Cancer patients are particularly susceptible to the development of severe
Covid-19, prompting us to investigate the serum metabolome of 204
cancer patients enrolled in the ONCOVID trial. We previously described that the immunosuppressive
tryptophan/
kynurenine metabolite
anthranilic acid correlates with poor prognosis in non-
cancer patients. In
cancer patients, we observed an elevation of
anthranilic acid at baseline (without
Covid-19 diagnosis) and no further increase with mild or severe
Covid-19. We found that, in
cancer patients,
Covid-19 severity was associated with the depletion of two bacterial metabolites, indole-3-proprionate and 3-phenylproprionate, that both positively correlated with the levels of several inflammatory
cytokines. Most importantly, we observed that the levels of acetylated
polyamines (in particular N1-acetylspermidine, N1,N8-diacetylspermidine and N1,N12-
diacetylspermine), alone or in aggregate, were elevated in severe
Covid-19 cancer patients requiring hospitalization as compared to uninfected
cancer patients or
cancer patients with mild
Covid-19. N1-acetylspermidine and N1,N8-diacetylspermidine were also increased in patients exhibiting prolonged viral shedding (>40 days). An abundant literature indicates that such acetylated
polyamines increase in the serum from patients with
cancer,
cardiovascular disease or neurodegeneration, associated with poor prognosis. Our present work supports the contention that acetylated
polyamines are associated with severe
Covid-19, both in the general population and in patients with malignant disease. Severe
Covid-19 is characterized by a specific metabolomic signature suggestive of the overactivation of
spermine/
spermidine N1-acetyl transferase-1 (SAT1), which catalyzes the first step of
polyamine catabolism.