Introduction: Serious harms of the COVID-19 vaccines have been underreported in published trial reports. Methods: Systematic review of papers with data on serious adverse events (SAEs) associated with a COVID-19 vaccine. Results: We included 18 systematic reviews, 14 randomised trials, and 34 other studies with a control group. Most studies were of poor quality. The most reliable one was a systematic review of regulatory data on the two pivotal randomised trials of the mRNA vaccines. It found significantly more SAEs of special interest with the vaccines than with placebo, and the excess risk was considerably larger than the benefit, measured as the risk of hospitalisation. The adenovirus vector vaccines increased the risk of venous thrombosis and thrombocytopenia, and the mRNA-based vaccines increased the risk of myocarditis, with a mortality of about 1-2 per 200 cases. We also found evidence of serious neurological harms, including Bel9s palsy, Guillain-Barre syndrome, myasthenic disorder and stroke, which are likely due to an autoimmune reaction, as has been suggested also for the HPV vaccines. Severe harms, i.e. those that prevent daily activities, were hugely underreported in the randomised trials. These harms were very common in studies of booster doses after a full vaccination and in a study of vaccination of previously infected people. Discussion: Serious and severe harms of the COVID-19 vaccines have been ignored or downplayed, and sometimes been deliberately excluded by the study sponsors in high impact medical journals. This area needs further study. Authorities have recommended virtually everyone get vaccinated and receive booster doses. They fail to consider that the balance between benefits and harms becomes negative in low-risk groups such as children and people who have already acquired natural immunity.
Objectives: We assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1 (IGF-1), estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Methods: We used a bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analysis to evaluate the direction, specificity, and causality of the association between CNS-regulated hormones and COVID-19 phenotypes. Genetic instruments for CNS-regulated hormones were selected from the largest publicly available genome-wide association studies in the European population. Summary-level data on COVID-19 severity, hospitalization, and susceptibility were obtained from the COVID-19 host genetic initiative. Results: DHEA was associated with increased risks of very severe respiratory syndrome (OR=4.21, 95% CI: 1.41-12.59), consistent with the results in multivariate MR (OR=3.72, 95% CI: 1.20-11.51), and hospitalization (OR = 2.31, 95% CI: 1.13-4.72) in univariate MR. LH was associated with very severe respiratory syndrome (OR=0.83; 95% CI: 0.71-0.96) in univariate MR. Estrogen was negatively associated with very severe respiratory syndrome (OR=0.09, 95% CI: 0.02-0.51), hospitalization (OR=0.25, 95% CI: 0.08-0.78), and susceptibility (OR=0.50, 95% CI: 0.28-0.89) in multivariate MR. Conclusions: We found strong evidence for the causal relationship of DHEA, LH, and estrogen with COVID-19 phenotypes.
Importance: Persistent symptoms after SARS-COV-2 infection, or long-COVID, may occur in anywhere from 10-55% of those who have had COVID-19, but the extent of impact on daily functioning and disability remains unquantified. Objective: To characterize physical and mental disability associated with long-COVID Design: Cross-sectional analysis of baseline data from a cohort study Setting: Online US nationwide survey Participants: Adults 18 years of age and older who live in the US who either report a history of COVID-19 illness (n=8,874) or report never having had COVID-19 (n=633) Main Outcome and Measures: Self-reported mobility disability (difficulty walking a quarter of a mile and/or up 10 stairs, instrumental activities of daily living [IADL] disability (difficulty doing light or heavy housework), and mental fatigue as measured by the Wood Mental Fatigue Inventory (WMFI). Results: Of 7,926 participants with long-COVID, the median age was 45 years, 84% were female, 89% self-reported white race, and 7.4% self-reported Hispanic/Latino ethnicity. Sixty-five percent of long-COVID participants were classified as having at least one disability, compared to 6% of those with resolved-COVID (n=948) and 14% of those with no-COVID (n=633). Of long-COVID participants, about 1% and 5% were classified as critically physically disabled or mentally fatigued, respectively. Age, prior comorbidity, increased BMI, female gender, hospitalization for COVID-19, non-white race, and multi-race were all associated with significantly higher disability burden. Dizziness at the time of infection (33% non-hospitalized, 39% hospitalized) was associated with all five disability components in both hospitalized and non-hospitalized groups. Heavy limbs, dyspnea, and tremors were associated with four of the five components of disability in the non-hospitalized group, and heavy limbs was associated with four of the five components in the hospitalized group. Vaccination was protective against development of disability. Conclusion and Relevance: We observed a high burden of physical and mental disability associated with long-COVID which has serious implications for individual and societal health that may be partially mitigated by vaccination. Longitudinal characterization and evaluation of COVID-19 patients is necessary to identify patterns of recovery and treatment options.
