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

Research output: Contribution to journalArticlepeer-review

Chun Pai Yang, Ching Mao Chang, Cheng Chia Yang, Carmine M. Pariante, Kuan Pin Su

Original languageEnglish
Pages (from-to)19-27
Number of pages9
JournalBrain, Behavior, and Immunity
Early online date4 Apr 2022
E-pub ahead of print4 Apr 2022
PublishedJul 2022

Bibliographical note

Funding Information: The authors of this work were supported by the following grants: MOST 109-2320-B-038-057-MY3, 109-2320-B-039-066, 110-2321-B-006-004, 110-2811-B-039-507, 110-2320-B-039-048-MY2, and 110-2320-B-039-047-MY3 from the Ministry of Science and Technology, Taiwan; ANHRF 109-31, 109-40, 110-13, 110-26, 110-44, and 110-45 from An-Nan Hospital, China Medical University, Tainan, Taiwan; and CMU104-S-16-01, CMU103-BC-4-1, CRS-108-048, DMR-102-076, DMR-103-084, DMR-106-225, DMR-107-204, DMR-108-216, DMR-109-102, DMR-109-244, DMR-HHC-109-11, DMR-HHC-109-12, DMR-HHC-110-10, DMR-110-124, and CMU110-AWARD-02 from the China Medical University Hospital, Taichung, Taiwan. Publisher Copyright: © 2022 Elsevier Inc.

King's Authors


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.

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