Background and objectives. SARS-CoV-2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T cell response to the resolution or progression of disease is still unclear. Optimal protective immunity may require activation of distinct immune pathways. As such, defining the contribution of individual T cell subsets to disease outcome is imperative to inform the development of next-generation COVID-19 vaccines. To address this, we performed immunophenotyping of T cell responses in unvaccinated individuals, representing the full spectrum of COVID-19 clinical presentation. Methods. Spectral cytometry was performed on peripheral blood mononuclear cell samples from patients with PCR-confirmed SARS-CoV-2 infection. Computational and manual analyses were used to identify T cell populations associated with distinct disease states through unbiased clustering, principal component analysis and discriminant analysis. Results. Critical SARS-CoV-2 infection was characterised by an increase in activated and cytotoxic CD4+ (CTL) cells of a T follicular helper (TFH) or effector memory re-expressing CD45RA (TEMRA) phenotype. These CD4+ CTLs were largely absent in those with less severe disease. In contrast, those with asymptomatic or mild disease were associated with high proportions of naive T cells and reduced expression of activation markers. Conclusion. Highly activated and cytotoxic CD4+ T cell responses may contribute to cell-mediated host tissue damage and progression of COVID-19. Potential for induction of these detrimental T cell responses should be considered when developing and implementing effective COVID-19 control strategies.
The COVID-19 pandemic has impacted the well-being of millions of people around the globe. During the COVID-19 pandemic, the mental health of the population was affected, which means that governments would need to implement different actions to mitigate and treat mental health disorders result of the pandemic. This study aims to estimate the prevalence of anxiety and depression for female and male adolescents and adults in Colombia before the COVID-19 pandemic. It also aimed to estimate the potential increase of the prevalence in each group as a result of the COVID-19 pandemic in 2020. We used the Individual Registry of Health Services Delivery data from 2015 - 2021 to estimate the observed prevalence of anxiety and depression. Using the National Mental Health Survey 2015, we simulated the expected prevalence of anxiety and depression for adolescents (12 to 17 years) and adults (18 or older) from 2016 to 2020. We used an arithmetic static Monte Carlo simulation process to estimate the expected prevalence. The results of the analysis using revealed an important increase in the observed prevalence of these disorders for adults and adolescents and men and women between 2015 and February 2020. When we simulated different scenarios using the National Mental Health Survey and estimated the prevalence of both depression and anxiety for adults and adolescents, we found that the prevalence of depression and anxiety has had an important increase in the last five years for all groups and had an important increase during the 2020. This increase has been greater for women than for men, and for adolescents than adults. Our results show the number of people who need potential attention from the health system in Colombia and highlight the importance to think about how to avoid and detect potential cases of anxiety and depression especially in female adolescents.
Studying the prevalence of SARS-CoV-2 specific antibodies (seroprevalence) allows assessing the impact of epidemic containment measures and vaccinations, as well as estimation of the number of infections regardless of viral testing. We assessed antibody-mediated immunity to SARS-CoV-2 induced by infections and vaccinations from April 2020 to December 2022 in Finland by measuring serum IgG to SARS-CoV-2 nucleoprotein (N-IgG) and spike glycoprotein from randomly selected 18-85-year-old subjects (n=9794). N-IgG seroprevalence remained at <7% until the last quartile (Q) of 2021. After the emergence of the omicron variant, N-IgG seroprevalence increased rapidly and was 31% in Q1/2022 and 54% in Q4/2022. Seroprevalence was highest in youngest age groups from Q2/2022 onwards. We estimated that 51% of the Finnish 18-85-year-old population had antibody-mediated hybrid immunity induced by a combination of vaccinations and infections by the end of 2022. In conclusion, major shifts in the COVID-19 pandemic and resulting population immunity could be observed by serological testing.
