Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial.
Science translational medicine. 2022;(654):eabo2652
Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer-N-acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19. Twenty-four patients classified as having severe COVID-19 with a baseline World Health Organization seven-point ordinal scale of ≥5 were randomized to receive a single intravenous dose of placebo (n = 7 patients) or OP-101 at 2 (n = 6), 4 (n = 6), or 8 mg/kg (n = 5 patients). All study participants received standard of care, including corticosteroids. OP-101 at 4 mg/kg was better than placebo at decreasing inflammatory markers; OP-101 at 4 and 8 mg/kg was better than placebo at reducing neurological injury markers, (neurofilament light chain and glial fibrillary acidic protein). Risk for the composite outcome of mechanical ventilation or death at 30 and 60 days after treatment was 71% (95% CI: 29%, 96%) for placebo and 18% (95% CI: 4%, 43%; P = 0.021) for the pooled OP-101 treatment arms. At 60 days, 3 of 7 patients given placebo and 14 of 17 OP-101-treated patients were surviving. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19.
Clinical (BMI and MRI) and Biochemical (Adiponectin, Leptin, TNF-α, and IL-6) Effects of High-Intensity Aerobic Training with High-Protein Diet in Children with Obesity Following COVID-19 Infection.
International journal of environmental research and public health. 2022;(12)
OBJECTIVE To find the clinical and biochemical effects of high-intensity aerobic training with a high-protein diet in children with obesity following COVID-19 infection. METHODS By using the block randomization method, the eligible participants were randomized into two groups. The first group received high-intensity aerobic training with a high-protein diet (Group A; n = 38) and the second group were allowed to do regular physical activities and eat a regular diet (Group B; n = 38) for 8 weeks. Clinical (basal metabolic index (BMI) and muscle-mass-cross-sectional area (CSA)) and biochemical (Adiponectin, leptin, TNF-α, and IL-6) measures were measured at baseline, on the 8th week, and at 6-months follow-up. RESULTS Baseline demographic and clinical attributes show homogenous presentation among the study groups (p > 0.05). After eight weeks of intervention, and at the end of 6-months follow-up, the basal metabolic index (BMI) (6.3) (CI 95% 4.71 to 7.88), mid-arm CSA (17) (CI 95% 14.70 to 19.29), mid-thigh CSA (13.10) (CI 95% 10.60 to 15.59), mid-calf CSA (11.3) (CI 95% 9.30 to 13.29), adiponectin (-1.9) (CI 95% -2.13 to -1.66), leptin (5.64) (CI 95% 5.50 to 5.77), TNF-α (0.5) (CI 95% 0.42 to 0.57), and IL-6 (0.21) (CI 95% 0.18 to 0.23) showed more improvement (p < 0.001) in Group A than Group B (p > 0.05). CONCLUSION Overall, this trial found that high-intensity aerobic training with a high-protein diet decreased the BMI percentile and muscle mass (arm, thigh, and calf), and positively altered the biochemical variables in children with obesity.
Harvest for Health, a Randomized Controlled Trial Testing a Home-Based, Vegetable Gardening Intervention Among Older Cancer Survivors Across Alabama: An Analysis of Accrual and Modifications Made in Intervention Delivery and Assessment During COVID-19.
Journal of the Academy of Nutrition and Dietetics. 2022;(9):1629-1643
BACKGROUND Accelerated functional decline is a concern among older cancer survivors that threatens independence and quality of life. Pilot studies suggest that vegetable gardening interventions ameliorate functional decline through improved diet and physical activity. OBJECTIVE The aim of this article was to describe the rationale, recruitment challenges, and enrollment for the Harvest for Health randomized controlled trial (RCT), which will test the impact of a home-based, vegetable gardening intervention on vegetable and fruit consumption, physical activity, and physical functioning among older cancer survivors. Modifications made to the intervention and assessments to assure safety and continuity of the RCT throughout the COVID-19 pandemic also are reported. DESIGN Harvest for Health is a 2-year, 2-arm, single-blinded, wait-list controlled RCT with cross-over. PARTICIPANTS/SETTING Medicare-eligible survivors of cancers with ≥60% 5-year survival were recruited across Alabama from October 1, 2016 to February 8, 2021. INTERVENTION Participants were randomly assigned to a wait-list control or a 1-year home-based gardening intervention and individually mentored by extension-certified master gardeners to cultivate spring, summer, and fall vegetable gardens. MAIN OUTCOME MEASURES Although the RCT's primary end point was a composite measure of vegetable and fruit consumption, physical activity, and physical functioning, this article focuses on recruitment and modifications made to the intervention and assessments during COVID-19. STATISTICAL ANALYSES PERFORMED χ2 and t tests (α < .05) were used to compare enrolled vs unenrolled populations. RESULTS Older cancer survivors (n = 9,708) were contacted via mail and telephone; 1,460 indicated interest (15% response rate), 473 were screened eligible and consented, and 381 completed baseline assessments and were randomized. Enrollees did not differ from nonrespondents/refusals by race and ethnicity, or rural-urban status, but comprised significantly higher numbers of comparatively younger survivors, those who were female, and survivors of breast cancer (P < .001). Although COVID-19 delayed trial completion, protocol modifications overcame this barrier and study completion is anticipated by June 2022. CONCLUSIONS This RCT will provide evidence on the effects of a mentored vegetable gardening program among older cancer survivors. If efficacious, Harvest for Health represents a novel, multifaceted approach to improve lifestyle behaviors and health outcomes among cancer survivors-one with capacity for sustainability and widespread dissemination.
Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.
Lancet (London, England). 2022;(10323):461-472
BACKGROUND A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.
A randomized pilot study using calcitriol in hospitalized COVID-19 patients.
The systemic illness associated with SARS-CoV-2 infection results in hospitalization rate of 380.3 hospitalizations per 100,000 population, overwhelming health care systems. Vitamin D regulates expression of approximately 11,000 genes spanning many physiologic functions that include regulation of both innate and adaptive immune function. We investigate potential benefit of calcitriol therapy given to patients hospitalized with COVID-19. This was an open label, randomized clinical trial of calcitriol or no treatment given to hospitalized adult patients with COVID-19. Subjects were randomly assigned treatment with calcitriol 0.5 μg daily for 14 days or hospital discharge; or no treatment (1:1) at time of enrollment. We enrolled 50 consecutive patients, 25 per trial arm. The change in peripheral arterial oxygen saturation to the inspired fraction of oxygen (SaO2/FIO2 ratio) was calculated on admission and discharge between the groups. The control group had an average increase of +13.2 (±127.7) on discharge and the calcitriol group had an increase of +91.04 (±119.08) (p = .0305), suggesting an improvement in oxygenation among subjects who received calcitriol. Additionally, 12 patients in the control group required oxygen supplementation on admission and 21 of them were discharged on room air. 14 subjects needed oxygen supplementation in the calcitriol group on admission while all 25 were discharged on room air. Other clinical markers showed the average length of stay was 9.24 (±9.4) in the control group compared to 5.5 (±3.9) days in the calcitriol group (p = .14). The need for ICU transfer was 8 in the control group and 5 in the calcitriol group. There were 3 deaths and 4 readmissions in the control group and 0 deaths and 2 readmissions in the calcitriol group. This pilot study illustrates improvement in oxygenation among hospitalized patients with COVID-19 treated with calcitriol and suggests the need for a larger randomized trial.
A randomized, controlled, blinded, parallel group, clinical trial to study the role of Ayurcov (AyurCoro3), one day regimen as an adjuvant therapy for COVID-19 disease management, at dedicated Covid Hospital (DCH) in India.
Complementary therapies in medicine. 2022;:102824
INTRODUCTION Limited treatment options exist for COVID-19 infections; thus, attempts from complementary and alternative systems (CAM) of medicine are being explored as possible therapeutic options. Ayurcov is a formulation made of ingredients mentioned in Ayurveda. These constituents have proven antiviral, detoxifying, immune-modulating, and bio-enhancing properties. The present study was carried out to evaluate the therapeutic effect and safety of Ayurcov in patients with various severity states of COVID-19 infections. METHODS A randomized, single blinded, controlled trial was carried out in adults diagnosed with mild-to-moderate, and severe COVID-19 infections confirmed by real time reverse transcriptase polymerase chain reaction (rRTPCR) test. The interventional group received three doses of 'Ayurcov'. It is constituted of Haridra Churna (Curcuma longa), Go ark (Bos Indicus Distilled Urine), Sphatika (Alum), Sita (Rock Candy), Godugdham (Bos Indicus Milk) milk, Goghritam (Bos Indicus ghee) on Day 1, as an adjuvant to the standard of care, and the control group received only the standard of care. Key outcomes included: proportion of patients and time taken for symptom resolution, reduction in the rRT-PCR Ct values, safety, and functional status until 42 days after discharge. RESULTS Ninety patients with mild-to-moderate and 30 patients with severe COVID-19 disease were recruited. It was observed that significantly more proportions of patients receiving Ayurcov had symptom relief much earlier than control group. Additionally, the interventional group showed significantly lower rRT-PCR Ct values. However, a shorter time of resolution of symptoms was observed with the interventional group in the mild to moderate category but not with those having severe symptoms. Similarly, a significantly better functional status was observed with interventional group on days 7 and 28 after discharge. Ayurcov was not observed with higher risks of any adverse/serious adverse events. CONCLUSIONS Ayurcov as adjuvant with standard of care was associated with significantly earlier resolution of COVID-19 related symptoms than standard of care alone.
