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Wimalawansa SJ. Enhancing the Design of Nutrient Clinical Trials for Disease Prevention-A Focus on Vitamin D: A Systematic Review. Nutr Rev 2025:nuae164. [PMID: 39928411 DOI: 10.1093/nutrit/nuae164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2025] Open
Abstract
OBJECTIVES This systematic review (SR) highlights principles for nutrient clinical trials and explore the diverse physiological functions of vitamin D beyond its traditional role in the musculoskeletal system related to clinical study designs. BACKGROUND Thousands of published research articles have investigated the benefits of vitamin D (a nutrient example taken in this SR) beyond the musculoskeletal system, including the immune, pulmonary, and cardiovascular systems; pregnancy; autoimmune disorders; and cancer. They illustrated vitamin D's molecular mechanisms, interactions, and genomic and nongenomic actions. METHODS This SR was designed to identify shortcomings in clinical study designs, statistical methods, and data interpretation that led to inconsistent findings in vitamin D-related publications. SR also highlights examples and insights into avoiding study design errors in future clinical studies, including randomized controlled clinical trials (RCTs). The SR adheres to the latest PRISMA statement, guidelines, and the PICOS process. RESULTS Inappropriate or flawed study designs were frequent in clinical trials. Major failures discussed here include too short clinical study duration, inadequate or infrequent doses, insufficient statistical power, failure to measure baseline and achieved levels, and recruiting vitamin D-sufficient participants. These design errors have led to misleading interpretations. Thus, conclusions from such studies should not be generalized or used in guidelines, recommendations, or policymaking. CONCLUSION Adequately powered epidemiological studies and RCTs with sufficient vitamin D and duration in individuals with vitamin D deficiency reported favorable clinical outcomes, enriching the literature, enabling to understand its physiology and mechanisms. Proper study designs with rigorous methodologies and cautious interpretation of outcomes are crucial in advancing the nutrient field. The principles discussed apply not only to vitamin D, but also other micro-nutrients and nutraceutical research. Adhering to them enhances the credibility and reliability of clinical trials, SRs, and meta-analysis outcomes. The study emphasizes the importance of focused, hypothesis-driven, well-designed, statistically powered RCTs to explore the diverse benefits of nutrients, conducted in index nutrient deficient participants, and avoidance of study design errors. Findings from such studies should be incorporated into clinical practice, policymaking, and public health guidelines, improving the health of the nation and reducing healthcare costs.
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Affiliation(s)
- Sunil J Wimalawansa
- Department of Medicine, Endocrinology & Human Nutrition, North Brunswick, NJ, United States
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Sümegi LD, Varga M, Kadocsa V, Szili B, Stempler M, Lakatos PA, Németh Z, Takács I. Effect of Moderately High-Dose Vitamin D3 Supplementation on Mortality in Patients Hospitalized for COVID-19 Infection. Nutrients 2025; 17:507. [PMID: 39940365 PMCID: PMC11820488 DOI: 10.3390/nu17030507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/27/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Despite a large number of published studies, the effect of vitamin D3 supplementation on mortality in hospitalized patients, as well as the recommended dose and duration of therapy, is unclear. In our retrospective study, we aimed to investigate the impact of vitamin D deficiency and moderately high-dose vitamin D3 supplementation on mortality and disease outcomes in patients with COVID-19 infection. METHODS We analyzed data from 148 COVID-19-infected hospitalized patients in two different departments, Internal Medicine and Oncology, at Semmelweis University. The severity of COVID-19 and the treatment used were the same except at one of the departments, where patients received circa 90,000 IU of vitamin D3. We compared in-hospital mortality rates between the groups. In a subgroup analysis, we evaluated the efficacy and safety of vitamin D3 supplementation by assessing 25(OH)D and 1,25(OH)2D concentrations on days 0, 4, and 8. RESULTS As a result of the supplementation, the deficiency was resolved in 4 days in deficient patients, and none of the 25(OH)D or 1,25(OH)2D concentrations exceeded the normal range. Mortality was significantly lower and decreased 67% in the group receiving vitamin D3 supplementation, regardless of baseline 25(OH)D concentrations. CONCLUSIONS The supplemental dosage, 3 × 30,000 IU of vitamin D3, is effective and safe and may reduce mortality in COVID-19 infection.
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Affiliation(s)
- Liza Dalma Sümegi
- Department of Internal Medicine and Oncology, Semmelweis University, Korányi S. U 2/a, 1083 Budapest, Hungary; (L.D.S.); (B.S.); (M.S.); (P.A.L.); (Z.N.)
| | - Marina Varga
- Department of Laboratory Medicine, Semmelweis University, Nagyvárad Tér 4, 1089 Budapest, Hungary;
| | - Veronika Kadocsa
- Department of Pulmonology, Semmelweis University, Tömő U. 25–29, 1083 Budapest, Hungary;
| | - Balázs Szili
- Department of Internal Medicine and Oncology, Semmelweis University, Korányi S. U 2/a, 1083 Budapest, Hungary; (L.D.S.); (B.S.); (M.S.); (P.A.L.); (Z.N.)
| | - Márk Stempler
- Department of Internal Medicine and Oncology, Semmelweis University, Korányi S. U 2/a, 1083 Budapest, Hungary; (L.D.S.); (B.S.); (M.S.); (P.A.L.); (Z.N.)
| | - Péter András Lakatos
- Department of Internal Medicine and Oncology, Semmelweis University, Korányi S. U 2/a, 1083 Budapest, Hungary; (L.D.S.); (B.S.); (M.S.); (P.A.L.); (Z.N.)
| | - Zsuzsanna Németh
- Department of Internal Medicine and Oncology, Semmelweis University, Korányi S. U 2/a, 1083 Budapest, Hungary; (L.D.S.); (B.S.); (M.S.); (P.A.L.); (Z.N.)
| | - István Takács
- Department of Internal Medicine and Oncology, Semmelweis University, Korányi S. U 2/a, 1083 Budapest, Hungary; (L.D.S.); (B.S.); (M.S.); (P.A.L.); (Z.N.)
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Mortazavi SM, Khoshnood S, Faraji R, Baravati RB, Khalili H, Radfar A, Jalali E, Nezam Nia M, Akrami S, Shirani M. Evaluation the level of vitamin D and its relationship with clinical symptoms in patients with COVID-19 referred to the medical center in Bam city. GMS HYGIENE AND INFECTION CONTROL 2024; 19:Doc57. [PMID: 39669534 PMCID: PMC11636272 DOI: 10.3205/dgkh000512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
Background Vitamin D is a steroid hormone that protects against viral infections by influencing innate and adaptive immune responses. The effectiveness of vitamin D3 supplementation in COVID-19 is unknown. The study's goal was to elucidate the relationship between blood vitamin D levels and COVID-19 clinical outcomes by examining the effect of a single high dose of vitamin D3 on the length of hospital stay in COVID-19 patients. Methods The descriptive, retrospective study was performed from March to May 2021 at a referral center for patients with COVID-19, in Bam, Iran. A checklist consisting of demographic variables was used to gather data, and laboratory assessments of serum 25(OH) D were evaluated and documented. The connection between serum vitamin D and patient clinical outcomes was investigated after patients were given a single oral dose of 200,000 IU of vitamin D3. Results 71 COVID-19 patients were treated. Radiological results did not change substantially amongst individuals with various levels of 25(OH)D. After a single dosage of vitamin D3, mean blood levels of 25-hydroxyvitamin D increased considerably and the need for intubation and SpO2 decreased, and as did the respiratory rate in patients requiring hospitalization due to COVID-19. Conclusion A single administration of 200,000 IU of vitamin D3 significantly reduced the severity of COVID-19.
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Affiliation(s)
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Reza Faraji
- Tuberculosis and Lung Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Hakime Khalili
- Pastor Educational Hospital, Bam University of Medical Sciences, Bam, Iran
| | - Ali Radfar
- Pastor Educational Hospital, Bam University of Medical Sciences, Bam, Iran
| | - Elham Jalali
- Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Maria Nezam Nia
- Department of Gynecology, School of Medicine, Pasteur Hospital,Bam University of Medical Sciences Bam, Bam, Iran
| | - Sousan Akrami
- Department of Microbiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Shirani
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Charoenporn V, Tungsukruthai P, Teacharushatakit P, Hanvivattanakul S, Sriyakul K, Sukprasert S, Kamalashiran C, Tungsukruthai S, Charernboon T. Effects of an 8-week high-dose vitamin D supplementation on fatigue and neuropsychiatric manifestations in post-COVID syndrome: A randomized controlled trial. Psychiatry Clin Neurosci 2024; 78:595-604. [PMID: 39072958 DOI: 10.1111/pcn.13716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 06/17/2024] [Accepted: 06/27/2024] [Indexed: 07/30/2024]
Abstract
AIM This study evaluated the effectiveness of high-dose vitamin D supplementation in alleviating fatigue and neuropsychiatric symptoms in post-COVID syndrome. METHODS In an 8-week, double-blind, randomized, placebo-controlled trial, 80 patients with post-COVID fatigue or neuropsychiatric symptoms were enrolled. Participants were randomly assigned to receive either 60,000 IU of vitamin D weekly (n = 40) or a placebo (n = 40) for 8 weeks. Clinical outcomes were assessed using the 11-item Chalder Fatigue Scale (CFQ-11); 21-item Depression, Anxiety, and Stress Scale (DASS-21); Pittsburgh Sleep Quality Index (PSQI); Addenbrooke's Cognitive Examination III (ACE); and Trail Making Test A and B (TMT-A and TMT-B). Baseline and 8-week measurements of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also collected. RESULTS Significant improvements were found in the vitamin D group for CFQ (coefficient -3.5, P = 0.024), DASS-anxiety (-2.0, P = 0.011), and ACE (2.1, P = 0.012). No significant differences were observed in PSQI, DASS-depression, TMT, IL-6, or CRP levels. The incidence of adverse events was comparable between groups, with no serious adverse events reported. CONCLUSION High-dose vitamin D supplementation may benefit patients with post-COVID syndrome by reducing fatigue, alleviating anxiety, and improving cognitive symptoms, with minimal side effects.
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Affiliation(s)
- Veevarin Charoenporn
- Faculty of Medicine, Thammasat University, Pathumthani, Thailand
- Department of Psychiatry, Thammasat University Hospital, Pathumthani, Thailand
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand
| | - Parunkul Tungsukruthai
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand
| | | | | | - Kusuma Sriyakul
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand
| | - Sophida Sukprasert
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand
| | - Chuntida Kamalashiran
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand
| | - Sucharat Tungsukruthai
- Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand
| | - Thammanard Charernboon
- Faculty of Medicine, Thammasat University, Pathumthani, Thailand
- Center of Excellence in Applied Epidemiology, Thammasat University, Pathumthani, Thailand
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Visuddho V, Welliam Y, Maitri Aldian F, Sampurna MTA, Irzaldy A. Exploring the Therapeutic Potential of Vitamin D in Kawasaki Disease and Its Interplay with the COVID-19. Turk Arch Pediatr 2024; 59:432-439. [PMID: 39439407 PMCID: PMC11391221 DOI: 10.5152/turkarchpediatr.2024.24141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 08/11/2024] [Indexed: 10/25/2024]
Abstract
Several studies have reported outbreaks of Kawasaki disease among children amid the coronavirus disease 2019 (COVID-19) pandemic. Vitamin D possesses high utility in modulating the immune system to repair and prevent severe inflammation in COVID-19. This study aims to explore the association between Kawasaki disease and vitamin D levels in pediatric patients and describe the potential role of vitamin D in promoting recovery and preventing complications associated with Kawasaki disease in pediatric patients with COVID-19. The association between Kawasaki disease and vitamin D was explored adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, utilizing databases such as PubMed, Google Scholar, and ScienceDirect. The association between COVID-19 and Kawasaki disease was also assessed by reviewing relevant literature.Most studies indicated that patients with Kawasaki disease had lower vitamin D levels. Vitamin D supplementation was also found to be deficient in the pediatric population with Kawasaki disease. Inflammation of the endothelium, cytokine storms, and endothelial dysfunction in patients suffering from COVID-19 may contribute to the development of Kawasaki disease. Vitamin D is believed to have protective potential for Kawasaki disease outcomes by modulating the inflammatory response. Administering vitamin D to pediatric patients with viral infections like COVID-19 is expected to accelerate clinical improvement and prevent complications from Kawasaki disease.
