Hypothyroxinaemia during gestation is associated with low ferritin and increased levels of inflammatory markers.

Objective: Pregnancy is a state of physiological inflammation facilitating implantation. Early isolated hypothyroxinaemia (IH) and increased inflammation (including obesity) have been associated with severe obstetric complications. The current study evaluated the association between IH, low ferritin and inflammation parameters (interleukin 6 (IL-6), C-reactive protein (CRP), human chorionic gonadotrophin (hCG) and obesity. Moreover, the course of these parameters throughout pregnancy was evaluated in relation to IH. Methods: In the cross-sectional study (A) at 12 weeks, 2759 women participated and 2433 participated in the longitudinal study (B) with assessments at 12, 20 and 28 weeks gestation. At the first trimester, 122 (4.4%) IH women (free thyroxine (FT4) <5th percentile, normal TSH levels) were compared with 2114 (76.6%) reference women (FT4 between tenth and 90th percentiles, normal thyrotrophin (TSH) levels), in study B these figures were 99 (4.1%) and 1847 (75.9%), respectively. Results: Cross-sectionally, compared to reference women, IH was independently associated with low ferritin (<5th percentile, OR: 2.6, 95% CI: 1.4-4.9), high CRP (>95th percentile: OR: 1.9, 95% CI: 1.04-3.7), low hCG ( 30, OR: 1.7, 95% CI: 1.12.9) and higher age (OR: 1.1, 95% CI: 1.04-1.15). Longitudinally, compared to reference women, women with IH at 12 weeks gestation showed persistently and significantly lower ferritin and hCG levels, and persistently higher CRP and IL-6 levels throughout gestation. Conclusion: Gestational IH could be viewed as a condition of increased inflammation, as reported in non-thyroidal illness syndrome. Less favourable inflammation parameters and low iron status during early gestation in IH women seem to persist throughout gestation.

Selenium speciation studies in cancer patients to evaluate the responses of biomarkers of selenium status to different selenium compounds.

This work presents the first systematic comparison of selenium (Se) speciation in plasma from cancer patients treated orally with three Se compounds (sodium selenite, SS; L-selenomethionine, SeMet; or Se-methylselenocysteine, MSC) at 400 µg/day for 28 days. The primary goal was to investigate how these chemical forms of Se affect the plasma Se distribution, aiming to identify the most effective Se compound for optimal selenoprotein expression. This was achieved using methodology based on HPLC-ICP-MS after sample preparation/fractionation approaches. Measurements of total Se in plasma samples collected before and after 4 weeks of treatment showed that median total Se levels increased significantly from 89.6 to 126.4 µg kg-1 Se (p < 0.001), particularly when SeMet was administered (190.4 µg kg-1 Se). Speciation studies showed that the most critical differences between treated and baseline samples were seen for selenoprotein P (SELENOP) and selenoalbumin after administration with MSC (p = 5.8 × 10-4) and SeMet (p = 6.8 × 10-5), respectively. Notably, selenosugar-1 was detected in all low-molecular-weight plasma fractions following treatment, particularly with MSC. Two different chromatographic approaches and spiking experiments demonstrated that about 45% of that increase in SELENOP levels (to ~ 8.8 mg L-1) with SeMet is likely due to the non-specific incorporation of SeMet into the SELENOP affinity fraction. To the authors' knowledge, this has not been reported to date. Therefore, SELENOP is probably part of both the regulated (55%) and non-regulated (45%) Se pools after SeMet administration, whereas SS and MSC mainly contribute to the regulated one.

EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update.

INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed. METHODS: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed. RESULTS: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work. CONCLUSIONS: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA.

Exploration of thyroglobulin as a biomarker of iodine status in iodine-sufficient and mildly iodine-deficient pregnant women.

