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.

Abstract

OBJECTIVE To examine changes in the prevalence of six key chronic disease risk factors (the "Big 6"), from before (2019) to during (2021) the COVID-19 pandemic, among a large and geographically diverse sample of adolescents, and whether differences over time are associated with lockdown status and gender. DESIGN Prospective cohort study. SETTING Three Australian states (New South Wales, Queensland and Western Australia) spanning over 3000 km. PARTICIPANTS 983 adolescents (baseline Mage=12.6, SD=0.5, 54.8% girl) drawn from the control group of the Health4Life Study. PRIMARY OUTCOMES The prevalence of physical inactivity, poor diet (insufficient fruit and vegetable intake, high sugar-sweetened beverage intake, high discretionary food intake), poor sleep, excessive recreational screen time, alcohol use and tobacco use. RESULTS The prevalence of excessive recreational screen time (prevalence ratios (PR)=1.06, 95% CI=1.03 to 1.11), insufficient fruit intake (PR=1.50, 95% CI=1.26 to 1.79), and alcohol (PR=4.34, 95% CI=2.82 to 6.67) and tobacco use (PR=4.05 95% CI=1.86 to 8.84) increased over the 2-year period, with alcohol use increasing more among girls (PR=2.34, 95% CI=1.19 to 4.62). The prevalence of insufficient sleep declined across the full sample (PR=0.74, 95% CI=0.68 to 0.81); however, increased among girls (PR=1.24, 95% CI=1.10 to 1.41). The prevalence of high sugar-sweetened beverage (PR=0.61, 95% CI=0.64 to 0.83) and discretionary food consumption (PR=0.73, 95% CI=0.64 to 0.83) reduced among those subjected to stay-at-home orders, compared with those not in lockdown. CONCLUSION Lifestyle risk behaviours, particularly excessive recreational screen time, poor diet, physical inactivity and poor sleep, are prevalent among adolescents. Young people must be supported to find ways to improve or maintain their health, regardless of the course of the pandemic. Targeted approaches to support groups that may be disproportionately impacted, such as adolescent girls, are needed. TRIAL REGISTRATION NUMBER Australian New Zealand Clinical Trials Registry (ACTRN12619000431123).

Abstract

BACKGROUND Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION ClinicalTrials.gov NCT04344041.

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

Due to the spread of COVID 2019, the Italian government imposed a lockdown on the national territory. Initially, citizens were required to stay at home and not to mix with others outside of their household (Phase 1); eventually, some of these restrictions were lifted (Phase 2). To investigate the impact of lockdown on emotional and binge eating, an online survey was conducted to compare measures of self-reported physical (BMI), psychological (Alexithymia), affective (anxiety, stress, and depression) and social (income, workload) state during Phase 1 and Phase 2. Data from 365 Italian residents showed that increased emotional eating was predicted by higher depression, anxiety, quality of personal relationships, and quality of life, while the increase of bingeing was predicted by higher stress. Moreover, we showed that higher alexithymia scores were associated by increased emotional eating and higher BMI scores were associated with both increased emotional eating and binge eating. Finally, we found that from Phase 1 to Phase 2 binge and emotional eating decreased. These data provide evidence of the negative effects of isolation and lockdown on emotional wellbeing, and, relatedly, on eating behaviour.

Abstract

The importance of balanced dietary habits, which include appropriate amounts of antioxidants to maintain the immune system, has become increasingly relevant during the current SARS-CoV-2/COVID-19 pandemic, because viral infections are characterized by high oxidative stress. Furthermore, the measures taken by governments to control the pandemic have led to increased anxiety, stress, and depression, which affect physical and mental health, all of which are influenced by nutritional status, diet, and lifestyle. The Mediterranean diet (MD), Atlantic diet (AD), and the Dietary Guidelines for Americans all provide the essential vitamins, minerals, and phenolic compounds needed to activate enzymatic and nonenzymatic antioxidant responses. However, viral pandemics such as the current COVID-19 crisis entail high oxidative damage caused by both the infection and the resultant social stresses within populations, which increases the probability and severity of infection. Balanced dietary patterns such as the MD and the AD are characterized by the consumption of fruit, vegetables, legumes, olive oil, and whole grains with low intakes of processed foods and red meat. For a healthy lifestyle in young adults, the MD in particular provides the required amount of antioxidants per day for vitamins D (0.3-3.8 μg), E (17.0 mg), C (137.2-269.8 mg), A (1273.3 μg), B-12 (1.5-2.0 μg), and folate (455.1-561.3 μg), the minerals Se (120.0 μg), Zn (11.0 mg), Fe (15.0-18.8 mg), and Mn (5.2-12.5 mg), and polyphenols (1171.00 mg) needed to maintain an active immune response. However, all of these diets are deficient in the recommended amount of vitamin D (20 μg/d). Therefore, vulnerable populations such as elders and obese individuals could benefit from antioxidant supplementation to improve their antioxidant response. Although evidence remains scarce, there is some indication that a healthy diet, along with supplemental antioxidant intake, is beneficial to COVID-19 patients.

