Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include an increased incidence of diabetes. Our objective was to describe the temporal relationship between new diagnoses of diabetes mellitus and SARS-CoV-2 infection in a nationally representative database. There appears to be a sharp increase in diabetes diagnoses in the 30 days surrounding SARS-CoV-2 infection, followed by a decrease in new diagnoses in the post-acute period, up to 360 days after infection. These results underscore the need for further investigation, as understanding the timing of new diabetes onset after COVID-19 has implications regarding potential etiology and screening and treatment strategies.
Objectives. This study describes trends in all-cause mortality and Years of Life Lost (YLL) before and after COVID-19 in Washington, DC, disaggregated by age, sex, race, and ward of residence as a proxy for socioeconomic status. Methods. We obtained mortality data from DC9s death records and calculated sex-age-race-specific death rates using information from the census and YLL using the life table approach and the difference in life expectancy between people with and without a COVID-19 diagnosis. Results. In 2020 there were 990 more deaths (139 per 100K) in the capital compared to the annual average over the previous five years, and 676 of these deaths (94.8 per 100K) listed COVID-19 as one of the causes of death. Excess deaths in 2020 were higher in April, May, and December than in other months by 100-300 deaths; were higher for men than women by about 10.2%, and occurred almost entirely among residents 55 and older. Moreover, excess deaths were higher for those identified as Black or Hispanic by about 300 or 150 per 100K, respectively–the highest proportional increase (almost twofold) for Hispanics in 2020 compared to the five previous years. Additionally, neighborhood differences reflect ethnic and socioeconomic inequality: increases in mortality during 2020 were most significant for those wards with the most Black and Hispanic residents and the lowest income and employment rates, corresponding with historical trends in illness and mortality. Indicating the intersectionality of these differences, in 2020, Black and Hispanic males lost 6 and 7 expected years of life, respectively, and Black and Hispanic females lost 5 and 6 years, respectively. In contrast, Whites lost no years of life during the pandemic. Conclusion. Examining mortality rates and life expectancy within population subgroups and using ward-level data allows us to understand how the pandemic has exacerbated health inequalities. Local-level sociodemographic research like ours reveals intersectional inequalities often obscured by the national statistics often used in popular and scholarly discourse. Our findings should promote actionable local policy to decrease YLL from preventable deaths and earlier mortality from COVID-19 among disadvantaged groups.
Background. Some months after the remission of acute COVID-19 infection, some people show depressive symptoms, which are predicted by increased peak body temperature (PBT) and lowered blood oxygen saturation (SpO2). Nevertheless, no data indicate whether Long COVID is associated with increased insulin resistance (IR) in association with depressive symptoms and immune, oxidative, and nitrosative (IO&NS) processes. Methods. We used the homeostasis Model Assessment 2 (HOMA2) calculator to compute beta-cell function, insulin sensitivity and resistance (HOMA2-IR) and measured the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HAMD) in 86 Long COVID patients and 39 controls. We examined the associations between the HOMA2 indices and PBT and SpO2 during acute infection, and depression, IO&NS biomarkers (C-reactive protein, NLRP3 activation, myeloperoxidase, and advanced oxidation protein products) 3-4 months after the acute infection. Results. Long COVID is accompanied by increased HOMA2-IR, fasting blood glucose, and insulin levels. We found that 33.7% of the patients versus 0% of the controls had HOMA2-IR values >1.8, suggesting IR. PBT, but not SpO2, during acute infection significantly predicted IR, albeit with a small effect size. Increased IR was significantly associated with depressive symptoms as assessed with the BDI and HAMD above and beyond the effects of IO&NS pathways. There were no significant associations between increased IR and the activated IO&NS pathways during Long COVID. Conclusion. Long COVID is associated with new-onset IR in a subset of patients. Increased IR may contribute to the onset of depressive symptoms due to Long COVID by enhancing overall neurotoxicity.
