bims-covind Biomed News
on COVID-19 and Immunology: nutrition and diet
Issue of 2020‒11‒15
forty-one papers selected by
Aimee Cook
Newcastle University

  1. Biomed Pharmacother. 2020 Nov 10. pii: S0753-3322(20)31166-5. [Epub ahead of print]133 110974
    Hamida RS, Shami A, Ali MA, Almohawes ZN, Mohammed AE, Bin-Meferij MM.
      Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a recently discovered coronavirus termed 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2). Several scholars have tested antiviral drugs and compounds to overcome COVID-19. 'Kefir' is a fermented milk drink similar to a thin yogurt that is made from kefir grains. Kefir and its probiotic contents can modulate the immune system to suppress infections from viruses (e.g., Zika, hepatitis C, influenza, rotaviruses). The antiviral mechanisms of kefir involve enhancement of macrophage production, increasing phagocytosis, boosting production of cluster of differentiation-positive (CD4+), CD8+, immunoglobulin (Ig)G+ and IgA+ B cells, T cells, neutrophils, as well as cytokines (e.g., interleukin (IL)-2, IL-12, interferon gamma-γ). Kefir can act as an anti-inflammatory agent by reducing expression of IL-6, IL-1, TNF-α, and interferon-γ. Hence, kefir might be a significant inhibitor of the 'cytokine storm' that contributes to COVID-19. Here, we review several studies with a particular emphasis on the effect of kefir consumption and their microbial composition against viral infection, as well as discussing the further development of kefir as a protective supplementary dietary against SARS-CoV-2 infection via modulating the immune response.
    Keywords:  Anti-inflammatory; Antiviral activity; Coronaviru; Immune system; Kefir
  2. Tidsskr Nor Laegeforen. 2020 11 10. 140(16):
    Hasle G.
  3. J Nutr. 2020 Nov 13. pii: nxaa332. [Epub ahead of print]
    Luo X, Liao Q, Shen Y, Li H, Cheng L.
      BACKGROUND: Vitamin D might have beneficial potential in influencing the natural history of the coronavirus disease 2019 (COVID-19) due to its immunomodulatory and anti-inflammatory properties.OBJECTIVE: The aim was to investigate whether vitamin D deficiency is associated with COVID-19 incidence and disease severity in Chinese people.
    METHODS: In a cross-sectional study we retrospectively analyzed 335 COVID-19 patients (median: 56.0; IQR: 43.0-64.0 y) who were admitted to the Wuhan Tongji Hospital between 27 February and 21 March 2020. We also included an age- and sex-matched population of 560 individuals (median: 55; IQR: 49.0-60.0 y) who underwent the physical examination program. Their serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured during the same period from 2018-2019. Serum 25(OH)D concentrations were measured for all COVID-19 patients on admission. Severity of COVID-19 was determined based on the level of respiratory involvement. A general linear model with adjustment for covariates was used to compare 25(OH)D concentrations between the COVID-19 and 2018-2019 control groups. Adjusted ORs with 95% CIs for associations between vitamin D status and COVID-19 severity were estimated via multivariable logistic regression.
    RESULTS: In the general linear model adjusted for age, sex, comorbidities, and BMI, serum 25(OH)D concentrations were significantly lower among COVID-19 patients than the 2018-2019 controls [ln transformed values of 3.32 ± 0.04 vs. 3.46 ± 0.022 ln (nmol/L), P = 0.014]. Multivariable logistic regression showed that male sex (OR: 2.26; 95% CI: 1.06, 4.82), advanced age (≥65 y) (OR: 4.93; 95% CI: 1.44, 16.9), and vitamin D deficiency (<30 nmol/L) (OR: 2.72; 95% CI: 1.23, 6.01) were significantly associated with COVID-19 severity (all P < 0.05).
    CONCLUSIONS: These findings suggested that vitamin D deficiency impacts COVID-19 hospitalization and severity in the Chinese population.
    Keywords:  COVID-19 severity; coronavirus disease; cross-sectional; deficiency; vitamin D
  4. Cureus. 2020 Nov 03. 12(11): e11315
    Go CC, Pandav K, Sanchez-Gonzalez MA, Ferrer G.
      The SARS-CoV-2 virus has created an unprecedented impact on healthcare globally. Being a novel virus, several treatments have been explored against COVID-19. During the early stages of the disease, treatment is mainly supportive. While several studies have suggested different treatment modalities, there is still no definitive treatment against COVID-19. Re-purposing already established medications, with excellent safety profiles, is a possible approach for treating the disease in its early stage. Having a mode of transmission as a droplet mode, several studies have supported how the nose can contain the primary route of entry of SARS-CoV-2. Hence, we postulated that re-purposing a commercially available nasal spray containing xylitol and grapefruit seed extract (GSE), namely Xlear Nasal Spray® (Xlear, Inc., American Fork, USA) could be used as an adjunct treatment of COVID-19. With a well-established safety profile, the components of this nasal spray have been studied and have been shown to have potential efficacy against viral pathogens, including coronavirus, and may potentially regulate pathways important in the initial entry of infection, replication, and systemic response to SARS-CoV-2. We present a series of three mild-moderate risks, symptomatic, COVID-19 patients, treated with the intranasal combination, as an adjuvant to their ongoing treatment, with rapid clinical improvement and shorten time to negativization on repeat intranasal swab test via PCR. No safety issues were noted during the course of treatment. Xlear nasal spray, containing xylitol plus GSE, given its established safety profile and compelling clinical results described here, could be a potential adjunct treatment option in mild-moderate COVID-19 cases.
    Keywords:  covid-19; grapefruit seed extract; intranasal; sars-cov-2; therapeutics; xylitol
  5. Int Immunopharmacol. 2020 Nov;pii: S1567-5769(20)33018-6. [Epub ahead of print]88 107001
    Padhi S, Suvankar S, Panda VK, Pati A, Panda AK.
      BACKGROUND: The role of vitamin D in the susceptibility and severity of various viral diseases has been well documented. Recently, some reports highlighted the possible importance of vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although India receives adequate sunlight throughout the year, the majority of Indians are deficient in vitamin D levels. In the present study, we hypothesized that vitamin D deficiency would be associated with the SARS-CoV-2 infection rate and mortality in the Indian population.MATERIALS AND METHODS: SARS-CoV-2 infection and mortality data were obtained from the Government of India's official website (accessed on 16th August 2020). Various literature databases like PubMed and Google Scholar were searched to find the mean of 25-hydroxyvitamin D [25(OH)D] levels in different states and union territories of India, Pearson correlation was carried out to investigate the possible link between mean 25(OH)D levels and SARS-CoV-2 infection and mortality per million of the population.
    RESULTS: An inverse correlation was observed between the mean level of 25(OH)D and SARS-CoV-2 infection rate (r = -0.43, p = 0.02) and mortality rate (r = -0.42, p = 0.02).
    CONCLUSIONS: The present observational study revealed an association of vitamin D with SARS-CoV-2 infection and related mortality. Further studies are required to validate our observations.
    Keywords:  COVID-19; Indian population; Infection; Mortality; SARS-CoV-2; Vitamin D
  6. Int Immunopharmacol. 2020 Nov;pii: S1567-5769(20)32897-6. [Epub ahead of print]88 106995
    Silberstein M.
      There is recent evidence that interleukin-6 (IL-6) levels are elevated in cases of complicated COVID-19, but it is also possible that this cytokine may have a far more important role in the pathogenesis of viral infection. IL-6 is known to be modulated by Vitamin D, and there is preliminary evidence that deficiency of this vitamin is linked to poorer outcomes. To identify whether IL-6 levels prior to infection might predict outcome, early data on COVID-19 mortality from Italy and the UK were compared with previously published results of mean IL-6 levels from these countries as well as from the USA. There was a highly significant correlation (r = 0.9883; p = 0.00025) between age-stratified mortality rates and IL-6 levels from previously published data on healthy individuals. To determine whether Vitamin D may be beneficial at lowering IL-6 levels in patients, a limited analysis of trials examining the relationship between these entities published since 2015 was undertaken. Eight out of 11 studies described a significant lowering effect of Vitamin D on IL-6. Given that IL-6 likely facilitates viral cell entry and replication, levels prior to infection may predict mortality. This provides a rationale for prophylactic and therapeutic measures directed at lowering IL-6, including Vitamin D prescription.
    Keywords:  ACE2; COVID-19; Cathepsin L; Cytokine storm; IL-6; Vitamin D
  7. Am J Physiol Endocrinol Metab. 2020 Nov 11.
    van Kempen TA, Deixler E.
      The use of vitamin D to reduce the severity of COVID-19 complications is receiving considerable attention, backed by encouraging data. Its purported mode of action is as an immune modulator. Vitamin D, however, also affects metabolism of phosphate and Mg, which may well play a critical role in SARS-CoV-2 pathogenesis. SARS-CoV-2 may induce a cytokine storm that drains ATP whose regeneration requires phosphate and Mg. These minerals, however, are often deficient in conditions that predispose people to severe COVID-19, including older age (especially males), diabetes, obesity, and usage of diuretics. Symptoms observed in severe COVID-19 also fit well with those seen in classical hypophosphatemia and hypomagnesemia, such as thrombocytopenia, coagulopathy, dysfunction of liver and kidneys, neurologic disturbances, immunodeficiency, failure of heart and lungs, delayed weaning from a respirator, cardiac arrhythmia, seizures, and finally multi-organ failure. Deficiencies of phosphate and Mg can be amplified by kidney problems commonly observed in COVID-19 patients resulting in their wastage into urine. Available data show that phosphate and Mg are deficient in COVID-19 with phosphate showing a remarkable correlation with its severity. In one experiment, COVID-19 patients were supplemented with a cocktail of vitamin D3, Mg, and vitamin B12, with very encouraging results. We thus argue that COVID-19 patients should be monitored and treated for phosphate and Mg deficiencies, ideally already in the early phases of infection. Supplementation of phosphate and Mg combined with vitamin D could also be implemented as a preventative strategy in populations at risk.
    Keywords:  COVID-19; Magnesium; Phosphate; SARS-CoV-2; vitamin D
  8. bioRxiv. 2020 Nov 04. pii: 2020.11.02.365833. [Epub ahead of print]
    Gopal V, Nilsson-Payant BE, French H, Siegers JY, tenOever BR, Yung WS, Hardwick M, Te Velthuis AJW.
      Infections with respiratory viruses can spread via liquid droplets and aerosols, and cause diseases such as influenza and COVID-19. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of respiratory droplets containing these viruses. However, influenza A viruses and coronaviruses are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as absorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here we used polyamide 6.6 (PA66) fibers that had zinc ions embedded during the polymerisation process and systematically investigated if these fibers can absorb and inactivate pandemic SARS-CoV-2 and influenza A virus H1N1. We find that these viruses are readily absorbed by PA66 fabrics and inactivated by zinc ions embedded into this fabric. The inactivation rate (pfu·gram -1 ·min -1 ) exceeds the number of active virus particles expelled by a cough and supports a wide range of viral loads. Overall, these results provide new insight into the development of "pathogen-free" PPE and better protection against RNA virus spread.Importance: Face masks and other PPE can reduce risk of spreading or getting infected with respiratory viruses, such as SARS-CoV-2, the causative agent of COVID-19. However, respiratory viruses can remain infectious in or on the outside of PPE for hours. We therefore explored if respiratory viruses can be inactivated via a mechanism involving absorption of droplets and inactivation of the virus on the surface and within the bulk of a fabric. To do this, we used fabrics constructed from polymers that maintain a moisture balance and contain embedded zinc ions within their matrix to inactivate human respiratory viruses. After addition of influenza A virus and SARS-CoV-2 to these fabrics, we find inactivation rates that exceed the number of virus particles present in a cough. We also find evidence that the influenza A virus surface protein haemagglutinin and the SARS-CoV-2 surface protein spike are destabilized on these fibers. These fibers may thus confer broad-spectrum viral inactivation properties to PPE and complement existing PPE by reducing the risk of respiratory virus transmission even further.
