Viral load is associated with mitochondrial dysfunction and altered monocyte phenotype in acute severe SARS-CoV-2 infection.

Monocytes play a major role in the initial innate immune response to SARS-CoV-2. Although viral load may correlate with several clinical outcomes in COVID-19, much less is known regarding their impact on innate immune phenotype. We evaluated the monocyte phenotype and mitochondrial function in severe COVID-19 patients (n = 22) with different viral burden (determined by the median of viral load of the patients) at hospital admission. Severe COVID-19 patients presented lower frequency of CD14 + CD16- classical monocytes and CD39 expression on CD14 + monocytes, and higher frequency of CD14 + CD16 + intermediate and CD14-CD16 + nonclassical monocytes as compared to healthy controls independently of viral load. COVID-19 patients with high viral load exhibited increased GM-CSF, PGE-2 and lower IFN-α as compared to severe COVID-19 patients with low viral load (p < 0.05). CD14 + monocytes of COVID-19 patients with high viral load presented higher expression of PD-1 but lower HLA-DR on the cell surface than severe COVID-19 patients with low viral load. All COVID-19 patients presented decreased monocyte mitochondria membrane polarization, but high SARS-CoV-2 viral load was associated with increased mitochondrial reactive oxygen species. In this sense, higher viral load induces mitochondrial reactive oxygen species generation associated with exhaustion profile in CD14 + monocytes of severe COVID-19 patients. Altogether, these data shed light on new pathological mechanisms involving SARS-CoV-2 viral load on monocyte activation and mitochondrial function, which were associated with COVID-19 severity.

The impact of intradialytic exercise on immune cells expressing CCR5+ in patients with chronic kidney disease: A cross-over trial.

The C-C chemokine receptor type 5 (CCR5) plays a role in the immunopathogenesis of chronic kidney disease (CKD). Exercise has anti-inflammatory properties that may contribute to the rehabilitation of CKD patients. To date, the impact of the intradialytic exercise on CCR5 expression in monocytes and lymphocytes of CKD patients is unknown. We aimed to evaluate the effects of an acute intradialytic moderate-intensity exercise on CD4+CCR5+ T-cells and CD14+CCR5+ monocytes of elderly individuals with Chronic Kidney Disease (CKD). Eight CKD elderly patients performed a single bout of 20 min intradialytic exercise and a control hemodialysis (HD) session. Blood samples were collected at baseline, during and immediately after the trials. HD therapy increased the peripheral frequency of CD4+CCR5+ T-cells. The systemic CCL5 levels and the peripheral CD14+CCR5+ proportions increased during and after HD therapy. No significant alterations in CD4+CCR5+ and CD14+CCR5+ proportions or CCL5 levels were identified in CKD patients during and after intradialytic exercise. A negative correlation between the peripheral frequency of CD14+CCR5+ and the creatinine levels was identified in the intradialytic exercise session. A single moderate-intensity intradialytic exercise imposes an immunomodulatory impact in CKD elderly patients, preventing an excessive inflammatory response induced by hemodialysis.