PURPOSE: Urinary iodine-to-creatinine ratio (UI/Creat) reflects recent iodine intake but has limitations for assessing habitual intake. Thyroglobulin (Tg) concentration, which increases with thyroid size, appears to be an indicator of longer-term iodine status in children and adults, however, less is known in pregnancy. This study investigated the determinants of serum-Tg in pregnancy and its use as an iodine-status biomarker in settings of iodine-sufficiency and mild-to-moderate deficiency. METHODS: Stored blood samples and existing data from pregnant women from the Netherlands-based Generation R (iodine-sufficient) and the Spain-based INMA (mildly-to-moderately iodine-deficient) cohorts were used. Serum-Tg and iodine status (as spot-urine UI/Creat) were measured at median 13 gestational weeks. Using regression models, maternal socio-demographics, diet and iodine-supplement use were investigated as determinants of serum-Tg, as well as the association between UI/Creat and serum-Tg. RESULTS: Median serum-Tg was 11.1 ng/ml in Generation R (n = 3548) and 11.5 ng/ml in INMA (n = 1168). When using 150 µg/g threshold for iodine deficiency, serum-Tg was higher in women with UI/Creat < 150 vs ≥ 150 µg/g (Generation R, 12.0 vs 10.4 ng/ml, P = 0.010; INMA, 12.8 vs 10.4 ng/ml, P < 0.001); after confounder adjustment, serum-Tg was still higher when UI/Creat < 150 µg/g (regression coefficients: Generation R, B = 0.111, P = 0.050; INMA, B = 0.157, P = 0.010). Iodine-supplement use and milk intake were negatively associated with serum-Tg, whereas smoking was positively associated. CONCLUSION: The association between iodine status and serum-Tg was stronger in the iodine-deficient cohort, than in the iodine-sufficient cohort. Serum-Tg might be a complementary (to UI/Creat) biomarker of iodine status in pregnancy but further evidence is needed.

Does atmospheric dimethyldiselenide play a role in reducing COVID-19 mortality?

Environmental selenium (Se) distribution in the US is uneven, yet US residents appear to have a relatively narrow range of serum Se concentrations, according to the NHANES III survey data; this is probably due to the modern food-distribution system. In the US, Se concentration in alfalfa leaves has been used as a proxy for regional Se exposure (low, medium or high, corresponding to ≤ 0.05, 0.06-0.10 and ≥ 0.11 ppm respectively). Se in plants, soil, water, and bacteria can be transformed into volatile dimethyldiselenide, which can be inhaled and excreted via the lung. Hence, pulmonary Se exposure may be different in states with different atmospheric Se levels. We found a significantly higher death rate from COVID-19 in low-Se states than in medium-Se or high-Se states, though the case densities of these states were not significantly different. Because inhaled dimethyldiselenide is a potent inducer of nuclear-factor erythroid 2 p45-related factor 2 (Nrf2), exposure to higher atmospheric dimethyldiselenide may increase Nrf2-dependent antioxidant defences, reducing the activation of NFκB by SARS-CoV-2 in the lung, thereby decreasing cytokine activation and COVID-19 severity. Atmospheric dimethyldiselenide may thereby play a role in COVID-19 mortality, although the extent of its involvement is unclear.

Iodine status of pregnant women from the Republic of Cyprus.

Iodine supply is crucial during pregnancy to ensure that the proper thyroid function of mother and baby support fetal brain development. Little is known about iodine status or its dietary determinants in pregnant women in the Republic of Cyprus. We therefore recruited 128 pregnant women at their first-trimester ultrasound scan to a cross-sectional study. We collected spot-urine samples for the measurement of urinary iodine concentration (UIC, µg/l) and creatinine concentration (Creat, g/l), the latter of which allows us to correct for urine dilution and to compute the iodine-to-creatinine ratio (UI/Creat). Women completed a FFQ and a general questionnaire. We used a General Linear model to explore associations between maternal and dietary characteristics with UI/Creat. The median UIC (105 µg/l) indicated iodine deficiency according to the WHO criterion (threshold for adequacy = 150 µg/l), and the UI/Creat was also low at 107 µg/g. Only 32 % (n 45) of women reported the use of iodine-containing supplements; users had a higher UI/Creat than non-users (131 µg/g v. 118 µg/g), though this difference was NS in the adjusted analysis (P = 0·37). Of the dietary components, only egg intake was significantly associated with a higher UI/Creat in adjusted analyses (P = 0·018); there was no significant association with milk, dairy products or fish intake. Our results suggest that pregnant women in Cyprus have inadequate iodine status and are at risk of mild-to-moderate iodine deficiency. Further research on dietary sources in this population is required.