Background Infectious diseases are a major driving force of natural selection. One human gene associated with strong evolutionary selection is APOL1. Two APOL1 variants, G1 and G2, emerged in sub-Saharan Africa in the last 10,000 years, possibly due to protection from the fatal African sleeping sickness, analogous to Plasmodium-driven selection of the sickle-cell trait. As homozygosity for the HbS allele causes sickle cell anaemia, homozygosity for the APOL1 G1 and G2 variants has also been associated with chronic kidney disease (CKD) and other kidney-related conditions. What is not known is the extend of non-kidney-related disorders and if there are clusters of diseases associated with individual APOL1 genotypes. Methods Using principal component analysis, we identified a cohort of 10,179 UK Biobank participants with recent African ancestry. We conducted a phenome-wide association test between all combinations of APOL1 G1 and G2 genotypes and conditions identified with International Classification of Disease phenotypes using Firth9s bias-reduced logistic regression and a false discovery rate to correct for multiple testing. We further examined associations with chronic kidney disease indicators: estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine (uACR). Results The phenome-wide screen revealed 74 (mostly deleterious) potential associations with hospitalisation for a range of conditions. G1/G2 compound heterozygotes were specifically associated with hospitalisation in 64 (86.5%) of these conditions, with an over-representation of infectious diseases (including COVID-19) and endocrine, nutritional, and metabolic diseases. The analysis also revealed complexities in the relationship between APOL1 and CKD that are not evident when the risk variants are grouped together: high uACR was associated specifically with G1 homozygosity; low eGFR with G2 homozygosity and G1/G2 compound heterozygosity; progression to end stage kidney disease was associated with G1/G2 compound heterozygosity. Conclusions Among 9,594 participants, stratifying individual APOL1 risk variant genotypes had a differential effect on associations with both kidney and non-kidney phenotypes. The compound heterozygous G1/G2 genotype was distinguished as uniquely deleterious in its association with a range of ICD-10 phenotypes. The epistatic nature of the G1/G2 interaction means that such associations may go undetected in a standard genome-wide association study. These observations have the potential to significantly impact the way that health risks are understood, particularly in populations where APOL1 G1 and G2 are common such as in sub-Saharan Africa and its diaspora.
Background: Post-COVID-19 sequalae involves a variety of new, returning or ongoing symptoms that people experience more than four weeks after getting COVID-19. The aims of this meta-analysis were to assess the prevalence of Post-Acute COVID-19 sequalae and estimate the average time to its diagnosis; and meta-regress for possible moderators. Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database. Search terms included; long COVID-19 or post-acute COVID-19 syndrome/sequalae. The criteria for inclusion were published clinical articles reporting the long COVID-19, further, the average time to diagnosis of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Eggers tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The trial was PROSPERO registered (CRD42022328509). Results: Prevalence of post-acute COVID-19 sequalae was 42.5% (95% confidence interval (CI) 36 % to 49.3%). The PACS event rates range was 25 % at four months and 66 % at two months and mostly, signs and symptoms of PASC were experienced at three (54.3%, P < 0.0001) to six months (57%, P < 0.0001), further increasing at 12 months (57.9%, P= 0.0148). At an average of two months, however with the highest event rate (66%), it was not significantly associated with PACS diagnosis (P=0.08). On meta-regression, comorbidities collectively contributed to 14% of PACS with a non-significant correlation (Q = 7.05, df = 8, p = 0.5313) (R-squared analog = 0.14). A cardiovascular disorder especially hypertension as a stand-alone, showed an event rate of 32% and significantly associated with PACS, 0.322 (95% CI 0.166, 0.532) (P < 0.001). Chronic obstructive pulmonary disorder (COPD) and abnormal basal metabolic index (BMI) had higher event rates of PACS (59.8 % and 55.9 %) respectively, with a non-significant correlation (P > 0.05). With a significant association, hospital re-admission contributed to 17% (Q = 8.70, df = 1, p = 0.0032) (R-squared analog= 0.17) and the study design 26% (Q = 14.32, df = 3, p = 0.0025) (R-squared analog= 0.26). All the covariates explained at least some of the variance in effect size on PACS at 53% (Q = 38.81, df = 19, p = 0.0047) (R-squared analog = 0.53). Conclusion: The prevalence of PACS in general population was 42.5%, of which cardiovascular disorders were highly linked with it with COPD and abnormal BMI also being possible conditions found in patients with PACS. Hospital re-admission predicted highly, an experience of PACS as well as prospective study design. Clinical and methodological characteristics in a specific study contributed to over 50% of PACS events. The PACS event rates ranged between 25 % at four months and 66 % at two months with most signs and symptoms experienced between three to six months increasing at 12 months.
