Abstract

The coronavirus disease 2019 (COVID-19) pandemic is remaining ravaging the world and challenging every aspect including medicine, society, politics, and science. Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) causing COVID-19 is a highly contagious virus that can result in fever, cough, loss of taste or smell, and pneumonia, while some hospitalized patients develop severe symptoms related to exacerbated systematic inflammation along with unmanageable cytokine storms, even deadly complications in some cases. Therefore, a thorough comprehension of the modulatory mechanism in COVID-19 progression is crucial for accurate prognosis and the development of effective therapies. In this study, the MS-based proteomics is applied in human serum and golden hamster plasma respectively to profile the proteome phenotype of COVID-19 infected groups, indicating pleckstrin (PLEK) is a significantly upregulated protein in the severe cohort compared to the non-severe cohort, which inspires correlation between severe COVID-19 and target protein PLEK. Subsequently, an animal experiment using the golden hamster as the model is conducted to investigate the effect of PLEK on COVID-19 progression. The hamster infected by Omicron variants with mild symptoms will develop severity due to the injection of PLEK. Likewise, pretreatment of exogenous PLEK is observed to promote viral invasion in Calu-3 cells as well. The combination of animal and cellular experiments demonstrates that PLEK dramatically exacerbates COVID-19 symptoms. All these results shed light that PLEK as a biomarker presents the association with immunomodulating that possesses the potential value in COVID-19 prognosis and treatment development.