Risk of thromboembolic events in non-hospitalized COVID-19 patients: A systematic review.

The risk of thromboembolism in non-hospitalized COVID-19 patients remains uncertain and was assessed in this review to better weigh benefits vs. risks of prophylactic anticoagulation in this population. A search was performed through three databases: Medline, Embase, and Cochrane Library until 2022. Self-controlled case series, case-control and cohort studies were included, and findings summarized narratively. Meta-analyses for risk of thromboembolism including deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) between COVID-19 and non-COVID-19 non-hospitalized patients were conducted. Frequency, incidence rate ratio (IRR), and risk ratio (RR) of stroke were used to assess risk in non-hospitalized COVID-19 patients considering the lack of studies to conduct a meta-analysis. Ten studies met inclusion criteria characterized by adult non-hospitalized COVID-19 patients. Risk of bias was relatively low. Risk of DVT (RR: 1.98 with 95% CI: 1.03-3.83) and PE (OR: 6.72 with 95% CI: 4.81-9.39 and RR: 4.44 with 95% CI: 1.98-9.99) increased in non-hospitalized COVID-19 patients compared to controls. Risk of MI (OR: 1.91 with 95% CI: 0.89-4.09) is possibly increased in non-hospitalized COVID-19 patients with moderate certainty when compared to controls. A trend in favor of stroke was documented in the first week following infection. Our meta-analyses support the increase in risk of DVT and PE, and likely increase of MI, in non-hospitalized COVID-19 patients. The risk of stroke appears significant in the first week following infection but drops to insignificance two weeks later. More studies are needed to establish evidence-based recommendations for prophylactic anticoagulation therapy in non-hospitalized COVID-19 patients.

Insights into the modulation of the interferon response and NAD+ in the context of COVID-19.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in dramatic worldwide mortality. Along with developing vaccines, the medical profession is exploring new strategies to curb this pandemic. A better understanding of the molecular consequences of SARS-CoV-2 cellular infection could lead to more effective and safer treatments. This review discusses the potential underlying impact of SARS-CoV-2 in modulating interferon (IFN) secretion and in causing mitochondrial NAD+ depletion that could be directly linked to COVID-19's deadly manifestations. What is known or surmised about an imbalanced innate immune response and mitochondrial dysfunction post-SARS-CoV-2 infection, and the potential benefits of well-timed IFN treatments and NAD+ boosting therapies in the context of the COVID-19 pandemic are discussed.

Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases.

Nicotinamide adenine dinucleotide (NAD) is an abundant cofactor that plays crucial roles in several cellular processes. NAD can be synthesized de novo starting with tryptophan, or from salvage pathways starting with NAD precursors like nicotinic acid (NA), nicotinamide (NAM) or nicotinamide riboside (NR), referred to as niacin/B3 vitamins, arising from dietary supply or from cellular NAD catabolism. Given the interconversion between its oxidized (NAD+ ) and reduced form (NADH), NAD participates in a wide range of reactions: regulation of cellular redox status, energy metabolism and mitochondrial biogenesis. Plus, NAD acts as a signalling molecule, being a cosubstrate for several enzymes such as sirtuins, poly-ADP-ribose-polymerases (PARPs) and some ectoenzymes like CD38, regulating critical biological processes like gene expression, DNA repair, calcium signalling and circadian rhythms. Given the large number of mitochondria present in cardiac tissue, the heart has the highest NAD levels and is one of the most metabolically demanding organs. In several models of heart failure, myocardial NAD levels are depressed and this depression is caused by mitochondrial dysfunction, metabolic remodelling and inflammation. Emerging evidence suggests that regulating NAD homeostasis by NAD precursor supplementation has therapeutic efficiency in improving myocardial bioenergetics and function. This review provides an overview of the latest understanding of the different NAD biosynthesis pathways, as well as its role as a signalling molecule particularly in cardiac tissue. We highlight the significance of preserving NAD equilibrium in various models of heart diseases and shed light on the potential pharmacological interventions aiming to use NAD boosters as therapeutic agents.