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Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.
Song, HJJMD, Chia, AZQ, Tan, BKJ, Teo, CB, Lim, V, Chua, HR, Samuel, M, Kee, A
Journal of endocrinological investigation. 2023;46(2):235-259
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Salt imbalances in individuals with Covid-19 are highly prevalent, however it is not fully understood if they determine whether a patient has a good or bad prognosis. This systematic review and meta-analysis of 28 observational studies aimed to determine the associations and prognostic value of different salt imbalances in individuals with Covid-19. The results showed that out of several salt imbalances analysed, high and low sodium levels and low calcium levels could predict poor outcomes in those with Covid-19. High sodium levels were particularly indicative, but this was not due to the relationship between high sodium and inflammation in the body and causal reasons remained undiscovered. It was concluded that sodium imbalances and low calcium levels were associated with poor clinical outcomes in individuals with Covid-19. This study could be used by healthcare professionals to understand that correcting these imbalances may be of benefit to individuals with Covid-19.
Abstract
PURPOSE Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.
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Impact of the COVID-19 pandemic on the glycemic control, eating habits, and body compositions of people with diabetes mellitus: A retrospective longitudinal observational study.
Sawada, M, Ohkuma, K, Aihara, M, Doi, S, Sekine, R, Kaneko, T, Iimuro, S, Ichi, I, Usami, S, Ohe, K, et al
Journal of diabetes investigation. 2023;14(2):321-328
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Several systematic reviews and meta-analyses conducted to evaluate the prognosis of coronavirus disease-2019 (COVID-19) in people with diabetes mellitus have reported an approximately two- to three-fold higher risk of mortality from COVID-19 in people with diabetes mellitus compared with those without diabetes mellitus. The aim of this study was to investigate the impact of the COVID-19 pandemic and the state of emergency on the glycaemic control, eating habits, and body composition of people with diabetes mellitus. This study is a retrospective, longitudinal observational study in outpatients with diabetes mellitus. A total of 408 participants were included in this study, including 239 men (58.6%) and 169 women (41.4%). People with type 2 diabetes mellitus were predominant in this study (96.8%). Results show that: - there was a significant increase of the haemoglobin A1c level in people with diabetes mellitus during the COVID-19 pandemic. - there was an increase in the changes in body weight and percent fat (increased) and skeletal muscle masses (decreased). Authors conclude that the COVID-19 pandemic caused a negative impact on the glycaemic control and body composition in people with diabetes mellitus. Furthermore, the increase of body weight and fat mass and the decrease of the skeletal muscle mass during the pandemic were associated with poor glycaemic control, independent of the age and sex, in people with diabetes mellitus.
Abstract
AIMS/INTRODUCTION To evaluate the impact of the COVID-19 pandemic on the glycemic control, eating habits, and body composition of people with diabetes mellitus; to identify the determinants of worsening glycemic control in people with diabetes mellitus. MATERIALS AND METHODS This retrospective, longitudinal observational study was performed in outpatients with diabetes mellitus who visited our hospital between April 2019 and March 2020 (pre-COVID-19 period) and continued for follow up from April 2020 to March 2021 (COVID-19 period). We compared the glycemic control, nutritional intakes, and body composition of people with diabetes mellitus between the two periods. The changes in the HbA1c values (ΔHbA1c) and other study variables were compared between the two periods. Logistic regression analysis was performed to identify the factors associated with the increase of HbA1c levels. RESULTS A significant increase of HbA1c was observed during the COVID-19 period. The percent fat mass (FM) also increased, while the percent skeletal muscle mass (SMM) decreased during the COVID-19 period. After adjustments for age and sex, the ΔBMI (OR:2.33), ΔFM (OR:1.45), and ΔSMM (OR:0.51) were identified as being associated with elevated levels of HbA1c. CONCLUSIONS The COVID-19 pandemic had a negative impact on the glycemic control and body composition of people with diabetes mellitus. The increased body weight and FM and decreased SMM observed during the pandemic were associated with poor glycemic control in people with diabetes mellitus.
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REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.