Abstract

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients-247 home-isolated and 65 hospitalized-comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

Abstract

BACKGROUND Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. METHODS For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. FINDINGS Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17-34·07), with 12·84% (12·36-13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78-48·09) and for a first diagnosis was 25·79% (23·50-28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50-0·63) for intracranial haemorrhage, 2·10% (1·97-2·23) for ischaemic stroke, 0·11% (0·08-0·14) for parkinsonism, 0·67% (0·59-0·75) for dementia, 17·39% (17·04-17·74) for anxiety disorder, and 1·40% (1·30-1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24-3·16) for intracranial haemorrhage, 6·92% (6·17-7·76) for ischaemic stroke, 0·26% (0·15-0·45) for parkinsonism, 1·74% (1·31-2·30) for dementia, 19·15% (17·90-20·48) for anxiety disorder, and 2·77% (2·31-3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40-1·47, for any diagnosis; 1·78, 1·68-1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14-1·17, for any diagnosis; 1·32, 1·27-1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50-1·67, for any diagnosis; 2·87, 2·45-3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events. INTERPRETATION Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings. FUNDING National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.

Abstract

BACKGROUND The restrictions associated with the 2020 COVID-19 pandemic has resulted in changes to young children's daily routines and habits. The impact on their participation in movement behaviours (physical activity, sedentary screen time and sleep) is unknown. This international longitudinal study compared young children's movement behaviours before and during the COVID-19 pandemic. METHODS Parents of children aged 3-5 years, from 14 countries (8 low- and middle-income countries, LMICs) completed surveys to assess changes in movement behaviours and how these changes were associated with the COVID-19 pandemic. Surveys were completed in the 12 months up to March 2020 and again between May and June 2020 (at the height of restrictions). Physical activity (PA), sedentary screen time (SST) and sleep were assessed via parent survey. At Time 2, COVID-19 factors including level of restriction, environmental conditions, and parental stress were measured. Compliance with the World Health Organizations (WHO) Global guidelines for PA (180 min/day [≥60 min moderate- vigorous PA]), SST (≤1 h/day) and sleep (10-13 h/day) for children under 5 years of age, was determined. RESULTS Nine hundred- forty-eight parents completed the survey at both time points. Children from LMICs were more likely to meet the PA (Adjusted Odds Ratio [AdjOR] = 2.0, 95%Confidence Interval [CI] 1.0,3.8) and SST (AdjOR = 2.2, 95%CI 1.2,3.9) guidelines than their high-income country (HIC) counterparts. Children who could go outside during COVID-19 were more likely to meet all WHO Global guidelines (AdjOR = 3.3, 95%CI 1.1,9.8) than those who were not. Children of parents with higher compared to lower stress were less likely to meet all three guidelines (AdjOR = 0.5, 95%CI 0.3,0.9). CONCLUSION PA and SST levels of children from LMICs have been less impacted by COVID-19 than in HICs. Ensuring children can access an outdoor space, and supporting parents' mental health are important prerequisites for enabling pre-schoolers to practice healthy movement behaviours and meet the Global guidelines.

Abstract

The Coronavirus disease 2019 (COVID-19) pandemic has significantly impacted and devastated the world. As the infection spreads, the projected mortality and economic devastation are unprecedented. In particular, racial and ethnic minorities may be at a particular disadvantage as many already assume the status of a marginalized group. Black Americans have a long-standing history of disadvantage and are in a vulnerable position to experience the impact of this crisis and the myth of Black immunity to COVID-19 is detrimental to promoting and maintaining preventative measures. We are the first to present the earliest available data in the peer-reviewed literature on the racial and ethnic distribution of COVID-19-confirmed cases and fatalities in the state of Connecticut. We also seek to explode the myth of Black immunity to the virus. Finally, we call for a National Commission on COVID-19 Racial and Ethnic Health Disparities to further explore and respond to the unique challenges that the crisis presents for Black and Brown communities.