Abstract
Severe COVID-19 disease leads to hypoxemia, inflammation and lymphopenia. Viral infection induces cellular stress and causes the activation of the innate immune response. The ubiquitin-proteasome system (UPS) is highly implicated in viral immune response regulation. The main function of the proteasome is protein degradation in its active form, which recognises and binds to ubiquitylated proteins. Some proteasome subunits have been reported to be upregulated under hypoxic and hyperinflammatory conditions. Here, we conducted a prospective cohort study of COVID-19 patients (n = 44) and age-and sex-matched controls (n = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the α and β core of the 20S proteasome and from regulatory particles (19S and 11S) in COVID-19 patients. Furthermore, the gene expression of proteasome subunits was associated with lymphocyte count reduction and positively correlated with inflammatory molecular and clinical markers. Given the importance of the proteasome in maintaining cellular homeostasis, including the regulation of the apoptotic and pyroptotic pathways, these results provide a potential link between COVID-19 complications and proteasome gene expression.
Highlights
Coronavirus disease 2019 (COVID-19) is a new respiratory disorder caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2)
Lymphopenia has been frequently associated in COVID-19 patients with severe and fatal disease, it has been observed in up to 96.1% of patients with severe COVID19 [2], and T cells are usually reduced in acute SARS-CoV-2 infection [5]
COVID-19 pneumonia patients and healthy control subjects were homogeneous in sex
Summary
Coronavirus disease 2019 (COVID-19) is a new respiratory disorder caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 range from asymptomatic to severe pneumonia. Growing evidence highlights the relevance of the immune response in severe COVID-19, including inflammatory cytokine storm, lymphopenia and non-T-cell response [1–4]. Lymphopenia has been frequently associated in COVID-19 patients with severe and fatal disease, it has been observed in up to 96.1% of patients with severe COVID19 [2], and T cells are usually reduced in acute SARS-CoV-2 infection [5]. A meta-analysis found that lymphopenia is prominent in severe COVID-19, suggesting that lymphocyte counts lower than 1.5 × 109 /L might be useful for predicting clinical outcome [4]. SARS-CoV-2 infection has been proposed to cause lymphopenia, mainly through lymphocyte apoptosis and pyroptosis, and T-cell exhaustion [6–8]
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