The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.

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Most COVID-19 patients experience a mild disease; a minority suffers from critical disease.We report about a biomarker validation study regarding 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France.Patients with critical disease had significantly less anti-HCoV OC43 nucleocapsid protein antibodies compared to other COVID-19 patients (p=0.007). In multivariate analysis, OC43 negative inpatients had an increased risk of critical disease, higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis.Our results indicate that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment. We expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination, especially with other risk factors prevailing.