  9. J Transl Med. 2020 Nov 07. 18(1): 415
    Di Renzo L, Gualtieri P, Pivari F, Soldati L, Attinà A, Leggeri C, Cinelli G, Tarsitano MG, Caparello G, Carrano E, Merra G, Pujia AM, Danieli R, De Lorenzo A.
      On December 12, 2019 a new coronavirus (SARS-CoV-2) emerged in Wuhan, China, triggering a pandemic of severe acute respiratory syndrome in humans (COVID-19). Today, the scientific community is investing all the resources available to find any therapy and prevention strategies to defeat COVID-19. In this context, immunonutrition can play a pivotal role in improving immune responses against viral infections. Immunonutrition has been based on the concept that malnutrition impairs immune function. Therefore, immunonutrition involves feeding enriched with various pharmaconutrients (Omega 3 Fatty Acids, Vitamin C, Arginine, Glutamine, Selenium, Zinc, Vitamin, E and Vitamin D) to modulate inflammatory responses, acquired immune response and to improve patient outcomes. In literature, significant evidences indicate that obesity, a malnutrition state, negatively impacts on immune system functionality and on host defense, impairing protection from infections. Immunonutrients can promote patient recovery by inhibiting inflammatory responses and regulating immune function. Immune system dysfunction is considered to increase the risk of viral infections, such as SARS-CoV-2, and was observed in different pathological situations. Obese patients develop severe COVID-19 sequelae, due to the high concentrations of TNF-α, MCP-1 and IL-6 produced in the meantime by visceral and subcutaneous adipose tissue and by innate immunity. Moreover, leptin, released by adipose tissue, helps to increase inflammatory milieu with a dysregulation of the immune response. Additionally, gut microbiota plays a crucial role in the maturation, development and functions of both innate and adaptive immune system, as well as contributing to develop obese phenotype. The gut microbiota has been shown to affect lung health through a vital crosstalk between gut microbiota and lungs, called the "gut-lung axis". This axis communicates through a bi-directional pathway in which endotoxins, or microbial metabolites, may affect the lung through the blood and when inflammation occurs in the lung, this in turn can affect the gut microbiota. Therefore, the modulation of gut microbiota in obese COVID-19 patients can play a key role in immunonutrition therapeutic strategy. This umbrella review seeks to answer the question of whether a nutritional approach can be used to enhance the immune system's response to obesity in obese patients affected by COVID-19.
    Keywords:  COVID-19; Gut microbiota; Immune system; Immunonutrition; Inflammation; Obesity
  10. BMJ Open Sport Exerc Med. 2020 ;6(1): e000882
    Saita Y.
    Keywords:  Stress fracture; nutrition; soccer; sports & exercise medicine; sports and nutrition
  11. Transl Med Commun. 2020 ;5(1): 21
    Paria K, Paul D, Chowdhury T, Pyne S, Chakraborty R, Mandal SM.
      Since the birth of Christ, in these 2019 years, the man on earth has never experienced a survival challenge from any acellular protist compared to SARS-CoV-2. No specific drugs yet been approved. The host immunity is the only alternative to prevent and or reduce the infection and mortality rate as well. Here, a novel mechanism of melanin mediated host immunity is proposed having potent biotechnological prospects in health care management of COVID-19. Vitamin D is known to enhance the rate of melanin synthesis; and this may concurrently regulate the expression of furin expression. In silico analyses have revealed that the intermediates of melanin are capable of binding strongly with the active site of furin protease. On the other hand, furin expression is negatively regulated via 1-α-hydroxylase (CYP27B1), that belongs to vitamin-D pathway and controls cellular calcium levels. Here, we have envisaged the availability of biological melanin and elucidated the bio-medical potential. Thus, we propose a possible synergistic application of melanin and the enzyme CYP27B1 (regulates vitamin D biosynthesis) as a novel strategy to prevent viral entry through the inactivation of furin protease and aid in boosting our immunity at the cellular and humoral levels.
    Keywords:  COVID-19; Furin; Melanin; Microbial melanin synthesis; SARS-CoV-2; Vitamin-D
  12. Front Plant Sci. 2020 ;11 568890
    Pandey A, Khan MK, Hamurcu M, Gezgin S.
      The sudden emergence of COVID-19 caused by a novel coronavirus (nCoV) led the entire world to search for relevant solutions to fight the pandemic. Although continuous trials are being conducted to develop precise vaccines and therapeutic antibodies, a potential remedy is yet to be developed. Plants have largely contributed to the treatment of several human diseases and different phytoconstituents have been previously described to impede the replication of numerous viruses. Despite the previous positive reports of plant-based medications, no successful clinical trials of phyto-anti-COVID drugs could be conducted to date. In this article, we discuss varying perspectives on why phyto-anti-viral drug clinical trials were not successful in the case of COVID-19. The issue has been discussed in light of the usage of plant-based therapeutics in previous coronavirus outbreaks. Through this article, we aim to identify the disadvantages in this research area and suggest some measures to ensure that phytoconstituents can efficiently contribute to future random viral outbreaks. It is emphasized that if used strategically phyto-inhibitors with pre-established clinical data for other diseases can save the time required for long clinical trials. The scientific community should competently tap into phytoconstituents and take their research up to the final stage of clinical trials so that potential phyto-anti-COVID drugs can be developed.
    Keywords:  clinical trials; coronavirus; coronavirus disease of 2019; molecular docking; natural compounds; phytoconstituents; severe acute respiratory syndrome coronavirus 2
  13. Med Clin (Barc). 2020 Sep 25. pii: S0025-7753(20)30669-2. [Epub ahead of print]
    Bartziokas K, Kostikas K.
  14. Biol Trace Elem Res. 2020 Nov 10.
    Sharma P, Reddy PK, Kumar B.