The relevance of selenium to viral disease with special reference to SARS-CoV-2 and COVID-19.

In this review, the relevance of selenium (Se) to viral disease will be discussed paying particular attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19). Se, the active centre in selenoproteins has an ongoing history of reducing the incidence and severity of viral infections. Host Se deficiency increased the virulence of RNA viruses such as influenza A and coxsackievirus B3, the latter of which is implicated in the development of Keshan disease in north-east China. Significant clinical benefits of Se supplementation have been demonstrated in HIV-1, in liver cancer linked to hepatitis B, and in Chinese patients with hantavirus that was successfully treated with oral sodium selenite. China is of particular interest because it has populations that have both the lowest and the highest Se status in the world. We found a significant association between COVID-19 cure rate and background Se status in Chinese cities; the cure rate continued to rise beyond the Se intake required to optimise selenoproteins, suggesting an additional mechanism. Se status was significantly higher in serum samples from surviving than non-surviving COVID-19 patients. As regards mechanism, SARS-CoV-2 may interfere with the human selenoprotein system; selenoproteins are important in scavenging reactive oxygen species, controlling immunity, reducing inflammation, ferroptosis and endoplasmic reticulum (ER) stress. We found that SARS-CoV-2 significantly suppressed mRNA expression of GPX4, of the ER selenoproteins, SELENOF, SELENOM, SELENOK and SELENOS and down-regulated TXNRD3. Based on the available data, both selenoproteins and redox-active Se species (mimicking ebselen, an inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host) could employ their separate mechanisms to attenuate virus-triggered oxidative stress, excessive inflammatory responses and immune-system dysfunction, thus improving the outcome of SARS-CoV-2 infection.

Dietary factors that affect the risk of pre-eclampsia.

Pre-eclampsia affects 3%-5% of pregnant women worldwide and is associated with a range of adverse maternal and fetal outcomes, including maternal and/or fetal death. It particularly affects those with chronic hypertension, pregestational diabetes mellitus or a family history of pre-eclampsia. Other than early delivery of the fetus, there is no cure for pre-eclampsia. Since diet or dietary supplements may affect the risk, we have carried out an up-to-date, narrative literature review to assess the relationship between nutrition and pre-eclampsia. Several nutrients and dietary factors previously believed to be implicated in the risk of pre-eclampsia have now been shown to have no effect on risk; these include vitamins C and E, magnesium, salt, ω-3 long-chain polyunsaturated fatty acids (fish oils) and zinc. Body mass index is proportionally correlated with pre-eclampsia risk, therefore women should aim for a healthy pre-pregnancy body weight and avoid excessive gestational and interpregnancy weight gain. The association between the risk and progression of the pathophysiology of pre-eclampsia may explain the apparent benefit of dietary modifications resulting from increased consumption of fruits and vegetables (≥400 g/day), plant-based foods and vegetable oils and a limited intake of foods high in fat, sugar and salt. Consuming a high-fibre diet (25-30 g/day) may attenuate dyslipidaemia and reduce blood pressure and inflammation. Other key nutrients that may mitigate the risk include increased calcium intake, a daily multivitamin/mineral supplement and an adequate vitamin D status. For those with a low selenium intake (such as those living in Europe), fish/seafood intake could be increased to improve selenium intake or selenium could be supplemented in the recommended multivitamin/mineral supplement. Milk-based probiotics have also been found to be beneficial in pregnant women at risk. Our recommendations are summarised in a table of guidance for women at particular risk of developing pre-eclampsia.

Prooxidant activity-based guideline for a beneficial combination of (-)-epigallocatechin-3-gallate and chlorogenic acid.

