Use of convalescent plasma therapy in eight individuals with mild COVID-19.

Coronavirus disease 2019 (COVID-19) is still a global epidemic. Several studies of individuals with severe COVID-19 regard convalescent plasma (CP) transfusion as an effective therapy. However, no significant improvements are found in randomized clinical trials of CP treatment. Until now, data for individuals with mild COVID-19 transfused CP were lacking. This study recruited eight individuals with mild COVID-19 who received at least one dose of CP transfusion. After CP therapy, the clinical symptoms of all individuals improved. Lymphocyte counts tended to increase, and lactate dehydrogenase, creatine kinase and aspartate aminotransferase tended to decrease. However, C-reactive protein increased transiently in three individuals. The median time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test to become negative was 2.5 days after CP transfusion. The study shows the potential benefits of CP. Meanwhile, CP probably enhances the inflammatory response to SARS-CoV-2 temporarily in people with insufficient antiviral immunity. However, the effects of CP are not permanent.

Correolide and derivatives are novel immunosuppressants blocking the lymphocyte Kv1.3 potassium channels.

The voltage-gated potassium channel, Kv1.3, is specifically expressed on human lymphocytes, where it controls membrane potential and calcium influx. Blockade of Kv1.3 channels by margatoxin was previously shown to prevent T cell activation and attenuate immune responses in vivo. In the present study, a triterpene natural product, correolide, was found to block Kv1.3 channels in human and miniswine T cells by electrophysiological characterization. T cell activation events, such as anti-CD3-induced calcium elevation, IL-2 production, and proliferation were inhibited by correolide in a dose-dependent manner. More potent analogs were evaluated for pharmacokinetic profiles and subsequently tested in a delayed-type hypersensitivity (DTH) response to tuberculin in the miniswine. Two compounds were dosed orally, iv, or im, and both compounds suppressed DTH responses, demonstrating that small molecule blockers of Kv1.3 channels can act as immunosuppressive agents in vivo. These studies establish correolide and its derivatives as novel immunosuppressants.