Background The role of thromboprophylaxis in the post-acute phase of COVID-19 is uncertain due to conflicting results from randomised controlled trials and observational studies. We aimed to determine the effectiveness of post-hospital apixaban in reducing the rate of death and hospital readmission of hospitalised adults with COVID-19. Methods HEAL COVID is an adaptive randomised open label multicentre platform trial recruiting participants from National Health Service Hospitals in the United Kingdom. Here we report the preliminary results of apixaban comparison of HEAL-COVID. Participants with a hospital admission related to confirmed COVID-19 and an expected date of discharge in the subsequent five days were randomised to either apixaban 2.5 mg twice daily or standard care (no anticoagulation) for 14 days. The primary outcome was hospital free survival at 12 months obtained through routine data sources. The trial was prospectively registered with ISRCTN (15851697) and Clincialtrials.gov (NCT04801940). Findings Between 19 May 2021 and 21 November 2022, 402 participants from 109 sites were randomised to apixaban and 399 to standard care. Seven participants withdrew from the apixaban group and one from the standard care group. Analysis was undertaken on an intention-to-treat basis. The apixaban arm was stopped on the recommendation of the oversight committees following an interim analysis due to no indication of benefit. Of the 402 participants randomised to apixaban, 117 experienced death or rehospitalisation during a median follow-up of 344.5 days (IQR 125 to 365), and 123 participants receiving standard care experienced death or rehospitalisation during a median follow-up of 349 days (IQR 124 to 365). There was no statistical difference in the rate of death and rehospitalisation (HR: 0.96 99%CI 0.69-1.34; p=0.75). Three participants in the apixaban arm experienced clinically significant bleeding during treatment. Interpretation Fourteen days of post-hospital anticoagulation with the direct oral anticoagulant apixaban did not reduce the rate of death or rehospitalisation of adults hospitalised with COVID-19. These data do not support the use of prophylactic post-hospital anticoagulation in adults with COVID-19. Funding HEAL-COVID is funded by the National Institute for Health and Care Research [NIHR133788] and the NIHR Cambridge Biomedical Research Centre [ BRC-1215-20014*].
Introduction: The increasing use of digital health solutions to monitor heart failure (HF) outpatients has been driven by the COVID-19 pandemic. An ideal technology should answer the specific needs of a public healthcare system: easy integration and proof of clinical benefit to justify investment in its long-term use. Through a consortium bringing together patients, physicians, industry, and hospital organizations, we developed a digital solution called Continuum, targeting patients with HF and other comorbidities. Hypothesis: A digital health solution combining remote patient monitoring (RPM) and digital therapeutics (DTx) was developed to ensure a better follow-up of patients and to rapidly optimize their medication and subsequently avoid future severe adverse events. Methods: A pilot intervention/control study with a three-month follow-up was conducted. Patients in the intervention group (remote patient monitoring group, RPM+) had a smartphone or tablet and entered in their mobile app their vital signs, weight, and HF symptoms daily. HF patients who either did not have a mobile device or the skills to use the app were enrolled in the control group (RPM-). The HealthCare Professionals (HCPs) used a web-based dashboard to follow the RPM+ patients. They could access the results of a DTx solution to help them optimize the HF treatment according to Canadian guidelines. Results: 52 HF patients were enrolled in this study, 32 in the RPM+: 69+/-9y age, 75% male, ejection fraction 42 +/- 14%. In the RPM- group, more patients had at least one hospitalization (all-cause) compared to the RPM+ group (35% versus 6% respectively; p=0.008). Similarly, the number of patients with at least one HF hospitalization was more significant in the RPM+ group compared to the RPM- (25% versus 6%, p=0.054). Finally, the intervention showed a medium effect on HF treatment optimization (w=0.26) and quality of life for the most compliant patients to the intervention (g=0.48). Conclusion: The results of this pilot study demonstrated the feasibility of an intervention combining RPM and DTx solutions for HF patients. Preliminary results suggest promising impacts on quality of life, hospitalizations, and patients9 medication optimization. However, they need to be confirmed in a more extensive study. Keywords: chronic heart failure, telemonitoring, digital therapeutics, software as medical device (SAMD), remote patient management, digital health, mobile health, algorithms