      With the advent of twenty-first century, we are in cruel grip of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the associated illness being called as COVID-19. Since its outbreak in December 2019 in Wuhan, China, there are no medicines to cure the disease till date. Based on their experience, scientists say that developing a coronavirus vaccine could take at least a year. There are many steps in place before the vaccine comes for the distribution like its safety and cost-effectiveness, especially for the developing countries. In this scenario, the only way to prevent the disease is by following certain safety guidelines and to boost up the body's immune system. Zinc, a crucial trace element involved in several biological and metabolic processes, has been found to play a pivotal role in promoting and appropriately regulating the host defense mechanisms against viral infections. Zinc is naturally present in some foods, fortified in others and also available as dietary supplement. The current RDA (Recommended Daily Allowance) of zinc is 12 and 10 mg for males and females respectively. Zinc is the second most common trace mineral after iron in the cell. It is present in all organs and tissues in the body as it forms catalytic component of all 6 classes of enzymes encompassing almost 2000 enzymes in the body. Zinc is biologically essential for cellular processes, including growth and development, as well as DNA synthesis and RNA transcription. Zinc deficiency results in a number of metabolic changes besides a compromised immune system. In this review, the role of zinc in regulating the host defense and viral replication is being discussed with the main focus on COVID-19.
    Keywords:  COVID-19; Host defense; SARS; Trace elements; Zinc
  15. Emerg Infect Dis. 2020 Nov 10. 27(1):
    Feehan AK, Velasco C, Fort D, Burton JH, Price-Haywood EG, Katzmarzyk PT, Garcia-Diaz J, Seoane L.
      By using paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined point prevalence and seroprevalence in Louisiana, USA, during the second phase of reopening. Infections were highly variable by race and ethnicity, work environment, and ZIP code. Census-weighted seroprevalence was 3.6%, and point prevalence was 3.0%.
    Keywords:  Baton Rouge; COVID-19; Louisiana; SARS virus; SARS-CoV-2; United States; convalescence; coronavirus disease; cross-sectional studies; healthcare disparities; prevalence; respiratory infections; seroepidemiologic studies; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses
  16. Clin Nutr ESPEN. 2020 Dec;pii: S2405-4577(20)30187-X. [Epub ahead of print]40 309-313
    Kuwabara A, Tsugawa N, Ao M, Ohta J, Tanaka K.
      BACKGROUND & AIMS: Respiratory tract infections (RTIs) are one of the major causes of morbidity and mortality in the elderly. Since vitamin D is known to play important roles in immunity, and its deficiency has been reported to be prevalent in the elderly, we have studied the relationship between serum 25-hydroxyvitamin D [25(OH)D] level, which is the most reliable marker for vitamin D status, and the incidence of RTIs in the institutionalized elderly by a prospective observational study.METHODS: From 208 Japanese subjects aged 60 and older fulfilling the inclusion criteria, 148 subjects remained after propensity score matching. Data were obtained from the medical records including their age, gender, histories of co-morbidities and medications, the incidence of acute RTIs including pneumonia. Measurement of serum 25(OH)D level and assessment of nutrients intake including vitamin D were done at baseline. Cox's proportional hazard analysis was performed to assess the significant predictors for RTIs during the follow-up period.
    RESULTS: The median observation duration was 354.2 days, and the incidence of RTIs was 75.8 person-years. Subjects with RTIs had significantly lower serum 25(OH)D concentration, and a higher prevalence of vitamin D deficiency (25(OH)D < 10 ng/mL). Cox's proportional hazard analysis revealed that vitamin D deficiency was a significant predictor for RTIs.
    CONCLUSIONS: Our results suggested that vitamin D deficiency was a significant predictor for an increased incidence of RTIs in institutionalized elderly, and the necessity of vitamin D supplementation for the prevention of RTIs was considered.
    Keywords:  25-Hydroxyvitamin D; Institutionalized elderly; Propensity score matching; Respiratory tract infections; Vitamin D deficiency
  17. Endocrinol Diabetes Nutr. 2020 Oct 21. pii: S2530-0164(20)30212-3. [Epub ahead of print]
    Rubio Herrera MA, Bretón Lesmes I.
      Obesity is a chronic disease that leads to an increased risk of mortality and morbidity, and the impact of the COVID-19 pandemic may create a new health challenge. There is clear evidence showing that some biological and social factors associated with obesity involve an increased risk of COVID-19 infection, hospitalization, and greater severity compared to people with normal weight. Undoubtedly, obesity involves a low-grade proinflammatory state that produces a dysregulation of the immune system that compromises its ability to respond to respiratory infection by COVID-19 and so produces a worsening of the disease. In this review, the main epidemiological and pathophysiological data that associate obesity with COVID-19 are described.
    Keywords:  COVID-19; Obesidad; Obesidad grave; Obesity; Severe obesity; Vitamin D; Vitamina D
  18. Microorganisms. 2020 Nov 06. pii: E1744. [Epub ahead of print]8(11):
    Sharma L, Riva A.
      Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and the gut barrier may be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and disruption of barrier functions or intestinal microbial dysbiosis may have an impact on the progression and severity of this new disease. In this review, we aim to provide an overview of current evidence on the involvement of gut alterations in human disease including COVID-19, with a prospective outlook on supportive therapeutic strategies that may be investigated to rescue intestinal barrier functions and possibly facilitate clinical improvement in these patients.
    Keywords:  COVID-19; FMT; SARS-CoV-2; gastrointestinal; gut barrier; gut permeability; gut–liver axis; immune; microbiota; probiotics
  19. J Nutr. 2020 Nov 13. pii: nxaa375. [Epub ahead of print]
    Wang J, Sato T, Sakuraba A.
    Keywords:  COVID-19; coronavirus; global; mortality; obesity; overweight
  20. Clin Nutr. 2020 Nov 02. pii: S0261-5614(20)30601-4. [Epub ahead of print]
    Cereda E, Bogliolo L, Klersy C, Lobascio F, Masi S, Crotti S, De Stefano L, Bruno R, Corsico AG, Di Sabatino A, Perlini S, Montecucco C, Caccialanza R, .
      BACKGROUND & AIMS: Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients are not conclusive. The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity.METHODS: In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 h since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (<30 - ≥20 ng/mL), moderately deficient (<20 - ≥10 ng/mL), severely deficient (<10 ng/mL).
    RESULTS: The prevalence of 25(OH)vitamin D insufficiency, moderate deficiency and severe deficiency was 13.2%, 22.5% and 54.3%, respectively. 25(OH)Vitamin D deficiency (<20 ng/mL) was not associated with COVID-19 clinical features and outcomes. Unexpectedly, after adjusting for major confounders, a significant positive association between increasing 25(OH)vitamin D levels and in-hospital mortality (on a continuous logarithmic scale, odds ratio = 1.73 [95% CI, 1.11 to 2.69]; P = .016) was observed.
