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Vitamin D, acute respiratory infections, and Covid-19: The curse of small-size randomised trials. A critical review with meta-analysis of randomised trials.
Autier, P, Doi, G, Mullie, P, Vankrunkelsven, P, D'Ecclesiis, O, Gandini, S
PloS one. 2025;(1):e0303316
Abstract
BACKGROUND Randomised trials conducted from 2006 to 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, larger randomised trials published in 2022 did not confirm the health benefits of VDS in COVID-19 patients. OBJECTIVE To examine through a systematic review with meta-analysis the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and of randomised trials on VDS for the prevention of ARI. METHOD A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al. 2021. Groups were formed including trials with total numbers of patients below or above the median size of all trials. The associations between VDS vs no VDS, and admission to ICU were evaluated using random-effects models from which summary odds ratios (SOR) and 95% confidence intervals (CI) were obtained. Meta-analyses were done for all trials and for each group of trials, which allowed testing a possible effect modification of trial size. Publication bias was assessed using the Louis-Furuya-Kanaruori (LFK) index (no bias if index between -1 and +1) and the trim and fill method. RESULTS Nine trials on VDS for preventing admission to ICU were identified, including 50 to 548 patients. The summary odds ratio (SOR) was 0.61 (95% CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (interaction p = 0.04). The LFK index was -3.79, and after trim and fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention included 25 to 16,000 patients. The SOR was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (interaction p = 0.0001). The LFK index was -3.11, and after trim and fill, the SOR was 0.96 (0.88-1.05). CONCLUSION Strong publication bias affected small randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.
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Incidence and Association of Uveitis with COVID-19 Vaccination: A Systematic Review and Meta-Analysis.
Padhi, BK, Gupta, PC, Al Kaabi, NA, Al-Subaie, MF, Alrasheed, HA, Sulaiman, T, Rabaan, AA, Khatib, MN, Gaidhane, S, Zahiruddin, QS, et al
Ophthalmic epidemiology. 2025;(1):112-120
Abstract
PURPOSE In the wake of the COVID-19 pandemic, vaccines have been pivotal in curbing disease spread and severity. However, concerns over post-vaccination adverse events, including uveitis, an inflammatory ocular condition, have been noted. This systematic review and meta-analysis aimed to evaluate the incidence and association of uveitis following COVID-19 vaccination. METHODS A literature search was performed across several databases on October 21, 2023. Human studies examining the incidence of uveitis post-COVID-19 vaccination were included. The Newcastle-Ottawa Scale was used for quality appraisal of the included studies. Meta-analysis was performed to assess the overall incidence of uveitis and the relative risk of developing the condition post-vaccination. All statistical analyses were performed using R software version 4.3. RESULTS Six studies involving over 2 billion vaccine doses were included. The overall incidence of uveitis was 0.016% (95% CI: 0.010 to 0.026). No significant association was found between vaccination and the onset of uveitis (Relative Risk: 1.45 (95% CI: 0.82 to 2.57, p = 0.12) from four studies. The evidence quality was rated very low due to the limited number of studies and imprecision. CONCLUSION This analysis indicates a low incidence of uveitis following COVID-19 vaccination and no significant association with the vaccine. The findings are constrained by the small number of studies and low certainty of evidence, underscoring the need for further research. Comprehensive and longitudinal studies are necessary to confirm these findings and reinforce public confidence in COVID-19 vaccination programs.
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Prevalence and prognostic role of thoracic lymphadenopathy in Covid-19.
, , ,
RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin. 2025;(2):163-171
Abstract
PURPOSE The prevalent coronavirus disease 2019 (COVID-19) pandemic has spread throughout the world and is considered a serious threat to global health. The prognostic role of thoracic lymphadenopathy in COVID-19 is unclear. The aim of the present meta-analysis was to analyze the prognostic role of thoracic lymphadenopathy for the prediction of 30-day mortality in patients with COVID-19. MATERIALS AND METHODS The MEDLINE library, Cochrane, and SCOPUS databases were screened for associations between CT-defined features and mortality in COVID-19 patients up to June 2021. In total, 21 studies were included in the present analysis. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The meta-analysis was performed using RevMan 5.3. Heterogeneity was calculated by means of the inconsistency index I2. DerSimonian and Laird random-effect models with inverse variance weights were performed without any further correction. RESULTS The included studies comprised 4621 patients. The prevalence of thoracic lymphadenopathy varied between 1 % and 73.4 %. The pooled prevalence was 16.7 %, 95 % CI = (15.6 %; 17.8 %). The hospital mortality was higher in patients with thoracic lymphadenopathy (34.7 %) than in patients without (20.0 %). The pooled odds ratio for the influence of thoracic lymphadenopathy on mortality was 2.13 (95 % CI = [1.80-2.52], p < 0.001). CONCLUSION The prevalence of thoracic lymphadenopathy in COVID-19 is 16.7 %. The presence of thoracic lymphadenopathy is associated with an approximately twofold increase in the risk for hospital mortality in COVID-19. KEY POINTS · The prevalence of lymphadenopathy in COVID-19 is 16.7 %.. · Patients with lymphadenopathy in COVID-19 have a higher risk of mortality during hospitalization.. · Lymphadenopathy nearly doubles mortality and plays an important prognostic role.. CITATION FORMAT · Bucher AM, Sieren M, Meinel F et al. Prevalence and prognostic role of thoracic lymphadenopathy in Covid-19. Rofo 2025; 197: 163 - 171.