Objectives: Sophisticated scores have been proposed for prognostication of mortality due to SARS-CoV-2 but perform inconsistently. We conducted these meta-analyses to uncover why and to pragmatically seek a single dependable biomarker for mortality. Design: We searched the PubMed database for the keywords SARS-CoV-2 with biomarker name and mortality. All studies published from 01st December 2019 to 30th June 2021 were surveyed. To aggregate the data, the meta library in R was used to report overall mean values and 95% confidence intervals. We fitted a random effects model to obtain pooled AUCs and associated 95% confidence intervals for the European/North American, Asian, and overall datasets. Setting and Participants: Data was collected from 131 studies on SARS-CoV-2 PCR-positive general hospital adult admissions (n=76,169 patients in total). Main Outcome Measures: We planned a comparison of pooled area under curves (AUCs) from Receiver Operator Characteristic curves plotted for admission D-dimer, CRP, urea, troponin and interleukin-6 levels. Main Results: Biomarker effectiveness varies significantly in different regions of the world. Admission CRP levels are a good prognostic marker for mortality due to SARS-CoV-2 in Asian countries, with a pooled area under curve (AUC) of 0.83 (95% CI 0.80-0.85), but only an average predictor of mortality in Europe/North America, with a pooled AUC of 0.67 (95% CI 0.63-0.71, P<0.0001). We observed the same pattern for D-dimer and IL-6. This variability explains why the proposed prognostic scores did not perform evenly. Notably, urea and troponin had pooled AUCs ≥ 0.78 regardless of location, implying that end-organ damage at presentation is a key prognostic factor. These differences might be due to age, genetic backgrounds, or different modes of death (younger patients in Asia dying of cytokine storm while older patients die of multi-organ failure). Conclusions: Biomarker effectiveness for prognosticating SARS-CoV-2 mortality varies significantly by geographical location. We propose that biomarkers and by extension prognostic scores need to be tailored for specific populations. This also implies that validation of commonly used prognostic scores for other conditions should occur before they are used in different populations.
The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and related sub-lineages. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants at two levels: (i) we tracked over 400,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using antibody pools. (ii) we mapped the antibody response at the individual level using blood from strigently curated vaccine and convalescent cohorts. In pooled antibody samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases we observed increased antibody breadth to variants that were yet to be in circulation. Resolution of viral neutralisation at the cohort level supported equivalent coverage across prior and emerging variants with emerging isolates BQ.1.1, XBB.1 and BR.2.1 the most evasive. Further, these emerging variants were resistant to Evusheld, whilst neutralization resistance to Sotrovimab was restricted to BQ.1.1 and further supported by lack of Spike glycoprotein binding to this variant. An outgrowth advantage through better utilization of TMPRSS2 was observed across BQ lineages and not those derived from BA.2.75. We conclude at this current point in time that variants derived from BQ lineages can evade antibodies at levels equivalent to their most evasive BA.2.75 counterparts but sustain an entry phenotype that would promote an additional outgrowth advantage.