    CONCLUSIONS: Very low 25(OH)vitamin D levels were highly prevalent and suggestive of deficiency among our hospitalized severe COVID-19 patients, but low 25(OH)vitamin D levels were not associated with outcome variables. Whether 25(OH)vitamin D adequacy may influence clinical outcomes in COVID-19 and the unexpected correlation between higher 25(OH)vitamin D levels and mortality require further investigations by large intervention trials.
    Keywords:  Coronavirus disease 2019; Disease severity; Hospitalized patients; Mortality; Vitamin D 25OH
  21. Rev Neurosci. 2020 Nov 12. pii: /j/revneuro.ahead-of-print/revneuro-2020-0074/revneuro-2020-0074.xml. [Epub ahead of print]
    de Barros Viana M, Rosário BDA, de Fátima Santana de Nazaré M, Estadella D, Ribeiro DA, Socorro de Barros Viana G.
      The coronavirus disease (COVID-19), identified in Wuhan, China, on December 2019, was declared a pandemic by the World Health Organization, on March, 2020. Since then, efforts have been gathered to describe its clinical course and to determine preventive measures and treatment strategies. Adults older than 65 years of age are more susceptible to serious clinical symptoms and present higher mortality rates. Angiotensin-converting enzyme 2 (ACE2) is a major receptor for some coronavirus infection, including SARS-COV-2, but is also a crucial determinant in anti-inflammation processes during the renin-angiotensin system (RAS) functioning - converting angiotensin II to angiotensin 1-7. The decline in ACE2 expression that occurs with aging has been associated to the higher morbidity and mortality rates in older adults. These observations highlight the importance of investigating the association between COVID-19 and age-related neurodegenerative disorders, i.e., Parkinson's and Alzheimer's diseases. A possible option to reduce the risk of COVID-19 is vitamin D supplementation, due to its anti-inflammatory and immune-system-modulating effects. It has also been suggested that vitamin D supplementation plays a role in slowing progression of Parkinson and Alzheimer. The present study is a literature review of articles published on the theme COVID-19, Parkinson and Alzheimer's diseases, and the role played by vitamin D. PUBMED, MEDLINE, and EMBASE databases were consulted. Results confirm neurodegenerative and neuroinflammatory effects of COVID-19, aggravated in Parkinson's and Alzheimer's patients, and the important role of vitamin D as a possible therapeutic strategy. Nevertheless, randomized controlled trials and large population studies are still warranted.
    Keywords:  COVID-19; dementia; neurodegeneration; neuroinflammation; vitamin D3
  22. Mol Med. 2020 Nov 07. 26(1): 101
    Li M, Chen WD, Wang YD.
      The gut microbiota regulates the biological processes of organisms acting like 'another' genome, affecting the health and disease of the host. MicroRNAs, as important physiological regulators, have been found to be involved in health and disease. Recently, the gut microbiota has been reported to affect host health by regulating host miRNAs. For example, Fusobacterium nucleatum could aggravate chemoresistance of colorectal cancer by decreasing the expression of miR-18a* and miR-4802. What's more, miRNAs can shape the gut microbiota composition, ultimately affecting the host's physiology and disease. miR-515-5p and miR-1226-5p could promote the growth of Fusobacterium nucleatum (Fn) and Escherichia coli (E.coli), which have been reported to drive colorectal cancer. Here, we will review current findings of the interactions between the gut microbiota and microRNAs and discuss how the gut microbiota-microRNA interactions affect host pathophysiology including intestinal, neurological, cardiovascular, and immune health and diseases.
    Keywords:  Gut microbiota; Host pathophysiology; miRNA
  23. Bratisl Lek Listy. 2020 ;121(11): 786-788
    Abdel Hafez SMN.
      Our understanding of the mechanisms responsible for death of aged people from Covid-19 became one of the major concerns of these days. Glucose-6-phosphate dehydrogenase (G6PD) enhances the normal senescence and accelerates the precocious removal of chronologically young, yet biologically aged cells. Thus, its deficiency is associated with an increase in the cellular oxidative stress. Accumulating evidence showed that oxidative stress has a fundamental role in several age-related diseases. Nowadays, Covid-19 is considered a serious health problem worldwide. The host cellular environment is the key determinant of pathogen Infectivity. Most respiratory viral infections have a strong association with Glucose-6-phosphate dehydrogenase. Unfortunately, this enzyme deficiency markedly decreases with aging what is involved in increasing of the morbidity rate. The aim of this mini review was to shed more light on the role of G6PD deficiency in aged people infected with Covid-19 (Ref. 20). Keywords: GSPD, Covid-19, elderly people.
  24. Curr Pharm Biotechnol. 2020 Nov 10.
    Khan MA, Younus H.
      BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic of coronavirus disease-2019 (COVID-19). The progression of COVID-19 is related to an excessive host inflammatory immune response to SARS-CoV-2 infection, which is considered a major cause of disease severity and death. Dysregulated immune response produces huge amounts of pro-inflammatory cytokines and chemokines called 'cytokine storm'. Moreover, the activation of microthrombi formation plays an important role in multiple organ failure.METHODS: Keeping into the consideration of the potent anti-inflammatory activity of black seed and its major constituent thymoquinone (TQ), we hypothesize their potential implication in the treatment of COVID-19 patients. A literature search was performed in PubMed, ScienceDirect, Google scholar and Scopus electronic databases by using the terms, including black seed, N. sativa, thymoquinone, SARS-CoV-2, COVID-19 and inflammatory immune response. Reslts: Various studies confirmed that Black seed and TQ reduced the thrombus formation, the expression of tissue factor and the immune activation. Furthermore, TQ demonstrated the broad spectrum antimicrobial activity that may be effective in controlling the secondary infections in COVID-19 patients.
    CONCLUSION: Keeping into consideration the multi-targeting nature of the black seed and TQ, they may be used as a potential therapeutic formulation or as an adjunct therapy in the treatment of COVID-19 patients.