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The impact of the COVID-19 pandemic on dietary behaviors among school-age children, adolescents, and young adults: a systematic review and meta-analysis.
Na, X, Zhang, J, Xie, C, Zeng, H, Wu, L, Fan, D, Yang, H, Shi, X, Zhou, Y, Yu, H, et al
Nutrition reviews. 2025;(2):e195-e210
Abstract
CONTEXT The COVID-19 pandemic has had a global impact on food security and nutrition, both in the short and long term. The influence on school-age children, adolescents, and young adults may be particularly significant and long-lasting. OBJECTIVE This systematic review and meta-analysis aimed to quantify the impact of the COVID-19 pandemic on dietary habits among school-age children, adolescents, and young adults worldwide. DATA SOURCES PubMed, Web of Science, and Embase were searched from inception to October 5, 2023. DATA EXTRACTION We included observational studies published in English that reported dietary quality scores and dietary intake quantities during and before the COVID-19 pandemic among school-age children, adolescents, and young adults. We included a total of 22 cohort studies and 20 cross-sectional studies of high or moderate quality. DATA ANALYSIS We conducted a meta-analysis, expressing dietary quality scores and dietary intake quantities as standardized mean differences (SMD) with 95% confidence intervals (CIs). For studies with low heterogeneity, we used a fixed-effects model; otherwise, we applied a random-effects model. The Newcastle-Ottawa Scale was employed by 2 reviewers independently to evaluate methodological quality. The analysis indicated that, overall, juice intake increased (SMD = 0.12, 95% CI: 0.04 to 0.20), while alcohol consumption reduced during the COVID-19 pandemic (SMD = -0.28, 95% CI: -0.47 to -0.08). However, the age-stratified results varied. Among school-age children, intake of fruit, dairy products, sugar, and juice increased. Adolescents showed an increase in meal frequency and vegetable intake. Young adults showed reduced carbohydrate and alcohol intakes, while protein and dairy product intakes increased, based on limited included studies. CONCLUSION Dietary changes in school-age children from before to during the pandemic were mixed, while dietary behavior changes in adolescents and young adults tended to be more positive. Considering the lasting effects of negative dietary behaviors, attention should be given to addressing the increased sugar and juice intakes. It is also crucial that caregivers and researchers monitor whether positive dietary behaviors will rebound after returning to normal study and life. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42023420923.
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Prevalence of cardiovascular risk factors according to Life's Essential 8 in children and adolescents during the COVID-19 pandemic: A systematic review and meta-analysis including 1 526 173 participants from 42 countries.
Núñez-Cortés, R, López-Bueno, R, Torres-Castro, R, Calatayud, J, Del Pozo Cruz, B
Pediatric obesity. 2025;(1):e13190
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INTRODUCTION Cardiovascular health is a crucial aspect of overall health. The aim of this study was to estimate the prevalence of cardiovascular risk factors among children and adolescents during the COVID-19 pandemic based on the Life's Essential 8 domains. METHODS PubMed, Scopus and Web of Science were systematically searched until 24 February 2023. Studies had to meet the following criteria: (1) observational studies, (2) studies reporting proportion of selected risk factors, (3) studies involving children or adolescents, (4) studies that collected data during the COVID-19 pandemic and (5) studies with representative samples. The outcomes included were diet, physical activity, nicotine exposure, sleep health, obesity, dyslipidaemia, diabetes and elevated blood pressure. RESULTS Sixty-two studies with 1 526 173 participants from 42 countries were included. Of these, 41 studies were used in the meta-analyses. The overall pooled prevalence of risk factors in the behavioural domain was as follows: poor quality diet 26.69% (95% CI 0.00%-85.64%), inadequate physical activity 70.81% (95% CI 64.41%-76.83%), nicotine exposure 9.24% (95% CI 5.53%-13.77%) and sleep disorders 33.49% (95% CI 25.24%-42.28%). The overall pooled prevalence of risk factors in the health domain was as follows: obesity 16.21% (95% CI 12.71%-20.04%), dyslipidaemia 1.87% (95% CI 1.73%-2.01%), diabetes 1.17% (95% CI 0.83%-1.58%) and elevated blood pressure 11.87% (95% CI 0.26%-36.50%). CONCLUSIONS These results highlight the need for prevention strategies to maintain better cardiovascular health from an early age, particularly by increasing physical activity levels, sleep time and promoting the consumption of more fruits and vegetables.