Bishop, CW, Ashfaq, A, Melnick, JZ, Vazquez-Escarpanter, E, Fialkow, JA, Strugnell, SA, Choe, J, Kalantar-Zadeh, K, Federman, NC, Ng, D, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2023;107:111899
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Literature shows that vitamin D repletion may reduce the risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigate severity of coronavirus disease (COVID-19), and accelerate recovery. Sufficient serum level of 25-hydroxyvitamin D (25D) is postulated to potentiate COVID-19 vaccine effectiveness, boost innate and control adaptive immunity, and reduce post-infection cytokine storm and lung injury. The aim of this study was to evaluate the safety and efficacy of extended-release calcifediol capsules to treat symptomatic patients infected with SARS-CoV-2. This study is a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial titled REsCue. One hundred seventy-one symptomatic COVID-19 outpatients participants were enrolled. Patients were randomised (1:1) to 4 weeks of treatment with extended-release calcifediol (30 mcg/capsule) or matching placebo and a 2-week follow-up. Results show that extended-release calcifediol treatment was effective in increasing serum 25D levels to ≥50 ng/mL, which may have yielded significantly shorter resolution times for three aggregated respiratory symptoms (trouble breathing, chest congestion, and dry or hacking cough) commonly observed in patients with mild to moderate COVID-19. Authors conclude that the positive findings from this study warrant confirmation in additional larger studies.
Abstract
OBJECTIVES This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19. METHODS COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.
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Efficacy and Safety of the Adjuvant Use of Probiotic Bacillus clausii Strains in Pediatric Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study.
Vázquez-Frias, R, Consuelo-Sánchez, A, Acosta-Rodríguez-Bueno, CP, Blanco-Montero, A, Robles, DC, Cohen, V, Márquez, D, Perez, M
Paediatric drugs. 2023;25(1):115-126
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Irritable bowel syndrome (IBS) is considered both a health and a socioeconomic burden. Curative treatment for IBS is currently not available and current management strategies vary. Gut microbiota dysbiosis is increasingly considered as a vital factor in the etiopathogenetic of IBS; thus, gut microbiota are a potential therapeutic target. The aim of this study was to investigate the efficacy and safety of Bacillus clausii plus conventional treatment, compared with placebo plus conventional treatment, in children with IBS in Mexico. This study is a phase III, multicentre, randomised, placebo-controlled, double-blind, parallel clinical trial. Patients (n=259) were centrally randomised 1:1 to treatment with either B. clausii or placebo. Results show that IBS symptom relief in children was very high in both groups (B. clausii and placebo). In fact, there weren’t any significant differences between groups for proportion of patients with clinical improvements at Week 8 or any of the key secondary endpoints. Furthermore, the adverse event profile was similar between groups. Authors conclude that their study was not able to demonstrate the efficacy of B. clausii as an adjuvant to conventional treatment of patients with IBS.
Abstract
OBJECTIVES Current irritable bowel syndrome (IBS) treatments have limited efficacy and probiotics like Bacillus clausii (B. clausii) were found to be effective in the management of several gastrointestinal disorders. This phase III trial assessed the efficacy and safety of adding B. clausii (four strains: O/C, N/R, SIN, T), versus placebo, to conventional treatment of pediatric IBS in Mexico. METHODS Patients aged 6-17 years 11 months with IBS (Rome IV) for at least 2 months were randomized to receive either B. clausii (oral suspension, total dose 4 billion spores/day) or placebo once daily for 8 weeks. All patients also received conventional treatment. The primary endpoint was the difference in the proportion of patients with clinical improvements at Week 8 (Global Assessment Questions [GAQ]). Secondary endpoints included responders by Subject's Global Assessment of Relief for Children with IBS (SGARC); number/consistency of stools; abdominal distention/bloating; abdominal pain/intensity; and IBS behavior. RESULTS 73.6% (95% confidence interval [CI] 67.3-80.0; B. clausii n = 129) and 78.5% (95% CI 72.5-84.4; placebo n = 130) of patients had symptom improvement (p = 0.8182). For Week 8 SGARC, 19.2% (B. clausii) and 20.9% (placebo) reported complete symptom relief. Stool evaluations, bloating, abdominal pain/intensity, and IBS behavior were similar between groups. Both treatments were well tolerated. CONCLUSION No significant differences in efficacy between B. clausii and placebo were demonstrated in addition to conventional treatment. The sample size calculation was based on an expected placebo/conventional treatment response of 30-40%. However, the actual treatment response observed was 80% and, thus, a study with larger population would be warranted. In addition, this study was conducted during the COVID-19 pandemic, when such controlled social conditions may have resulted in better diet, greater family stability, less psychological stress, and lower risk of infections exacerbating IBS, thereby improving symptoms in both groups. EUDRACT NUMBER 2018-004519-31.