    Keywords:  COVID-19; Cell signaling pathways; Immunopathogenesis; SARS-CoV-2; Thymoquinone; secondary infections
  25. J Clin Med. 2020 Nov 11. pii: E3630. [Epub ahead of print]9(11):
    Mitsuyama K, Tsuruta K, Takedatsu H, Yoshioka S, Morita M, Niwa M, Matsumoto S.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global coronavirus disease 2019 (COVID-19) outbreak. Along with the respiratory tract, the gastrointestinal (GI) tract is one of the main extra-pulmonary targets of SARS-CoV-2 with respect to symptom occurrence and is a potential route for virus transmission, most likely due to the presence of angiotensin-converting enzyme 2. Therefore, understanding the mechanisms of GI injury is crucial for a harmonized therapeutic strategy against COVID-19. This review summarizes the current evidence for the clinical features of and possible pathogenic mechanisms leading to GI injury in COVID-19.
    Keywords:  ACE2; COVID-19; SARS-CoV-2; TMPRSS2; gastrointestinal tract; gut microbiota; intestine; renin-angiotensin-aldosterone system; thrombosis; tryptophan
  26. J Food Biochem. 2020 Nov 10. e13557
    Lammi C, Arnoldi A.
      SARS-CoV-2 (previously 2019-nCoV), the pathogenic agent of COVID-19 disease, started to expand from Wuhan, China, on December 2019 and in 2 months, it spread worldwide giving origin to a pandemic. COVID-19 has a stronger transmission capacity by inhalation of infectious aerosols and after an incubation time of 3-14 days, it may be responsible for diseases ranging from the asymptomatic to fatal consequences. COVID-19 has emerged as a multifaceted, multisystem, multi-organ disorder, which produces its pathogenic effects through a quite ubiquitous target at the level of multiple organs and in which oxidative stress and inflammatory process play relevant roles. Thus, besides the development of a pharmacological therapy, in the field of alternative and coadjutant therapeutic, the use of dietary supplements or nutraceuticals for the prevention or treatment of SARS-CoV-2 infection may be a useful strategy. Herein, we specifically comment on some literature evidences, which link the food-derived antioxidants and metal-chelating agents with treatment and prevention of oxidative stress and inflammation that play a key role in the progression of COVID-19. PRACTICAL APPLICATIONS: Oxidative stress and inflammation are key factors increasing COVID-19 severity especially in the presence of chronic diseases associated with the antioxidant system fragility. These evidences support the recommendation of antioxidants supplementation as useful strategies against COVID-19. In light with these observations, herein, a comment which describes the major antioxidants and metal-chelating agents from food sources that might be useful for the treatment and prevention of oxidative stress and inflammation during COVID-19.
    Keywords:  COVID-19; SARS-CoV-2; food antioxidants; metal-cheating agents
  27. Postgrad Med J. 2020 Nov 12. pii: postgradmedj-2020-139065. [Epub ahead of print]
    Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, Puri GD, Malhotra P.
      BACKGROUND: Vitamin D has an immunomodulatory role but the effect of therapeutic vitamin D supplementation in SARS-CoV-2 infection is not known.AIM: Effect of high dose, oral cholecalciferol supplementation on SARS-CoV-2 viral clearance.
    DESIGN: Randomised, placebo-controlled.
    PARTICIPANTS: Asymptomatic or mildly symptomatic SARS-CoV-2 RNA positive vitamin D deficient (25(OH)D<20 ng/ml) individuals.
    INTERVENTION: Participants were randomised to receive daily 60 000 IU of cholecalciferol (oral nano-liquid droplets) for 7 days with therapeutic target 25(OH)D>50 ng/ml (intervention group) or placebo (control group). Patients requiring invasive ventilation or with significant comorbidities were excluded. 25(OH)D levels were assessed at day 7, and cholecalciferol supplementation was continued for those with 25(OH)D <50 ng/ml in the intervention arm. SARS-CoV-2 RNA and inflammatory markers fibrinogen, D-dimer, procalcitonin and (CRP), ferritin were measured periodically.
    OUTCOME MEASURE: Proportion of patients with SARS-CoV-2 RNA negative before day-21 and change in inflammatory markers.
    RESULTS: Forty SARS-CoV-2 RNA positive individuals were randomised to intervention (n=16) or control (n=24) group. Baseline serum 25(OH)D was 8.6 (7.1 to 13.1) and 9.54 (8.1 to 12.5) ng/ml (p=0.730), in the intervention and control group, respectively. 10 out of 16 patients could achieve 25(OH)D>50 ng/ml by day-7 and another two by day-14 [day-14 25(OH)D levels 51.7 (48.9 to 59.5) ng/ml and 15.2 (12.7 to 19.5) ng/ml (p<0.001) in intervention and control group, respectively]. 10 (62.5%) participants in the intervention group and 5 (20.8%) participants in the control arm (p<0.018) became SARS-CoV-2 RNA negative. Fibrinogen levels significantly decreased with cholecalciferol supplementation (intergroup difference 0.70 ng/ml; P=0.007) unlike other inflammatory biomarkers.
    CONCLUSION: Greater proportion of vitamin D-deficient individuals with SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen on high-dose cholecalciferol supplementation.
    Keywords:  Diabetes & endocrinology; Infectious diseases; Virology
  28. Nutr Res Rev. 2020 Nov 13. 1-34
    Morais AHA, Passos TS, Vale SHL, Maia JKDS, Maciel BLL.
      The global COVID-19 pandemic has become a complex problem that overlaps with a growing public health problem, obesity. Obesity alters different components of the innate and adaptive immune responses, creating a chronic and low-grade state of inflammation. Nutritional status is closely related to a better or worse prognosis of viral infections. Excess weight was recognized as a risk factor for COVID-19 complications. In addition to the direct risk, obesity triggers other diseases such as diabetes and hypertension, increasing the risk of severe COVID-19. This review explains the diets that induce obesity and the importance of different foods in this process. We also review tissue disruption in obesity, leading to impaired immune responses and the possible mechanisms by which obesity and its comorbidities increase COVID-19 morbidity and mortality. Nutritional strategies that support the immune system in patients with obesity and with COVID-19 are also discussed in light of the available data, considering the severity of the infection. The discussions held may contribute to combating this global emergency and planning specific public health policy.