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Daily routine disruptions and psychiatric symptoms amid COVID-19: a systematic review and meta-analysis of data from 0.9 million individuals in 32 countries.
Liu, H, Tao, TJ, Chan, SKY, Ma, JCH, Lau, AYT, Yeung, ETF, Hobfoll, SE, Hou, WK
BMC medicine. 2024;(1):49
Abstract
BACKGROUND There is currently a deficit of knowledge about how to define, quantify, and measure different aspects of daily routine disruptions amid large-scale disasters like COVID-19, and which psychiatric symptoms were more related to the disruptions. This study aims to conduct a systematic review and meta-analysis on the probable positive associations between daily routine disruptions and mental disorders amid the COVID-19 pandemic and factors that moderated the associations. METHODS PsycINFO, Web of Science, PubMed, and MEDLINE were systematically searched up to April 2023 (PROSPERO CRD42023356846). Independent variables included regularity, change in frequency, and change in capability of different daily routines (i.e., physical activity, diet, sleep, social activities, leisure activities, work and studies, home activities, smoking, alcohol, combined multiple routines, unspecified generic routines). Dependent variables included symptoms and/or diagnoses of mental disorders (i.e., depression, anxiety, post-traumatic stress disorder, and general psychological distress). RESULTS Fifty-three eligible studies (51 independent samples, 910,503 respondents) were conducted in five continents. Daily routine disruptions were positively associated with depressive symptoms (r = 0.13, 95% CI = [0.06; 0.20], p < 0.001), anxiety symptoms (r = 0.12, 95% CI = [0.06; 0.17], p < 0.001), and general psychological distress (r = 0.09, 95% CI = [0.02; 0.16], p = 0.02). The routine-symptom associations were significant for physical activity, eating, sleep, and smoking (i.e., type), routines that were defined and assessed on regularity and change in capability (i.e., definition and assessment), and routines that were not internet-based. While the positive associations remained consistent across different sociodemographics, they were stronger in geo-temporal contexts with greater pandemic severity, lower governmental economic support, and when the routine-symptom link was examined prospectively. CONCLUSIONS This is one of the first meta-analytic evidence to show the positive association between daily routine disruptions and symptoms of mental disorders among large populations as COVID-19 dynamically unfolded across different geo-temporal contexts. Our findings highlight the priority of behavioral adjustment for enhancing population mental health in future large-scale disasters like COVID-19.
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The effect of the urban exposome on COVID-19 health outcomes: A systematic review and meta-analysis.
Houweling, L, Maitland-Van der Zee, AH, Holtjer, JCS, Bazdar, S, Vermeulen, RCH, Downward, GS, Bloemsma, LD
Environmental research. 2024;(Pt 2):117351
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BACKGROUND The global severity of SARS-CoV-2 illness has been associated with various urban characteristics, including exposure to ambient air pollutants. This systematic review and meta-analysis aims to synthesize findings from ecological and non-ecological studies to investigate the impact of multiple urban-related features on a variety of COVID-19 health outcomes. METHODS On December 5, 2022, PubMed was searched to identify all types of observational studies that examined one or more urban exposome characteristics in relation to various COVID-19 health outcomes such as infection severity, the need for hospitalization, ICU admission, COVID pneumonia, and mortality. RESULTS A total of 38 non-ecological and 241 ecological studies were included in this review. Non-ecological studies highlighted the significant effects of population density, urbanization, and exposure to ambient air pollutants, particularly PM2.5. The meta-analyses revealed that a 1 μg/m3 increase in PM2.5 was associated with a higher likelihood of COVID-19 hospitalization (pooled OR 1.08 (95% CI:1.02-1.14)) and death (pooled OR 1.06 (95% CI:1.03-1.09)). Ecological studies, in addition to confirming the findings of non-ecological studies, also indicated that higher exposure to nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), and carbon monoxide (CO), as well as lower ambient temperature, humidity, ultraviolet (UV) radiation, and less green and blue space exposure, were associated with increased COVID-19 morbidity and mortality. CONCLUSION This systematic review has identified several key vulnerability features related to urban areas in the context of the recent COVID-19 pandemic. The findings underscore the importance of improving policies related to urban exposures and implementing measures to protect individuals from these harmful environmental stressors.