In the current study, the prooxidant activities of (-)-epigallocatechin-3-gallate (EGCG) and chlorogenic acid (CGA) were systematically compared both in multiple in vitro models and in mice. At equimolar concentrations in vitro and in vivo, EGCG displayed powerful prooxidant effects though CGA exhibited none. In vitro, though CGA and EGCG synergistically produced hydrogen peroxide, CGA was able to scavenge hydroxyl radicals generated by EGCG/copper. Consistent with the selective modulation of reactive oxygen species produced from EGCG, CGA lowered hepatotoxicity but did not perturb hepatic AMPK activation nor the increase of hepatic Nrf2-associated proteins induced by high-dose EGCG. CGA, along with low-dose EGCG, synergistically activated hepatic AMPK and increased hepatic Nrf2-associated proteins without causing toxicity in mice. This proof-of-principle study suggests that polyphenols with potent prooxidant activities (e.g., EGCG) together with antioxidant polyphenols with noticeably low prooxidant activities (e.g., CGA) may yield health benefits with a low risk of side effects.

The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities.

This review addresses the role of the essential trace element, selenium, in type-2 diabetes mellitus (T2DM) and its metabolic co-morbidities, i.e., metabolic syndrome, obesity and non-alcoholic fatty liver disease. We refer to the dietary requirements of selenium and the key physiological roles of selenoproteins. We explore the dysregulated fuel metabolism in T2DM and its co-morbidities, emphasizing the relevance of inflammation and oxidative stress. We describe the epidemiology of observational and experimental studies of selenium in diabetes and related conditions, explaining that the interaction between selenium status and glucose control is not limited to hyperglycemia but extends to hypoglycemia. We propose that the association between high plasma/serum selenium and T2DM/fasting plasma glucose observed in many cross-sectional studies may rely on the upregulation of hepatic selenoprotein-P biosynthesis in conditions of hyperglycemia and insulin resistance. While animal studies have revealed potential molecular mechanisms underlying adverse effects of severe selenium/selenoprotein excess and deficiency in the pathogenesis of insulin resistance and ß-cell dysfunction, their translational significance is rather limited. Importantly, dietary selenium supplementation does not appear to be a major causal factor for the development of T2DM in humans though we cannot currently exclude a small contribution of selenium on top of other risk factors, in particular if it is ingested at high (supranutritional) doses. Elevated selenium biomarkers that are often measured in T2DM patients are more likely to be a consequence, rather than a cause, of diabetes.

Prospective Selective Mechanism of Emerging Senolytic Agents Derived from Flavonoids.

Senescent cells (SCs) are associated with the onset and development of multiple chronic diseases. Selective clearance of SCs by senolytic drugs is a potential therapeutic option for a number of age-related diseases. Among senolytic candidates, only dasatinib with quercetin and fisetin meet the rigorous criteria for senolytic drugs, according to a modified version of Koch's postulates. It is astonishing that two of the three agents, i.e., quercetin and fisetin, are flavonoids, although the mechanism by which they preferentially eliminate SCs is unclear. Herein, we propose a possible selective mechanism; prooxidant activities of quercetin or fisetin are inevitably involved in killing apoptosis-resistant SCs. Among the dietary flavonoids, quercetin is a potent redox-active flavonoid with strong prooxidant activities, and transition metals, such as copper and iron, hugely amplify its prooxidant activities. Fisetin, which has higher senolytic activities than quercetin, has higher prooxidant effects than quercetin in the absence or presence of copper. It appears that the prooxidant activity of flavonoids is an important consideration for screening senolytics. SCs accumulate high levels of copper and iron, and the selective mechanism of quercetin or fisetin is probably associated with copper/iron-promoted oxidative damage in SCs. Copper and iron dramatically enhanced the prooxidant effects of the flavonoid, epigallocatechin-3-gallate, having shown a depletion effect on SCs in rats and high therapeutic efficacy in patients with idiopathic pulmonary fibrosis, largely caused by SCs. Further investigation to evaluate whether epigallocatechin-3-gallate is a senolytic drug, according to Koch's postulates, is warranted.

Boosting and lassoing new prostate cancer SNP risk factors and their connection to selenium.

