CASPASE-3 expression and activity in PBMCs associate with SARS-CoV-2 infection and clinical features

Vanessa Mylenna Florêncio de Carvalho , Bárbara de Oliveira Silva , Priscilla Stela Santana de Oliveira , Thacianna Barreto da Costa , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , Michelly Cristiny Pereira , Maira Galdino da Rocha Pitta
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Abstract

Background

Although vaccines and treatments exist, new SARS-CoV-2 variants continue to emerge. An imbalance between apoptosis and autophagy may contribute to COVID-19 pathogenesis, leading to tissue damage and inflammation.

Objective

To investigate the role of cell death-related proteins during SARS-CoV-2 infection and their associations with clinical variables.

Methods

A total of 140 samples were analyzed (n = 73 infected, n = 67 uninfected). Gene expression of apoptotic and autophagic markers was evaluated by RT-qPCR in peripheral blood mononuclear cells. Caspase 3/7 activity was assessed using flow cytometry.

Results

Infected patients showed higher expression of CASPASE 3, BID (p < 0.05), and MAP1LC3 (p < 0.01). CASPASE 3 expression was higher in variant omicron, male sex, high viral load, and various clinical symptoms. Caspase 3/7 activity increased in CD4⁺ T and B cells of individuals infected with SARS-CoV-2.

Conclusions

Although our previous results with CASPASE 3 are promising and suggest that it may become a potential therapeutic target, additional studies are needed to confirm these hypotheses and evaluate potential intervention strategies.

Abstract Image

CASPASE-3在PBMCs中的表达和活性与SARS-CoV-2感染和临床特征相关
尽管已有疫苗和治疗方法,但新的SARS-CoV-2变体仍在不断出现。细胞凋亡和自噬之间的不平衡可能导致新冠肺炎的发病机制,导致组织损伤和炎症。目的探讨细胞死亡相关蛋白在SARS-CoV-2感染中的作用及其与临床变量的关系。方法对140份样本进行分析,其中感染病例73例,未感染病例67例。采用RT-qPCR技术检测外周血单核细胞凋亡和自噬标志物的基因表达。流式细胞术检测Caspase 3/7活性。结果感染患者CASPASE 3、BID (p < 0.05)、MAP1LC3表达升高(p < 0.01)。CASPASE 3在变异组粒、男性、高病毒载量和各种临床症状中表达较高。SARS-CoV-2感染者CD4 + T和B细胞中Caspase 3/7活性升高。尽管我们之前关于CASPASE 3的研究结果是有希望的,并表明它可能成为一个潜在的治疗靶点,但需要进一步的研究来证实这些假设并评估潜在的干预策略。
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