    Keywords:  SARS-CoV-2; coronavirus; immunity; nutritional status; overweight; viral infection
  29. Int J Infect Dis. 2020 Nov 04. pii: S1201-9712(20)32304-3. [Epub ahead of print]
    Grimes JM, Khan S, Badeaux M, Rao RM, Rowlinson SW, Carvajal RD.
      The COVID-19 pandemic, caused by SARS-CoV-2, is a source of significant morbidity and mortality worldwide, and effective treatments are urgently needed. Clinical trials have largely focused on direct anti-viral therapies or on immunomodulation in patients with severe manifestations of COVID-19. One therapeutic approach that remains to be clinically investigated is disruption of the host-virus relationship through amino acid restriction, a strategy utilized successfully in the setting of cancer treatment. Arginine is an amino acid that has been shown in non-clinical studies to be essential in the life cycle of many viruses. As such, arginine depletion may represent an effective therapeutic approach against SARS-CoV-2. Several arginine-metabolizing enzymes in clinical development may represent a viable approach to induce a low arginine environment to treat COVID-19 and other viruses. Herein, we explore the rationale for arginine depletion as a therapeutic approach for COVID-19.
    Keywords:  COVID-19; SARS-CoV-2; arginine depletion
  30. J Oral Sci. 2020 Nov 12.
    Takahashi Y, Watanabe N, Kamio N, Kobayashi R, Iinuma T, Imai K.
      Coronavirus infectious disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic in March 2020 by the World Health Organization. Periodontitis, one of the most prevalent diseases worldwide, leads to alveolar bone destruction and subsequent tooth loss, and develops due to pro-inflammatory cytokine production induced by periodontopathic bacteria. Periodontopathic bacteria are involved in respiratory diseases, including aspiration pneumonia and chronic obstructive pulmonary disease (COPD), and other systemic diseases, such as diabetes and cardiovascular disease. Patients with these diseases have an increased COVID-19 aggravation rate and mortality. Because aspiration of periodontopathic bacteria induces the expression of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, and production of inflammatory cytokines in the lower respiratory tract, poor oral hygiene can lead to COVID-19 aggravation. Conversely, oral care, including periodontal treatment, prevents the onset of pneumonia and influenza and the exacerbation of COPD. The reduced chance of receiving professional oral care owing to long-term hospitalization of patients with COVID-19 may increase the aggravation risk of infection in the lower respiratory tract. It can be hypothesized that periodontopathic bacteria are involved in the COVID-19 aggravation and therefore, the management of good oral hygiene potentially contributes to its prevention.
    Keywords:  ACE2; COVID-19; SARS-CoV-2; oral hygiene; periodontitis; periodontopathic bacteria
  31. Clin Nutr ESPEN. 2020 Dec;pii: S2405-4577(20)31053-6. [Epub ahead of print]40 110-114
    Gonçalves TJM, Gonçalves SEAB, Guarnieri A, Risegato RC, Guimarães MP, de Freitas DC, Razuk-Filho A, Benedito Junior PB, Parrillo EF.
      BACKGROUND & AIM: Verify the prevalence of hypovitaminosis D and obesity in elderly patients infected by new coronavirus. The patients developed severe symptoms and were admitted in intensive care unit (ICU) to receive invasive ventilation due to diagnosis of acute respiratory distress syndrome (ARDS).METHODS: A cross-sectional descriptive study composed of elderly (age ≥ 60 years) admitted to the ICU. Were collected demographic (sex, age), anthropometric data, presence of comorbidities (hypertension, diabetes, heart disease, lung, neurological and oncological diseases), severity score in ICU (SAPS III), PaO2/FiO2 ratio, analysis of C-reactive protein (CRP) and serum dosage of 25-hydroxy vitamin D (25 OHD) in the first day of hospitalization to identify elderly with hypovitaminosis D (low values < 30 ng/mL). The diagnosis of obesity in elderly was determined by calculating the body mass index (BMI) ≥ 30 kg/m2.
    RESULTS: A total of 176 elderly met the inclusion criteria. 54% were elderly men and mean age of 72.9 ± 9.1 years. The median BMI was 30.5 (28.1-33) kg/m2 with 68.7% having a nutritional diagnosis of obesity and 15.3% had BMI ≥ 35 kg/m2. The most prevalent comorbidities were hypertension (72.2%) and diabetes (40.9%). Prevalence of hypovitaminosis D with values of 25 OHD <30 ng/mL, < 20 ng/mL and <10 ng/mL was 93.8%, 65.9% and 21% respectively. The prevalence of hypovitaminosis D (<30 ng/mL) in obese elderly was 94.2%. There was a negative and significant bivariate correlation between BMI and levels of 25 OHD (r = - 0.15; p = 0.04).
    CONCLUSION: Hypovitaminosis D and obesity in elderly have a high prevalence in critically ill patients in ICU infected by the new coronavirus. Laboratory investigation of vitamin D becomes important, especially in obese elderly patients.
    Keywords:  COVID-19; Elderly; ICU; Obesity; SARS-CoV-2; Vitamin D
  32. Sci Afr. 2020 Nov 02. e00620
    Orisakwe OE, Orish CN, Nwanaforo EO.
      At last the WHO declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) now known as COVID-19 a pandemic. Amidst uncertainty both in the pathophysiology and the management of COVID-19, many African countries in the face of either over-stretched or non-existent healthcare infrastructure resorted to home remedies as immediate alternative or first line of action. The present study is a synoptic capture of these home remedies with an attempt to understand the pharmacological basis on which these choices are predicated. Literature was compiled from google, social media, Radio and Television commentaries and news with stringent inclusion and exclusion criteria. Natural spices (turmeric, ginger, garlic etc) and leaves (neem, paw paw, guava, etc) with notable antioxidant and anti-inflammatory properties were found to be beneficial. These home remedies may hold promise in the prophylaxis and cure of COVID-19 infection.