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Affiliation(s)
- Visuddho Visuddho
- Medical Program, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia
| | - Yongki Welliam
- Medical Program, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia
| | - Fan Maitri Aldian
- Medical Program, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia
| | - Mahendra Tri Arif Sampurna
- Department of Pediatrics, Airlangga Teaching Hospital, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia
- Department of Pediatrics, Dr Soetomo General Hospital, Universitas Airlangga Faculty of Medicine, Surabaya, Indonesia
| | - Abyan Irzaldy
- Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands, GD
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Salehi Z, Askari M, Jafari A, Ghosn B, Surkan PJ, Hosseinzadeh-Attar MJ, Pouraram H, Azadbakht L. Dietary patterns and micronutrients in respiratory infections including COVID-19: a narrative review. BMC Public Health 2024; 24:1661. [PMID: 38907196 PMCID: PMC11193220 DOI: 10.1186/s12889-024-18760-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 05/02/2024] [Indexed: 06/23/2024] Open
Abstract
BACKGROUND COVID-19 is a pandemic caused by nCoV-2019, a new beta-coronavirus from Wuhan, China, that mainly affects the respiratory system and can be modulated by nutrition. METHODS This review aims to summarize the current literature on the association between dietary intake and serum levels of micronutrients, malnutrition, and dietary patterns and respiratory infections, including flu, pneumonia, and acute respiratory syndrome, with a focus on COVID-19. We searched for relevant articles in various databases and selected those that met our inclusion criteria. RESULTS Some studies suggest that dietary patterns, malnutrition, and certain nutrients such as vitamins D, E, A, iron, zinc, selenium, magnesium, omega-3 fatty acids, and fiber may have a significant role in preventing respiratory diseases, alleviating symptoms, and lowering mortality rates. However, the evidence is not consistent and conclusive, and more research is needed to clarify the mechanisms and the optimal doses of these dietary components. The impact of omega-3 and fiber on respiratory diseases has been mainly studied in children and adults, respectively, and few studies have examined the effect of dietary components on COVID-19 prevention, with a greater focus on vitamin D. CONCLUSION This review highlights the potential of nutrition as a modifiable factor in the prevention and management of respiratory infections and suggests some directions for future research. However, it also acknowledges the limitations of the existing literature, such as the heterogeneity of the study designs, populations, interventions, and outcomes, and the difficulty of isolating the effects of single nutrients from the complex interactions of the whole diet.
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Affiliation(s)
- Zahra Salehi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IR, Iran
| | - Mohammadreza Askari
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IR, Iran
| | - Alireza Jafari
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IR, Iran
| | - Batoul Ghosn
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IR, Iran
| | - Pamela J Surkan
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Mohammad Javad Hosseinzadeh-Attar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran
- Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, IR, Iran
| | - Hamed Pouraram
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IR, Iran
| | - Leila Azadbakht
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IR, Iran.
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, IR, Iran.
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, IR, Iran.
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Jamilian A, Ghalichi F, Hamedi Kalajahi F, Radkhah N, Jourabchi N, Musazadeh V, Amini-Salehi E, Zarezadeh M, Ostadrahimi A. The role of vitamin D in outcomes of critical care in COVID-19 patients: evidence from an umbrella meta-analysis of interventional and observational studies. Public Health Nutr 2024; 27:e127. [PMID: 38654693 PMCID: PMC11112434 DOI: 10.1017/s1368980024000934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 11/10/2023] [Accepted: 02/08/2024] [Indexed: 04/26/2024]
Abstract
OBJECTIVES Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella meta-analysis aims to evaluate influence of vitamin D supplementation on clinical outcomes and the mortality rate of COVID-19 patients. DESIGN Present study was designed as an umbrella meta-analysis. The following international databases were systematically searched till March 2023: Web of Science, PubMed, Scopus, and Embase. SETTINGS Random-effects model was employed to perform meta-analysis. Using AMSTAR critical evaluation tools, the methodological quality of the included meta-analyses was evaluated. PARTICIPANTS Adult patients suffering from COVID-19 were studied. RESULTS Overall, 13 meta-analyses summarising data from 4 randomised controlled trial and 9 observational studies were identified in this umbrella review. Our findings revealed that vitamin D supplementation and status significantly reduced mortality of COVID-19 [Interventional studies: (ES = 0·42; 95 % CI: 0·10, 0·75, P < 0·001; I2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I2 = 00·0 %, P = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients. CONCLUSION Overall, vitamin D status is a critical factor influencing the mortality rate, disease severity, admission to intensive care unit and being detached from mechanical ventilation. It is vital to monitor the vitamin D status in all patients with critical conditions including COVID patients.
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Affiliation(s)
- Abdolreza Jamilian
- City of London Dental School, University of Bolton, London, UK
- Orthodontic Department, Dental School, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Faezeh Ghalichi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Hamedi Kalajahi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nima Radkhah
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Jourabchi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vali Musazadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Meysam Zarezadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Attar-Neishaburi St., Golgasht Alley, Azadi Blvd., Tabriz, Iran
| | - Alireza Ostadrahimi
- Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Attar-Neishaburi St., Golgasht Alley, Azadi Blvd., Tabriz, Iran
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Totan M, Matacuta-Bogdan IO, Hasegan A, Maniu I. Vitamin D Levels in COVID-19 and NonCOVID-19 Pediatric Patients and Its Relationship with Clinical and Laboratory Characteristics. Biomedicines 2024; 12:905. [PMID: 38672258 PMCID: PMC11048677 DOI: 10.3390/biomedicines12040905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/14/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
25-hydroxyvitamin D [25(OH)D] is a marker with an important role in regulating the inflammatory response. Low concentrations of this vitamin are often found among the population, correlated with increased risk of respiratory tract infections. The aim of the study is to evaluate the relationship between vitamin D levels and clinical and laboratory markers in children and adolescents hospitalized with and without COVID-19. A retrospective study, including all patients tested for SARS-CoV-2 and having vitamin D measured, was performed. All included hospitalized cases, 78 COVID-19 patients and 162 NonCOVID-19 patients, were divided into subgroups according to their 25(OH)D serum levels (<20 ng/mL-deficiency, 20-30 ng/mL-insufficiency, ≥30 ng/mL-normal or <30 ng/mL, ≥30 ng/mL) and age (≤2 years, >2 years). Vitamin D deficiency and insufficiency increased with age, in both COVID-19 and NonCOVID-19 groups. All symptoms were encountered more frequently in cases of pediatric patients with COVID-19 in comparison with NonCOVID-19 cases. The most frequently encountered symptoms in the COVID-19 group were fever, loss of appetite, and nasal congestion. In the NonCOVID-19 group, serum 25(OH)D concentrations were positively correlated with leukocytes, lymphocytes, and LMR and negatively correlated with neutrophils, NLR, and PLR while no significant correlation was observed in the case of COVID-19 group. Differences between vitamin D status and clinical and laboratory parameters were observed, but their clinical significance should be interpreted with caution. The results of this study may offer further support for future studies exploring the mechanisms of the relationship between vitamin D and clinical and laboratory markers as well as for studies investigating the implications of vitamin D deficiency/supplementation on overall health/clinical outcomes of patients with/without COVID-19.
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Affiliation(s)
- Maria Totan
- Faculty of Medicine, Lucian Blaga University of Sibiu, 2A Lucian Blaga Str., 550169 Sibiu, Romania; (M.T.); (A.H.)
- Clinical Laboratory, Pediatric Clinical Hospital Sibiu, 2-4 Pompeiu Onofreiu Str., 550166 Sibiu, Romania
| | | | - Adrian Hasegan
- Faculty of Medicine, Lucian Blaga University of Sibiu, 2A Lucian Blaga Str., 550169 Sibiu, Romania; (M.T.); (A.H.)
| | - Ionela Maniu
- Research Team, Pediatric Clinical Hospital Sibiu, 550166 Sibiu, Romania
- Research Center in Informatics and Information Technology, Mathematics and Informatics Department, Faculty of Sciences, Lucian Blaga University of Sibiu, 550025 Sibiu, Romania
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Jiao T, Huang Y, Sun H, Yang L. Research progress of post-acute sequelae after SARS-CoV-2 infection. Cell Death Dis 2024; 15:257. [PMID: 38605011 PMCID: PMC11009241 DOI: 10.1038/s41419-024-06642-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 04/13/2024]
Abstract
SARS-CoV-2 has spread rapidly worldwide and infected hundreds of millions of people worldwide. With the increasing number of COVID-19 patients discharged from hospitals, the emergence of its associated complications, sequelae, has become a new global health crisis secondary to acute infection. For the time being, such complications and sequelae are collectively called "Post-acute sequelae after SARS-CoV-2 infection (PASC)", also referred to as "long COVID" syndrome. Similar to the acute infection period of COVID-19, there is also heterogeneity in PASC. This article reviews the various long-term complications and sequelae observed in multiple organ systems caused by COVID-19, pathophysiological mechanisms, diagnosis, and treatment of PASC, aiming to raise awareness of PASC and optimize management strategies.
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Affiliation(s)
- Taiwei Jiao
- Department of Gastroenterology and Endoscopy, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, P.R. China
| | - Yuling Huang
- Department of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, P.R. China
| | - Haiyan Sun
- Department of Endodontics, School of Stomatology, China Medical University, Shenyang, Liaoning, 110001, P.R. China.
| | - Lina Yang
- Department of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, P.R. China.
- Department of International Physical Examination Center, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, P.R. China.
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Choi MG, Joo YW, Kim MH, Park S, Shin YY, Chun EM. Prognostic Factors for Predicting Post-COVID-19 Condition in Patients With COVID-19 in an Outpatient Setting. J Korean Med Sci 2024; 39:e23. [PMID: 38225786 PMCID: PMC10789531 DOI: 10.3346/jkms.2024.39.e23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 10/26/2023] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND Although data on post-coronavirus disease 2019 (COVID-19) conditions are extensive, the prognostic factors affecting symptom duration in non-hospitalized patients with COVID-19 are currently not well known. We aimed to investigate the various prognostic factors affecting symptom duration among outpatients with COVID-19. METHODS Data were analyzed from 257 patients who were diagnosed with mild COVID-19 and visited the 'post-COVID-19 outpatient clinic' between April and December 2022 after a mandatory isolation period. The symptom duration was measured from diagnosis to symptom resolution. Laboratory and pulmonary function test results from their first visit were collected. RESULTS The mean age of patients was 55.7 years, and the median symptom duration was 57 days. The development of post-COVID-19 conditions (> 12 weeks) were significantly correlated with not using antiviral drugs, leukocytosis (white blood cell > 10,000/µL), lower 25(OH)D3 levels, forced vital capacity (FVC) < 90% predicted, and presence of dyspnea and anxiety/depression. Additionally, in multivariable Cox regression analysis, not using antiviral drugs, lower 25(OH)D3 levels, and having dyspnea were poor prognostic factors for longer symptom duration. Particularly, vitamin D deficiency (< 20 ng/mL) and not using antivirals during the acute phase were independent poor prognostic factors for both post-COVID-19 condition and longer symptom duration. CONCLUSION The non-use of antivirals, lower 25(OH)D3 levels, leukocytosis, FVC < 90% predicted, and the presence of dyspnea and anxiety/depression symptoms could be useful prognostic factors for predicting post-COVID-19 condition in outpatients with COVID-19. We suggest that the use of antiviral agents during the acute phase and vitamin D supplements might help reduce COVID-19 symptom duration.
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Affiliation(s)
- Myeong Geun Choi
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea
| | - Young Woong Joo
- Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea
| | - Min-Ho Kim
- Informatization Department, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Korea
| | - Sojung Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea
| | - Yune-Young Shin
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea
| | - Eun Mi Chun
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.
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11
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Tziolos NR, Ioannou P, Baliou S, Kofteridis DP. Long COVID-19 Pathophysiology: What Do We Know So Far? Microorganisms 2023; 11:2458. [PMID: 37894116 PMCID: PMC10609046 DOI: 10.3390/microorganisms11102458] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/17/2023] [Accepted: 09/29/2023] [Indexed: 10/29/2023] Open
Abstract
Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome.
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Affiliation(s)
- Nikolaos-Renatos Tziolos
- Department of Internal Medicine & Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece (D.P.K.)
| | - Petros Ioannou
- Department of Internal Medicine & Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece (D.P.K.)
- School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Stella Baliou
- School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Diamantis P. Kofteridis
- Department of Internal Medicine & Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece (D.P.K.)
- School of Medicine, University of Crete, 71003 Heraklion, Greece
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12
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Murugan AK, Alzahrani AS. Potential impacts of SARS-CoV-2 on parathyroid: current advances and trends. Endocrine 2023; 81:391-408. [PMID: 37328666 DOI: 10.1007/s12020-023-03415-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/31/2023] [Indexed: 06/18/2023]
Abstract
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection affects several important organs including endocrine glands. Experimental studies demonstrated that the virus exploits the ACE2, a transmembrane glycoprotein on the cell surface as a receptor for cellular entry. This entry process is exclusively facilitated by other intracellular protein molecules such as TMPRSS2, furin, NRP1, and NRP2. Recent findings documented the involvement of the SARS-CoV-2 in inducing various parathyroid disorders including hypoparathyroidism and hypocalcemia, which received significant attention. This review extensively describes rapidly evolving knowledge on the potential part of SARS-CoV-2 in emerging various parathyroid disorders due to SARS-CoV-2 infection particularly parathyroid malfunction in COVID-19 cases, and post-COVID-19 conditions. Further, it presents the expression level of various molecules such as ACE2, TMPRSS2, furin, NRP1, and NRP2 in the parathyroid cells that facilitate the SARS-CoV-2 entry into the cell, and discusses the possible mechanism of parathyroid gland infection. Besides, it explores parathyroid malfunction in COVID-19 vaccine-administered cases. It also explains the possible long-COVID-19 effect on parathyroid and post-COVID-19 management of parathyroid. A complete understanding of the mechanisms of SARS-CoV-2-triggered pathogenesis in parathyroid dysfunctions may curtail treatment options and aid in the management of SARS-CoV-2-infected cases.
