Circulating acetylated polyamines correlate with Covid-19 severity in cancer patients

Aging (Albany NY). 2021 Sep 13;13(17):20860-20885. doi: 10.18632/aging.203525. Epub 2021 Sep 13.

Abstract

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.

Keywords: COVID-19; cancer; metabolomics; microbiota; polyamines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • COVID-19 / blood*
  • COVID-19 / microbiology
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Cohort Studies
  • Cytokines / blood
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Metabolome
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / virology*
  • Polyamines / blood*
  • Propionates / blood
  • Severity of Illness Index
  • Young Adult
  • ortho-Aminobenzoates / blood

Substances

  • Cytokines
  • Inflammation Mediators
  • Polyamines
  • Propionates
  • ortho-Aminobenzoates
  • anthranilic acid