We begin by arguing that the often used algorithm for the discovery and use of disease risk factors, stepwise logistic regression, is unstable. We then argue that there are other algorithms available that are much more stable and reliable (e.g. the lasso and gradient boosting). We then propose a protocol for the discovery and use of risk factors using lasso or boosting variable selection. We then illustrate the use of the protocol with a set of prostate cancer data and show that it recovers known risk factors. Finally, we use the protocol to identify new and important SNP based risk factors for prostate cancer and further seek evidence for or against the hypothesis of an anticancer function for Selenium in prostate cancer. We find that the anticancer effect may depend on the SNP-SNP interaction and, in particular, which alleles are present.

SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, endoplasmic reticulum stress and DNA synthesis.

Higher selenium status has been shown to improve the clinical outcome of infections caused by a range of evolutionally diverse viruses, including SARS-CoV-2. However, the impact of SARS-CoV-2 on host-cell selenoproteins remains elusive. The present study investigated the influence of SARS-CoV-2 on expression of selenoprotein mRNAs in Vero cells. SARS-CoV-2 triggered an inflammatory response as evidenced by increased IL-6 expression. Of the 25 selenoproteins, SARS-CoV-2 significantly suppressed mRNA expression of ferroptosis-associated GPX4, DNA synthesis-related TXNRD3 and endoplasmic reticulum-resident SELENOF, SELENOK, SELENOM and SELENOS. Computational analysis has predicted an antisense interaction between SARS-CoV-2 and TXNRD3 mRNA, which is translated with high efficiency in the lung. Here, we confirmed the predicted SARS-CoV-2/TXNRD3 antisense interaction in vitro using DNA oligonucleotides, providing a plausible mechanism for the observed mRNA knockdown. Inhibition of TXNRD decreases DNA synthesis which is thereby likely to increase the ribonucleotide pool for RNA synthesis and, accordingly, RNA virus production. The present findings provide evidence for a direct inhibitory effect of SARS-CoV-2 replication on the expression of a specific set of selenoprotein mRNAs, which merits further investigation in the light of established evidence for correlations between dietary selenium status and the outcome of SARS-CoV-2 infection.

Perceived insufficient milk among primiparous, fully breastfeeding women: Is infant crying important?

Breastfeeding mothers often report perceived insufficient milk (PIM) believing their infant is crying too much, which leads to introducing formula and the early abandonment of breastfeeding. We sought to determine if infant crying was associated with reported PIM (yes/no) and number of problems associated with lactation (lactation problem score [LPS] 6-point Likert scale) before formula introduction. Primiparous breastfeeding mothers were recruited at birth and visited at 1, 2 and 4 weeks. Among those fully breastfeeding at 1 week (N = 230), infant crying variables based on maternal reports were not associated with PIM at 1 week, but LPS was. However, a mother's expectation that her infant would cry more than other infants was associated with increased odds of reporting PIM at 2 and 4 weeks, as were delayed onset of lactation and previous LPS. At 1 week, crying variables (frequency, difficulty in soothing) were associated with LPS along with percent weight change. Delayed onset of lactation, infant care style, number of breastfeeds and previous LPS were longitudinally associated with change in LPS from 1 to 2 weeks and 2 to 4 weeks. Our data suggest that reported infant crying is associated with PIM and LPS in the first 4 weeks of life. Guidance on what to expect in crying behaviour and the impact of infant care style may be beneficial in reducing PIM and LPS in the first month.

Endoplasmic reticulum stress and oxidative stress drive endothelial dysfunction induced by high selenium.

Selenium is an essential trace element important for human health. A balanced intake is, however, crucial to maximize the health benefits of selenium. At physiological concentrations, selenium mediates antioxidant, anti-inflammatory, and pro-survival actions. However, supra-nutritional selenium intake was associated with increased diabetes risk leading potentially to endothelial dysfunction, the initiating step in atherosclerosis. High selenium causes apoptosis in cancer cells via endoplasmic reticulum (ER) stress, a mechanism also implicated in endothelial dysfunction. Nonetheless, whether ER stress drives selenium-induced endothelial dysfunction, remains unknown. Here, we investigated the effects of increasing concentrations of selenium on endothelial cells. High selenite reduced nitric oxide bioavailability and impaired angiogenesis. High selenite also induced ER stress, increased reactive oxygen species (ROS) production, and apoptosis. Pretreatment with the chemical chaperone, 4-phenylbutyrate, prevented the toxic effects of selenium. Our findings support a model where high selenite leads to endothelial dysfunction through activation of ER stress and increased ROS production. These results highlight the importance of tailoring selenium supplementation to achieve maximal health benefits and suggest that prophylactic use of selenium supplements as antioxidants may entail risk.