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Affiliation(s)
- Avaniyapuram Kannan Murugan
- Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
| | - Ali S Alzahrani
- Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia
- Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia
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13
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Piater T, Gietl M, Hofer S, Gostner JM, Sahanic S, Tancevski I, Sonnweber T, Pizzini A, Egger A, Schennach H, Loeffler-Ragg J, Weiss G, Kurz K. Persistent Symptoms and IFN-γ-Mediated Pathways after COVID-19. J Pers Med 2023; 13:1055. [PMID: 37511668 PMCID: PMC10382041 DOI: 10.3390/jpm13071055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/18/2023] [Accepted: 06/20/2023] [Indexed: 07/30/2023] Open
Abstract
After COVID-19, patients have reported various complaints such as fatigue, neurological symptoms, and insomnia. Immune-mediated changes in amino acid metabolism might contribute to the development of these symptoms. Patients who had had acute, PCR-confirmed COVID-19 infection about 60 days earlier were recruited within the scope of the prospective CovILD study. We determined the inflammatory parameters and alterations in tryptophan and phenylalanine metabolism in 142 patients cross-sectionally. Symptom persistence (pain, gastrointestinal symptoms, anosmia, sleep disturbance, and neurological symptoms) and patients' physical levels of functioning were recorded. Symptoms improved in many patients after acute COVID-19 (n = 73, 51.4%). Still, a high percentage of patients had complaints, and women were affected more often. In many patients, ongoing immune activation (as indicated by high neopterin and CRP concentrations) and enhanced tryptophan catabolism were found. A higher phenylalanine to tyrosine ratio (Phe/Tyr) was found in women with a lower level of functioning. Patients who reported improvements in pain had lower Phe/Tyr ratios, while patients with improved gastrointestinal symptoms presented with higher tryptophan and kynurenine values. Our results suggest that women have persistent symptoms after COVID-19 more often than men. In addition, the physical level of functioning and the improvements in certain symptoms appear to be associated with immune-mediated changes in amino acid metabolism.
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Affiliation(s)
- Talia Piater
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Mario Gietl
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Stefanie Hofer
- Institute of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria
| | - Johanna M Gostner
- Institute of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria
| | - Sabina Sahanic
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Ivan Tancevski
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Thomas Sonnweber
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Alex Pizzini
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Alexander Egger
- Central Institute for Medical and Chemical Laboratory Diagnostics (ZIMCL), Tirol Kliniken GmbH, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Harald Schennach
- Central Institute for Blood Transfusion and Immunological Department, Tirol Kliniken GmbH, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Judith Loeffler-Ragg
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Guenter Weiss
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Katharina Kurz
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
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14
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Abroug H, Maatouk A, Bennasrallah C, Dhouib W, Ben Fredj M, Zemni I, Kacem M, Mhalla S, Nouira S, Ben Belgacem M, Nasri A, Klii R, Loussaief C, Ben Alya N, Bouanene I, Belguith Sriha A. Effect of vitamin D supplementation versus placebo on recovery delay among COVID-19 Tunisian patients: a randomized-controlled clinical trial. Trials 2023; 24:123. [PMID: 36803273 PMCID: PMC9940050 DOI: 10.1186/s13063-023-07114-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 01/23/2023] [Indexed: 02/22/2023] Open
Abstract
INTRODUCTION The present study aimed to determine the impact of vitamin D supplementation (VDs) on recovery delay among COVID-19 patients. METHODS We performed a randomized controlled clinical trial at the national COVID-19 containment center in Monastir (Tunisia), from May to August 2020. Simple randomization was done in a 1:1 allocation ratio. We included patients aged more than 18 years who had confirmed reverse transcription-polymerase chain reaction (RT-PCR) and who remained positive on the 14th day. The intervention group received VDs (200,000 IU/1 ml of cholecalciferol); the control group received a placebo treatment (physiological saline (1 ml)). We measured the recovery delay and the cycle threshold (Ct) values in RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The log-rank test and hazard ratios (HR) were calculated. RESULTS A total of 117 patients were enrolled. The mean age was 42.7 years (SD 14). Males represented 55.6%. The median duration of viral RNA conversion was 37 days (95% confidence interval (CI): 29-45.50) in the intervention group and 28 days (95% CI: 23-39) in the placebo group (p=0.010). HR was 1.58 (95% CI: 1.09-2.29, p=0.015). Ct values revealed a stable trend over time in both groups. CONCLUSION VDs was not associated with a shortened recovery delay when given to patients for whom the RT-PCR remained positive on the 14th day. TRIAL REGISTRATION This study was approved by the Human Subjects Protection Tunisia center (TN2020-NAT-INS-40) on April 28, 2020, and by ClinicalTrial.gov on May 12, 2021 with approval number ClinicalTrials.gov ID: NCT04883203 .
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Affiliation(s)
- Hela Abroug
- Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia. .,Department of Community Medicine, Faculty of Medicine, University of Monastir, Monastir, Tunisia. .,Research LaboratoryTechnology and Medical Imaging - LTIM - LR12ES06, University of Monastir, Monastir, Tunisia.
| | - Amani Maatouk
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia
| | - Cyrine Bennasrallah
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia
| | - Wafa Dhouib
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia
| | - Manel Ben Fredj
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Department of Community Medicine, Faculty of Medicine, University of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Research LaboratoryTechnology and Medical Imaging - LTIM - LR12ES06, University of Monastir, Monastir, Tunisia
| | - Imen Zemni
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Department of Community Medicine, Faculty of Medicine, University of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Research LaboratoryTechnology and Medical Imaging - LTIM - LR12ES06, University of Monastir, Monastir, Tunisia
| | - Meriem Kacem
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Department of Community Medicine, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Salma Mhalla
- grid.411838.70000 0004 0593 5040Laboratory of Microbiology, University of Monastir, Monastir, Tunisia
| | - Sarra Nouira
- grid.411838.70000 0004 0593 5040Laboratory of Microbiology, University of Monastir, Monastir, Tunisia
| | - Manel Ben Belgacem
- grid.411838.70000 0004 0593 5040Department of Family Medicine, University of Monastir, Monastir, Tunisia
| | - Aymen Nasri
- grid.411838.70000 0004 0593 5040Department of Family Medicine, University of Monastir, Monastir, Tunisia
| | - Rim Klii
- grid.411838.70000 0004 0593 5040Department of Internal Medicine, University of Monastir, Monastir, Tunisia
| | - Chawki Loussaief
- grid.411838.70000 0004 0593 5040Department of Infectious Diseases, University of Monastir, Monastir, Tunisia
| | | | - Ines Bouanene
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Department of Community Medicine, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Asma Belguith Sriha
- grid.420157.5Department of Epidemiology and Preventive Medicine, University Hospital of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Department of Community Medicine, Faculty of Medicine, University of Monastir, Monastir, Tunisia ,grid.411838.70000 0004 0593 5040Research LaboratoryTechnology and Medical Imaging - LTIM - LR12ES06, University of Monastir, Monastir, Tunisia
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15
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Pinzariu AC, Sova IA, Maranduca MA, Filip N, Drochioi IC, Vamesu CG, Clim A, Hurjui LL, Moscalu M, Soroceanu RP, Serban DN, Serban IL. Vitamin D Deficiency in Both Oral and Systemic Manifestations in SARS-CoV-2 Infection: Updated Review. Medicina (B Aires) 2022; 59:medicina59010068. [PMID: 36676692 PMCID: PMC9866644 DOI: 10.3390/medicina59010068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022] Open
Abstract
The specialized literature emphasizes the fact that vitamin D has a potentially beneficial effect in the context of the current COVID-19 pandemic. The purpose of this article is to highlight the role of vitamin D, both prophylactic and curative, in the treatment of patients diagnosed with COVID-19. Even though its relevance is still unknown and causes various controversies, there is currently no specific treatment for patients diagnosed with COVID-19. There are various prevention strategies with new vaccination schedules, but additional randomized and clinical trials are still needed to combat this pandemic. In addition to the systemic manifestations of SARS-CoV-2 infection, oral manifestations of this disease have also been described in the literature. The etiology of oral manifestations associated with COVID-19 infection and vitamin D deficiency remains controversial. In the present studies, oral manifestations such as salivary gland infections, aphthae, erythema, gingivitis, ulcers, etc. have been reported. This is a new topic, and the prevalence of manifestations is described in only a few studies, which is inconsistent with the number of COVID-19 cases reported since the beginning of the pandemic. The clinical symptomatology in patients with current COVID-19 infection is polymorphic. Whether the oral manifestation is directly caused by SARS-CoV-2 or a secondary manifestation remains an important topic to analyze and discuss.
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Affiliation(s)
- Alin Constantin Pinzariu
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Ivona Andreea Sova
- IOSUD Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Minela Aida Maranduca
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Internal Medicine Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700115 Iasi, Romania
| | - Nina Filip
- Department of Morpho-Functional Sciences II, Discipline of Biochemistry, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Ilie Cristian Drochioi
- Department of Oral and Maxillofacial Surgery and Reconstructive, Faculty of Dental Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700020 Iasi, Romania
| | - Calin George Vamesu
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Andreea Clim
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Correspondence: (A.C.); (M.M.)
| | - Loredana Liliana Hurjui
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Mihaela Moscalu
- Department of Preventive Medicine and Interdisciplinarity, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Correspondence: (A.C.); (M.M.)
| | - Radu Petru Soroceanu
- Department of Surgery I, Discipline of Surgical Semiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Dragomir Nicolae Serban
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Ionela Lacramioara Serban
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
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16
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Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, Primus-de Jong C, Cleemput I, Van den Heede K. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med 2022; 54:1473-1487. [PMID: 35594336 PMCID: PMC9132392 DOI: 10.1080/07853890.2022.2076901] [Citation(s) in RCA: 303] [Impact Index Per Article: 101.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/12/2022] [Accepted: 05/07/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as "long COVID", and it was defined more recently as "Post COVID-19 condition" by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic. AIM To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID. METHOD We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation. RESULTS A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far. CONCLUSION Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms. KEY MESSAGESLong-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.
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Affiliation(s)
- D. Castanares-Zapatero
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - P. Chalon
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - L. Kohn
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - M. Dauvrin
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - J. Detollenaere
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - C. Maertens de Noordhout
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - C. Primus-de Jong
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - I. Cleemput
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
| | - K. Van den Heede
- Centre Administratif du Botanique, Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium
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17
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Bičíková M, Máčová L, Hill M. Vitamin D as a Possible COVID-19 Prevention Strategy. Int J Mol Sci 2022; 23:10532. [PMID: 36142443 PMCID: PMC9501571 DOI: 10.3390/ijms231810532] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/05/2022] [Accepted: 09/08/2022] [Indexed: 11/18/2022] Open
Abstract
Vitamin D is no longer considered an agent only affecting calcium phosphate metabolism. A number of studies over the past few years have demonstrated its role in immunomodulation and its influence on the development and functioning of the brain and nervous system. In the current epidemiological crisis caused by coronavirus disease 2019 (COVID-19), the immunoprotective role of vitamin D has been discussed by some authors regarding whether it contributes to protection against this serious disease or whether its use does not play a role. Non-standard approaches taken by laboratories in examining the serum levels of the vitamin D metabolite calcidiol have contributed to inconsistent results. We examined the serum of 60 volunteers in the spring and autumn of 2021 who declared whether they were taking vitamin D at the time of sampling. Furthermore, the tested participants noted whether they had experienced COVID-19. A newly developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to measure calcidiol levels. The analysis of variance (ANOVA) model of Statgraphics Centurion 18 statistical software from Statgraphics Technologies was used for calculations. The results of this study showed that those who took vitamin D suffered significantly less often from COVID-19 than those who did not take vitamin D.
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Affiliation(s)
| | - Ludmila Máčová
- Department of Steroids and Proteofactors, Institute of Endocrinology, Národni 8, 11694 Prague, Czech Republic
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18
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Foshati S, Mirjalili F, Rezazadegan M, Fakoorziba F, Amani R. Antioxidants and clinical outcomes of patients with coronavirus disease 2019: A systematic review of observational and interventional studies. Food Sci Nutr 2022; 10:FSN33034. [PMID: 36245940 PMCID: PMC9538172 DOI: 10.1002/fsn3.3034] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 07/22/2022] [Accepted: 07/31/2022] [Indexed: 12/14/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a newly emerging viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oxidative stress appears to be a prominent contributor to the pathogenicity of SARS-CoV-2. Therefore, we carried out a systematic review of human observational and interventional studies to investigate the role of some antioxidants such as vitamins A, E, D, and C, selenium, zinc, and α-lipoic acid in the main clinical outcomes of subjects with COVID-19. Google Scholar, Cochrane Library, Web of Science, Scopus, and Medline were searched using Medical Subject Headings (MeSH) and non-MeSH terms without restrictions. Finally, 36 studies for vitamins C and D, selenium, and zinc were included in this systematic review; however, no eligible studies were found for vitamins A and E as well as α-lipoic acid. The results showed the promising role of vitamin C in inflammation, Horowitz index, and mortality; vitamin D in disease manifestations and severity, inflammatory markers, lung involvement, ventilation requirement, hospitalization, intensive care unit (ICU) admission, and mortality; selenium in cure rate and mortality; and zinc in ventilation requirement, hospitalization, ICU admission, biomarkers of inflammation and bacterial infection, and disease complications. In conclusion, it seems that antioxidants, especially vitamins C and D, selenium, and zinc, can improve multiple COVID-19 clinical outcomes. Nevertheless, more studies are necessary to affirm these results.