The debate around vaccine prioritization for COVID-19 has revolved around balancing the benefits from: (1) the direct protection conferred by the vaccine amongst those at highest risk of severe disease outcomes, and (2) the indirect protection through vaccinating those that are at highest risk of being infected and of transmitting the virus. While adults aged 65+ are at highest risk for severe disease and death from COVID-19, essential service and other in-person workers with greater rates of contact may be at higher risk of acquiring and transmitting SARS-CoV-2. Unfortunately, there have been relatively little data available to understand heterogeneity in contact rates and risk across these demographic groups. Here, we retrospectively analyze and evaluate vaccination prioritization strategies by age and worker status. We use a mathematical model of SARS-CoV-2 transmission and uniquely detailed contact data collected as part of the Berkeley Interpersonal Contact Survey to evaluate five vaccination prioritization strategies: (1) prioritizing only adults over age 65, (2) prioritizing only high-contact workers, (3) splitting prioritization between adults 65+ and high-contact workers, (4) tiered prioritization of adults over age 65 followed by high-contact workers, and (5) tiered prioritization of high-contact workers followed by adults. We find that for the primary two-dose vaccination schedule, assuming 70% uptake, a tiered roll-out that first prioritizes adults 65+ averts the most deaths (31% fewer deaths compared to a no-vaccination scenario) while a tiered roll-out that prioritizes high contact workers averts the most number of clinical infections (14% fewer clinical infections compared to a no-vaccination scenario). We also consider prioritization strategies for booster doses during a subsequent outbreak of a hypothetical new SARS-CoV-2 variant. We find that a tiered roll-out that prioritizes adults 65+ for booster doses consistently averts the most deaths, and it may also avert the most number of clinical cases depending on the epidemiology of the SARS-CoV-2 variant and the vaccine efficacy.
Health technology assessments (HTAs) of vaccines typically focus on the direct health benefits to individuals and healthcare systems. COVID-19 highlighted the widespread societal impact of infectious diseases and the value of vaccines in averting adverse clinical consequences and in maintaining or resuming social and economic activities. Using COVID-19 as a case study, this research work aimed to set forth a conceptual framework capturing the broader value elements of vaccines and to identify appropriate methods to quantify value elements not routinely considered in HTAs. A two-step approach was adopted combining a targeted literature review and three rounds of expert elicitation based on a modified Delphi method, leading to a conceptual framework of 30 value elements related to broader health effects, societal and economic impact, public finances, and uncertainty value. When applying the framework to COVID-19 vaccines in post-pandemic settings, 13 value elements were consensually rated highly important by the experts for consideration in HTAs. The experts reviewed over 10 methods that could be leveraged to quantify broader value elements and provided technical forward-looking recommendations. Limitations of the framework and the identified methods were discussed. This study supplements on-going efforts aimed towards a broader recognition of the full societal value of vaccines.
Background Patients on kidney replacement therapy (KRT; dialysis and kidney transplantation) are at the highest risk of severe outcomes from COVID-19. Due to limited inclusion of patients on KRT in clinical trials, information is limited on the effectiveness of sotrovimab (a neutralising monoclonal antibody). We sought to address this by comparing its effectiveness against molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised adults with symptomatic COVID-19. Methods With the approval of NHS England we used routine clinical data from 24 million patients in England linked to the UK Renal Registry (UKRR) to identify patients on KRT, and data on antiviral treatments, COVID-19 test results, hospitalisation events and death from the OpenSAFELY-TPP data resource. Cox proportional hazards models (stratified for region) were used to estimate hazard ratios of sotrovimab vs. molnupiravir with regards to COVID-19 related hospitalisation or deaths in the subsequent 28 days (as the primary outcome). Further analyses were conducted using propensity score weighting (adjusted for region) and to investigate robustness of results with regards to different time periods, missing data, and adjustment variables. We also conducted a complementary analysis using data from patients in the Scottish Renal Registry (SRR) treated with sotrovimab or molnupiravir, following similar analytical approaches. Results Among the 2367 renal patients treated with sotrovimab (n=1852) or molnupiravir (n=515) between December 16, 2021 and August 1, 2022 in England, 38 cases (1.6%) of COVID-19 related hospitalisations/deaths were observed during the 28 days of follow-up after treatment initiation, with 21 (1.1%) in the sotrovimab group and 17 (3.3%) in the molnupiravir group. In multiple-adjusted analysis sotrovimab was associated with substantially lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (hazard ratio, HR=0.35, 95% CI: 0.17 to 0.71; P=0.004), with results remaining robust in sensitivity analyses. In the SRR cohort, there were 19 cases (1.9%) of COVID-19 related hospitalisations/deaths during the 28 days of follow-up after treatment initiation of sotrovimab (n=723) or molnupiravir (n=270). In multiple-adjusted analysis, sotrovimab showed a trend toward lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (HR=0.40, 95% CI: 0.13 to 1.21; P=0.106). In both datasets, sotrovimab had no evidence of association with other hospitalisation/death compared with molnupiravir (HRs ranging from 0.73-1.20; P>0.05). Conclusions In routine care of non-hospitalised patients with COVID-19 on kidney replacement therapy, those who received sotrovimab had substantially lower risk of severe COVID-19 outcomes than those receiving molnupiravir.
The ARTIC protocol uses a multiplexed PCR approach with two primer pools tiling the entire SARS-CoV-2 genome. Primer pool updates are necessary for accurate amplicon sequencing of evolving SARS-CoV-2 variants with novel mutations. The suitability of the ARTIC V4 and updated V4.1 primer scheme was assessed using whole genome sequencing of Omicron from clinical samples using Oxford Nanopore Technology. Analysis of Omicron BA.1 genomes revealed that 93.22% of clinical samples generated improved genome coverage at 50x read depth with V4.1 primers when compared to V4 primers. Additionally, the V4.1 primers improved coverage of BA.1 across amplicons 76 and 88, which resulted in the detection of the variant defining mutations G22898A, A26530G and C26577G. The Omicron BA.2 sub-variant (VUI-22JAN-01) replaced BA.1 as the dominant variant by March 2022, and analysis of 168 clinical samples showed reduced coverage across amplicons 15 and 75. Upon further interrogation of primer binding sites, a mutation at C4321T (present in 163/168, 97% of 30 samples) was identified as a possible cause of complete dropout of amplicon 15. Furthermore, two mutations were identified within the primer binding regions for amplicon 75: A22786C (present in 90% of samples) and C22792T (present in 12.5% of samples). Together, these mutations may result in reduced coverage of amplicon 75 and further primer updates would allow the identification of the two BA.2 defining mutations present in amplicon 75; A22688G and T22679C. This work highlights the need for ongoing surveillance of primer matches as circulating variants evolve and change.
BACKGROUND: With widespread transmission of the Omicron SARS-CoV-2 variant, reinfections have become increasingly common. Here, we explored the role hybrid immunity, primary infection severity, and variant predominance on the risk of reinfection and severe COVID-19 during periods of Omicron predominance in Mexico. METHODS: We analyzed reinfections in Mexico in individuals with ≥90 days from a previous primary infection using a national surveillance registry of SARS-CoV-2 cases from March 3rd, 2020, until August 13th, 2022. Immunity-generating events included primary infection, partial or full vaccination and vaccine boosting. Reinfections were matched by age and sex with controls with primary SARS-CoV-2 infection and negative RT-PCR or antigen test ≥90 days after infection to explore risk factors for reinfection and reinfection-associated severe COVID-19. We also explored the protective role of heterologous vs. homologous vaccine boosters against reinfection or severe COVID-19 in fully vaccinated individuals. RESULTS: We detected 231,202 SARS-CoV-2 reinfections in Mexico, with most occurring in unvaccinated individuals (41.55%). Over 207,623 reinfections occurred during periods of Omicron (89.8%), BA.1 (36.74%) and BA.5 (33.67%) subvariant predominance and a case-fatality rate of 0.22%. Vaccination protected against reinfection, without significant influence of the order of immunity-generating events and provided >90% protection against severe reinfections. Heterologous booster schedules were associated with ~11% and ~54% lower risk for reinfection and reinfection-associated severe COVID-19 respectively, modified by time-elapsed since the last immunity-generating event. CONCLUSIONS: SARS-CoV-2 reinfections have increased during periods of Omicron predominance. Hybrid immunity provides protection against reinfection and reinfection-associated severe COVID-19, with potential benefit from heterologous booster schemes.