A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial.
BMC medicine. 2022;(1):83
BACKGROUND Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).
Feasibility and Effectiveness of a Preventive Care Program during the Compound Humanitarian Crisis and COVID-19 Pandemic in Venezuela.
Effective preventive care programs are urgently needed during humanitarian crises, as has been especially obvious during the COVID-19 pandemic. A pragmatic trial was designed: hybridized intervention (Diabetes Prevention Program [DPP] + medical nutrition therapy + liquid diet [LD]; LD group) vs. DPP only (DPP group). The participants were adults who were overweight/obese and at high risk of type 2 diabetes mellitus (T2DM). The LD consisted of a "homemade" milk- and fruit-juice-based beverage. Pandemic restrictions delayed the program by nine months, tripled the amount of time required for screening, and reduced the total sample to 60%. Eventually, 127 participants were randomized, and 94/127 participants (74.0%) completed the first phase. Participant dropout was influenced by migration, COVID-19 symptoms, education level, and socioeconomic status. In two months, the LD group lost 2.9 kg (p < 0.001) and the DPP group, 2.2 kg (p < 0.001) (between-group p = 0.170), with improvements in their cardiometabolic risk factors. At this stage, the DPP was shown to be feasible and effective, demonstrating weight loss with the improvement of cardiometabolic risk factors in a primary setting in Venezuela, a middle-income country with a chronic humanitarian crisis, during the COVID-19 pandemic.
Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study.
Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p < 0.001). The serum 25(OH)D level on the ninth day was negatively associated with the number of bed days (r = -0.23, p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27-CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27-CD38- DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19.
Effects of a community-driven water, sanitation, and hygiene programme on COVID-19 symptoms, vaccine acceptance and non-COVID illnesses: A cluster-randomised controlled trial in rural Democratic Republic of Congo.
Tropical medicine & international health : TM & IH. 2022;(9):795-802
OBJECTIVE The government of the Democratic Republic of Congo (DRC) responded to COVID-19 with policy measures, such as business and school closures and distribution of vaccines, which rely on citizen compliance. In other settings, prior experience with effective government programmes has increased compliance with public health measures. We study the effect of a national water, sanitation, and hygiene programme on compliance with COVID-19 policies. METHODS Prior to the COVID-19 pandemic, 332 communities were randomly assigned to the Villages et Écoles Assainis (VEA) programme or control. After COVID-19 reached DRC, individuals who owned phones (590/1312; 45%) were interviewed by phone three times between May 2020 and August 2021. Primary outcomes were COVID symptoms, non-COVID illness symptoms, child health, psychological well-being, and vaccine acceptance. Secondary outcomes included COVID-19 preventive behaviour and knowledge, and perceptions of governmental performance, including COVID response. All outcomes were self-reported. Outcomes were compared between treatment and control villages using linear models. RESULTS The VEA programme did not affect respondents' COVID symptoms (-0.11, 95% CI -0.55 to 0.33), non-COVID illnesses (-0.01, 95% CI -0.05 to 0.03), child health (0.07, 95% CI -0.19 to 0.33), psychological well-being (-0.05, 95% CI -0.35 to 0.24), or vaccine acceptance (-0.04, 95% CI -0.19 to 0.10). There was no effect on village-level COVID-19 preventive behaviour (0.03, 95% CI -0.23 to 0.29), COVID-19 knowledge (0.16, 95% CI -0.08 to 0.39), or trust in institutions. CONCLUSIONS Although the VEA programme increased access to improved water and sanitation, we found no evidence that it increased trust in government or compliance with COVID policies, or reduced illness.