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Affiliation(s)
- Sahar Foshati
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research CenterIsfahan University of Medical SciencesIsfahanIran
| | - Fatemeh Mirjalili
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research CenterIsfahan University of Medical SciencesIsfahanIran
| | - Mahsa Rezazadegan
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research CenterIsfahan University of Medical SciencesIsfahanIran
| | | | - Reza Amani
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research CenterIsfahan University of Medical SciencesIsfahanIran
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19
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Migliorini F, Vaishya R, Eschweiler J, Oliva F, Hildebrand F, Maffulli N. Vitamins C and D and COVID-19 Susceptibility, Severity and Progression: An Evidence Based Systematic Review. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:941. [PMID: 35888660 PMCID: PMC9318801 DOI: 10.3390/medicina58070941] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/02/2022] [Accepted: 07/12/2022] [Indexed: 04/07/2023]
Abstract
Background and Objectives: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. Material and Methods: In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. Results: The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. Conclusions: While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.
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Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedic, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany; (J.E.); (F.H.)
| | - Raju Vaishya
- Department of Orthopaedics, Indraprastha Apollo Hospitals Institutes of Orthopaedics, New Delhi 110076, India;
| | - Jörg Eschweiler
- Department of Orthopaedic, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany; (J.E.); (F.H.)
| | - Francesco Oliva
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (F.O.); (N.M.)
| | - Frank Hildebrand
- Department of Orthopaedic, Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany; (J.E.); (F.H.)
| | - Nicola Maffulli
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (F.O.); (N.M.)
- School of Pharmacy and Bioengineering, Keele University Faculty of Medicine, Thornburrow Drive, Stoke on Trent ST5 5BG, UK
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Centre for Sports and Exercise Medicine, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK
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20
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Passini CSM, Cavalcanti MB, Ribas SA, de Carvalho CMP, Bocca C, Lamarca F. Conflict of Interests in the Scientific Production on Vitamin D and COVID-19: A Scoping Review. Front Public Health 2022; 10:821740. [PMID: 35903374 PMCID: PMC9320027 DOI: 10.3389/fpubh.2022.821740] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 06/06/2022] [Indexed: 11/25/2022] Open
Abstract
The use of scientific evidence to support the process of formulating and implementing public policies might be biased by studies funded by the pharmaceutical and food industry, which more often than not meet corporate interests. This review aimed to analyze the occurrence of conflict of interest (COI) in academic production regarding vitamin D and COVID-19, considering the facility offered during the pandemic for academic publications of heterogeneous quality. A scoping review of observational studies published in Medline, Lilacs, and Google Scholar databases was carried out. The selected studies were published between December 2019 and August 2021, focused on the relationship between vitamin D and prevention or treatment of COVID-19 in non-institutionalized individuals, with no language restrictions. Twenty-nine studies met eligibility criteria. COI was disclosed in five papers and further identified by review authors in eight other papers, meaning COI was present in thirteen papers (44.8%). Studies were funded by companies in the diagnostics, pharmaceutical and food sectors. Conclusions favorable to vitamin D supplementation were more prevalent in papers where COI was identified (9/13, 69.2%) than among papers where COI was not found (4/16, 25.0%). Omissions of disclosure of COI, funding source, and sponsor functions were observed. The identification of possible corporate political activities in scientific papers about vitamin D published during the COVID-19 pandemic signals a need for greater transparency and guideline development on the prevention of COI in scientific production.
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Affiliation(s)
| | - Maria Birman Cavalcanti
- School of Nutrition, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil
| | - Simone Augusta Ribas
- Department of Public Health Nutrition, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil
- Graduate Program in Food and Nutrition Security (PPGSAN), Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil
| | | | - Cláudia Bocca
- Department of Public Health Nutrition, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil
- Graduate Program in Food and Nutrition Security (PPGSAN), Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil
| | - Fernando Lamarca
- Department of Applied Nutrition, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil
- Department of Applied Nutrition, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil
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21
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Dhar A, Mir H, Koul PA. Vitamin D Levels and Length of Hospitalization in Indian Patients With COVID-19: A Single-Center Prospective Study. Cureus 2022; 14:e26704. [PMID: 35959182 PMCID: PMC9359910 DOI: 10.7759/cureus.26704] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2022] [Indexed: 12/15/2022] Open
Abstract
Introduction The role of vitamin D deficiency in increasing susceptibility or modifying outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness is unclear, and data about the association is scant in low- and middle-income countries. We set out to investigate any correlation between baseline vitamin D status and the length of hospital stay in laboratory-confirmed SARS-CoV-2 patients in India. Methods Two hundred patients with SARS-CoV-2 infection requiring admission in a North Indian 1200-bedded tertiary care hospital were recruited prospectively from November 2020 to March 2021. Baseline serum 25 hydroxyvitamin D [25(OH)D] levels were measured within 24 hours of admission using chemiluminescent immunoassay. Patients were managed as per hospital management protocol for COVID-19. The primary outcome was the length of hospital stay; secondary outcomes were comparative clinical severity between two groups, rate of requirement of mechanical ventilation and/or non-invasive ventilation (NIV), and mortality. Vitamin D deficiency (VDD) was defined as baseline vitamin D levels of <30 ng/ml. Results Of the 200 recruited patients, 57.5% (n = 115) patients were vitamin D deficient, and the overall median length of hospital stay was around 12 days (IQR: 8-15 days). There was no statistically significant difference in the length of hospital stay between patients with normal serum vitamin D (VDS) and those with VDD, median LOS being 12 days (95% CI: 10, 12 days) in VDD cases and 11 days (95% CI: 10,13 days) in VDS cases (p = 0.176). No association between baseline 25(OH)D and any of the secondary outcomes could be established. Conclusions In Indian patients, baseline vitamin D levels are not associated with the length of hospital stay, need for mechanical ventilation, or mortality.
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Affiliation(s)
- Amrit Dhar
- Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, IND
| | - Hyder Mir
- Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, IND
| | - Parvaiz A Koul
- Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, IND
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22
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Li J, Scarano A, Gonzalez NM, D'Orso F, Yue Y, Nemeth K, Saalbach G, Hill L, de Oliveira Martins C, Moran R, Santino A, Martin C. Biofortified tomatoes provide a new route to vitamin D sufficiency. NATURE PLANTS 2022; 8:611-616. [PMID: 35606499 PMCID: PMC9213236 DOI: 10.1038/s41477-022-01154-6] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 04/12/2022] [Indexed: 05/04/2023]
Abstract
Poor vitamin D status is a global health problem; insufficiency underpins higher risk of cancer, neurocognitive decline and all-cause mortality. Most foods contain little vitamin D and plants are very poor sources. We have engineered the accumulation of provitamin D3 in tomato by genome editing, modifying a duplicated section of phytosterol biosynthesis in Solanaceous plants, to provide a biofortified food with the added possibility of supplement production from waste material.
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Affiliation(s)
- Jie Li
- John Innes Centre, Norwich Research Park, Norwich, UK
| | - Aurelia Scarano
- Institute of Sciences of Food Production, C.N.R., Unit of Lecce, Lecce, Italy
| | - Nestor Mora Gonzalez
- Recombinant Biopharmaceutical Laboratory, Department of Pharmacology, Biological Sciences Faculty, University of Concepción, Concepción, Chile
| | - Fabio D'Orso
- John Innes Centre, Norwich Research Park, Norwich, UK
- CREA-Research Centre for Genomics and Bioinformatics, Rome, Italy
| | - Yajuan Yue
- John Innes Centre, Norwich Research Park, Norwich, UK
| | | | | | - Lionel Hill
- John Innes Centre, Norwich Research Park, Norwich, UK
| | | | | | - Angelo Santino
- Institute of Sciences of Food Production, C.N.R., Unit of Lecce, Lecce, Italy
| | - Cathie Martin
- John Innes Centre, Norwich Research Park, Norwich, UK.
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23
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Degarege A, Naveed Z, Kabayundo J, Brett-Major D. Heterogeneity and Risk of Bias in Studies Examining Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-Analysis. Pathogens 2022; 11:563. [PMID: 35631084 PMCID: PMC9147100 DOI: 10.3390/pathogens11050563] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/02/2022] [Accepted: 05/05/2022] [Indexed: 02/07/2023] Open
Abstract
This systematic review and meta-analysis synthesized the evidence on the impacts of demographics and comorbidities on the clinical outcomes of COVID-19, as well as the sources of the heterogeneity and publication bias of the relevant studies. Two authors independently searched the literature from PubMed, Embase, Cochrane library, and CINAHL on 18 May 2021; removed duplicates; screened the titles, abstracts, and full texts by using criteria; and extracted data from the eligible articles. The variations among the studies were examined by using Cochrane, Q.; I2, and meta-regression. Out of 11,975 articles that were obtained from the databases and screened, 559 studies were abstracted, and then, where appropriate, were analyzed by meta-analysis (n = 542). COVID-19-related severe illness, admission to the ICU, and death were significantly correlated with comorbidities, male sex, and an age older than 60 or 65 years, although high heterogeneity was present in the pooled estimates. The study design, the study country, the sample size, and the year of publication contributed to this. There was publication bias among the studies that compared the odds of COVID-19-related deaths, severe illness, and admission to the ICU on the basis of the comorbidity status. While an older age and chronic diseases were shown to increase the risk of developing severe illness, admission to the ICU, and death among the COVID-19 patients in our analysis, a marked heterogeneity was present when linking the specific risks with the outcomes.
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Affiliation(s)
- Abraham Degarege
- Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA; (Z.N.); (J.K.); (D.B.-M.)
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24
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Kazemi E, Mansursamaei A, Rohani-Rasaf M, Sheibani H. Comparison of the cardiovascular system, clinical condition, and laboratory results in COVID-19 patients with and without vitamin D insufficiency. BMC Infect Dis 2022; 22:441. [PMID: 35525957 PMCID: PMC9077635 DOI: 10.1186/s12879-022-07438-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 05/03/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Serum vitamin D levels may have a protective role against severe coronavirus disease 2019 (COVID-19). Studies have shown that deficiency in vitamin D may be a significant risk factor for poor outcomes. This study aims to compare the outcome and clinical condition of patients diagnosed with COVID-19 infection considering serum vitamin D levels. METHODS In this cross-sectional study, 202 COVID-19 patients without known cardiovascular disease (reduced ejection fraction, uncontrolled arrhythmia, pericardial effusion, cardiac block, valvular disease, or hypertension) were included. Patients were divided into three groups of insufficient (< 30 ng/mL), normal (30 to 50 ng/mL), and high (> 50 ng/mL) serum vitamin D levels. Clinical outcome was defined as severe if invasive respiratory intervention and ICU admission was required. RESULTS The patients were divided into three groups based on their vitamin D level: 127 cases in the insufficient vitamin D group, 53 cases in the normal vitamin D group, and 22 cases in the high vitamin D group. The mean age of the population study was 56 years. Thirty-four patients had severe clinical outcomes. The distribution of this group was as follows: 21 patients in the insufficient vitamin D group (16.5%), eight patients in the normal vitamin D group (15.1%), and five patients in the high vitamin D group (22.7%); P = 0.74. No significant differences were found between the groups in terms of mortality rate (P = 0.46). Moreover, the mean of leukocytes (mean ± SD = 6873.5 ± 4236.2), ESR (mean ± SD = 38.42 ± 26.7), and CPK-MB (mean ± SD = 63 ± 140.7) were higher in the insufficient vitamin D group, but it was not statistically significant (P > 0.05). CONCLUSION The finding of the present study showed that vitamin D could not make a significant difference in cardiovascular systems, laboratory results, and severity of the disease in COVID-19 patients.
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Affiliation(s)
- Erfan Kazemi
- grid.444858.10000 0004 0384 8816Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Ali Mansursamaei
- grid.444858.10000 0004 0384 8816Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Marzieh Rohani-Rasaf
- grid.444858.10000 0004 0384 8816Department of Epidemiology, School of Public Health, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Hossein Sheibani
- grid.444858.10000 0004 0384 8816Clinical Research Development Unit, Imam Hossein Hospital, Shahroud University of Medical Sciences, Imam Ave., Shahroud, 3616911151 Iran
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25
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Scavone C, Mascolo A, Rafaniello C, Sportiello L, Trama U, Zoccoli A, Bernardi FF, Racagni G, Berrino L, Castaldo G, Coscioni E, Rossi F, Capuano A. Therapeutic strategies to fight COVID-19: Which is the status artis? Br J Pharmacol 2022; 179:2128-2148. [PMID: 33960398 PMCID: PMC8239658 DOI: 10.1111/bph.15452] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 03/02/2021] [Accepted: 03/05/2021] [Indexed: 02/06/2023] Open
Abstract
COVID-19 is a complex disease, and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated and evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, whereas the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. There are conflicting data on the use of convalescent plasma and vitamin D. According to the World Health Organization (WHO), many vaccines are in Phase III clinical trials, and some of them have already received marketing approval in European countries and in the United States. In conclusion, drug repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, analysis of efficacy and safety data of drugs and vaccines used in real-life context is strongly needed. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.
