Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19

Talasaz, Azita Hajhossein; Sadeghipour, Parham; Aghakouchakzadeh, Maryam; Dreyfus, Isaac; Kakavand, Hessam; Ariannejad, Hamid; Gupta, Aakriti; Madhavan, Mahesh V.; Tassell, Benjamin Van; Jiménez, David; Monréal, Manuel; Vaduganathan, Muthiah; Fanikos, John; Dixon, Dave L.; Piazza, Gregory; Parikh, Sahil A.; Bhatt, Deepak L.; Lip, Gregory Y.H.; Stone, Gregg W.; Krumholz, Harlan M.; Libby, Peter; Goldhaber, Samuel Z.; Bikdeli, Behnood

doi:10.1016/j.jacc.2021.08.021

Cited by 46 publications

(48 citation statements)

References 79 publications

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“…By contrast, CCBs may interfere with SARS‐CoV‐2 replication by reducing intracellular calcium levels, and the resulting anti‐inflammatory (reduction of COVID‐19 related inflammation), anticoagulatory (reduction of microvascular coagulation) and vasodilatory (improvement of local vasoconstriction) effects, may decrease COVID‐19 severity and associated mortality. 18 Lastly, LMDs have also been reported to possess antiviral, immunomodulatory, anti‐inflammatory and antithrombotic properties, 19 , 20 which may all contribute to better COVID‐19 clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular drugs and COVID‐19 clinical outcomes: a systematic review and meta‐analysis of randomized controlled trials

Asiimwe

Pushpakom

Turner

et al. 2022

Brit J Clinical Pharma

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Aims: To update our previously reported systematic review and meta‐analysis of observational studies on cardiovascular drug exposure and COVID‐19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). Methods: More than 500 databases were searched between 1 November 2020 and 2 October 2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness. Results: After screening 22 414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta‐analyses, ACEI/ARBs did not affect hospitalization length (mean difference −0.42, 95% confidence interval [CI] −1.83; 0.98 d, n = 1183), COVID‐19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference −0.29, 95% CI −1.13 to 0.56 d, n = 1449; severity RR 0.86, 95% CI 0.70; 1.04, n = 2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n = 5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid‐modifying drugs (atorvastatin, 1 trial). Conclusion: Moderate‐ to high‐certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID‐19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID‐19 unless they are needed for an underlying currently approved therapeutic indication.

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Section: Introductionmentioning

confidence: 99%

Cardiovascular drugs and COVID‐19 clinical outcomes: a systematic review and meta‐analysis of randomized controlled trials

Asiimwe

Pushpakom

Turner

et al. 2022

Brit J Clinical Pharma

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“… 45 , 46 A series of randomized controlled trials (RCTs) have been conducted to explore the clinical efficacy of lipid-modulating agents on COVID-19, and has revealed that they may offer therapeutic potential in COVID-19. 47 Omega-3 polyunsaturated fatty acids (PUFAs), stains and fibrates are expected to ameliorate dyslipidemia by lowering TG and raising HDL. 48–52 Moreover, HDL-increasing drugs, such as cholesterol acyltransferase (LCAT) and Niacin, have also been studied as potential therapeutic strategies for COVID-19 treatment.…”

Section: Discussionmentioning

confidence: 99%

“… 48–52 Moreover, HDL-increasing drugs, such as cholesterol acyltransferase (LCAT) and Niacin, have also been studied as potential therapeutic strategies for COVID-19 treatment. 47 , 49 …”

Section: Discussionmentioning

confidence: 99%

Triglyceride/High-Density Lipoprotein Cholesterol Ratio is Associated with the Mortality of COVID-19: A Retrospective Study in China

