Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19

Brain Behav Immun. 2022 Jul:103:19-27. doi: 10.1016/j.bbi.2022.04.001. Epub 2022 Apr 4.


The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus-pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.

Keywords: Cognition; Depression; Immunity; Inflammation; Long COVID; Mood; Omega-3 PUFAs; Sickness.

Publication types

  • Review
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / complications
  • Fatty Acids
  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Hypothalamo-Hypophyseal System
  • Inflammation / drug therapy
  • Pituitary-Adrenal System
  • Post-Acute COVID-19 Syndrome
  • SARS-CoV-2


  • Fatty Acids
  • Fatty Acids, Omega-3