Evaluation of 34 Cytokines and Vitamin D Status Reveal A Sexually-Dimorphic Active Immune Response to SARS-CoV-2.

Background: Several observational studies have inconsistently demonstrated that vitamin D deficiency is a risk factor for coronavirus disease-19 (COVID-19) infection and severity. Discrepancies in results may partially be explained by the individuals' immune profiles, which are modulated, in varying degrees, by vitamin D status and sex hormones. Methods: In this study we evaluated the differences and associations of serum levels of 25(OH)D with 34 cytokines in 220 adults (82 controls (41 males; 41 females) and 138 SARS-CoV-2 patients (79 males and 59 females)) with and without COVID-19. Results: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 group than in the controls. Serum IP-10, MCP-1, CRP, IFNγ, IL-10, IL-13, IL-17α, IL-23, and IL-6 were significantly higher in COVID-19 patients compared to controls. Serum levels of VEGF, IFNγ, IL-13, and IL-5 were significantly higher in male patients than in females. 25(OH)D was significantly correlated with EFG (R = 0.39, p < 0.05) and IL-15 (R = 0.39, p < 0.05) in male patients, while it was inversely correlated with CRP (R = −0.51, p < 0.05) in female patients. Conclusions: Altered levels of cytokines, chemokines, and vitamin D were observed in SARS-CoV-2 adult patients. These expressions were sexually dimorphic and thus highlight the sex-specific nature of the active immune response following SARS-CoV-2 infection.

Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.

OBJECTIVE: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study.

OBJECTIVES: Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities. METHODS: In this multi-center, case-control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations. RESULTS: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity. CONCLUSIONS: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Effects of home quarantine during COVID-19 lockdown on physical activity and dietary habits of adults in Saudi Arabia.

Public health endorsements during the present COVID-19 pandemic has led the governments of largely affected countries to imply policies that restrict social mobility to slow COVID-19 spread. The study aimed to explore the effects of COVID-19 home quarantine on lifestyle and health behavior of Saudi residents. An online survey in Saudi Arabia was launched from May 11 to June 6, 2020. The survey was designed by multidisciplinary scientists and academics uploaded and shared through the Google platform in Arabic and English languages. Questions presented related to responses "before" and "during" COVID-19 home quarantine. A total of 1965 respondents participated and were included in the analysis [921 (47.0%) males and 1044 (53.0%) females]. Non-Saudis were more likely to increase their physical activity during quarantine [odds ratio (95% confidence interval 1.41 (1.11-1.79); p < 0.005]. Prevalence of participants walking daily for more than 4 times per week significantly decreased during pandemic (before vs during, 30.5% vs 29.1%) which was in parallel to the significant increase in the prevalence of participants who did not perform daily walking during the quarantine (21% vs 22.9%; p < 0.001). The prevalence of participants who often consume snacks between meals increased during quarantine (27.4% vs 29.4%, p < 0.001), while the prevalence of participants who never consumed fresh fruits and vegetables significantly increased during home quarantine (2.4% vs 3.7%; p = 0.019). The lockdown imposed in Saudi Arabia modestly but significantly impacted physical activity and dietary behaviors of several citizens and residents in an unhealthy way. Interventions to alleviate these acute adverse lifestyle behaviors during pandemic should be formulated.

Early-Pregnancy Metabolic Syndrome and Subsequent Incidence in Gestational Diabetes Mellitus in Arab Women.

Introduction: This study aimed to investigate the association between components of metabolic syndrome (MetS) at first trimester and development of Gestational diabetes mellitus (GDM) in 498 Saudi pregnant women. Materials and Methods: Biochemical and anthropometric parameters were determined at the first trimester and MetS components were defined. Participants were screened for GDM at follow up according to International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. The main outcome measures were development of GDM and GDM risk vs. MetS components at first trimester. Results: One hundred twenty three (24.7%) were diagnosed with GDM according to IADPSG criteria. GDM risk was significantly higher for participants with hypertriglyceridemia at 1st trimester even after adjusting for age, BMI and parity (OR: 1.82; CI: 1.1-3.7, p = 0.04). Furthermore, the odds of hyperglycemia at 1st trimester was significantly higher in GDM than in non-GDM participants even after adjustments (OR: 2.13, 95% CI: 1.1 to 4.3, p = 0.038). The receiver operating characteristic (ROC) for predicting GDM revealed an area under the curve (AUC) of 0.69 (95% CI: 0.64 to 0.74, p < 0.001) and 0.71 (95% CI: 0.65 to 0.77, p < 0.001) for first-trimester hyperglycemia and hypertriglyceridemia respectively. Conclusions: The incidence of GDM in Saudi pregnant women was strongly associated with hyperglycemia and hypertriglyceridemia at first trimester. These findings are of clinical importance, as an assessment of MetS in early pregnancy can identify women at higher risk of developing GDM.

