventually worsening of the tissue damage. Huang et al, 2019, andQin et al, 2020, studies reported that patients with weakened immunity due to a preexisting disease such as kidney, liver diseases, different malignancies and diabetes are more susceptible to catch COVID-19 infection with bad prognostic disease sequences.…”

Section: Discussionmentioning

confidence: 99%

Study of CD4+ T-lymphocytes in chronic kidney disease patients with COVID-19 infection

Mohamed

2024

EJI

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Chronic kidney disease (CKD) is a functional and/or structural kidney damage that lasts more than three months duration. This study aimed to analyze CD4+ T-lymphocytes levels in chronic CKD patients specifically, during the coronavirus disease 2019 (COVID-19) pandemic to assess the adaptive cell-mediated immunity. The study measured absolute CD4+ T-lymphocytes counts by flowcytometry among participating individuals. The study included 146 subjects, 40 CKD patients and tested positive for COVID-19, 44 CKD patients and tested negative for COVID-19 and 62 normal individuals as controls. There was a significant impact of COVID-19 infection in CKD patients showing lower absolute CD4+ T-lymphocytes values to more than six folds compared to the control individuals (Odds Ratio: 72.63, p= 0.0001). Also, there was a significant correlation between the decrease in absolute CD4+ T-lymphocytes counts and the advanced stages of CKD. Therefore, the study indicated that CKD causes an obvious alteration in the body immune system as decreased CD4+ T-lymphocytes levels alongside with the advanced CKD stages. While COVID-19 infection exposes CKD patients to be 50% more likely to express lower values of CD4+ T-lymphocytes levels compared to the negative tested CKD patients. In conclusion, poor immune response and increased morbidity and mortality could be correlated with CKD patients especially when associated with COVID-19 infection as comorbidity.

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Section: Discussionmentioning

confidence: 99%

Study of CD4+ T-lymphocytes in chronic kidney disease patients with COVID-19 infection

Mohamed

2024

EJI

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“…Renal involvement is a frequent occurrence in individuals affected by acute Omicron infection, wherein subclinical inflammation and injury may persist over an extended period, leading to acute lung injury and a progressive decline in kidney function, ultimately culminating in chronic kidney disease ( Yende and Parikh, 2021 ; Yan et al, 2023 ). Given the ongoing global burden of repetitive SARS-CoV-2 infections, particularly the Omicron variant, concerns have emerged regarding the heightened risk of AKI severity and exacerbations in individuals already afflicted with AKI ( Yende and Parikh, 2021 ; Fan et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…A potential association between COVID-19 infection and the onset of AKI has been investigated. Research suggests that nearly 28% of patients admitted to the hospital for COVID-19 receive an AKI diagnosis, and about 9% of these cases necessitate renal replacement therapy ( Yende and Parikh, 2021 ; Yan et al, 2023 ). SARS-CoV-2 infection exerts both direct and indirect effects contributing to AKI development ( Yende and Parikh, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Deciphering the molecular nexus between Omicron infection and acute kidney injury: a bioinformatics approach

Wang,

Chen,

Zhang

et al. 2024

Front. Mol. Biosci.

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BackgroundThe ongoing global health crisis of COVID-19, and particularly the challenges posed by recurrent infections of the Omicron variant, have significantly strained healthcare systems worldwide. There is a growing body of evidence indicating an increased susceptibility to Omicron infection in patients suffering from Acute Kidney Injury (AKI). However, the intricate molecular interplay between AKI and Omicron variant of COVID-19 remains largely enigmatic.MethodsThis study employed a comprehensive analysis of human RNA sequencing (RNA-seq) and microarray datasets to identify differentially expressed genes (DEGs) associated with Omicron infection in the context of AKI. We engaged in functional enrichment assessments, an examination of Protein-Protein Interaction (PPI) networks, and advanced network analysis to elucidate the cellular signaling pathways involved, identify critical hub genes, and determine the relevant controlling transcription factors and microRNAs. Additionally, we explored protein-drug interactions to highlight potential pharmacological interventions.ResultsOur investigation revealed significant DEGs and cellular signaling pathways implicated in both Omicron infection and AKI. We identified pivotal hub genes, including EIF2AK2, PLSCR1, GBP1, TNFSF10, C1QB, and BST2, and their associated regulatory transcription factors and microRNAs. Notably, in the murine AKI model, there was a marked reduction in EIF2AK2 expression, in contrast to significant elevations in PLSCR1, C1QB, and BST2. EIF2AK2 exhibited an inverse relationship with the primary AKI mediator, Kim-1, whereas PLSCR1 and C1QB demonstrated strong positive correlations with it. Moreover, we identified potential therapeutic agents such as Suloctidil, Apocarotenal, 3′-Azido-3′-deoxythymidine, among others. Our findings also highlighted a correlation between the identified hub genes and diseases like myocardial ischemia, schizophrenia, and liver cirrhosis. To further validate the credibility of our data, we employed an independent validation dataset to verify the hub genes. Notably, the expression patterns of PLSCR1, GBP1, BST2, and C1QB were consistent with our research findings, reaffirming the reliability of our results.ConclusionOur bioinformatics analysis has provided initial insights into the shared genetic landscape between Omicron COVID-19 infections and AKI, identifying potential therapeutic targets and drugs. This preliminary investigation lays the foundation for further research, with the hope of contributing to the development of innovative treatment strategies for these complex medical conditions.