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Hypnotherapy, Intermittent Fasting, and Exercise Group Programs in Atopic Dermatitis: A Randomized Controlled Explorative Clinical Trial During the COVID-19 Pandemic.
Rotter, G, Teut, M, Schleicher, R, Dell'Oro, M, Ortiz, M, Binting, S, Tissen-Diabaté, T, Roll, S, Michalsen, A, Staab, D, et al
Journal of integrative and complementary medicine. 2023;29(2):99-110
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Relaxation techniques, diet, and exercise can diminish atopic dermatitis (AD) symptoms. Patients with AD worry about the side-effects of the medical treatment for AD thus the majority try to engage in potentially healthy lifestyle behaviours. The aim of this study was to exploratively investigate the effectiveness of hypnotherapy, fasting with diet adjustments, and exercise in adult AD patients This study is a four-armed, randomised controlled, single-centre, open explorative clinical trial. Patients were randomly assigned to one of the four groups: i) hypnotherapy group program (HTP), ii) intermittent fasting with diet adjustment group program (IFDP), iii) an exercise group program or the control group. The study was strongly impacted by confinements and research restrictions due to the coronavirus 2019 pandemic. However, results showed potential beneficial changes to baseline in perceived itching intensity, disease severity, and disease-specific quality of life for HTP and IFDP. Authors conclude that further high-quality clinical trials should be performed investigating the effectiveness and safety of hypnotherapy, fasting with diet adjustments, as well as exercise.
Abstract
Background: Patients with atopic dermatitis (AD) frequently use healthy lifestyle behaviors, although their benefits are unclear. This study's aim was to investigate the effectiveness of hypnotherapy, fasting with diet adjustments, and exercise in AD patients. Methods: In a four-armed randomized controlled monocenter open explorative clinical trial, adult patients with mild-to-moderate severe AD underwent, over 16 weeks, a five-session hypnotherapy group program (HTP), a five-session intermittent fasting with diet adjustment group program (IFDP), a five-session exercise group program (EP), or no study intervention (control) as add-on to topical corticosteroid use if required. Endpoints included subjectively perceived itching on a visual analogue scale (VAS, 0-100 mm); disease severity by SCORing Atopic Dermatitis (SCORAD); and adverse events (AEs). Endpoints were analyzed descriptively in the Full Analysis Set (FAS). Due to the coronavirus disease 2019 (COVID-19) pandemic, relevant changes to the study protocol included online in addition to "in-presence" group interventions, closing the study arm EP and premature trial termination before randomization of 120 intended patients. Results: During the COVID-19 pandemic, study recruitment was poor. The FAS included 20 patients (17 female) with 35.0 ± 12.1 (mean ± standard deviation [SD]) years of age. At baseline, mean ± SD for HTP (n = 6), IFDP (n = 4), EP (n = 1), and control (n = 9) were VAS itching 63.2 ± 18.0, 65.0 ± 13.9, 43.0 mm, 62.1 ± 17.3; SCORAD 43.0 ± 13.6, 47.0 ± 21.0, 60.3, 39.1 ± 15.6. After 16 weeks, endpoints were VAS itching 26.0 ± 16.4, 31.7 ± 9.9, 23.0 mm, 39.3 ± 27.0; SCORAD 24.1 ± 12.2, 29.1 ± 19.1, 49.1, 25.5 ± 14.4. No serious AEs related to the interventions were observed. Conclusion: Despite very small groups, study results indicated potential beneficial changes to baseline in perceived itching intensity, disease severity, and disease-specific quality of life for HTP and IFDP. Therefore, further clinical trials should be performed investigating the effectiveness and safety of all interventions. Clinical Trial Registration: January 31, 2020 German Clinical Trials Register (DRKS): DRKS00020557, Universal Trial Number (UTN): U1111-1247-1512.