Vitamin D Deficiency Prevalence and Predictors in Early Pregnancy among Arab Women.

Data regarding the prevalence and predictors of vitamin D deficiency during early pregnancy are limited. This study aims to fill this gap. A total of 578 Saudi women in their 1st trimester of pregnancy were recruited between January 2014 and December 2015 from three tertiary care antenatal clinics in Riyadh, Saudi Arabia. Information collected includes socio-economic, anthropometric, and biochemical data, including serum vitamin D (25(OH)D) levels, intake of calcium and vitamin D, physical activity, and sun exposure indices. Pregnant women with 25(OH)D levels <50 nmol/L were considered vitamin D deficient. The majority of participants (n = 468 (81%)) were vitamin D deficient. High levels of indoor activity, whole body clothing, multiparity, total cholesterol/HDL ratio(>3.5), low HDL-cholesterol, and living in West Riyadh were significant independent predictors for vitamin D deficiency, with odds ratios (ORs) (95% confidence interval) of 25.4 (5.5–117.3), 17.8 (2.3–138.5), 4.0 (1.7–9.5), 3.3 (1.4–7.9), 2.8 (1.2–6.4), and 2.0 (1.1–3.5), respectively. Factors like increased physical activity, sun exposure at noon, sunrise or sunset, high educational status, and residence in North Riyadh were protective against vitamin D deficiency with ORs 0.2 (0.1–0.5); 0.2 (0.1–0.6); 0.3 (0.1–0.9); and 0.4 (0.2–0.8), respectively. All ORs were adjusted for age, BMI, sun exposure, parity, summer season, vitamin D intake, multivitamin intake, physical activity, education, employment, living in the north, and coverage with clothing. In conclusion, the prevalence of vitamin D deficiency among Saudi women during early pregnancy was high (81%). Timely detection and appropriate supplementation with adequate amounts of vitamin D should reduce the risks of vitamin D deficiency and its complications during pregnancy.

Lower vitamin D levels in Saudi pregnant women are associated with higher risk of developing GDM.

BACKGROUND: Gestational diabetes mellitus (GDM) has serious consequences such as increased risks of preeclampsia, macrosomia and cesarean delivery. Even though the mechanistic basis of GDM has not been completely understood, several risk factors have been identified and one of these is vitamin D. However, the link between vitamin D deficiency and development of GDM is yet to be proven with certainty. METHODS: This study aimed to investigate the link between the incidence of GDM and serum vitamin D level in pregnant women of Saudi Arabia. 515 Saudi women (ages 18-46) in their 24-28th week of pregnancy, visiting various hospitals of Riyadh, participated in this study. Serum vitamin D and various biochemical and anthropometric parameters were determined in the first trimester and the recruits were screened for GDM by OGTT according to IADPSG criteria in their 2nd trimester. The association between vitamin D deficiency and development of GDM was calculated based on odds ratio of the incidence of GDM among vitamin D deficient and normal women. RESULTS: In this study cohort of 515 pregnant women, in the first trimester vitamin D deficiency (< 50 nmol/l) was detected in 425 (82.5%). On their 2nd visit (2nd trimester), 116 (27.7%) were diagnosed with GDM out of 419 with OGTT, according to IADPSG criteria. GDM risk was significantly higher among vitamin D deficient than non-deficient women (Odds Ratio: 2.87; Confidence Interval: 1.32-6.25; P = 0.008) even after adjusting for season, sun exposure and vitamin D intake (OR: 2.9; CI: 1.07-7.89). Of the various anthropometric and biochemical parameters, the GDM women differed significantly from non-GDM women with respect to serum levels of triglycerides (in mmol/l) (1.3 ± 0.6; 1.5 ± 0.6, p = 0.018) and fasting glucose (in mmol/l) [4.7 (4.3-5.2); 5.1 (4.6-5.6), p < 0.01]. Also, fasting glucose level in the 2nd trimester correlated inversely to serum vitamin D level determined during the 1st trimester (r = - 0.121; p = 0.014). CONCLUSIONS: Results of our study reveal a significantly higher risk of development of GDM among pregnant women having deficient vitamin D status.