The COVID-19 pandemic directly impacted diagnostic services in the UK and globally. This exacerbated the rapid rise in demand for diagnostics that existed before the pandemic, resulting in significant numbers of patients requiring various diagnostic services and increased waiting times for diagnostics and treatment. In 2021, community diagnostic centres were launched in England. As diagnostic services account for over 85% of clinical pathways within the NHS and cost over six billion pounds per year, diagnostic centres across a broader range of diagnostic services may be effective, efficient, and cost-effective in the UK health sector. This rapid review aimed to identify and examine the evidence on the effectiveness of community diagnostic centres. A prior Research Evidence Map was used, along with the stakeholder input, to select a substantive focus for the rapid review. Comparative studies examining community diagnostic centres that accept referrals from primary care as a minimum were included. Prioritised outcomes included those relating to impact on capacity and pressure on secondary care, ensuring equity in uptake or access, and economic outcomes. The review included evidence available up until August 2022. Twenty primary studies were included. Twelve individual diagnostic centres were evaluated across the 20 studies. Most studies evaluated diagnostic centres located within hospital settings. One study evaluated a mobile diagnostic ultrasound service. Most studies were specific to cancer diagnoses. Six studies covered multiple health conditions, which will have also included cancer. Other conditions reported included: severe anaemia, fever of uncertain nature, and multiple sclerosis. A range of outcomes was identified. 11 studies conducted in Spain evaluated the same type of clinic i.e. Quick Diagnostic Unit and seven studies evaluated the same centre at different time intervals. No evidence relating to equity of access was identified. The evidence relating to effectiveness appeared mixed. There is evidence to suggest that diagnostic centres can reduce various waiting times, including time to surgical consultation, time from consultation to treatment, time from cancer suspicion to treatment, time from diagnosis to specialist consultation and time from diagnosis to treatment. Diagnostic centres could help reduce pressure on secondary care by avoiding hospitalisations in stable patients. Cost-effectiveness may depend on whether the diagnostic centre is running at full capacity. Factors that could determine the costs incurred by a centre include the diagnostic and clinical complexity of patients, and the characteristics of the unit including the number of staff and contribution of staff time.
To better understand the drivers of spread of an infectious disease such as COVID-19, it is crucial to identify the most likely individuals to become infected. The continued circulation of SARS-CoV-2 remains a global concern, however with falls in testing only a small fraction of infections are now being recorded. Comprehensive data from earlier periods may then prove a unique resource for probing finer patterns of infection. To this end we analyse the fine spatio-temporal distribution of over 450,000 cases of COVID-19 in Scotland in waves of the B.1.1.529 Omicron and B.1.617.2 Delta lineages, from May 2021 to January 2022. We use random forest regression on case numbers, informed by measures of geography, sociodemographics, testing and vaccination. We then identify indicators for higher case numbers, showing that despite marked differences in the velocity of the outbreaks, the risk factors are remarkably similar. We show how finer variation is only adequately explained through the use of multiple explanatory variables, implying that case heterogeneity resulted from a complex interplay of individual behaviour, immunity, and willingness to test. This analysis also provides evidence that the case distribution may be biased relative to that of all infections, particularly with respect to local deprivation.
Pilot Clinical Trial to Explore Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients - Condition: COVID-19
Intervention: Drug: Pyramax
Sponsor: Shin Poong Pharmaceutical Co. Ltd.
Completed
Animation Supported COVID-19 Education - Condition: COVID-19 Pandemic
Intervention: Other: Animation-Supported Education
Sponsor: Siirt University
Completed
CareSuperb COVID-19 Antigen Test Usability - Condition: COVID-19
Intervention: Device: CareSuperb COVID-19 Antigen Home Test Kit
Sponsor: AccessBio, Inc.