Peng¹,

Liu²,

Zhang³

et al. 2022

IJGM

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Background Triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-c) is crucial when researching metabolic and vascular diseases, and its involvement in COVID-19 was sparsely elaborated on. The purpose of the study was to explore the inflammatory associations between the TG/HDL-c ratio and COVID-19 prognosis. Methods A total of 262 COVID-19 patients consisting of 244 survivors and 18 non-survivors were retrospectively investigated. The clinical features and baseline hematological parameters were recorded and analyzed. The receiver operating characteristic curve (ROC) was used to explore the role of TG/HDL-c in predicting the mortality of COVID-19, the Spearman’s rank correlation coefficients were used to measure the correlation between TG/HDL-c and inflammatory indicators, and the Kaplan–Meier (KM) curve was used to estimate the survival of COVID-19 patients with high and low TG/HDL-c ratio. Logistic regression analyses were performed to investigate the role of TG/HDL-c ratio on mortality of COVID-19 with no underlying diseases. Results Compared with the survivors, the non-survivors of COVID-19 had significantly higher levels of white blood cells (4.7 vs 13.0 × 10 9 /L; P < 0.001), neutrophils (3.0 vs 11.6 × 10 9 /L; P < 0.001), C-reactive proteins (15.7 vs 76.7 mg/L; P < 0.001) and TG/HDL-c ratio (1.4 vs 2.5; P = 0.001). The ROC curve [area under the curve (AUC), 0.731; 95% confidence interval ( CI ), 0.609–0.853; P = 0.001] suggested that the TG/HDL-c ratio could predict the mortality of COVID-19. The TG/HDL-c ratio was positively correlated with white blood cells ( r = 0.255, P < 0.001), neutrophils ( r = 0.243, P < 0.001) and C-reactive proteins ( r = 0.170, P < 0.006). Patients with high TG/HDL-c ratio showed a worse survival compared with those with low TG/HDL-c ratio (Log rank P = 0.003). Moreover, TG/HDL-c ratio was an independent factor in predicting the mortality of COVID-19 patients with no underlying diseases. Conclusion Our study demonstrated that TG/HDL-c ratio might potentially be a predictive marker for mortality in COVID-19 patients.

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“…A pilot study suggested that the risk of death from COVID-19 inversely correlates with the red blood cell level of the long-chain n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ( 4 ). Currently, at least 14 RCTs with different n-3 PUFA formulations are ongoing to investigate their preventive and therapeutic potential in COVID-19 ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Amelioration of Endotoxemia by a Synthetic Analog of Omega-3 Epoxyeicosanoids

et al. 2022

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Sepsis, a systemic inflammatory response to pathogenic factors, is a difficult to treat life-threatening condition associated with cytokine and eicosanoid storms and multi-organ damage. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic (EPA) and docosahexaenoic acid, are the precursors of potent anti-inflammatory lipid mediators, including 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), the main metabolite of EPA generated by cytochrome P450 epoxygenases. Searching for novel therapeutic or preventative agents in sepsis, we tested a metabolically robust synthetic analog of 17,18-EEQ (EEQ-A) for its ability to reduce mortality, organ damage, and pro-inflammatory cytokine transcript level in a mouse model of lipopolysaccharide (LPS)-induced endotoxemia, which is closely related to sepsis. Overall survival significantly improved following preventative EEQ-A administration along with decreased transcript level of pro-inflammatory cytokines. On the other hand, the therapeutic protocol was effective in improving survival at 48 hours but insignificant at 72 hours. Histopathological analyses showed significant reductions in hemorrhagic and necrotic damage and infiltration in the liver. In vitro studies with THP-1 and U937 cells showed EEQ-A mediated repression of LPS-induced M1 polarization and enhancement of IL-4-induced M2 polarization of macrophages. Moreover, EEQ-A attenuated the LPS-induced decline of mitochondrial function in THP-1 cells, as indicated by increased basal respiration and ATP production as well as reduction of the metabolic shift to glycolysis. Taken together, these data demonstrate that EEQ-A has potent anti-inflammatory and immunomodulatory properties that may support therapeutic strategies for ameliorating the endotoxemia.

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Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19

Cited by 46 publications

References 79 publications

Cardiovascular drugs and COVID‐19 clinical outcomes: a systematic review and meta‐analysis of randomized controlled trials

Cardiovascular drugs and COVID‐19 clinical outcomes: a systematic review and meta‐analysis of randomized controlled trials

Triglyceride/High-Density Lipoprotein Cholesterol Ratio is Associated with the Mortality of COVID-19: A Retrospective Study in China

Amelioration of Endotoxemia by a Synthetic Analog of Omega-3 Epoxyeicosanoids

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