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Affiliation(s)
- Cristina Scavone
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Annamaria Mascolo
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Concetta Rafaniello
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Liberata Sportiello
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Ugo Trama
- Regional Pharmaceutical UnitU.O.D. 06 Politica del Farmaco e DispositiviNaplesItaly
| | - Alice Zoccoli
- Clinical Innovation OfficeUniversità Campus Bio‐MedicoRomeItaly
| | - Francesca Futura Bernardi
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
- Regional Pharmaceutical UnitU.O.D. 06 Politica del Farmaco e DispositiviNaplesItaly
| | - Giorgio Racagni
- Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
| | - Liberato Berrino
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Giuseppe Castaldo
- Department of Molecular Medicine and Medical BiotechnologyUniversity of Napoli Federico IINaplesItaly
- CEINGE—Advanced Biotechnology ScarlNaplesItaly
| | | | - Francesco Rossi
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
- Clinical Innovation OfficeUniversità Campus Bio‐MedicoRomeItaly
| | - Annalisa Capuano
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
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26
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Tentolouris N, Samakidou G, Eleftheriadou I, Tentolouris A, Jude EB. The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression. Diabetes Metab Res Rev 2022; 38:e3517. [PMID: 34965318 PMCID: PMC9015406 DOI: 10.1002/dmrr.3517] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 11/16/2021] [Accepted: 11/26/2021] [Indexed: 12/02/2022]
Abstract
AIMS The aim of this systematic review and meta-analysis was to investigate the effect of vitamin D supplementation on mortality and admission to intensive care unit (ICU) of COVID-19 patients. METHODS A systematic search of PubMed, Google Scholar, Embase, Web of Science and medRxiv with terms relative to vitamin D supplementation and COVID-19 was conducted on 26 March 2021. Comprehensive Meta-Analysis software was used for the quantitative assessment of data and random-effects model was applied. To investigate the association between the dose of vitamin D and the outcomes of interest, meta-regression analysis was performed. RESULTS Two thousand and seventy-eight patients from nine studies with data on mortality were included (583 received vitamin D supplementation, while 1495 did not). Sixty-one (10.46%) individuals in the treated group died, compared to 386 (25.81%) in the non-treated group (odds ratio [OR]: 0.597; 95% CI: 0.318-1.121; p = 0.109). Eight hundred and sixty patients from six studies with data on ICU admission were included (369 received vitamin D supplementation, while 491 did not). Forty-five (12.19%) individuals in the treated group were admitted to ICU, compared to 129 (26.27%) in the non-treated group (OR: 0.326; 95% CI: 0.149-0.712; p = 0.005). No significant linear relationship between vitamin D dose and log OR of mortality or log OR of ICU admission was observed. CONCLUSION This meta-analysis indicates a beneficial role of vitamin D supplementation on ICU admission, but not on mortality, of COVID-19 patients. Further research is urgently needed to understand the benefit of vitamin D in COVID-19.
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Affiliation(s)
- Nikolaos Tentolouris
- First Department of Propaedeutic Internal MedicineDiabetes CentreMedical SchoolNational and Kapodistrian University of AthensLaiko General HospitalAthensGreece
| | - Georgia Samakidou
- First Department of Propaedeutic Internal MedicineDiabetes CentreMedical SchoolNational and Kapodistrian University of AthensLaiko General HospitalAthensGreece
| | - Ioanna Eleftheriadou
- First Department of Propaedeutic Internal MedicineDiabetes CentreMedical SchoolNational and Kapodistrian University of AthensLaiko General HospitalAthensGreece
| | - Anastasios Tentolouris
- First Department of Propaedeutic Internal MedicineDiabetes CentreMedical SchoolNational and Kapodistrian University of AthensLaiko General HospitalAthensGreece
| | - Edward B. Jude
- Tameside and Glossop Integrated Care NHS Foundation TrustAshton‐under‐LyneUK
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27
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Vitamin D: A Role Also in Long COVID-19? Nutrients 2022; 14:nu14081625. [PMID: 35458189 PMCID: PMC9028162 DOI: 10.3390/nu14081625] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/20/2022] [Accepted: 04/01/2022] [Indexed: 12/11/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) has quickly become a global pandemic. Reports from different parts of the world indicate that a significant proportion of people who have recovered from COVID-19 are suffering from various health problems collectively referred to as “long COVID-19”. Common symptoms include fatigue, shortness of breath, cough, joint pain, chest pain, muscle aches, headaches, and so on. Vitamin D is an immunomodulatory hormone with proven efficacy against various upper respiratory tract infections. Vitamin D can inhibit hyperinflammatory reactions and accelerate the healing process in the affected areas, especially in lung tissue. Moreover, vitamin D deficiency has been associated with the severity and mortality of COVID-19 cases, with a high prevalence of hypovitaminosis D found in patients with COVID-19 and acute respiratory failure. Thus, there are promising reasons to promote research into the effects of vitamin D supplementation in COVID-19 patients. However, no studies to date have found that vitamin D affects post-COVID-19 symptoms or biomarkers. Based on this scenario, this review aims to provide an up-to-date overview of the potential role of vitamin D in long COVID-19 and of the current literature on this topic.
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28
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di Filippo L, Doga M, Frara S, Giustina A. Hypocalcemia in COVID-19: Prevalence, clinical significance and therapeutic implications. Rev Endocr Metab Disord 2022; 23:299-308. [PMID: 33846867 PMCID: PMC8041474 DOI: 10.1007/s11154-021-09655-z] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/09/2021] [Indexed: 01/08/2023]
Abstract
COVID-19 extra-pulmonary features include several endocrine manifestations and these are becoming strongly clinically relevant in patients affected influencing disease severity and outcomes.At the beginning of COVID-19 pandemic no population data on calcium levels in patients affected were available and in April 2020 a first case of severe acute hypocalcemia in an Italian patient with SARS-CoV-2 infection was reported. Subsequently, several studies reported hypocalcemia as a highly prevalent biochemical abnormality in COVID-19 patients with a marked negative influence on disease severity, biochemical inflammation and thrombotic markers, and mortality. Also a high prevalence of vertebral fractures with worse respiratory impairment in patients affected and a widespread vitamin D deficiency have been frequently observed, suggesting an emerging "Osteo-Metabolic Phenotype" in COVID-19.To date, several potential pathophysiological factors have been hypothesized to play a role in determining hypocalcemia in COVID-19 including calcium dependent viral mechanisms of action, high prevalence of hypovitaminosis D in general population, chronic and acute malnutrition during critical illness and high levels of unbound and unsaturated fatty acids in inflammatory responses.Since hypocalcemia is a frequent biochemical finding in hospitalized COVID-19 patients possibly predicting worse outcomes and leading to acute cardiovascular and neurological complications if severe, it is reasonable to assess, monitor and, if indicated, replace calcium at first patient hospital evaluation and during hospitalization.
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Affiliation(s)
- Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Mauro Doga
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Frara
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
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29
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Nimavat N, Singh S, Patel D, Singh P, Hasan MM, Mandala G, Bhangu R, Priya A. The Relationship Between Vitamin D Levels and Severity in Illness in COVID-19 Patients: A Cross-Sectional Study. Cureus 2022; 14:e23146. [PMID: 35444872 PMCID: PMC9010000 DOI: 10.7759/cureus.23146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2022] [Indexed: 11/05/2022] Open
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30
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Tomaszewska A, Rustecka A, Lipińska-Opałka A, Piprek RP, Kloc M, Kalicki B, Kubiak JZ. The Role of Vitamin D in COVID-19 and the Impact of Pandemic Restrictions on Vitamin D Blood Content. Front Pharmacol 2022; 13:836738. [PMID: 35264968 PMCID: PMC8899722 DOI: 10.3389/fphar.2022.836738] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 01/24/2022] [Indexed: 12/20/2022] Open
Abstract
Vitamin D is a hormone regulating the immune system and playing a pivotal role in responses to microbial infections. It regulates inflammatory processes by influencing the transcription of immune-response genes in macrophages, T cells, and dendritic cells. The proven role of vitamin D in many infectious diseases of the respiratory tract indicated that vitamin D should also play a role in SARS-CoV-2 infection. Vitamin D inhibits cytokine storm by switching the pro-inflammatory Th1 and Th17 to the anti-inflammatory Th2 and Treg response. Vitamin D is therefore expected to play a role in preventing, relieving symptoms, or treating SARS-CoV-2 infection symptoms, including severe pneumonia. There are several possible mechanisms by which vitamin D may reduce the risk of COVID-19 infection, such as induction of the transcription of cathelicidin and defensin. Also a nongenomic antiviral action of vitamin D and lumisterol, the molecule closely related to vitamin D, was reported. Despite this enormous progress, currently, there is still insufficient scientific evidence to support the claim that vitamin D supplementation may help treat COVID-19 infection. The pandemic restrictions were also shown to impact vitamin D uptake by limiting exposure to sunlight.
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Affiliation(s)
- Agata Tomaszewska
- Pediatric, Nephrology, and Allergology Clinic, Military Institute of Medicine, Warsaw, Poland
| | - Agnieszka Rustecka
- Pediatric, Nephrology, and Allergology Clinic, Military Institute of Medicine, Warsaw, Poland
| | | | - Rafal P Piprek
- Department of Comparative Anatomy, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
| | - Małgorzata Kloc
- The Houston Methodist Research Institute, Houston, TX, United States.,Department of Surgery, The Houston Methodist Hospital, Houston, TX, United States.,Department of Genetics, M.D. Anderson Cancer Center, The University of Texas, Houston, TX, United States
| | - Bolesław Kalicki
- Pediatric, Nephrology, and Allergology Clinic, Military Institute of Medicine, Warsaw, Poland
| | - Jacek Z Kubiak
- Faculty of Medicine, CNRS, UMR 6290, Institute of Genetics and Development of Rennes, University Rennes, Rennes, France.,Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, Warsaw, Poland
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31
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de Melo Bacha FV, Gomez FLC, Silva ALG, Reis MD, Cabral EDL, de Carvalho LD. Vitamin D: a 14-year retrospective study at a clinical laboratory in Brazil. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 66:19-31. [PMID: 35029851 PMCID: PMC9991022 DOI: 10.20945/2359-3997000000427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE This study aimed to assess vitamin D (25OHD) levels in individuals who underwent an examination at a private laboratory (between latitudes 14° and 22° south) over 14 years, stratified by sex, age, and epidemiological profiles, and determine variations in the number of tests performed over the years. METHODS All records of 25OHD tests performed at a private clinical laboratory in Brazil were analyzed. This retrospective cross-sectional study included patients stratified by sex (female or male), age range (0-17, 18-40, 41-59, and ≥ 60 years), and year of testing. The final sample size was 193,725 patients. Categorical variables are presented as absolute and relative frequencies and numerical variables as means ± standard deviation. Comparisons between groups were performed using the equality of proportions test. RESULTS The number of tests performed steeply increased since 2010. More tests were performed in female individuals (73.3%) and individuals aged 41-59 years (32.2%). Most samples (68.0%) demonstrated sufficient vitamin D status. Women had a higher incidence of vitamin D deficiency than men (33.1% and 26.6%, respectively; p < 0.001). Individuals aged ≥ 60 years had the highest incidence of vitamin D deficiency (68.4%), while individuals aged 0-17 years had the lowest (32.2%) (p < 0.001). CONCLUSION Despite increased testing and attention given to vitamin D in recent years, our study demonstrates high levels of deficiency in a country with geographical conditions favorable to its production.
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Affiliation(s)
| | | | | | - Mariana Didier Reis
- Faculdade Ciências Médicas de Minas Gerais (FCMMG), Belo Horizonte, MG, Brasil
| | - Eliane Dias Lustosa Cabral
- Centro de Desenvolvimento, Inovação, Ciência e Tecnologia/Labtest Diagnóstica S.A., Lagoa Santa, MG, Brasil
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32
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Esgin Ö, Erten T. Nutrition and a Balanced Diet in the Elderly During the COVID-19 Pandemic. CURRENT NUTRITION & FOOD SCIENCE 2022. [DOI: 10.2174/1573401318666220308154735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Age is an important risk factor in the mortality ratio of the COVID-19 disease and mostly, the hospitalised patients over 60 years with chronic diseases are at high risk of death. With preventive measures, proper nutrient intake might be helpful to maintain a healthy state or reduce the severity of the COVID-19 disease in the elderly.
Methods:
Database searches of PubMed, Scopus, Medline, Google Scholar and Web of Science were performed by the following terms of pandemic; COVID-19; coronavirus; elderly; elderly nutrition.