Background: The Coronavirus Disease of 2019 (COVID-19) has impacted the health and day-to-day life of individuals, especially the elderly and people with certain pre-existing medical conditions, including cancer. The purpose of this study was to investigate how COVID-19 impacted access to cancer screenings and treatment, by studying the participants in the Multiethnic Cohort (MEC) study. <br /><br />Methods: The MEC has been following over 215,000 residents of Hawai‘i and Los Angeles for the development of cancer and other chronic diseases since 1993-1996. It includes men and women of five racial and ethnic groups: African American, Japanese American, Latino, Native Hawaiian, and White. In 2020, surviving participants were sent an invitation to complete an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening and treatment. Approximately 7,000 MEC participants responded. A cross-sectional analysis was performed to investigate the relationships between the postponement of regular health care visits and cancer screening procedures or treatment with race and ethnicity, age, education, and comorbidity. <br /><br />Results: Women with more education, women with lung disease, COPD, or asthma, and women and men diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Groups less likely to postpone cancer screening included older women compared to younger women and Japanese American men and women compared to White men and women. <br /><br />Conclusions: This study revealed specific associations of race/ethnicity, age, education level, and comorbidities with the cancer-related screening and healthcare of MEC participants during the COVID-19 pandemic. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis is increased as a result of delayed screening and treatment.<br /><br />Funding: This research was partially supported by the Omidyar 9Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.
Background: Long-term outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized as an emerging public health challenge - a condition termed post-acute coronavirus 2019 syndrome (PACS) or Long-COVID. The pathophysiology of Long-COVID remains to be established, several mechanisms in study focus on the role of P-selectin, an inflammation-induced protein expressed by platelets and endothelial cells. Functional P-selectin activity, potentially implicated in COVID-19 and Long-COVID sequelae, was measured for a Long-COVID subject at 68 weeks from the SARS-CoV-2 infection after fully recover from the syndrome. It was compared with the results from the same subject at 20 weeks post-infection, when subject experienced severe Long-COVID symptoms. Methods: Flow adhesion of whole blood or isolated white blood cells to P-selectin (FA-WB-Psel and FA-WBC-Psel) was measured using a standardized microfluidics clinical assay; impedance aggregometry with a collagen agonist was measured using model 590 Chrono-Log impedance aggregometer; standard laboratory assays were performed to evaluate changes in blood chemistries. Results: After recovery from Long-COVID, RBC count and D-dimer remained elevated and other blood chemistry results remained within the normal range as compared to 20 weeks post infection when severe Long-COVID symptoms were present. Total iron and transferrin-iron saturation percentage values that were elevated when symptoms were present, declined to normal range. Whole blood aggregometry results indicate an absence of previously present platelet hyperactivity. FA-WB-PSel that was significantly elevated during Long-COVID (590 +/- 260 cells/mm2) was significantly reduced after the resolution of Long-COVID symptoms (98 +/- 38 cells/mm2). However, supplementation of whole blood with crizanlizumab did not result in any measurable inhibition of cell adhesion to P-selectin, similarly with previously reported. Similar to what was observed for the subject when Long-COVID symptoms were present, crizanlizumab, even at a dose 10-fold lower than clinical, induced pronounced inhibition of FA-WBC-Psel when tested in buffer, but not in patient own plasma. Conclusions: This report documents the changes in leukocyte adhesion properties for a patient at more than a year from the initial infection after the gradual resolution of Long-COVID symptoms, as compared to when Long-COVID symptoms were present. Recovery from Long-COVID may be associated with normalization of platelet activity, but not necessarily with complete alleviation of endothelial activation. It remains to be determined to what extent changes in leukocyte adhesion to P-selectin may represent a new risk factor for a mechanism driving Long-COVID syndrome.
The vaccine supply chain (VSC) integrates all the activities from production to dispensing. It is characterized by its complexity and low responsiveness, highlighting the importance of defining key performance indicators (KPIs). The design science research methodology was used to develop 38 KPIs, which were grouped into humanitarian and technological dimensions. The former includes demographic, epidemiological, and vaccination indicators, while the latter is classified into five groups according to the echelons of the supply chain. Public and private health organizations and research groups validated the indicators. They were calculated and recorded daily to monitor the logistics progress of the National Vaccination Plan against covid-19 in Colombia. These tailored KPIs, made it possible to evaluate and compare the results of the execution and effectiveness of public policies, and to redefine the strategies, showing that the logistics point of view helps identify the impact of good practices and transfer them promptly.
Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent (“leaky”) protection remains unknown. We examined the effect of prior infection and vaccination on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, unit, and no documented exposures to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection and vaccination reduced the infection risk of residents without a documented exposure (Hazards ratio: infection, 0.36 [0.25-0.54]; vaccination, 0.57 [0.42-0.78]) and with cellblock exposures (infection, 0.61 [0.49-0.75]; vaccination, 0.69 [0.58-0.83]) but not with cell exposures (infection, 0.89 [0.58-1.35]; vaccination, 0.96 [0.64-1.46]). Associations were similar during the Delta period and when analyses were restricted to residents who underwent testing. These findings suggest that SARS-CoV-2 infection and COVID-19 vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in densely crowded settings.
Background: Amid persistent disparities in Covid-19 vaccination, we conducted a scoping review to identify multilevel determinants of Covid-19 vaccine hesitancy (VH) and undervaccination among marginalized populations in the U.S. Methods: We utilized the scoping review methodology developed by the Joanna Briggs Institute and report all findings according to PRISMA-ScR guidelines. We developed a search string and explored 7 databases to identify peer-reviewed articles published from January 1, 2020–October 31, 2021, the initial period of U.S. Covid-19 vaccine availability. We combine frequency analysis and narrative synthesis to describe factors influencing Covid-19 vaccination among marginalized populations. Results: The search captured 2,496 non-duplicated records, which were scoped to 50 peer-reviewed articles: 11 (22%) focused on African American/Black people, 9 (18%) people with disabilities, 4 (8%) justice-involved people, and 2 (4%) each on Latinx, people living with HIV/AIDS, people who use drugs, and LGBTQ+ people. Forty-four articles identified structural factors, 36 social/community, 27 individual, and 40 vaccine-specific factors. Structural factors comprised medical mistrust (of healthcare systems, government public health) and access barriers due to unemployment, unstable housing, lack of transportation, no/low paid sick days, low internet/digital technology access, and lack of culturally and linguistically appropriate information. Social/community factors including trust in a personal healthcare provider (HCP), altruism, family influence, and social proofing mitigated VH. At the individual level, low perceived Covid-19 threat and negative vaccine attitudes were associated with VH. Discussion: This review indicates the importance of identifying and disaggregating structural factors underlying Covid-19 undervaccination among marginalized populations, both cross-cutting and population-specific—including multiple logistical and economic barriers in access, and systemic mistrust of healthcare systems and government public health—from individual and social/community factors, including trust in personal HCPs/clinics as reliable sources of vaccine information, altruistic motivations, and family influence, to effectively address individual decisional conflict underlying VH as well as broader determinants of undervaccination.
Healthcare workers (HCWs) face a high risk of infection during pandemics or public health emergencies as demonstrated in the ongoing COVID-19 pandemic. Understanding how governments respond can inform public health control measures and support health system functioning. An economic impact analysis examining HCW COVID-19 infections in Kenya and three other countries estimated that the total economic costs related to HCW COVID-19 infections costs and deaths in Kenya were US$113.2 million (range US$35.8-US$246.1). We examined the governance arrangements for and implementation of HCW protection during the COVID-19 pandemic in Kenya between March 2020 and March 2021. We conducted a scoping review of 44 policy and legislative documents and reports on HCW protection and 22 media articles. We adopted the transparency, accountability, participation, integrity and capacity (TAPIC) governance framework to analyse and summarize our findings into policy gaps and implementation challenges. Policy design gaps included inadequate provisions for emerging threats, inconsistencies with the devolved context and inadequate structures to monitor, inform and respond to HCW COVID-19 infections. Implementation challenges were attributed to inadequate quantity and quality of PPE, difficulty in accessing medical care for HCWs, delays in HCW remuneration, insufficient infection prevention and control measures, the top-down application of plans, difficulties in working in a decentralized context, and pre-existing public finance management (PFM) bottlenecks. Implementation of HCW protection during the COVID-19 pandemic and beyond could leverage the revamping of current legislation on labour relations to reflect devolved governance and develop a broader and long-term approach to occupational health and safety implementation that considers all HCWs. Improvements in PFM arrangements coupled with increased investment in the health sector and attention to efficient use of resources will also impact positively on HCW protection.