Recruiting
COVID-19 Huashi Baidu Formula Clinical Study - Condition: COVID-19
Interventions: Drug: Huashi Baidu Granule; Drug: Monapiravir
Sponsors: Xiyuan Hospital of China Academy of Chinese Medical Sciences; Beijing YouAn Hospital; Kossamak Hospital; Kamuzu University of Health Sciences
Not yet recruiting
Shaping Care Home COVID-19 Testing Policy - Condition: COVID-19
Intervention: Diagnostic Test: Lateral Flow Device
Sponsor: University College, London
Not yet recruiting
Asunercept for the Treatment of Patients With Moderate to Severe COVID-19 Disease - Condition: COVID-19
Interventions: Biological: Asunercept; Other: Placebo
Sponsor: Apogenix AG
Recruiting
Study in Adults to Assess the Safety and Efficacy of Inhaled IBIO123, for Post-exposure Prophylaxis of COVID-19 - Condition: COVID-19
Interventions: Biological: IBIO123; Other: Placebo
Sponsor: Immune Biosolutions Inc
Not yet recruiting
Feasibility and Usability of COVID-19 Antigen RDTs in Uganda - Condition: COVID-19 Pandemic
Interventions: Diagnostic Test: PMC Sure Status COVID-19 Antigen Test; Diagnostic Test: Acon Flowflex COVID-19 Antigen Home Test
Sponsor: PATH
Not yet recruiting
The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID - Condition: Post-acute COVID-19 Syndromes
Interventions: Other: Vitamin D; Other: Placebo
Sponsor: China Medical University Hospital
Recruiting
A Study to Learn About Bivalent COVID-19 RNA Vaccine Candidate(s) in Healthy Infants and Children - Condition: COVID-19
Interventions: Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 1 microgram dose
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
SUNRISE-3: Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients With COVID-19 - Conditions: SARS CoV 2 Infection; COVID-19
Interventions: Drug: Bemnifosbuvir (BEM); Drug: Placebo
Sponsor: Atea Pharmaceuticals, Inc.
Recruiting
Evaluation of an Integrative Medicine Outpatient Clinical Setting for Post-COVID-19 Patients - Conditions: COVID-19; Fatigue
Interventions: Behavioral: outpatient clinic with multimodal integrative medicine and naturopathy for post-COVID-19 patients; Other: waiting group
Sponsor: Universität Duisburg-Essen
Recruiting
A Study to Evaluate the Efficacy, Safety, and Immunogenicity of SARS-CoV-2 Variant (BA.4 /5) mRNA Vaccine - Condition: COVID-19
Interventions: Biological: ABO1020; Biological: Placebo
Sponsor: Suzhou Abogen Biosciences Co., Ltd.
Active, not recruiting
Prednisolone and Vitamin B1/6/12 in Patients With Post-Covid-Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Drug: Prednisolone 20 mg/ 5 mg; Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12); Drug: Placebo for Vitamin B compound; Drug: Placebo for Prednisolon
Sponsors: Wuerzburg University Hospital; University Hospital Tuebingen; University Hospital Schleswig-Holstein
Recruiting
Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Rapid Panel Professional Use Product Using Mid-Turbinate Nasal Swabs - Conditions: COVID-19; Influenza A; Influenza Type B
Intervention: Diagnostic Test: Panbio™
Sponsor: Abbott Rapid Dx
Not yet recruiting
Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes - No abstract
Screening of Selected Stingless Bee Honey Varieties for ACE2-Spike Protein-Binding Inhibition Activity: A Potential Preventive Medicine Against SARS-Cov-2 Infection - No abstract
Steroid treatment suppresses the CD4+ T-cell response to the third dose of mRNA COVID-19 vaccine in systemic autoimmune rheumatic disease patients - No abstract
Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry - No abstract
SARS-CoV-2 Non-Structural Protein 1(NSP1) Mutation Virulence and Natural Selection: Evolutionary Trends in the Six Continents - No abstract
Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination - No abstract
Mechanistic investigation of SARS-CoV-2 main protease to accelerate design of covalent inhibitors - No abstract
FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2 - No abstract
The impact of sphinogosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination - No abstract
Correction: A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines - No abstract
Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial - No abstract
Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein - No abstract
Real-time monitoring of enzyme-catalyzed phosphoribosylation of anti-influenza prodrug favipiravir by time-lapse NMR spectroscopy - No abstract
Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections - No abstract
Establishment of Quality Evaluation Method for Yinqiao Powder: A Herbal Formula against COVID-19 in China - No abstract