Physical activity levels, gut permeability, circulating inflammatory cytokines and TLR4 signalling in PBMCs of COVID-19 patients

Abstract

Physical exercise could confer some protection against the inflammatory cytokine storm induced by SARS-CoV-2 infection and against severe COVID-19 symptomatology. However, the mechanisms underlying this protective effect of exercise have not been elucidated yet. Therefore, the aim of this study was to investigate the activation of the inflammatory pathway in peripheral blood mononuclear cells (PBMCs) and to test a possible association between the regulation of this pathway and the expression of plasma inflammatory cytokine markers as well as with physical activity levels. All patients (n = 31; 21 males and 10 females) had at least three symptoms associated with COVID-19 and were recruited in the emergency unit. They were immediately tested for COVID-19 by polymerase chain reaction (COVID-19 n = 18, amongst which 9 were hospitalized and 9 quarantined; Non-COVID-19 n = 13) and a blood sample was collected. Physical activity levels were determined using the international physical activity questionnaire (IPAQ). No differences in physical activity levels nor sitting time were found between the COVID-19 and the Non-COVID-19 group. However, moderate to vigorous physical activity was lower in the hospitalized compared to the quarantined group. Toll-like receptor 4 (TLR4) and MyD88 protein expression in PBMCs was lower in the COVID-19 than in the Non-COVID-19 group. Moreover, TLR4 protein expression was lower in the hospitalized than in the quarantined subgroup. While no difference was observed in plasma zonulin levels between COVID-19 and Non-COVID-19 patients, quarantined patients had lower plasma zonulin levels compared to hospitalized patients. In conclusion, patients hospitalized with severe COVID-19 were less physically active and presented greater gut permeability and a downregulation of the TLR4 pathway in PBMCs compared to quarantined and Non-COVID-19 individuals. The lower expression of TLR4 could be a mechanism to prevent, or at least to mitigate, the inflammatory cytokine storm related to the severe form of COVID-19.