Systematic study of the selenium fractionation in human plasma from a cancer prevention trial using HPLC hyphenated to ICP-MS and ESI-MS/MS.

This work represents the first systematic speciation study of selenium (Se) in plasma from subjects participating in a pilot study for a cancer prevention trial (PRECISE). This involved supplementation of elderly British and Danish individuals with selenised yeast for 6 months and 5 years, respectively, at 100, 200, and 300 µg Se/day or placebo. Speciation data was obtained for male plasma using HPLC-ICP-MS and HPLC-ESI-MS/MS. With the proposed strategy, approximately 1.5 mL of plasma was needed to determine total Se concentration and the fractionation of Se in high molecular weight (HMW) and low molecular weight (LMW) pools, and for quantification and identification of small Se species. For the first time, Se-methyl-selenocysteine (MSC) and methyl-2-acetamido-2deoxy1-seleno-ß-D-galactopyranoside (Selenosugar-1) were structurally confirmed in plasma after supplementation with selenised yeast within the studied range. Determination of selenomethionine (SeMet) incorporated non-specifically into albumin (SeALB) was achieved by HPLC-ICP-MS after hydrolysis. By subtracting this SeMet concentration from the total Se in the HMW pool, the concentration of Se incorporated into selenoproteins was calculated. Results from the speciation analysis of the free Se metabolite fraction (5% of total plasma Se) suggest a significant increase in the percentage of Se (as SeMet plus Selenosugar-1) of up to 80% of the total Se in the LMW fraction after 6 months of supplementation. The Se distribution in the HMW fraction reflects a significant increase in SeALB with Se depletion from selenoproteins, which occurs most significantly at doses of over 100 µg Se/day after 5 years. The results of this work will inform future trial design. Graphical abstract.

Selenium and selenoproteins in viral infection with potential relevance to COVID-19.

Selenium is a trace element essential to human health largely because of its incorporation into selenoproteins that have a wide range of protective functions. Selenium has an ongoing history of reducing the incidence and severity of various viral infections; for example, a German study found selenium status to be significantly higher in serum samples from surviving than non-surviving COVID-19 patients. Furthermore, a significant, positive, linear association was found between the cure rate of Chinese patients with COVID-19 and regional selenium status. Moreover, the cure rate continued to rise beyond the selenium intake required to optimise selenoproteins, suggesting that selenoproteins are probably not the whole story. Nonetheless, the significantly reduced expression of a number of selenoproteins, including those involved in controlling ER stress, along with increased expression of IL-6 in SARS-CoV-2 infected cells in culture suggests a potential link between reduced selenoprotein expression and COVID-19-associated inflammation. In this comprehensive review, we describe the history of selenium in viral infections and then go on to assess the potential benefits of adequate and even supra-nutritional selenium status. We discuss the indispensable function of the selenoproteins in coordinating a successful immune response and follow by reviewing cytokine excess, a key mediator of morbidity and mortality in COVID-19, and its relationship to selenium status. We comment on the fact that the synthetic redox-active selenium compound, ebselen, has been found experimentally to be a strong inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host. That finding suggests that redox-active selenium species formed at high selenium intake might hypothetically inhibit SARS-CoV-2 proteases. We consider the tactics that SARS-CoV-2 could employ to evade an adequate host response by interfering with the human selenoprotein system. Recognition of the myriad mechanisms by which selenium might potentially benefit COVID-19 patients provides a rationale for randomised, controlled trials of selenium supplementation in SARS-CoV-2 infection.