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A Systematic Review of the Impact of the First Year of COVID-19 on Obesity Risk Factors: A Pandemic Fueling a Pandemic?
Daniels, NF, Burrin, C, Chan, T, Fusco, F
Current developments in nutrition. 2022;6(4):nzac011
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Coronavirus disease 2019 (COVID-19) is one of the most serious infectious disease outbreaks in recent history. Among the factors that can increase the risk of obesity, some seem to play a more prominent role than others such as depression, emotional eating, sedentary lifestyle and the socioeconomic status. The aim of this study was to explore the indirect effects of the first year of COVID-19 on obesity and its risk factors. This study is a systematic review of 87 studies with over 350,000 participants. Results show that: - overall, there was a general trend of weight gain during the pandemic. - there were differences in dietary changes, with some studies showing an improvement in diet. - some beneficial effects were observed in the dieting domain, such as higher consumption of home-cooked meals and healthy food (e.g., vegetables). However, there was an increasing trend in the overall food and alcohol consumption. - financial hardship and job loss were unavoidable consequences of the pandemic lockdown. However, although the impact of the countermeasures used to curb the COVID-19 pandemic was evident on obesity risk factors, none of the studies included in the research explored the direct impact of the risk factors on obesity itself. Authors conclude by pointing out the need for future research that aims at strengthening the link between stressful circumstances and a rise in risk factors for obesity and weight gain.
Abstract
Obesity is increasingly prevalent worldwide. Associated risk factors, including depression, socioeconomic stress, poor diet, and lack of physical activity, have all been impacted by the coronavirus disease 2019 (COVID-19) pandemic. This systematic review aims to explore the indirect effects of the first year of COVID-19 on obesity and its risk factors. A literature search of PubMed and EMBASE was performed from 1 January 2020 to 31 December 2020 to identify relevant studies pertaining to the first year of the COVID-19 pandemic (PROSPERO; CRD42020219433). All English-language studies on weight change and key obesity risk factors (psychosocial and socioeconomic health) during the COVID-19 pandemic were considered for inclusion. Of 805 full-text articles that were reviewed, 87 were included for analysis. The included studies observed increased food and alcohol consumption, increased sedentary time, worsening depressive symptoms, and increased financial stress. Overall, these results suggest that COVID-19 has exacerbated the current risk factors for obesity and is likely to worsen obesity rates in the near future. Future studies, and policy makers, will need to carefully consider their interdependency to develop effective interventions able to mitigate the obesity pandemic.
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Evidence for the Efficacy of a High Dose of Vitamin D on the Hyperinflammation State in Moderate-to-Severe COVID-19 Patients: A Randomized Clinical Trial.
Sarhan, N, Abou Warda, AE, Sarhan, RM, Boshra, MS, Mostafa-Hedeab, G, ALruwaili, BF, Ibrahim, HSG, Schaalan, MF, Fathy, S
Medicina (Kaunas, Lithuania). 2022;58(10)
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Vitamin D insufficiency is an example of the factors which may affect snowballed COVID-19 risk and mortality. The aim of this study was to determine whether the clinical results and prognoses of COVID-19 patients are enhanced by supplementing a high dose of vitamin D relative to the conventional low dose. This study is a randomised controlled trial of 116 patients. Participants were randomly assigned to one of the two groups i.e. 58 patients received treatment with low-dose vitamin D and 58 received treatment with high-dose vitamin D. Results show that the incidence of mechanical ventilation, intensive care unit hospitalisation, death, sepsis, and atrial fibrillation in the high-dosage vitamin D group was considerably reduced compared to the low-dosage vitamin D group. However, the need for high oxygen was significantly higher in the high-dose vitamin D group compared to the low-dose group. Additionally, there was a significant difference in the monitored parameters before and after treatment in favour of the high-dose vitamin D group, which were significantly lower in the high-dose vitamin D group compared to the low-dose group. Authors conclude that the sooner micronutrients are administered to outpatients, the better the outcome, especially before supportive or specific treatment is commenced.