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“…Identifying biomarkers that predict the curative effect of Nirmatrelvir may help physicians conduct evidence-based treatments for COVID-19. The immune response is closely related to the pathogenesis, progression, and prognosis of COVID-19 patients, especially the activation of adaptive immune function (18). CD4+ and CD8+ T cells are the most basic components of adaptive immunity, with various helper and effector functionalities and the ability to kill infected cells respectively (7).…”

Section: Discussionmentioning

confidence: 99%

Immunophenotyping characteristics and outcome of COVID‐19 patients: peripheral blood CD8+T cell as a prognostic biomarker for patients with Nirmatrelvir

Sun,

Dian,

Gao

et al. 2023

Front. Immunol.

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BackgroundNirmatrelvir has been authorized for the treatment of both hospitalized and non-hospitalized COVID-19 patients. However, the association between T lymphocyte subsets and the outcome of hospitalized COVID-19 patients treated with oral Nirmatrelvir has not been investigated. The objective of this study was to examine whether lymphocyte subsets could serve as biomarkers to assess the risk of mortality in COVID-19 patients undergoing Nirmatrelvir treatment, with the aim of enhancing medication management for COVID-19 patients.MethodsWe conducted a retrospective cohort study at the Xiangya Hospital of Central South University in China between December 5, 2022 and January 31, 2023. The study reported demographic, clinical, T lymphocyte subsets, and inflammatory cytokine data of COVID-19 patients. We evaluated the associations of T lymphocyte subsets on admission with the composite outcome or death of patients using univariate and multivariable Cox regression analyses with hazards ratios (HRs) and 95% confidence intervals (CIs).ResultsWe identified 2118 hospitalized COVID-19 patients during the study period, and conducted a follow-up of up to 38 days. Of these, 131 patients received Nirmatrelvir, with 56 (42.7%) in the composite outcome group, and 75 (57.3%) in the non-composite outcome group. Additionally, 101 (77.1%) patients were discharged, while 30 (22.9%) died. Our results showed a significant decrease in the CD3+, CD4+, and CD8+ T cell counts of patients in the composite outcome group and mortality group compared to the non-composite outcome group and discharged group, respectively. Multivariate Cox regression analysis showed that the significant decrease in CD8+ T cell count in peripheral blood was independently associated with the composite outcome in COVID-19 patients treated with Nirmatrelvir, with an HR of 1.96 (95%CI: 1.01-3.80). The significant decrease in CD4+ and CD8+ T cell counts in peripheral blood increased the hazard of developing mortality, with HRs of 6.48 (95%CI: 1.47-28.63) and 3.75 (95%CI: 1.27-11.11), respectively.ConclusionOur study revealed a significant positive correlation between a decrease in CD8+ T cell counts and progression and mortality of hospitalized COVID-19 patients treated with Nirmatrelvir. Lower counts (/μL) of CD8+ T cell (<201) were associated with a higher risk of in-hospital severity and death. Our findings may provide valuable references for physicians in optimizing the use of Nirmatrelvir.

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Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge

Cited by 4 publications

References 34 publications

Study of CD4+ T-lymphocytes in chronic kidney disease patients with COVID-19 infection

Study of CD4+ T-lymphocytes in chronic kidney disease patients with COVID-19 infection

Deciphering the molecular nexus between Omicron infection and acute kidney injury: a bioinformatics approach

Immunophenotyping characteristics and outcome of COVID‐19 patients: peripheral blood CD8+T cell as a prognostic biomarker for patients with Nirmatrelvir

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