    Keywords:  COVID-19; home remedies; natural products, public health; viral infection
  33. Acta Biomed. 2020 11 09. 91(13-S): e2020008
    Kiani AK, Dhuli K, Anpilogov K, Bressan S, Dautaj A, Dundar M, Beccari T, Ergoren MC, Bertelli M.
      BACKGROUND AND AIM: The recent COVID-19 pandemic caused by SARS-CoV-2 affected more than six million people and caused thousands of deaths. The lack of effective drugs or vaccines against SARS-CoV-2 further worsened the situation. This review is focused on the identification of molecules that may inhibit viral entry into host cells by endocytosis.METHODS: We performed the literature search for these natural compounds in the articles indexed in PubMed.
    RESULTS: Natural products against viral infections have been gaining importance in recent years. Specific natural compounds like phytosterols, polyphenols, flavonoids, citrus, galangal, curcuma and hydroxytyrosol are being analyzed to understand whether they could inhibit SARS-CoV-2.
    CONCLUSIONS: We reviewed natural compounds with potential antiviral activity against SARS-CoV-2 that could be used as a treatment for COVID-19.
  34. J Adv Nurs. 2020 Nov 11.
    Wu XV, Dong Y, Chi Y, Yu M, Wang W.
      AIM: To examine the literature on Traditional Chinese Medicine (TCM) used in the treatment, prevention and supportive care in patients with COVID-19.DESIGN: A narrative review was performed.
    DATA SOURCES: A systematic and comprehensive search was conducted on both Chinese and English electronic databases: China National Knowledge Infrastructure, Wanfang Data, CINAHL, Embase, Cochrane, PubMed, PsycINFO. Articles published from 1 December 2019 to 1 April 2020 were included in this review.
    REVIEW METHODS: Studies reporting on the treatment and prevention of COVID-19 using TCM regardless of study designs were included. In addition, grey literatures, including media reports on Chinese government websites or official media websites and treatment guidelines were searched for TCM treatment and prevention on COVID-19.
    RESULTS: Limited research has been published on the use of TCM for COVID-19. We qualitatively described and synthesized the published research and current clinical practice on the use of TCM for COVID-19, and focused on the following areas: TCM treatment used in SARS, MERS, H1N1; TCM treatment plan for COVID-19; TCM in Prevention and Treatment at Early Stage of COVID-19; TCM emotional therapy; and personalized TCM treatment plan.
    CONCLUSION: The combination of western medicine and TCM in treatment, and treatment based on the local condition, isolation, personal protective measures are of great significance for the prevention and treatment of COVID-19. Relevant laboratory research and clinical evaluation should be continued to collect scientific evidences on the efficacy of TCM.
    IMPACT: TCM has been used in the treatment and prevention of COVID-19 in China, and the clinical evidences indicated that TCM regulates immunity and exerts anti-viral effect simultaneously. This review provides practical recommendation for the policymakers in the selection process of the treatment and preventive measures for the global pandemic of COVID-19.
    Keywords:  Chinese herbs; Coronavirus; TCM emotional therapy; TCM prevention for COVID-19; TCM treatment for COVID-19; Traditional Chinese Medicine; complementary therapy; narrative review; nurses/midwives/nursing; personalized TCM treatment
  35. Eur J Dev Res. 2020 Nov 02. 1-34
    Cuesta J, Pico J.
      Everyone, across borders, race and gender, is affected by the global COVID-19 pandemic-but not equally. In this paper, we examine a burgeoning new literature discussing the employment effects of COVID-19. We explore the extent to which COVID-19 will exacerbate gendered employment disparities, income generation gaps, and, ultimately, poverty gaps, using a simple microsimulation methodology. We test our approach in Colombia, which has implemented an unparalleled number of mitigation measures and has reopened its economy earlier than regional neighbors. We find that COVID-19 increases the poverty headcount to a daunting degree (between 3.0 and 9.1 pp increases). Mitigation measures vary considerably in their individual impact (up to 0.9 pp poverty reduction). A fiscally neutral Universal Basic Income program would cause larger poverty reductions. Importantly, both men and women report similar poverty impacts from the pandemic and mitigation policies, reflecting the magnitude of the downturn, the design of interventions and our own poverty measure.
    Keywords:  COVID-19; Colombia; Gender; Microsimulations; Poverty
  36. Acta Neuropsychiatr. 2020 Nov 13. 1-27
    Galyuk TM, Loonen AJM.
      OBJECTIVE: Vitamin D deficiency may be a clinical problem in patients with addictions. The authors systematically searched for studies addressing vitamin D and addiction and develop a hypothesis which can direct future research of the possible mechanistic role of vitamin D in the process of addiction.METHODS: Systematic review of the literature found in PubMed and EMBASE followed by narrative review combined with clinical experiences leading to hypotheses for future research.
    RESULTS: Only five articles were identified about a role of vitamin D in the pathophysiology of addiction. Their results are in line with a possible influence of vitamin D in dopaminergic transmission. The cerebral vitamin D status depends upon the functionality of genetic variants of Vitamin D Receptor (VDR) and other involved genes. Routine serum calcidiol levels may not adequately reflect cerebral vitamin D status. Uncertainty exists regarding appropriate calcidiol blood levels and proper dosages for affecting the central nervous system (CNS).
    CONCLUSIONS: The putative pathophysiological role of vitamin D in substance abuse has been insufficiently studied which calls to more studies how to measure cerebral vitamin D status in clinical practice. Research is indicated whether vitamin D supplementation should use higher dosages and aim to reach higher calcidiol serum levels. Measuring dopaminergic functioning within the prefrontal cortex as reflected by neuropsychological tests selected as suitable could be a suitable proxy for the cerebral vitamin D status when studying the pharmacogenomics of this functionality in patients.
    Keywords:  Addiction; Dopaminergic neurotransmission; Vitamin D Receptor; calcidiol; calcitriol
  37. Endocrinol Diabetes Metab. 2020 Oct 21. e00189
    Gonzáles Yovera JG, Concepción-Zavaleta MJ, Coronado Arroyo J, Moreno Marreros D.
      The direct relation between the overweight/obesity, MAFLD and the severity SARS-CoV-2 infection. increase number of cases of obesity and MAFLD is an important risk factor for high mortality of COVID-19 patients.