Results:
The requirement of some macro and micro nutrients increases especially the nutrients that support the immune activity. During the pandemic, the daily energy requirement for the elderly is stated as 27-30 kcal/kg while the protein intake is recommended as at least 1g/kg, and the ratio of fat and carbohydrate is 30:70 or 50:50. The daily intake of Vitamin A, B6, B12, C, D, zinc and selenium can also be increased due to their supporting function in the immune system. Probiotics such as Bifidobacterium longum MM-2, Lactobacillus plantarum 06CC2, Lactobacillus bulgaricus OLL1073R-1 and Lactobacillus rhamnosus M21 and the consumption of prebiotics in diet enhance the immune function. Additionally, flavonoids such as baicalin, epigallocatechin gallate, gallocatechin gallate, kaempferol, luteolin, resveratrol and quercetin improve immunity by reducing oxidative stress in the elderly.
Conclusion:
Adequate and balanced nutrition should be provided during the pandemic; in addition to this, micronutrient deficiencies should also be prevented in this period in the elderly at every stage of life.
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Affiliation(s)
- Özge Esgin
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Ankara University, Ankara, Turkey
| | - Tayyibe Erten
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Bayburt University, Bayburt, Turkey
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33
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Karonova TL, Kudryavtsev IV, Golovatyuk KA, Aquino AD, Kalinina OV, Chernikova AT, Zaikova EK, Lebedev DA, Bykova ES, Golovkin AS, Shlyakhto EV. Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19. Pharmaceuticals (Basel) 2022; 15:305. [PMID: 35337103 PMCID: PMC8955127 DOI: 10.3390/ph15030305] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/22/2022] [Accepted: 02/26/2022] [Indexed: 12/17/2022] Open
Abstract
A low 25-hydroxyvitamin D (25(OH)D) level is considered as an independent risk factor for COVID-19 severity. However, the association between vitamin D status and outcomes in COVID-19 is controversial. In the present study we investigate the association between the serum 25(OH)D level, immune response, and clinical disease course in patients with COVID-19. A total of 311 patients hospitalized with COVID-19 were enrolled. For patients with a vitamin D deficiency/insufficiency, the prevalence of severe COVID-19 was higher than in those with a normal 25(OH)D level (p < 0.001). The threshold of 25(OH)D level associated with mortality was 11.4 ng/mL (p = 0.003, ROC analysis). The frequency of CD3+CD4+ T helper (Th) cells was decreased in patients with 25(OH)D level ≤ 11.4 ng/mL, compared to healthy controls (HCs). There were no differences in the frequency of naive, central memory (CM), effector memory (EM), and terminally differentiated effector memory Th cells in patients with COVID-19 compared to HCs. The frequency of T-follicular helpers was decreased both in patients with 25(OH)D level > 11.4 ng/mL (p < 0.001) and 25(OH)D level ≤ 11.4 ng/mL (p = 0.003) compared to HCs. Patients with 25(OH)D level > 11.4 ng/mL had an increased frequency of Th2 CM (p = 0.010) and decreased Th17 CM (p < 0.001). While the frequency of Th2 EM was significantly increased, the frequency of Th17 EM was significantly decreased in both groups compared to HCs. Thus, 25(OH)D level is an independent risk factor for the disease severity and mortality in patients with COVID-19. We demonstrate that the serum 25(OH)D level ≤ 11.4 ng/mL is associated with the stimulation of Th2 and the downregulation of Th17 cell polarization of the adaptive immunity in patients with COVID-19.
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Affiliation(s)
- Tatiana L. Karonova
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Igor V. Kudryavtsev
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
- Institute of Experimental Medicine, 197376 Saint-Petersburg, Russia
| | - Ksenia A. Golovatyuk
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Arthur D. Aquino
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Olga V. Kalinina
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Alena T. Chernikova
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Ekaterina K. Zaikova
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Denis A. Lebedev
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Ekaterina S. Bykova
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Alexey S. Golovkin
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
| | - Evgeny V. Shlyakhto
- Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia; (I.V.K.); (K.A.G.); (A.D.A.); (O.V.K.); (A.T.C.); (E.K.Z.); (D.A.L.); (E.S.B.); (A.S.G.); (E.V.S.)
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Wang Z, Joshi A, Leopold K, Jackson S, Christensen S, Nayfeh T, Mohammed K, Creo A, Tebben P, Kumar S. Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis. Clin Endocrinol (Oxf) 2022; 96:281-287. [PMID: 34160843 PMCID: PMC8444883 DOI: 10.1111/cen.14540] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/07/2021] [Accepted: 05/31/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND We sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID-19) infection. METHODS Multiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID-19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission. RESULTS Seventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50-4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40-7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48-3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25-0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut-offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends. CONCLUSIONS Vitamin D deficiency is associated with greater severity of COVID-19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID-19.
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Affiliation(s)
- Zhen Wang
- Division of Health Care Delivery Research, Robert D. and Patricia E. Kern Center for the Science of Health Care Division of Health Care Delivery ResearchMayo ClinicRochesterMinnesotaUSA
| | - Avni Joshi
- Division of Allergic Diseases, Department of MedicineMayo ClinicRochesterMinnesotaUSA
- Division of Pediatric Allergy and Immunology, Department of Pediatric and Adolescent MedicineMayo ClinicRochesterMinnesotaUSA
| | - Kaitlin Leopold
- Department of Pediatric and Adolescent MedicineMayo ClinicRochesterMinnesotaUSA
| | - Sarah Jackson
- Division of Pediatric Endocrinology, Department of Pediatric and Adolescent MedicineMayo ClinicRochesterMinnesotaUSA
| | | | - Tarek Nayfeh
- Division of Health Care Delivery Research, Robert D. and Patricia E. Kern Center for the Science of Health Care Division of Health Care Delivery ResearchMayo ClinicRochesterMinnesotaUSA
- Mayo Clinic Evidence-based Practice CenterRochesterMinnesotaUSA
| | - Khaled Mohammed
- Community Pediatric and Adolescent MedicineMayo ClinicRochesterMinnesotaUSA
| | - Ana Creo
- Division of Pediatric Endocrinology, Department of Pediatric and Adolescent MedicineMayo ClinicRochesterMinnesotaUSA
| | - Peter Tebben
- Division of Pediatric Endocrinology, Department of Pediatric and Adolescent MedicineMayo ClinicRochesterMinnesotaUSA
- Division of Endocrinology and Metabolism, Department of MedicineMayo ClinicRochesterMinnesotaUSA
| | - Seema Kumar
- Division of Pediatric Endocrinology, Department of Pediatric and Adolescent MedicineMayo ClinicRochesterMinnesotaUSA
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Halim C, Mirza AF, Sari MI. The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis. Pathogens 2022; 11:195. [PMID: 35215138 PMCID: PMC8879207 DOI: 10.3390/pathogens11020195] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/19/2022] [Accepted: 01/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND An increasing number of scientific journals have proposed a connection between tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the severity of COVID-19. Vitamin D has been discussed as a potential therapy for COVID-19 due to its immunomodulatory effects. This meta-analysis aims to determine the relationship, if any, between TNF-α, IL-6, vitamin D, and COVID-19 severity and mortality. METHODS The design of the study is a systematic review and meta-analysis. A literature search is performed using PubMed, Cochrane, ProQuest, and Google Scholar. RESULTS TNF-α insignificantly increases the risk of COVID-19 severity (adjusted odds ratio (aOR) = 1.0304; 95% CI 0.8178-1.2983; p = 0.80) but significantly increases the risk of COVID-19 mortality (crude hazard ratio (HR) = 1.0640; 95% CI 1.0259-1.1036; p = 0.0009). IL-6 significantly increases the risk of COVID-19 severity (aOR = 1.0284; 95% CI 1.0130-1.0441; p = 0.0003) and mortality (aOR = 1.0076; 95% CI 1.0004-1.0148; p = 0.04; adjusted hazard ratio (aHR) = 1.0036; 95% CI 1.0010-1.0061; p = 0.006). There is a statistically insignificant difference of the mean vitamin D levels between patients with severe COVID-19 and non-severe COVID-19 (mean difference (MD) = -5.0232; 95% CI 11.6832-1.6368; p = 0.14). A vitamin D deficiency insignificantly increases the risk of mortality of COVID-19 patients (aOR = 1.3827; 95% CI 0.7103-2.6916; p = 0.34). CONCLUSION IL-6 is an independent prognostic factor towards COVID-19 severity and mortality.
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Affiliation(s)
| | | | - Mutiara Indah Sari
- Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Sumatera Utara, Indonesia; (C.H.); (A.F.M.)
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Pedrosa LFC, Barros ANAB, Leite-Lais L. Nutritional risk of vitamin D, vitamin C, zinc, and selenium deficiency on risk and clinical outcomes of COVID-19: A narrative review. Clin Nutr ESPEN 2022; 47:9-27. [PMID: 35063248 PMCID: PMC8571905 DOI: 10.1016/j.clnesp.2021.11.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/27/2021] [Accepted: 11/01/2021] [Indexed: 02/06/2023]
Abstract
The pathogenicity of the current coronavirus disease (COVID-19) shows postulates that optimal status of essential nutrients is crucial in supporting both the early viraemic and later hyperinflammatory phases of COVID-19. Micronutrients such as vitamin C, D, zinc, and selenium play roles in antioxidant, anti-inflammatory, antithrombotic, antiviral, and immuno-modulatory functions and are useful in both innate and adaptive immunity. The purpose of this review is to provide a high-level summary of evidence on clinical outcomes associated with nutritional risk of these micronutrients observed in patients with COVID-19. A literature search was performed on PubMed and Google Scholar to obtain findings of cross-sectional and experimental studies in humans. The search resulted in a total of 1212 reports including all nutrients, but only 85 were included according to the eligibility criteria. Despite the diversity of studies and the lack of randomized clinical trials and prospective cohorts, there is evidence of the potential protective and therapeutic roles of vitamin C, D, zinc, and selenium in COVID-19. The findings summarized in this review will contribute to guide interventions in clinical practice or in future clinical studies.
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Affiliation(s)
- Lucia F C Pedrosa
- Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, 59078-970, Brazil; Department of Nutrition, Federal University of Rio Grande do Norte, Natal, RN, 59078-970, Brazil.
| | - Acsa N A B Barros
- Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, 59078-970, Brazil
| | - Lucia Leite-Lais
- Department of Nutrition, Federal University of Rio Grande do Norte, Natal, RN, 59078-970, Brazil
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Karonova TL, Chernikova AT, Golovatyuk KA, Bykova ES, Grant WB, Kalinina OV, Grineva EN, Shlyakhto EV. Vitamin D Intake May Reduce SARS-CoV-2 Infection Morbidity in Health Care Workers. Nutrients 2022; 14:505. [PMID: 35276863 PMCID: PMC8839300 DOI: 10.3390/nu14030505] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/19/2022] [Accepted: 01/21/2022] [Indexed: 02/04/2023] Open
Abstract
In the last 2 years, observational studies have shown that a low 25-hydroxyvitamin D (25(OH)D) level affected the severity of infection with the novel coronavirus (COVID-19). This study aimed to analyze the potential effect of vitamin D supplementation in reducing SARS-CoV-2 infection morbidity and severity in health care workers. Of 128 health care workers, 91 (consisting of 38 medical doctors (42%), 38 nurses (42%), and 15 medical attendants (16%)) were randomized into two groups receiving vitamin D supplementation. Participants of group I (n = 45) received water-soluble cholecalciferol at a dose of 50,000 IU/week for 2 consecutive weeks, followed by 5000 IU/day for the rest of the study. Participants of group II (n = 46) received water-soluble cholecalciferol at a dose of 2000 IU/day. For both groups, treatment lasted 3 months. Baseline serum 25(OH)D level in health care workers varied from 3.0 to 65.1 ng/mL (median, 17.7 (interquartile range, 12.2; 24.7) ng/mL). Vitamin D deficiency, insufficiency, and normal vitamin D status were diagnosed in 60%, 30%, and 10%, respectively. Only 78 subjects completed the study. Vitamin D supplementation was associated with an increase in serum 25(OH)D level, but only intake of 5000 IU/day was accompanied by normalization of serum 25(OH)D level, which occurred in 53% of cases. Neither vitamin D intake nor vitamin D deficiency/insufficiency were associated with a decrease in SARS-CoV-2 morbidity (odds ratio = 2.27; 95% confidence interval, 0.72 to 7.12). However, subjects receiving high-dose vitamin D had only asymptomatic SARS-CoV-2 in 10 (26%) cases; at the same time, participants who received 2000 IU/day showed twice as many SARS-CoV-2 cases, with mild clinical features in half of them.
