The current coronavirus disease 2019 (COVID‐19) pandemic presents a global challenge for managing acutely ill patients and complications from viral infection. Systemic inflammation accompanied by a “cytokine storm,” hemostasis alterations and severe vasculitis have all been reported to occur with COVID‐19, and emerging evidence suggests that dysregulation of lipid transport may contribute to some of these complications. Here, we aim to summarize the current understanding of the potential mechanisms related to COVID‐19 dyslipidemia and propose possible adjunctive type therapeutic approaches that modulate lipids and lipoproteins. Specifically, we hypothesize that changes in the quantity and composition of high‐density lipoprotein (HDL) that occurs with COVID‐19 can significantly decrease the anti‐inflammatory and anti‐oxidative functions of HDL and could contribute to pulmonary inflammation. Furthermore, we propose that lipoproteins with oxidized phospholipids and fatty acids could lead to virus‐associated organ damage via overactivation of innate immune scavenger receptors. Restoring lipoprotein function with ApoA‐I raising agents or blocking relevant scavenger receptors with neutralizing antibodies could, therefore, be of value in the treatment of COVID‐19. Finally, we discuss the role of omega‐3 fatty acids transported by lipoproteins in generating specialized proresolving mediators and how together with anti‐inflammatory drugs, they could decrease inflammation and thrombotic complications associated with COVID‐19.

Background: Low-density lipoprotein cholesterol (LDL-C) is an established marker for cardiovascular disease (CVD) and a therapeutic target. Oxidized LDL (oxLDL) is known to be associated with excessive inflammation and abnormal lipoprotein metabolism. Chronic inflammatory diseases confer an elevated risk of premature atherosclerosis and adverse cardiovascular events. Whether oxLDL may serve as a potential biomarker for CVD stratification in populations with chronic inflammatory conditions remains understudied.Objective: To perform a systematic review and meta-analysis evaluating the relationship between oxLDL and CVD (defined by incident CVD events, carotid intima-media thickness, presence of coronary plaque) in patients with chronic inflammatory diseases.Methods: A systematic literature search was performed using studies published between 2000 and 2022 from PubMed, Cochrane Library, Embase (Elsevier), CINHAL (EBSCOhost), Scopus (Elsevier), and Web of Science: Core Collection (Clarivate Analytics) databases on the relationship between oxLDL and cardiovascular risk on inflamed population. The pooled effect size was combined using the random effect model and publication bias was assessed if P < 0.05 for the Egger or Begg test along with the funnel plot test.Results: A total of three observational studies with 1,060 participants were ultimately included in the final meta-analysis. The results demonstrated that oxLDL is significantly increased in participants with CVD in the setting of chronic inflammatory conditions. This meta-analysis suggests that oxLDL may be a useful biomarker in risk stratifying cardiovascular disease in chronically inflamed patients.

Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy- or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene–related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber–mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch.