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1.
J Am Coll Cardiol ; 78(16): 1635-1654, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1454219

ABSTRACT

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , Fatty Acids, Omega-3/therapeutic use , Fibric Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Niacin/therapeutic use , Amides/pharmacology , Amides/therapeutic use , Esters/pharmacology , Esters/therapeutic use , Fatty Acids, Omega-3/pharmacology , Fibric Acids/pharmacology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lipid Regulating Agents/pharmacology , Lipid Regulating Agents/therapeutic use , Niacin/pharmacology , Randomized Controlled Trials as Topic , Sulfhydryl Compounds/pharmacology , Sulfhydryl Compounds/therapeutic use
2.
Biochimie ; 179: 275-280, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1326919

ABSTRACT

In around 10% of SARS-CoV-2 infected patients, coronavirus disease-2019 (Covid-19) symptoms are complicated with a severe lung damage called Acute Respiratory Distress Syndrome (ARDS), which is often lethal. ARDS is mainly associated with an uncontrolled overproduction of immune cells and cytokines, called "cytokine storm syndrome"; it appears 7-15 days following the onset of symptoms, leading to systemic inflammation and multiple organ failure. Because they are well-known metabolic precursors of specialized pro-resolving lipid mediators (SPMs), omega-3 long-chain polyunsaturated fatty acids (omega-3 LC-PUFAs) could help improve the resolution of the inflammatory balance, limiting therefore the level and duration of the critical inflammatory period. Omega-3 LC-PUFAs may also interact at different stages of the viral infection, notably on the virus entry and replication. In the absence of demonstrated treatment and while waiting for vaccine possibility, the use of omega-3 LC-PUFAs deserve therefore to be considered, based on previous clinical studies suggesting that omega-3 supplementation could improve clinical outcomes of critically ill patients at the acute phase of ARDS. In this context, it is crucial to remind that the omega-3 PUFA dietary intake levels in Western countries remains largely below the current recommendations, considering both the omega-3 precursor α-linolenic acid (ALA) and long chain derivatives such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). An optimized omega-3 PUFAs status could be helpful to prevent infectious diseases, including Covid-19.


Subject(s)
COVID-19/complications , Dietary Supplements , Fatty Acids, Omega-3/pharmacology , Animals , Clinical Trials as Topic , Humans
3.
Clin Nutr ESPEN ; 43: 1-8, 2021 06.
Article in English | MEDLINE | ID: covidwho-1240256

ABSTRACT

BACKGROUND & AIMS: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. METHOD: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. RESULTS: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. CONCLUSIONS: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.


Subject(s)
Brain , COVID-19/complications , Choline/therapeutic use , Fetal Development , Mothers , Nutritional Status , Pregnancy Complications, Infectious/virology , Animals , Brain/drug effects , COVID-19/metabolism , COVID-19/virology , Child Development/drug effects , Choline/pharmacology , Developmental Disabilities/etiology , Developmental Disabilities/prevention & control , Dietary Supplements , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Female , Fetal Development/drug effects , Fetus/drug effects , Folic Acid/pharmacology , Folic Acid/therapeutic use , Humans , Infant , Inflammation/complications , Inflammation/metabolism , Nutritional Requirements , Pandemics , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/metabolism , SARS-CoV-2 , Vitamin D/pharmacology , Vitamin D/therapeutic use
4.
J Transl Med ; 19(1): 128, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1158209

ABSTRACT

BACKGROUND: Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19. METHODS: A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups. Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention. RESULTS: The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 0.05). There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups. CONCLUSION: Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19. Further clinical studies are warranted. Trial registry Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020.5.20; URL of trial registry record: https://en.irct.ir/trial/48213.


Subject(s)
COVID-19/diet therapy , COVID-19/diagnosis , Critical Illness/therapy , Fatty Acids, Omega-3/pharmacology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Biomarkers/blood , Blood Gas Analysis , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19/mortality , COVID-19/physiopathology , Critical Illness/mortality , Dietary Supplements , Double-Blind Method , Fatty Acids, Omega-3/administration & dosage , Female , Hematocrit , Humans , Inflammation Mediators/analysis , Inflammation Mediators/blood , Iran/epidemiology , Kidney/drug effects , Kidney/physiopathology , Kidney/virology , Male , Middle Aged , Mortality , Prognosis , Respiratory System/drug effects , Respiratory System/physiopathology , Respiratory System/virology , SARS-CoV-2/drug effects , Survival Analysis , Treatment Outcome
5.
Clin Nutr ESPEN ; 43: 39-48, 2021 06.
Article in English | MEDLINE | ID: covidwho-1157201

ABSTRACT

BACKGROUND: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.


Subject(s)
COVID-19/drug therapy , Dietary Supplements , Fatty Acids, Omega-3/therapeutic use , Immunologic Factors/therapeutic use , Trace Elements/therapeutic use , Vitamins/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , COVID-19/immunology , Comorbidity , Fatty Acids, Omega-3/pharmacology , Female , Humans , Immunologic Factors/pharmacology , Male , Micronutrients/pharmacology , Micronutrients/therapeutic use , Nutritional Status , Pandemics , Pregnancy , SARS-CoV-2 , Selenium/pharmacology , Selenium/therapeutic use , Switzerland , Trace Elements/pharmacology , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamins/pharmacology , Zinc/pharmacology , Zinc/therapeutic use
6.
Sci Rep ; 11(1): 5207, 2021 03 04.
Article in English | MEDLINE | ID: covidwho-1118818

ABSTRACT

The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.


Subject(s)
COVID-19/prevention & control , Fatty Acids, Omega-3/therapeutic use , SARS-CoV-2/drug effects , Virus Attachment/drug effects , Virus Internalization/drug effects , A549 Cells , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Cathepsin L/antagonists & inhibitors , Fatty Acids, Omega-3/pharmacology , Humans , Serine Endopeptidases/drug effects
7.
Molecules ; 26(3)2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1055087

ABSTRACT

SARS-CoV-2 infects host cells by interacting its spike protein with surface angiotensin-converting enzyme 2 (ACE2) receptors, expressed in lung and other cell types. Although several risk factors could explain why some countries have lower incidence and fatality rates than others, environmental factors such as diet should be considered. It has been described that countries with high polyunsaturated fatty acid (PUFA) intake have a lower number of COVID-19 victims and a higher rate of recovery from the disease. Moreover, it was found that linoleic acid, an omega-6 PUFA, could stabilize the spike protein in a closed conformation, blocking its interaction with ACE2. These facts prompted us to perform in silico simulations to determine if other PUFA could also stabilize the closed conformation of spike protein and potentially lead to a reduction in SARS-CoV-2 infection. We found that: (a) countries whose source of omega-3 is from marine origin have lower fatality rates; and (b) like linoleic acid, omega-3 PUFA could also bind to the closed conformation of spike protein and therefore, could help reduce COVID-19 complications by reducing viral entrance to cells, in addition to their known anti-inflammatory effects.


Subject(s)
COVID-19/epidemiology , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Computer Simulation , Eating , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Unsaturated/pharmacology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Seafood , Virus Internalization/drug effects
8.
Nutrients ; 12(10)2020 Oct 20.
Article in English | MEDLINE | ID: covidwho-890393

ABSTRACT

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).


Subject(s)
Coronavirus Infections/drug therapy , Dietary Supplements , Fatty Acids, Omega-3/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory Tract Infections/drug therapy , Trace Elements/therapeutic use , Virus Diseases/drug therapy , Vitamins/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Fatty Acids, Omega-3/pharmacology , Humans , Immunity/drug effects , Micronutrients/therapeutic use , Nutritional Status , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/virology , SARS-CoV-2 , Trace Elements/pharmacology , Virus Diseases/immunology , Virus Diseases/virology , Vitamins/pharmacology , Zinc/pharmacology , Zinc/therapeutic use
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