Zinc Supplementation Associated With a Decrease in Mortality in COVID-19 Patients: A Meta-Analysis.

The COVID-19 pandemic has had a significant impact on the world, resulting in millions of deaths worldwide and imposing economic, political, and social problems. The use of nutritional supplementation for the prevention and mitigation of COVID-19 remains controversial. This meta-analysis aims to investigate the association between zinc supplementation, mortality, and symptomatology, among COVID-19-infected patients. A meta-analysis was conducted to compare the outcomes of mortality and symptomology of patients with COVID-19 receiving zinc supplementation and those not receiving zinc supplementation. PubMed/Medline, Cochrane, Web of Science, and CINAHL Complete were independently searched with the search terms "zinc" AND "covid" OR "sars-cov-2" "COVID-19" OR "coronavirus". After duplicates were removed, 1215 articles were identified. Five of these studies were used to assess mortality outcomes, and two were used to assess symptomatology outcomes. The meta-analysis was conducted through R 4.2.1 software (R Foundation, Vienna, Austria). Heterogeneity was evaluated by calculating the I2 index. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. It was found that COVID-19-infected individuals treated with zinc supplements had a reduced risk of mortality compared with individuals not treated with a zinc supplement RR=0.63 (95%CI;0.52,0.77), p=0.005. For symptomology, it was found that COVID-19-infected individuals treated with zinc had no difference in symptomology than individuals not treated with a zinc supplement RR=0.52 (95%CI;0.00,24315.42), p=0.578. This data indicates that zinc supplementation is associated with decreased mortality in those with COVID-19 but does not change symptomatology. This is promising as zinc is widely available and may be valuable as a cost-effective way to prevent poor outcomes for those with COVID-19.

Evaluation and comparison of the mitochondrial and developmental toxicity of three strobilurins in zebrafish embryo/larvae.

Strobilurin fungicides have been frequently detected in aquatic environments and can induce mitochondrial toxicity to non-target aquatic organisms. However, the derived toxicity and subsequent mechanisms related to their adverse effects are not fully elucidated. In the present study, we compared the mitochondrial and developmental toxicity of azoxystrobin, pyraclostrobin, and trifloxystrobin using zebrafish embryo/larvae. The results showed that all three strobilurins inhibited mitochondrial and non-mitochondrial respiration (the potency is pyraclostrobin ≈ trifloxystrobin > azoxystrobin). Behavioral changes indicated that sublethal doses of pyraclostrobin and azoxystrobin caused hyperactivity of zebrafish larvae in dark cycles, whereas trifloxystrobin resulted in hypoactivity of zebrafish larvae. In addition, pyraclostrobin exposure impaired the inflation of swim bladder, and caused down-regulation of annexin A5 (anxa5) mRNA levels, and up-regulated transcript levels of pre-B-cell leukemia homeobox 1a (pbx1a); conversely, azoxystrobin and trifloxystrobin did not cause detectable effects with swim bladder inflation. Molecular docking results indicated that azoxystrobin had higher interacting potency with iodotyrosine deiodinase (IYD), prolactin receptor (PRLR), antagonistic conformation of thyroid hormone receptor ß (TRß) and glucocorticoid receptor (GR) compared to pyraclostrobin and trifloxystrobin; pyraclostrobin and azoxystrobin were more likely to interact with the antagonistic conformation of TRß and GR, respectively. These results may partially explain the different effects observed in behavior and swim bladder inflation, and also point to potential endocrine disruption induced by these strobilurins. Taken together, our study revealed that all three strobilurins alter mitochondrial bioenergetics and cause developmental toxicity. However, the toxic phenotypes and underlying mechanisms of each chemical may differ, and this requires further investigation. Pyraclostrobin showed higher mitochondrial toxicity at lethal doses and higher developmental toxicity at sublethal doses compared to the two other strobilurins tested. These results provide novel information for toxicological study as well as risk assessment of strobilurin fungicides.

Sub-lethal toxicity assessment of the phenylurea herbicide linuron in developing zebrafish (Danio rerio) embryo/larvae.

Due to run-off and rain events, agrochemicals can enter water catchments, exerting endocrine disruption effects and toxicity to aquatic organisms. Linuron is a phenylurea herbicide used to control a wide variety of vegetative weeds in agriculture in addition to residential applications. However, there are few studies that quantify its toxicity to early developmental stages of fish. The objectives of this study were to assess the acute toxicity of linuron to zebrafish embryos/larvae by measuring mortality, morphological deformities, oxidative respiration, gene expression, and locomotor activity via the Visual Motor Response test. Zebrafish embryos at ~6-h post-fertilization (hpf) were exposed to either embryo rearing medium (ERM), or one dose of 0.625, 1.25, 2.5, 5, and 10 µM linuron for up to 7 days post-fertilization (dpf) depending on the assay. Zebrafish larvae exposed to linuron displayed pericardial edema, yolk sac edema, and spinal curvature. Oxidative respiration assessments in embryos using the Agilent XFe24 Flux Analyzer revealed that linuron decreased mean basal respiration and oligomycin-induced ATP-linked respiration in 30 hpf embryos at 20 µM after a 24-hour exposure. In 7 dpf larvae, transcript abundance was determined for 6 transcripts that have a role in oxidative respiration (atp06, cox1, cox4-1, cox5a1, cytb, and nd1); the relative abundance of these transcripts was not altered with linuron treatment. A Visual Motor Response test was conducted on 7 dpf larvae to determine whether linuron (0.625 to 5 µM) impaired locomotor activity. Larval activity in the dark period decreased in a dose dependent manner and there were indications of hypoactivity as low as 1.25 µM. Transcript abundance was thus determined for tyrosine hydroxylase (th1) and glutamic acid decarboxylase 67 (gad1b), two rate limiting enzymes that control the production of dopamine and gamma-aminobutyric acid respectively. The mRNA levels of gad1b (p = 0.019) were reduced with increasing concentrations of linuron while th1 (p = 0.056) showed a similar decreasing trend, suggesting that neurotransmitter biosynthesis may be altered with exposure to linuron. This study improves knowledge related to the toxicity mechanisms for linuron and is the first to demonstrate that this anti-androgenic chemical impairs oxidative respiration and exerts neurotoxic effects associated with neurotransmitter biosynthesis during early development. These data are significant for environmental risk assessment of agrochemicals.