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Systematic review and meta-analysis on the impact of COVID-19 related restrictions on air quality in low- and middle-income countries.
Navaratnam, AMD, Williams, H, Sharp, SJ, Woodcock, J, Khreis, H
The Science of the total environment. 2024;:168110
Abstract
BACKGROUND Low- and middle-income countries (LMIC) are disproportionately affected by air pollution and its health burden, representing a global inequity. The COVID-19 pandemic provided a unique opportunity to investigate the impact of unprecedented lockdown measures on air pollutant concentrations globally. We aim to quantify air pollutant concentration changes across LMIC settings as a result of COVID-19 restrictions. METHODS Searches for this systematic review and meta-analysis were carried out across five databases on 30th March 2022; MEDLINE, Embase, Web of Science, Scopus and Transport Research Information Documentation. Modelling and observational studies were included, as long as the estimates reflected city or town level data and were taken exclusively in pre-lockdown and lockdown periods. Mean percentage changes per pollutant were calculated and meta-analyses were carried out to calculate mean difference in measured ground-level observed concentrations for each pollutant (PROSPERO CRD42022326924). FINDINGS Of the 2982 manuscripts from initial searches, 256 manuscripts were included providing 3818 percentage changes of all pollutants. No studies included any countries from Sub-Saharan Africa and 34 % and 39.4 % of studies were from China and India, respectively. There was a mean percentage change of -37.4 %, -21.7 %, -54.6 %, -39.1 %, -48.9 %, 16.9 %, -34.9 %, -30.6 % and - 14.7 % for black carbon (BC), carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), oxides of nitrogen (NOx), ozone (O3), particulate matter 10 (PM10) and 2.5 (PM2.5) and sulphur dioxide (SO2), respectively. Meta-analysis included 100 manuscripts, providing 908 mean concentration differences, which showed significant reduction in mean concentration in all study settings for BC (-0.46 μg/m3, PI -0.85; -0.08), CO (-0.25 mg/m3, PI -0.44; -0.03), NO2 (-19.41 μg/m3, PI -31.14; -7.68) and NOx (-22.32 μg/m3, PI -40.94; -3.70). INTERPRETATION The findings of this systematic review and meta-analysis quantify and confirm the trends reported across the globe in air pollutant concentration, including increases in O3. Despite the majority of global urban growth occurring in LMIC, there are distinct geographical gaps in air pollution data and, where it is available, differing approaches to analysis and reporting.
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Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials.
Heydari, B, Sahebnasagh, A, Omrani, MA, Azimi, S, Dehghani, MH, Salehi-Abargouei, A, Farman, F, Saghafi, F
Current medicinal chemistry. 2024;(29):4745-4755
Abstract
OBJECTIVE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. METHODS We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. RESULTS Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I2 = 26.798%, P-value = 0.242). CONCLUSION CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.
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Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis.
Sharma, Y, Sumanadasa, S, Shahi, R, Woodman, R, Mangoni, AA, Bihari, S, Thompson, C
Scientific reports. 2024;(1):11846
Abstract
Community-acquired pneumonia (CAP) poses a significant global health challenge, prompting exploration of innovative treatments. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of vitamin C supplementation in adults undergoing treatment for CAP. A comprehensive search of the MEDLINE, Embase, CINAHL, the Cochrane Central Register of Controlled Trials, and Clinical Trials.gov databases from inception to 17 November 2023 identified six randomized-controlled-trials (RCTs) meeting inclusion criteria. The primary outcome analysis revealed a non-significant trend towards reduced overall mortality in the vitamin C group compared to controls (RR 0.51; 95% CI 0.24 to 1.09; p = 0.052; I2 = 0; p = 0.65). Sensitivity analysis, excluding corona-virus-disease 2019 (COVID-19) studies and considering the route of vitamin C administration, confirmed this trend. Secondary outcomes, including hospital length-of-stay (LOS), intensive-care-unit (ICU) LOS, and mechanical ventilation, exhibited mixed results. Notably, heterogeneity and publication bias were observed in hospital LOS analysis, necessitating cautious interpretation. Adverse effects were minimal, with isolated incidents of nausea, vomiting, hypotension, and tachycardia reported. This meta-analysis suggests potential benefits of vitamin C supplementation in CAP treatment. However, inconclusive findings and methodological limitations warrants cautious interpretation, emphasising the urgency for high-quality trials to elucidate the true impact of vitamin C supplementation in CAP management.