Nucleotide, Phospholipid, and Kynurenine Metabolites Are Robustly Associated with COVID-19 Severity and Time of Plasma Sample Collection in a Prospective Cohort Study.

Understanding the molecular underpinnings of disease severity and progression in human studies is necessary to develop metabolism-related preventative strategies for severe COVID-19. Metabolites and metabolic pathways that predispose individuals to severe disease are not well understood. In this study, we generated comprehensive plasma metabolomic profiles in >550 patients from the Longitudinal EMR and Omics COVID-19 Cohort. Samples were collected before (n = 441), during (n = 86), and after (n = 82) COVID-19 diagnosis, representing 555 distinct patients, most of which had single timepoints. Regression models adjusted for demographics, risk factors, and comorbidities, were used to determine metabolites associated with predisposition to and/or persistent effects of COVID-19 severity, and metabolite changes that were transient/lingering over the disease course. Sphingolipids/phospholipids were negatively associated with severity and exhibited lingering elevations after disease, while modified nucleotides were positively associated with severity and had lingering decreases after disease. Cytidine and uridine metabolites, which were positively and negatively associated with COVID-19 severity, respectively, were acutely elevated, reflecting the particular importance of pyrimidine metabolism in active COVID-19. This is the first large metabolomics study using COVID-19 plasma samples before, during, and/or after disease. Our results lay the groundwork for identifying putative biomarkers and preventive strategies for severe COVID-19.

Exacerbations of multiple sclerosis in patients treated with gamma interferon.

In an open, randomised study, 18 patients with clinically definite, relapsing-remitting multiple sclerosis (MS) received 1 microgram, 30 micrograms, or 1000 micrograms doses of recombinant gamma interferon (IFN-gamma), given by intravenous infusion twice a week for four weeks. 7 patients had exacerbations during treatment. This exacerbation rate, compared retrospectively with the pretreatment rate and prospectively with the post-treatment rate, was significantly greater than expected. Exacerbations were not precipitated by fever or other dose-dependent side-effects. A concomitant increase in circulating monocytes bearing class II (HLA-DR) surface antigen suggested that the attacks induced during treatment were immunologically mediated. IFN-gamma is unsuitable for treatment of MS.

Systemic recombinant alpha-2 interferon therapy in relapsing multiple sclerosis.

This report describes the first use of recombinant-DNA-produced human interferon in patients with multiple sclerosis (MS). Ninety-eight patients who were clinically definite for MS with two or more documented exacerbations during the preceding two years were admitted to this placebo-controlled double-blind randomized trial. Although both groups were similar, placebo patients had later MS onset. Patients injected themselves with 2 X 10(6) IU of alpha-2 interferon or placebo three times each week for up to 52 weeks. This dose of interferon was well tolerated in that side effects were minimal. During the trial, the exacerbation rate was sharply reduced in both groups. In the three-month follow-up period after stopping treatment, more patients who were receiving interferon than placebo became worse neurologically. More patients who were receiving interferon than placebo changed from exacerbating MS to progressive MS during the trial. Thus, no clear therapeutic benefit of alpha-2 interferon for MS was detected.