Background: Research demonstrates that SARS-CoV-2 infection (COVID-19) among adults disproportionately impacts racial and ethnic minorities and those living in lower-income communities. Similar research in children is limited due, in part, to the relatively low incidence in children compared to adults. This analysis, conducted as part of the RECOVER Initiative, explores this question. Methods: Electronic health record (EHR) data from PEDSnet, a multi-institutional research network of pediatric healthcare organizations, were geocoded and linked to two indices of contextual social deprivation: the Area Deprivation Index and the Child Opportunity Index. Univariate statistics were employed to test the association between each index and COVID19 positivity among children ages 0-20 tested at one of six Childrens hospitals. Multivariate logistic regression was used to explore the relationship between these social context indices and racial disparities in positivity, controlling co-variates. Results: Both ADI and COI were significantly associated with COVID-19 positivity in univariate and adjusted models, particularly in the pre-delta and delta variant waves. ADI showed a stronger association. Higher rates of positivity were found for non-Hispanic Black, Hispanic, and multi-racial children compared to non-Hispanic White children. These racial disparities remained significant after control for either index and other variables. Conclusion: ADI and COI are significantly associated with COVID-19 test positivity in a population of children and adolescents tested in childrens hospital settings. These social contextual variables do not fully explain racial disparities arguing that racial disparities are not solely a reflection of socioeconomic status. Future disparities research should consider both race and social context.
The Polio eradication campaign has been set back substantially since 2020 due to the COVID-19 pandemic. Recent detections of poliovirus transmission in multiple high-income countries suggest suboptimal population immunity in many parts of the world even though polio vaccination has been included in routine childhood immunization for decades. We reviewed polio vaccination schedules and vaccine uptake in the Western Pacific Region countries and assessed the potential shortfall in population immunity against polio resurgence across these populations. In addition, we conducted a repeated cross-sectional study between 2021 and 2022 in the Western Pacific Region to understand factors contributing to polio vaccine hesitancy. Our results reveal potential shortfalls in population immunity against polio in Western Pacific Region and provide insights into how vaccination programs and campaigns can be strengthened to ensure continual progress towards polio eradication.
Short-term forecasts can provide predictions of how an epidemic will change in the near future and form a central part of outbreak mitigation and control. Renewal-equation based models are increasingly popular. They infer key epidemiological parameters from historical epidemiological data and forecast future epidemic dynamics without requiring complex mechanistic assumptions. However, these models typically ignore interaction between age-groups, partly due to challenges in parameterising a time varying interaction matrix. Social contact data collected regularly by the CoMix survey during the COVID-19 epidemic in England, provide a means to inform interaction between age-groups in real-time. We developed an age-specific forecasting framework and applied it to two age-stratified time-series: incidence of SARS-CoV-2 infection, estimated from a national infection and antibody prevalence survey; and, reported cases according to the UK national COVID-19 dashboard. Jointly fitting our model to social contact data from the CoMix study, we inferred a time-varying next generation matrix which we used to project infections and cases in the four weeks following each of 29 forecast dates between October 2021 and November 2022. We evaluated the forecasts using proper scoring rules and compared performance with three other models with alternative data and specifications alongside two naive baseline models. Overall, incorporating age-interaction improved forecasts of infections and the CoMix-data-informed model was the best performing model at time horizons between two and four weeks. However, this was not true when forecasting cases. We found that age-group-interaction was most important for predicting cases in children and older adults. The contact-data-informed models performed best during the winter months of 2020 - 2021, but performed comparatively poorly in other periods. We highlight challenges regarding the incorporation of contact data in forecasting and offer proposals as to how to extend and adapt our approach, which may lead to more successful forecasts in future.