Extremely High Prevalence of Maternal and Neonatal Vitamin D Deficiency in the Arab Population.

BACKGROUND: Vitamin D deficiency is a global public health problem. The published literature on vitamin D deficiency is limited among Arab pregnant women and its association with different metabolic markers. OBJECTIVE: To determine the prevalence of vitamin D deficiency in Arab pregnant women and neonates and its association with various biomarker profiles. METHODS: This is a multicenter study taken from a large prospective project in Riyadh, the capital city of Saudi Arabia. Maternal biochemical levels were measured routinely. Maternal and neonatal 25(OH)D levels were assessed using a chemiluminescence immunoassay. A total of 1,097 pregnant women >16 years old with gestational ages <24 weeks were recruited from different tertiary hospitals in Riyadh between February 2011 and June 2012. RESULTS: Almost 85% of pregnant subjects had 25(OH)D level <50 nmol/L. Vitamin D deficiency among neonates was 88%. Maternal 25(OH)D was significantly associated with neonatal 25(OH)D (r = 0.54, p < 0.01), as well as serum calcium (r = 0.16, p = 0.02) and phosphate levels (r = 0.17, p = 0.02), and had an inverse correlation with parathyroid hormone (r = -0.22, p = 0.001). CONCLUSION: Maternal and neonatal vitamin D deficiency is alarmingly high in Arabs and significantly associated with each another. Universal screening for serum 25(OH)D may be appropriate for Arab mothers and vitamin D supplementation mandatory until term. The study puts a spotlight on vitamin D deficiency with the hope that health professionals will address it adequately to prevent the known long-term consequences for metabolism and bone health of both mothers and their children.

Vitamin D deficiency and dyslipidemia in early pregnancy.

BACKGROUND: Vitamin D deficiency is a common nutritional issue and dietary supplementation in the general population, including pregnant women, is generally advised. Appropriately high levels of vitamin D are expected to play a role in containing the glycemic and atherogenic profiles observed in pregnancy. However, the relation between vitamin D status and the lipid metabolic profile in Saudi women, who are known to suffer from chronic vitamin D deficiency and high incidence of obesity and type II DM, during the course of pregnancy is not known. METHODS: In this study, we analyzed the relation between serum vitamin D level and various serum metabolic markers among Saudi women (n = 515) in their first trimester of pregnancy (11.2 ± 3.4 weeks). Coefficients of Pearson correlation and Spearman rank correlation were calculated for Gaussian and non-Gaussian variables, respectively. Serum vitamin D status was defined as (in nmol/L): deficient (<25), insufficient (25-50); sufficient (50-75) and desirable (>75). RESULTS: Results indicated that vitamin D status was sufficient in only 3.5% of the study participants and insufficient and deficient in 26.2% and 68.0% of participants, respectively. Serum vitamin D values in the overall study population correlated positively with serum levels of total cholesterol (R = 0.172; p < 0.01), triglycerides (R = 0.184; p < 0.01) and corrected calcium (R = 0.141; p < 0.05). In the subgroup of vitamin D deficient subjects (n = 350), log serum vitamin D values correlated with serum triglycerides (R = 0.23; p = 0.002) and cholesterol (R = 0.26; p = 0.001). CONCLUSIONS: The positive correlations between serum vitamin D and the atherogenic factors such as total cholesterol and triglycerides indicate a pro-atherogenic metabolic status in vitamin D deficient expectant mothers. This may represent an adaptation to the high metabolic demands of pregnancy.