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Affiliation(s)
- Tatiana L. Karonova
- Clinical Endocrinology Laboratory, Department of Endocrinology, Almazov National Medical Research Centre, 194021 Saint Petersburg, Russia; (A.T.C.); (K.A.G.); (E.S.B.); (O.V.K.); (E.N.G.); (E.V.S.)
| | - Alena T. Chernikova
- Clinical Endocrinology Laboratory, Department of Endocrinology, Almazov National Medical Research Centre, 194021 Saint Petersburg, Russia; (A.T.C.); (K.A.G.); (E.S.B.); (O.V.K.); (E.N.G.); (E.V.S.)
| | - Ksenia A. Golovatyuk
- Clinical Endocrinology Laboratory, Department of Endocrinology, Almazov National Medical Research Centre, 194021 Saint Petersburg, Russia; (A.T.C.); (K.A.G.); (E.S.B.); (O.V.K.); (E.N.G.); (E.V.S.)
| | - Ekaterina S. Bykova
- Clinical Endocrinology Laboratory, Department of Endocrinology, Almazov National Medical Research Centre, 194021 Saint Petersburg, Russia; (A.T.C.); (K.A.G.); (E.S.B.); (O.V.K.); (E.N.G.); (E.V.S.)
| | - William B. Grant
- Sunlight, Nutrition, and Health Research Center, San Francisco, CA 94164-1603, USA;
| | - Olga V. Kalinina
- Clinical Endocrinology Laboratory, Department of Endocrinology, Almazov National Medical Research Centre, 194021 Saint Petersburg, Russia; (A.T.C.); (K.A.G.); (E.S.B.); (O.V.K.); (E.N.G.); (E.V.S.)
| | - Elena N. Grineva
- Clinical Endocrinology Laboratory, Department of Endocrinology, Almazov National Medical Research Centre, 194021 Saint Petersburg, Russia; (A.T.C.); (K.A.G.); (E.S.B.); (O.V.K.); (E.N.G.); (E.V.S.)
| | - Evgeny V. Shlyakhto
- Clinical Endocrinology Laboratory, Department of Endocrinology, Almazov National Medical Research Centre, 194021 Saint Petersburg, Russia; (A.T.C.); (K.A.G.); (E.S.B.); (O.V.K.); (E.N.G.); (E.V.S.)
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The Prognostic Role of Metabolic and Endocrine Parameters for the Clinical Severity of COVID-19. DISEASE MARKERS 2022; 2022:5106342. [PMID: 35096202 PMCID: PMC8794698 DOI: 10.1155/2022/5106342] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 12/14/2021] [Accepted: 12/23/2021] [Indexed: 12/13/2022]
Abstract
Objective An outbreak of coronavirus disease-19 (COVID-19) began in December 2019 and spread globally, overwhelming the entire world. COVID-19 is a public health emergency of international concern. Due to its high morbidity and mortality rate, recognition of its risk and prognostic factors is important. We aimed to understand the relationship between metabolic and endocrine parameters and the prognosis of COVID-19. Methods and Materials This was a cross-sectional clinical study. A total of 70 patients with severe COVID-19 were enrolled. Laboratory results at the first admission time (including complete blood count, C-reactive protein, lactate dehydrogenase, blood glucose, calcium, phosphate, albumin, creatinine, magnesium, lipid profiles, liver enzymes, thyroid hormones, cortisol, and vitamin D) and outcome data were recorded. We divided patients into (1) intensive care unit- (ICU-) admitted and non-ICU-admitted and (2) survivors and nonsurvivors for estimation of severity and prognosis. We determined the risk factors associated with critical illness and poor prognosis. Results Patients with higher white blood cell (WBC) count and phosphate levels had significantly higher ICU admission rates. According to univariate analysis, serum levels of T3, phosphate, and WBC as well as the duration of hospitalization were associated with mortality. Multivariate analysis revealed that only WBC and duration of hospitalization were independent predictors for mortality rate in COVID-19 patients. Conclusion Our findings suggest that longer duration of hospitalization and higher WBC count are associated with poor outcomes in patients with COVID-19.
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di Filippo L, Allora A, Doga M, Formenti AM, Locatelli M, Rovere Querini P, Frara S, Giustina A. Vitamin D Levels Are Associated With Blood Glucose and BMI in COVID-19 Patients, Predicting Disease Severity. J Clin Endocrinol Metab 2022; 107:e348-e360. [PMID: 34383926 PMCID: PMC8385994 DOI: 10.1210/clinem/dgab599] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Indexed: 12/15/2022]
Abstract
CONTEXT A high prevalence of vitamin D (VD) deficiency in COVID-19 patients has been reported and hypothesized to increase COVID-19 severity likely because of its negative impact on immune and inflammatory responses. Furthermore, clear associations between hypovitaminosis D and fat body mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized. OBJECTIVE The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, body mass index (BMI), blood glucose (GLU), and disease severity. METHODS Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD metabolism. 25-Hydroxyvitamin D levels, plasma GLU levels, BMI, and inflammatory parameters were evaluated at admission. RESULTS A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD deficiency was found in 68.2% of patients. VD deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma GLU, BMI, neutrophil/lymphocyte ratio, C-reactive protein, and interleukin 6. Patients with both hypovitaminosis D and diabetes mellitus, as well those with hypovitaminosis D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions. CONCLUSION We showed, for the first-time, a strict association of VD levels with blood GLU and BMI in COVID-19 patients. VD deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.
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Affiliation(s)
- Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
| | - Agnese Allora
- Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
| | - Mauro Doga
- Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
| | - Anna Maria Formenti
- Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
| | - Massimo Locatelli
- Laboratory Medicine Service, IRCCS San Raffaele Hospital, Milan, Italy
| | - Patrizia Rovere Querini
- Vita-Salute San Raffaele University and Division of Transplantation, Immunology and Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy
| | - Stefano Frara
- Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
| | - Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
- Correspondence: Prof. Andrea Giustina, Division of Endocrinology, IRCCS San Raffaele Hospital, via Olgettina 60, 20132 Milano, Italy;
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Efird JT, Anderson EJ, Jindal C, Redding TS, Thompson AD, Press AM, Upchurch J, Williams CD, Choi YM, Suzuki A. The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 19:447. [PMID: 35010701 PMCID: PMC8744830 DOI: 10.3390/ijerph19010447] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 12/21/2021] [Accepted: 12/28/2021] [Indexed: 12/15/2022]
Abstract
This data-based cohort consisted of 26,508 (7%) United States veterans out of the 399,290 who tested positive for SARS-CoV-2 from 1 March to 10 September 2020. We aimed to assess the interaction of post-index vitamin D (Vit D) and corticosteroid (CRT) use on 30-day mortality among hospitalized and non-hospitalized patients with coronavirus disease 2019 (COVID-19). Combination Vit D and CRT drug use was assessed according to four multinomial pairs (-|+, -|-, +|+, +|-). Respective categorical effects were computed on a log-binomial scale as adjusted relative risk (aRR). Approximately 6% of veterans who tested positive for SARS-CoV-2 died within 30 days of their index date. Among hospitalized patients, a significantly decreased aRR was observed for the use of Vit D in the absence of CRTs relative to patients who received CRTs but not Vit D (aRR = 0.30; multiplicity corrected, p = 0.0004). Among patients receiving systemically administered CRTs (e.g., dexamethasone), the use of Vit D was associated with fewer deaths in hospitalized patients (aRR = 0.51) compared with non-hospitalized patients (aRR = 2.5) (P-for-Interaction = 0.0071). Evaluating the effect of modification of these compounds in the context of hospitalization may aid in the management of COVID-19 and provide a better understanding of the pathophysiological mechanisms underlying this and future infectious disease outbreaks.
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Affiliation(s)
- Jimmy T. Efird
- Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; (T.S.R.); (A.D.T.); (A.M.P.); (J.U.); (C.D.W.); (A.S.)
| | | | - Charulata Jindal
- Harvard Medical School, Harvard University, Boston, MA 02115, USA;
| | - Thomas S. Redding
- Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; (T.S.R.); (A.D.T.); (A.M.P.); (J.U.); (C.D.W.); (A.S.)
| | - Andrew D. Thompson
- Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; (T.S.R.); (A.D.T.); (A.M.P.); (J.U.); (C.D.W.); (A.S.)
| | - Ashlyn M. Press
- Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; (T.S.R.); (A.D.T.); (A.M.P.); (J.U.); (C.D.W.); (A.S.)
| | - Julie Upchurch
- Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; (T.S.R.); (A.D.T.); (A.M.P.); (J.U.); (C.D.W.); (A.S.)
| | - Christina D. Williams
- Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; (T.S.R.); (A.D.T.); (A.M.P.); (J.U.); (C.D.W.); (A.S.)
- Department of Medicine, Duke University, Durham, NC 27710, USA
- Duke Cancer Institute, Duke University, Durham, NC 27710, USA
| | | | - Ayako Suzuki
- Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; (T.S.R.); (A.D.T.); (A.M.P.); (J.U.); (C.D.W.); (A.S.)
- Division of Gastroenterology, Duke University, Durham, NC 27710, USA
- The Division of Gastroenterology, Durham VA Medical Center, Durham, NC 27705, USA
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Chiodini I, Gatti D, Soranna D, Merlotti D, Mingiano C, Fassio A, Adami G, Falchetti A, Eller-Vainicher C, Rossini M, Persani L, Zambon A, Gennari L. Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes. Front Public Health 2021; 9:736665. [PMID: 35004568 PMCID: PMC8727532 DOI: 10.3389/fpubh.2021.736665] [Citation(s) in RCA: 94] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 11/11/2021] [Indexed: 12/17/2022] Open
Abstract
Background: Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints). Methods: A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization. Findings: Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45-4.77; 2.16, 1.43-3.26; 2.83, 1.74-4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93-3.49; 1.84, 1.26-2.69; 4.15, 1.76-9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32-2.13; 1.83, 1.43-2.33; 1.49, 1.16-1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63-3.85; 2.38, 1.56-3.63; 1.82, 1.43-2.33). Considering specific subgroups (i.e., Caucasian patients, high quality studies, and studies reporting adjusted association estimates) the results of primary endpoints did not change. Interpretations: Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.
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Affiliation(s)
- Iacopo Chiodini
- Department of Endocrine and Metabolic Diseases, Istituto di Ricovero e Cura a Caratttere Scientifico (IRCCS), Istituto Auxologico Italiano, Milan, Italy
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Davide Gatti
- Rheumatology Unit, University of Verona, Verona, Italy
| | - Davide Soranna
- Biostatistic Unit, Istituto di Ricovero e Cura a Caratttere Scientifico (IRCCS), Istituto Auxologico Italiano, Milan, Italy
| | - Daniela Merlotti
- Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Christian Mingiano
- Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Angelo Fassio
- Rheumatology Unit, University of Verona, Verona, Italy
| | | | - Alberto Falchetti
- Unit of Rehabilitation Medicine, San Giuseppe Hospital, Istituto di Ricovero e Cura a Caratttere Scientifico (IRCCS), Istituto Auxologico Italiano, Piancavallo, Italy
| | - Cristina Eller-Vainicher
- Unit of Endocrinology, Fondazione Istituto di Ricovero e Cura a Caratttere Scientifico (IRCCS) Cà Granda, Milan, Italy
| | | | - Luca Persani
- Department of Endocrine and Metabolic Diseases, Istituto di Ricovero e Cura a Caratttere Scientifico (IRCCS), Istituto Auxologico Italiano, Milan, Italy
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Antonella Zambon
- Biostatistic Unit, Istituto di Ricovero e Cura a Caratttere Scientifico (IRCCS), Istituto Auxologico Italiano, Milan, Italy
- Department of Statistics and Quantitative Methods, Università di Milano-Bicocca, Milan, Italy
| | - Luigi Gennari
- Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
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Madani S, Shahin S, Yoosefi M, Ahmadi N, Ghasemi E, Koolaji S, Mohammadi E, Mohammadi Fateh S, Hajebi A, Kazemi A, Pakatchian E, Rezaei N, Jamshidi H, Larijani B, Farzadfar F. Red flags of poor prognosis in pediatric cases of COVID-19: the first 6610 hospitalized children in Iran. BMC Pediatr 2021; 21:563. [PMID: 34893036 PMCID: PMC8660655 DOI: 10.1186/s12887-021-03030-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 11/26/2021] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION COVID-19 clinical course, effective therapeutic regimen, and poor prognosis risk factors in pediatric cases are still under investigation and no approved vaccinehas been introduced for them. METHODS This cross-sectional study evaluated different aspect of COVID-19 infection in hospitalized COVID-19 positive children (≺18 years oldwith laboratory confirmed COVID-19 infection, using the national COVID-19 registry for all admitted COVID-19 positive cases from February 19 until November 13,2020, in Iran. RESULTS We evaluated 6610 hospitalized children. Fifty-four percent (3268) were male and one third of them were infants younger than 1 year. Mortality rate in total hospitalized children was 5.3% and in children with underlying co-morbidities (14.4%) was significantly higher (OR: 3.6 [2.7-4.7]). Chronic kidney disease (OR: 3.42 [1.75-6.67]), Cardiovascular diseases (OR: 3.2 [2.09-5.11]), chronic pulmonary diseases (OR: 3.21 [1.59-6.47]), and diabetes mellitus (OR: 2.5 [1.38-4.55]), resulted in higher mortality rates in hospitalized COVID-19 children. Fever (41%), cough (36%), and dyspnea (27%) were the most frequent symptoms in hospitalized children and dyspnea was associated with near three times higher mortality rate among children with COVID-19 infection (OR: 2.65 [2.13-3.29]). CONCLUSION Iran has relatively high COVID-19 mortality in hospitalized children. Pediatricians should consider children presenting with dyspnea, infants≺ 1 year and children with underlying co-morbidities, as high-risk groups for hospitalization, ICU admission, and death.