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
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
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
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
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
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
Efficacy of a Physical and Respiratory Rehabilitation Program for Patients With Persistent COVID-19 (SARS-CoV-2). - Conditions: SARS-CoV-2 Infection; COVID-19 Recurrent; Cognitive Dysfunction; Fatigue
Intervention: Other: COPERIA-REHAB
Sponsors: Fundacin Biomedica Galicia Sur; University of Vigo; Galician South Health Research Institute
Not yet recruiting
Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Covid-19 - Condition: SARS-CoV-2 Infection
Interventions: Drug: Azvudine; Drug: Placebo
Sponsors: Shanghai Henlius Biotech; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd
Not yet recruiting
Randomised Clinical Trial to Evaluate the Efficacy of an Online Cognitive Rehabilitation Programme (COPERIA-COG) for Patients With Persistent COVID-19 - Conditions: COVID-19; Neuro-Degenerative Disease; Psychological; SARS CoV 2 Infection
Intervention: Other: Sessions of cognitive stimulation
Sponsors: Fundacin Biomedica Galicia Sur; Centro de Investigación Biomédica en Red de Salud Mental; Galician South Health Research Institute
Not yet recruiting
VNS for Long-COVID-19 - Conditions: Post-COVID-19 Syndrome; Postural Tachycardia Syndrome; Dysautonomia
Interventions: Device: Non-invasive vagus nerve stimulation; Device: Sham Intervention
Sponsor: Icahn School of Medicine at Mount Sinai
Recruiting
Differential Diagnosis of Persistent COVID-19 by Artificial Intelligence - Conditions: COVID-19; Fatigue; Distress Respiratory Syndrome; Cognitive Dysfunction; COVID-19 Recurrent; SARS CoV 2 Infection
Intervention: Other: Experimental tests
Sponsors: Fundacin Biomedica Galicia Sur; University of Vigo; Galician South Health Research Institute
Not yet recruiting
Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection - Conditions: Health Behavior; Child Development; Adolescent Obesity
Interventions: Dietary Supplement: Probiotics; Behavioral: Counselling on healthy eating, physical activity, and psychosocial stimulation; Dietary Supplement: Placebo probiotics
Sponsors: Indonesia University; Gadjah Mada University; Universitas Airlangga; University of Melbourne; The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia
Recruiting
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
Identification of FDA-approved drugs against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through computational virtual screening - No abstract
Identification of highly effective inhibitors against SARS-CoV-2 main protease: From virtual screening to in vitro study - No abstract
Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D - No abstract
Increased IL-26 associates with markers of hyperinflammation and tissue damage in patients with acute COVID-19 - No abstract
Repurposing of drugs for combined treatment of COVID-19 cytokine storm using machine learning - No abstract
The evolution of the global COVID-19 epidemic in Morocco and understanding the different therapeutic approaches of chitosan in the control of the pandemic - No abstract
Discovery of Novel Thioquinazoline-N-aryl-acetamide/N-arylacetohydrazide Hybrids as Anti-SARS-CoV-2 Agents: Synthesis, in vitro Biological Evaluation, and Molecular Docking Studies - No abstract
Small molecules in the treatment of COVID-19 - No abstract
Staff experiences, perceptions of care, and communication in the intensive care unit during the COVID-19 pandemic in Australia - No abstract
RBM24 inhibits the translation of SARS-CoV-2 polyproteins by targeting the 5’-untranslated region - No abstract
Agent-based model using GPS analysis for infection spread and inhibition mechanism of SARS-CoV-2 in Tokyo - No abstract
Platelets in COVID-19 disease: friend, foe, or both? - No abstract
Effect of colonisation with Neisseria lactamica on cross-reactive anti-meningococcal B-cell responses: a randomised, controlled, human infection trial - No abstract