Abstract
Background and Objectives: Vitamin D supplementation plays a key effect in lowering cytokine storms among COVID-19 patients by influencing the activity of the renin-angiotensin system and the production of the angiotensin-2 converting enzyme. The study was conducted to explore the effect of high-dose intramuscular vitamin D in hospitalized adults infected with moderate-to-severe SARS-CoV-2 in comparison with the standard of care in the COVID-19 protocol. Materials and Methods: Two groups of patients were compared in this prospective randomized controlled trial as the vitamin D was administered orally to group 1 (alfacalcidol 1 mcg/day) and intramuscularly to group 2 (cholecalciferol 200,000 IU). One hundred and sixteen participants were recruited in total, with fifty-eight patients in each group. Following the Egyptian Ministry of Health's policy for COVID-19 management, all patients received the same treatment for a minimum of five days. Results: A significant difference was recorded in the length of hospital stay (8.6 versus 6.8 days), need for high oxygen or non-invasive mechanical ventilator (67% versus 33%), need for a mechanical ventilator (25% versus 75%), clinical improvement (45% versus 55%), the occurrence of sepsis (35% versus 65%), and in the monitored laboratory parameters in favor of high-dose vitamin D. Moreover, clinical improvement was significantly associated with the need for low/high oxygen, an invasive/non-invasive mechanical ventilator (MV/NIMV), and diabetes, while mortality was associated with the need for MV, ICU admission, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and the occurrence of secondary infection. Conclusions: Our study showed that high-dose vitamin D was considered a promising treatment in the suppression of cytokine storms among COVID-19 patients and was associated with better clinical improvement and fewer adverse outcomes compared to low-dose vitamin D.
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Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.
De Niet, S, Trémège, M, Coffiner, M, Rousseau, AF, Calmes, D, Frix, AN, Gester, F, Delvaux, M, Dive, AF, Guglielmi, E, et al
Nutrients. 2022;14(15)
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Literature shows that having enough vitamin D can help prevent many diseases, such as heart disease, bone disease and cancer. Recent data also showed that vitamin D can reduce the risk of respiratory tract infections, and particularly, the risk of viral infections. The aim of this study was to assess whether the proposed dosing regimen of a daily dose of 25,000 international units (IU) vitamin D administered over 4 consecutive days, followed by a weekly dose of 25,000 IU, was adequate to rapidly increase the concentrations of calcifediol in patients hospitalized with COVID-19 and to explore its impact on hospital length and other clinical outcomes of the disease. This study is an interventional, randomized, parallel, two-treatment, two-arm, double-blind and placebo-controlled pilot study, carried out in one clinical site in Belgium. The patients (n=50) were randomized in the two different treatment groups (vitamin D (n=26) or placebo (n=24)). Patients participated in the study for a maximum of 9 weeks, including an up to 6-week treatment period and a maximum of 3-week follow-up period. Results show that the study’s regimen was adequate to rapidly raise the calcifediol level above 20 ng/mL and improve the clinical outcome of patients requiring hospitalization for COVID-19. In fact, administration of cholecalciferol significantly reduced the hospital length of stay, reduced the duration of supplemental oxygen and improved the clinical status assessed by the World Health Organisation scale. Authors conclude that further studies with a larger number of patients are needed in order to further confirm their study’s findings.
Abstract
Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D.
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Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis.
Dissanayake, HA, de Silva, NL, Sumanatilleke, M, de Silva, SDN, Gamage, KKK, Dematapitiya, C, Kuruppu, DC, Ranasinghe, P, Pathmanathan, S, Katulanda, P
The Journal of clinical endocrinology and metabolism. 2022;107(5):1484-1502
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Vitamin D is implicated in optimum function of the immune system. Its deficiency has been linked to susceptibility to respiratory infections. It is postulated that vitamin D deficiency/insufficiency is also associated with COVID-19. The aim of this study was to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment. This study is a systematic review and meta-analysis of seventy-six publications. Results show increased odds of developing COVID-19, progression to severe COVID-19 and death in people with vitamin D deficiency/insufficiency. In fact, people who developed COVID-19, severe COVID-19 and fatal disease had lower 25-hydroxy vitamin D concentration compared to people without COVID-19 or non-severe COVID-19 or non-fatal COVID-19 respectively. Authors conclude that Vitamin D deficiency/insufficiency may increase the risk of developing COVID-19 infection and susceptibility to more severe disease.
