Evidence showing lipotoxicity worsens outcomes in covid-19 patients and insights about the underlying mechanisms

Rodrigo Cartin-Ceba, Biswajit Khatua, Bara El-Kurdi, Shubham Trivedi, Sergiy Kostenko, Zaid Imam, Ryan Smith, Christine Snozek, Sarah Navina, Vijeta Sharma, Bryce McFayden, Filip Ionescu, Eugene Stolow, Sylvia Keiser, Aziz Tejani, Allison Harrington, Phillip Acosta, Saatchi Kuwelker, Juan Echavarria, Girish B. NairAdam Bataineh, Vijay P. Singh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


We compared three hospitalized patient cohorts and conducted mechanistic studies to determine if lipotoxicity worsens COVID-19. Cohort-1 (n = 30) compared COVID-19 patients dismissed home to those requiring intensive-care unit (ICU) transfer. Cohort-2 (n = 116) compared critically ill ICU patients with and without COVID-19. Cohort-3 (n = 3969) studied hypoalbuminemia and hypocalcemia's impact on COVID-19 mortality. Patients requiring ICU transfer had higher serum albumin unbound linoleic acid (LA). Unbound fatty acids and LA were elevated in ICU transfers, COVID-19 ICU patients and ICU non-survivors. COVID-19 ICU patients (cohort-2) had greater serum lipase, damage-associated molecular patterns (DAMPs), cytokines, hypocalcemia, hypoalbuminemia, organ failure and thrombotic events. Hypocalcemia and hypoalbuminemia independently associated with COVID-19 mortality in cohort-3. Experimentally, LA reacted with albumin, calcium and induced hypocalcemia, hypoalbuminemia in mice. Endothelial cells took up unbound LA, which depolarized their mitochondria. In mice, unbound LA increased DAMPs, cytokines, causing endothelial injury, organ failure and thrombosis. Therefore, excessive unbound LA in the circulation may worsen COVID-19 outcomes.

Original languageEnglish (US)
Article number104322
Issue number5
StatePublished - May 20 2022


  • health sciences
  • medical microbiology
  • virology

ASJC Scopus subject areas

  • General


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