Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms

COVID-19 has caused millions of deaths globally, yet the cellular mechanisms underlying the various effects of the disease remain poorly understood. Recently, a new analytical platform for comprehensive analysis of plasma protein profiles using proximity extension assays combined with next generation sequencing has been developed. Here, we describe the analysis of the plasma profiles of COVID-19 patients with mild and moderate symptoms by comparing the protein levels in newly diagnosed patients with the plasma profiles in the same individuals after recovery 14 days later. The study has identified more than 200 proteins that are significantly elevated at infection and many of these are related to cytokine response and other immune-related functions. In addition, several other proteins are shown to be elevated, including SCARB2, a host cell receptor protein involved in virus entry. A comparison with the plasma protein response in patients with severe symptoms shows a highly similar pattern, but with some interesting differences. In conclusion, the results will facilitate further studies to understand the molecular mechanism of the immune-related response of the SARS-CoV-2 virus.

Combined metabolic cofactor supplementation accelerates recovery in mild-to-moderate COVID-19

There is a need to treat COVID-19 patients suffering from respiratory problems, resulting in decreased oxygen levels and thus leading to mitochondrial dysfunction and metabolic abnormalities. Here, we investigated if a high oral dose of a mixture of Combined Metabolic Activators (CMA) can restore metabolic function and thus aid the recovery of COVID-19 patients. We conducted a placebo-controlled, open-label phase 2 study and a double-blinded phase 3 clinical trials to investigate the time of symptom-free recovery on ambulatory patients using a mixture of CMA consisting of NAD+ and glutathione precursors. The results of both studies showed that the time to complete recovery was significantly shorter in the CMA group (6.6 vs 9.3 days) in phase 2 and (5.7 vs 9.2 days) in phase 3 trials. A comprehensive analysis of the blood metabolome and proteome showed that the plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with the metabolic activators as compared to placebo. The results show that treating patients infected with COVID-19 with a high dose of CMAs leads to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.