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.

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.

Abstract

AIM: Persistent symptoms in adults after COVID-19 are emerging and the term long COVID is increasingly appearing in the literature. However, paediatric data are scarce. METHODS This paper contains a case report of five Swedish children and the long-term symptoms reported by their parents. It also includes a systematic literature review of the MEDLINE, EMBASE and Web of Science databases and the medRxiv/bioRxiv pre-print servers up to 2 November 2020. RESULTS The five children with potential long COVID had a median age of 12 years (range 9-15) and four were girls. They had symptoms for 6-8 months after their clinical diagnoses of COVID-19. None were hospitalised at diagnosis, but one was later admitted for peri-myocarditis. All five children had fatigue, dyspnoea, heart palpitations or chest pain, and four had headaches, difficulties concentrating, muscle weakness, dizziness and sore throats. Some had improved after 6-8 months, but they all suffered from fatigue and none had fully returned to school. The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail. None contained any information on long COVID in children. CONCLUSION Children may experience similar long COVID symptoms to adults and females may be more affected.

Abstract

OBJECTIVE In March 2020, several countries banned unnecessary outdoor activities during COVID-19, commonly called 'lockdowns. These lockdowns have the potential to impact associated levels of physical activity and sedentary behaviour. Given the numerous health outcomes associated with physical activity and sedentary behaviour, the aim of this review was to summarise literature that investigated differences in physical activity and sedentary behaviour before vs during the COVID-19 lockdown. DESIGN DATA SOURCES AND ELIGIBILITY CRITERIA Electronic databases were searched from November 2019 to October 2020 using terms and synonyms relating to physical activity, sedentary behaviour and COVID-19. The coprimary outcomes were changes in physical activity and/or sedentary behaviour captured via device-based measures or self-report tools. Risk of bias was measured using the Newcastle-Ottawa Scale. RESULTS Sixty six articles met the inclusion criteria and were included in the review (total n=86 981). Changes in physical activity were reported in 64 studies, with the majority of studies reporting decreases in physical activity and increases in sedentary behaviours during their respective lockdowns across several populations, including children and patients with a variety of medical conditions. CONCLUSION Given the numerous physical and mental benefits of increased physical activity and decreased sedentary behaviour, public health strategies should include the creation and implementation of interventions that promote safe physical activity and reduce sedentary behaviour should other lockdowns occur.

Abstract

BACKGROUND The role of vitamin D supplementation as a treatment for COVID-19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID-19 based on randomised controlled trials is required. OBJECTIVES To assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS We searched the Cochrane COVID-19 Study Register, Web of Science and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021. SELECTION CRITERIA We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)). DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID-19: all-cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all-cause mortality, development of severe clinical COVID-19 symptoms, quality of life, adverse events, serious adverse events. MAIN RESULTS We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID-19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7,  whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All-cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all-cause mortality at hospital discharge (very low-certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low-certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID-19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low-certainty). Effectiveness and safety of vitamin D supplementation for people with COVID-19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL. AUTHORS' CONCLUSIONS There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well-designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double-blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.

Abstract

Fatigue is common not only in cancer patients but also after viral and other infections. Effective treatment options are still very rare. Therefore, the present knowledge on the pathophysiology of fatigue and the potential positive impact of treatment with vitamin C is illustrated. Additionally, the effectiveness of high-dose IV vitamin C in fatigue resulting from various diseases was assessed by a systematic literature review in order to assess the feasibility of vitamin C in post-viral, especially in long COVID, fatigue. Nine clinical studies with 720 participants were identified. Three of the four controlled trials observed a significant decrease in fatigue scores in the vitamin C group compared to the control group. Four of the five observational or before-and-after studies observed a significant reduction in pre-post levels of fatigue. Attendant symptoms of fatigue such as sleep disturbances, lack of concentration, depression, and pain were also frequently alleviated. Oxidative stress, inflammation, and circulatory disorders, which are important contributors to fatigue, are also discussed in long COVID fatigue. Thus, the antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects of high-dose IV vitamin C might be a suitable treatment option.

Abstract

Eating behaviour is a complex construct that is liable to be modified by external factors. Due to the outbreak of coronavirus disease 2019 (COVID-19), many restrictive measures were carried out with the aim of reducing the impact of this disease. As a result, lifestyles were disrupted, which could affect eating behaviours. The aim of this systematic review of longitudinal studies was to assess changes in eating behaviour during the COVID-19 pandemic by establishing a comparison of eating behaviours before and after the outbreak of the pandemic. This study followed the PRISMA guidelines (PROSPERO CRD42020203246), whereas to assess the quality of the studies, the Newcastle-Ottawa Quality Assessment Scale (NOS) was applied. Out of a set of 826 studies, 23 were included in this systematic review. The main findings provided information about a shift towards modified eating behaviours, characterized by an increased snack frequency and a preference for sweets and ultra-processed food rather than fruits, vegetables, and fresh food. Additionally, an increased alcohol consumption was found among different countries. Consequently, adherence to healthy diets decreased. These findings are relevant to future policies and strategies to assess nutrition in cases of alarming situations such as the current COVID-19 pandemic.

Abstract

Importance: Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy. Objective: To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection. Evidence Review: A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19, SARS-CoV-2, coronavirus, 2019-nCoV, long-term, after recovery, long-haul, persistent, outcome, symptom, follow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality. Findings: A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity. Conclusions and Relevance: This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.

Abstract

BACKGROUND Micronutrients play roles in strengthening and maintaining immune function, but their supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. METHODS Systematic literature searches conducted in five electronic databases identified 751 unique studies, of which 33 studies (five supplementation studies, one supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. FINDINGS A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset when combined as a severity outcome (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures, namely mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. CONCLUSION The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.

Abstract

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.