Induction of Caspase-7 Serum and P53 Gene Expression in Severe Omicron Variant SARS-CoV-2 Infection

Abstract

     The COVID-19 pandemic has caused significant global health issues, with the Omicron variant emerging in South Africa in November 2021. Apoptosis is a natural antiviral defense; however, in SARS-CoV-2 infection, it may paradoxically enhance viral replication, worsening the severity instead of eradicating it. This study aims to investigate viral infection by analyzing serum levels of caspase-7 and gene expression of P⁵³ during the severe and late stages of Omicron infection, as well as their correlation with severity, inflammatory biomarkers, and blood cell counts. A case-control study involved 124 participants aged 25-69, with 74 being SARS-CoV-2 patients and 50 healthy controls. The study found that patients had significantly lower median levels of caspase-7 and P⁵³ than healthy controls. Most patients were considered low producers of caspase-7 and P⁵³. A caspase-7 level greater than 3169 pg/ml (area under the curve=0.790; p < 0.0001) in receiver operating characteristic curve (ROC) analysis; therefore, it is considered a good marker to predict the outcome of COVID-19 patients. The caspase-7 levels showed a significant relationship with biomarkers (ferritin, D-dimer, and blood cells). Our findings with the Omicron variant revealed low levels of caspase-7 and P⁵³ at early infection stages and in older patients with a low Ct value (indicating a high viral load). Thus, the P⁵³ expression induces caspase-7 production, affecting the viral load outcome and control. Further research on the relationship between the severity of Omicron SARS-CoV-2 infections and the activity level of apoptotic caspases is necessary to fully comprehend the hidden potential and characteristics of the current subject of study.