Elevated CD39+T-Regulatory Cells and Reduced Levels of Adenosine Indicate a Role for Tolerogenic Signals in the Progression from Moderate to Severe COVID-19.

Viral infections trigger inflammation by controlling ATP release. CD39 ectoenzymes hydrolyze ATP/ADP to AMP, which is converted by CD73 into anti-inflammatory adenosine (ADO). ADO is an anti-inflammatory and immunosuppressant molecule which can enhance viral persistence and severity. The CD39-CD73-adenosine axis contributes to the immunosuppressive T-reg microenvironment and may affect COVID-19 disease progression. Here, we investigated the link between CD39 expression, mostly on T-regs, and levels of CD73, adenosine, and adenosine receptors with COVID-19 severity and progression. Our study included 73 hospitalized COVID-19 patients, of which 33 were moderately affected and 40 suffered from severe infection. A flow cytometric analysis was used to analyze the frequency of T-regulatory cells (T-regs), CD39+ T-regs, and CD39+CD4+ T-cells. Plasma concentrations of adenosine, IL-10, and TGF-ß were quantified via an ELISA. An RT-qPCR was used to analyze the gene expression of CD73 and adenosine receptors (A1, A2A, A2B, and A3). T-reg cells were higher in COVID-19 patients compared to healthy controls (7.4 ± 0.79 vs. 2.4 ± 0.28; p < 0.0001). Patients also had a higher frequency of the CD39+ T-reg subset. In addition, patients who suffered from a severe form of the disease had higher CD39+ T-regs compared with moderately infected patients. CD39+CD4+ T cells were increased in patients compared to the control group. An analysis of serum adenosine levels showed a marked decrease in their levels in patients, particularly those suffering from severe illness. However, this was paralleled with a marked decline in the expression levels of CD73. IL-10 and TGF-ß levels were higher in COVID-19; in addition, their values were also higher in the severe group. In conclusion, there are distinct immunological alterations in CD39+ lymphocyte subsets and a dysregulation in the adenosine signaling pathway in COVID-19 patients which may contribute to immune dysfunction and disease progression. Understanding these immunological alterations in the different immune cell subsets and adenosine signaling provides valuable insights into the pathogenesis of the disease and may contribute to the development of novel therapeutic approaches targeting specific immune mechanisms.

Efficacy of dexmedetomidine versus magnesium sulfate as an adjuvant to intraperitoneal bupivacaine in pediatric laparoscopic surgery: a randomized clinical trial.

BACKGROUND: We evaluated the efficacy of dexmedetomidine versus magnesium sulfate as an adjuvant to intraperitoneal (IP) bupivacaine in pediatric laparoscopic inguinal herniorrhaphy. METHODS: Ninety-seven male children, ASA I-II, 1-6 years old, undergoing laparoscopic inguinal herniorrhaphy, were randomized to receive before peritoneal insufflation, IP 2 mg.kg-1 bupivacaine 0.5% combined with either 1 µg.kg-1 of dexmedetomidine (Group D), 30 mg.kg-1 of magnesium sulfate (Group M), or normal saline (Group C). All tested drugs were diluted to the volume of 10 mL with normal saline. FLACC pain scores, need for rescue analgesics, time to flatus and first stool, emetic events, adverse effects, functional recovery, and parents' satisfaction were recorded for the first 48 h postoperatively. RESULTS: FLACC scores were significantly higher in Group C than in the other two groups at 6, 8, 12, 18, 24, and 48 hours after surgery with no differences between Groups D and M. Rescue analgesia was significantly higher in Group C with none of the children in Groups D and M requiring rescue analgesia (p = 0.001). Times to first flatus and stool, emetic events, and adverse effects did not differ among groups. Times to return to normal functional activity were comparable in all groups. Parents' satisfaction was greater in Groups D and M than in Group C (p = 0.026). CONCLUSION: Dexmedetomidine and magnesium sulfate added to IP bupivacaine improved the analgesia afforded by bupivacaine in the first two postoperative days in children scheduled for laparoscopic herniorrhaphy.