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Affiliation(s)
- Sedigheh Madani
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sarvenaz Shahin
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moein Yoosefi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Naser Ahmadi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Erfan Ghasemi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sogol Koolaji
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Esmaeil Mohammadi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Mohammadi Fateh
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirali Hajebi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ameneh Kazemi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Erfan Pakatchian
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Negar Rezaei
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hamidreza Jamshidi
- Research Institute for Endocrine Sciences, School of Medicine, Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farshad Farzadfar
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Verma S, Chaturvedi V, Ganguly NK, Mittal SA. Vitamin D deficiency: concern for rheumatoid arthritis and COVID-19? Mol Cell Biochem 2021; 476:4351-4362. [PMID: 34453644 PMCID: PMC8401347 DOI: 10.1007/s11010-021-04245-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 08/16/2021] [Indexed: 12/24/2022]
Abstract
Vitamin D is an immunomodulatory hormone with an established role in calcium and phosphate metabolism and skeletal mineralization. Evidence showing its immunological benefits by regulating essential components of the innate and adaptive immune system is prevalent. Vitamin D deficiency is reported worldwide and is thereby found to be associated with various immune-related diseases. Rheumatoid Arthritis and COVID-19 are two such diseases, sharing a similar hyperinflammatory response. Various studies have found an association of lower Vitamin D levels to be associated with both these diseases. However, contrasting data is also reported. We review here the available scientific data on risk factor association and supplementation benefits of Vitamin D in Rheumatoid Arthritis and COVID-19, intending to critically evaluate the literature.
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Affiliation(s)
- Sneha Verma
- Department of Research, Sir Ganga Ram Hospital, New Delhi, India
| | - Ved Chaturvedi
- Department of Rheumatology & Clinical Immunology, Sir Ganga Ram Hospital, New Delhi, India
| | - N K Ganguly
- Department of Research, Sir Ganga Ram Hospital, New Delhi, India
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Cromer SJ, Yu EW. Challenges and Opportunities for Osteoporosis Care During the COVID-19 Pandemic. J Clin Endocrinol Metab 2021; 106:e4795-e4808. [PMID: 34343287 PMCID: PMC8385842 DOI: 10.1210/clinem/dgab570] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Indexed: 12/21/2022]
Abstract
PURPOSE The coronavirus disease 2019 (COVID-19) has both directly and indirectly affected osteoporosis diagnosis and treatment throughout the world. METHODS This mini-review summarizes the available evidence regarding the effects of COVID-19, its treatment, and the consequences of the pandemic itself on bone health. Additionally, we review evidence and expert recommendations regarding putative effects of osteoporosis medications on COVID-19 outcomes and vaccine efficacy and summarize recommendations for continuation of osteoporosis treatment during the pandemic. RESULTS The use of standard screening procedures to assess for osteoporosis and fracture risk declined dramatically early in the pandemic, while rates of fragility fractures were largely unchanged. COVID-19, its treatments, and public health measures to prevent viral spread are each likely to negatively affect bone health. Osteoporosis treatments are not known to increase risk of adverse events from COVID-19, and preclinical data suggest possible beneficial effects of some therapies. Vitamin D deficiency is clearly associated with adverse outcomes from COVID-19, but it remains unclear whether vitamin D supplementation may improve outcomes. Osteoporosis treatment should be continued whenever possible, and recommendations for substituting therapies, if required, are available. CONCLUSION The COVID-19 pandemic has decreased screening and disrupted treatment for osteoporosis. Osteoporosis medications are safe and effective during the pandemic and should be continued whenever possible. Further studies are needed to fully understand the impact of the COVID-19 pandemic on long-term bone health.
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Affiliation(s)
- Sara J Cromer
- Division of Endocrinology, Diabetes, and Metabolism; Massachusetts General Hospital; Boston, MA
- Harvard Medical School;Boston, MA
| | - Elaine W Yu
- Division of Endocrinology, Diabetes, and Metabolism; Massachusetts General Hospital; Boston, MA
- Harvard Medical School;Boston, MA
- Corresponding Author: Elaine W. Yu, MD, MGH Endocrine Unit, 50 Blossom Street, Thier 1051, Boston, MA 02114,
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Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1. Nutrients 2021; 13:nu13114047. [PMID: 34836309 PMCID: PMC8618389 DOI: 10.3390/nu13114047] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 11/05/2021] [Accepted: 11/11/2021] [Indexed: 02/07/2023] Open
Abstract
Background: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. Methods: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. Results: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. Conclusions: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.
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di Filippo L, Allora A, Locatelli M, Rovere Querini P, Frara S, Banfi G, Giustina A. Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response. Endocrine 2021; 74:219-225. [PMID: 34586582 PMCID: PMC8480127 DOI: 10.1007/s12020-021-02882-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 09/15/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND Hypocalcemia has been identified as a major distinctive feature of COVID-19, predicting poor clinical outcomes. Among the mechanisms underlying this biochemical finding, high prevalence of vitamin D (VD) deficiency in COVID-19 patients reported so far in several studies was advocated. However, robust data in favor of this hypothesis are still lacking. Therefore, aim of our study was to investigate the role of hypovitaminosis D and parathyroid hormone (PTH) levels in the development of hypocalcemia in COVID-19 patients. METHODS Patients admitted to IRCCS Ospedale San Raffaele for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing calcium and VD metabolism. Serum levels of total calcium (tCa), ionized calcium (Ca2+), 25-OH-VD, and PTH were evaluated at admission. We defined VD deficiency as VD below 20 ng/mL, hypocalcemia as tCa below 2.2 mmol/L or as Ca2+ below 1.18 mmol/L, and hyperparathyroidism as PTH above 65 pg/mL. RESULTS A total of 78 patients were included in the study. Median tCa and Ca2+ levels were 2.15 and 1.15 mmol/L, respectively. Total and ionized hypocalcemia were observed in 53 (67.9%) and 55 (70.5%) patients, respectively. VD deficiency was found in 67.9% of patients, but secondary hyperparathyroidism was detected in 20.5% of them, only. tCa levels were significantly lower in patients with VD deficiency and regression analyses showed a positive correlation between VD and tCa. CONCLUSIONS In conclusion, we confirmed a high prevalence of hypocalcemia in COVID-19 patients and we showed for the first time that it occurred largely in the context of marked hypovitaminosis D not adequately compensated by secondary hyperparathyroidism.
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Affiliation(s)
- Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Agnese Allora
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Massimo Locatelli
- Laboratory Medicine Service, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Patrizia Rovere Querini
- Division of Immunology, Transplantation and Infectious Diseases, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Frara
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Giuseppe Banfi
- IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry & Molecular Biology, Università Vita-Salute San Raffaele, Milan, Italy
| | - Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy.
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Ribeiro HG, Dantas-Komatsu RCS, Medeiros JFP, Carvalho MCDC, Soares VDL, Reis BZ, Luchessi AD, Silbiger VN. Previous vitamin D status and total cholesterol are associated with SARS-CoV-2 infection. Clin Chim Acta 2021; 522:8-13. [PMID: 34364853 PMCID: PMC8340549 DOI: 10.1016/j.cca.2021.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/20/2021] [Accepted: 08/03/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND The relationship of vitamin D status and other biochemical parameters with the risk of SARS-CoV-2 infection remains inconclusive, especially in regions with high solar incidence. Therefore, we aimed to associate the 25-hydroxyvitamin D (25(OH)D) concentrations and lipid profile prior to the SARS-CoV-2 tests in a population from a sunny region in Brazil (5 degrees S, 35 degrees W). METHODS This retrospective cohort study enrolled 1634 patients tested for SARS-CoV-2 of a private medical laboratory with 25(OH)D concentration and lipid profile measured ≥ 7 days before the date of the first SARS-CoV-2 RT-PCR test and were categorized according to 25(OH)D sufficiency (≥30 ng/mL) or insufficiency (<30 ng/mL). Multiple logistic regression analyses were performed to assess risk factors associated with positive tests for SARS-CoV-2. RESULTS Average serum 25(OH)D was 33.6 ng/mL. Vitamin D deficiency (<20 ng/mL) was only found in 2.6% of the participants. Multivariate analysis demonstrated that patients > 49 y with insufficient 25(OH)D (<30 ng/mL) presented increased odds to test positive for SARS-CoV-2 (OR: 2.02, 95 %CI: 1.15 to 3.55, P = 0.015). The same is observed among those with total cholesterol > 190 mg/dL (OR: 1.90, 95 %CI: 1.10 to 3.28, P = 0.020). CONCLUSIONS Previous insufficient 25(OH)D (<30 ng/mL) concentration and high total cholesterol were associated with SARS-CoV-2 infection among adults > 48 y in the study population. Further studies should be conducted to confirm whether measurement of 25(OH)D and lipid profile could be useful to identify patients who are more susceptible to COVID-19.
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Affiliation(s)
- Heriks Gomes Ribeiro
- Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | | | | | | | | | - Bruna Zavarize Reis
- Department of Nutrition, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil; Postgraduate Program in Nutrition, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
| | - André Ducati Luchessi
- Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, RN, Brazil; Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Vivian Nogueira Silbiger
- Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, RN, Brazil; Postgraduate Program in Nutrition, Center for Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil
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Bianconi V, Mannarino MR, Figorilli F, Cosentini E, Batori G, Marini E, Lombardini R, Gargaro M, Fallarino F, Scarponi AM, Sahebkar A, Pirro M. Prevalence of vitamin D deficiency and its prognostic impact on patients hospitalized with COVID-19. Nutrition 2021; 91-92:111408. [PMID: 34388589 PMCID: PMC8247197 DOI: 10.1016/j.nut.2021.111408] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/18/2021] [Accepted: 06/22/2021] [Indexed: 01/14/2023]
Abstract
OBJECTIVES Although hypovitaminosis D appears to be highly prevalent in patients with coronavirus disease 2019 (COVID-19), its impact on their prognosis remains unclear. METHODS In this study, serum 25-hydroxyvitamin D (Vit-D) level was measured in 200 patients hospitalized with COVID-19. The association between Vit-D and the composite endpoint of intensive care unit (ICU) admission/in-hospital death was explored using univariable and multivariable analyses. Also, serum Vit-D level in patients with COVID-19 was compared with that in age- and sex-balanced COVID-19-negative controls (i.e., 50 inpatients with sepsis). RESULTS Serum Vit-D level was comparable between patients with COVID-19 and COVID-19-negative inpatients with sepsis (P = 0.397). No significant differences were found in serum Vit-D level according to COVID-19 severity at the time of hospital admission (P = 0.299). Incidence rates of the composite endpoint of ICU admission/in-hospital death did not differ significantly between patients with either Vit-D deficiency (i.e., Vit-D <20 ng/mL) or severe Vit-D deficiency (i.e., Vit-D <12 ng/mL) and those without (31% vs 35% with P = 0.649, and 34% vs 30% with P = 0.593, respectively). Vit-D level and status (i.e., Vit-D deficiency and severe Vit-D deficiency) were not prospectively associated with the risk of the composite endpoint of ICU admission/in-hospital death (P > 0.05 for all Cox regression models). CONCLUSIONS Regardless of the potential usefulness of Vit-D measurement to guide appropriate supplementation, Vit-D does not appear to provide helpful information for the stratification of in-hospital prognosis in patients with COVID-19.
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Affiliation(s)
- Vanessa Bianconi
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Massimo R Mannarino
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
| | - Filippo Figorilli
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Elena Cosentini
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Giuseppe Batori
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Ettore Marini
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Rita Lombardini
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Marco Gargaro
- Unit of Pharmacology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Francesca Fallarino
- Unit of Pharmacology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Anna Maria Scarponi
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Matteo Pirro
- Unit of Internal Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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Crafa A, Cannarella R, Condorelli RA, Mongioì LM, Barbagallo F, Aversa A, La Vignera S, Calogero AE. Corrigendum to: Influence of 25‑hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis [EClinicalMedicine 37 (2021) 100,967]. EClinicalMedicine 2021; 41:101168. [PMID: 34693235 PMCID: PMC8527185 DOI: 10.1016/j.eclinm.2021.101168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
[This corrects the article DOI: 10.1016/j.eclinm.2021.100967.].
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Affiliation(s)
- Andrea Crafa
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Rossella Cannarella
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Rosita A. Condorelli
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Laura M. Mongioì
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Federica Barbagallo
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Antonio Aversa
- Department of Experimental and Clinical Medicine, University “Magna Græcia”, Catanzaro, Italy
| | - Sandro La Vignera
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Aldo E. Calogero
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
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50
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Borsche L, Glauner B, von Mendel J. COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients 2021; 13:3596. [PMID: 34684596 PMCID: PMC8541492 DOI: 10.3390/nu13103596] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/09/2021] [Accepted: 10/11/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic. METHODS Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates versus D3 blood levels. Mortality rates from clinical studies were corrected for age, sex, and diabetes. Data were analyzed using correlation and linear regression. RESULTS One population study and seven clinical studies were identified, which reported D3 blood levels preinfection or on the day of hospital admission. The two independent datasets showed a negative Pearson correlation of D3 levels and mortality risk (r(17) = -0.4154, p = 0.0770/r(13) = -0.4886, p = 0.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/mL (17.4-26.8), and a significant Pearson correlation was observed (r(32) = -0.3989, p = 0.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/mL D3. CONCLUSIONS The datasets provide strong evidence that low D3 is a predictor rather than just a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/mL to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.
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Affiliation(s)
| | | | - Julian von Mendel
- Artificial Intelligence, IU International University of Applied Sciences, D-99084 Erfurt, Germany;
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