Abstract
PURPOSE Vitamin D deficiency/insufficiency may increase the susceptibility to coronavirus disease 2019 (COVID-19). We aimed to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality, and role of vitamin D in its treatment. METHODS We searched CINAHL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science up to May 30, 2021, for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease, and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. Risk of bias was assessed using Newcastle-Ottawa scale for observational studies and AUB-KQ1 Cochrane tool for RCTs. Study-level data were analyzed using RevMan 5.3 and R (v4.1.0). Heterogeneity was determined by I2 and sources were explored through prespecified sensitivity analyses, subgroup analyses, and meta-regressions. RESULTS Of 1877 search results, 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis (n = 1 976 099). Vitamin D deficiency/insufficiency increased the odds of developing COVID-19 (odds ratio [OR] 1.46; 95% CI, 1.28-1.65; P < 0.0001; I2 = 92%), severe disease (OR 1.90; 95% CI, 1.52-2.38; P < 0.0001; I2 = 81%), and death (OR 2.07; 95% CI, 1.28-3.35; P = 0.003; I2 = 73%). The 25-hydroxy vitamin D concentrations were lower in individuals with COVID-19 compared with controls (mean difference [MD] -3.85 ng/mL; 95% CI, -5.44 to -2.26; P ≤ 0.0001), in patients with severe COVID-19 compared with controls with nonsevere COVID-19 (MD -4.84 ng/mL; 95% CI, -7.32 to -2.35; P = 0.0001) and in nonsurvivors compared with survivors (MD -4.80 ng/mL; 95% CI, -7.89 to -1.71; P = 0.002). The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses. Discrepancies in timing of vitamin D testing, definitions of severe COVID-19, and vitamin D deficiency/insufficiency partly explained the heterogeneity. Four RCTs were widely heterogeneous precluding meta-analysis. CONCLUSION Multiple observational studies involving nearly 2 million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.
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Effects of Vitamin D Serum Level on Morbidity and Mortality in Patients with COVID-19: A Systematic Review and Meta-Analysis.
Hu, Y, Kung, J, Cave, A, Banh, HL
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 2022;25:84-92
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COVID-19 caused by SARS-CoV-2 infection is associated with severe acute respiratory syndrome resulting from the excessive inflammatory response at 5-7 days. It has been shown that low Vitamin D serum concentration is associated with increased pneumonia and viral respiratory infections. The aim of this study was to determine the clinical effects of Vitamin D serum concentration in COVID-19 patients. This study is a systematic review and meta-analysis of 20 studies. Results show that Vitamin D serum concentration was not statistically associated with mortality and ICU admission, ventilator support requirement, and length of hospital stay. Authors conclude that additional randomized controlled trials are required to provide a specific supplemental vitamin dose and Vitamin D serum concentration.
Abstract
PURPOSE It has been shown that low Vitamin D serum concentration is associated with increased pneumonia and viral respiratory infections. Vitamin D is readily available, inexpensive, and easy to administer to subjects infected with COVID-19. If effective in reducing the severity of COVID-19, it could be an important and feasible therapeutic intervention. METHODS We performed a systematic review and meta-analysis of the literature to determine the effects of Vitamin D serum concentration on mortality and morbidity in COVID-19 patients. The primary objectives were to determine if Vitamin D serum concentration decrease mortality, ICU admissions, ventilator support, and length of hospital stay in COVID-19 patients. RESULTS A total of 3572 publications were identified. Ultimately, 20 studies are included. A total of 12,806 patients aged between 42 to 81 years old were analyzed. The pooled estimated RR for mortality, ICU admission, ventilator support and length of hospital stay were 1.49 (95% CI: 1.34, 1.65), 0.87 (95% CI: 0.67, 1.14), 1.29 (95% CI: 0.79, 1.84), and 0.84 (95% CI -0.45, 2.13). CONCLUSION There is no statistical difference in mortality, ICU admission rate, ventilator support requirement, and length of hospital stay in COVID-19 patients with low and high Vitamin D serum concentration.