Aims: To utilise environmental surface sampling to evaluate areas of SARS-CoV-2 contamination within workplaces to identify trends and improve local COVID-control measures. Methods and Results: Surface sampling was undertaken at 12 workplaces that experienced a cluster of COVID-19 cases in the workforce between March 2021 and March 2022. 7.4% (61/829) of samples collected were positive for SARS-CoV-2 RNA by qPCR with only 1.8% (15/829) of samples identified with crossing threshold (Ct) values below 35.0. No sample returned whole genome sequence inferring RNA detected was degraded. Conclusions: Few workplace surface samples were positive for SARS-CoV-2 RNA and positive samples typically contained low levels of nucleic acid. Although these data may infer a low probability of fomite transmission or other forms of transmission within the workplace, Ct values may have been lower at the time of contamination. Workplace environmental sampling identified lapses in COVID-control measures within individual sites and showed trends through the pandemic. Significance and Impact of the Study: Prior to this study, few published reports investigated SARS-CoV-2 RNA contamination within workplaces experiencing cases of COVID-19. This report provides extensive data on environmental sampling identifying trends across workplaces and through the pandemic.
Rationale: Multiple pulmonary, sleep, and other disorders are associated with the severity of Covid-19 infections but may or may not directly affect the etiology of acute Covid-19 infection. Identifying the relative importance of concurrent risk factors may prioritize respiratory disease outbreaks research. Objectives: To identify associations of common preexisting pulmonary and sleep disease on acute Covid-19 infection severity, investigate the relative contributions of each disease and selected risk factors, identify sex-specific effects, and examine whether additional electronic health record (EHR) information would affect these associations. Methods: 45 pulmonary and 6 sleep diseases were examined in 37,020 patients with Covid-19. We analyzed three outcomes: death; a composite measure of mechanical ventilation and/or ICU admission; and inpatient admission. The relative contribution of pre-infection covariates including other diseases, laboratory tests, clinical procedures, and clinical note terms was calculated using LASSO. Each pulmonary/sleep disease model was then further adjusted for covariates. Measurements and main results: 37 pulmonary/sleep diseases were associated with at least one outcome at Bonferroni significance, 6 of which had increased relative risk in LASSO analyses. Multiple prospectively collected non-pulmonary/sleep diseases, EHR terms and laboratory results attenuated the associations between preexisting disease and Covid-19 infection severity. Adjustment for counts of prior “blood urea nitrogen” phrases in clinical notes attenuated the odds ratio point estimates of 12 pulmonary disease associations with death in women by >=1. Conclusions: Pulmonary diseases are commonly associated with Covid-19 infection severity. Associations are partially attenuated by prospectively-collected EHR data, which may aid in risk stratification and physiological studies.
Background Interventions introduced in 2020 to reduce the spread of SARS-CoV-2 led to a widespread reduction in childhood infections, including respiratory syncytial virus (RSV), in the subsequent year. However, from the spring of 2021 onwards the United Kingdom and Ireland began to experience an unusual out of season epidemic of childhood respiratory disease. Methods We conducted a prospective observational cohort study (BronchStart), enrolling children aged 0-23 months presenting with clinician-diagnosed bronchiolitis, lower respiratory tract infection or first episode of wheeze in 59 Emergency Departments (ED) across England, Scotland and Ireland from 1 May 2021 to 30 April 2022. We collected baseline data on patient demographics and clinical presentation, and follow-up data at 7 days. We used high-granularity BronchStart clinical data together with national English and Scottish admission datasets to infer the impact of RSV disease in a typical year before the Covid-19 pandemic, and to provide an up-to-date estimate of the annual impact of disease to inform implementation of anti-RSV interventions. Findings The BronchStart study collected data on 17,899 ED presentations for 17,179 children. Of these, 6,825 (38.1%) were admitted to hospital for further observation or treatment, 458 (2.6%) required care in a high dependency unit (HDU), and 154 (0.9%) were admitted to a paediatric intensive care unit (PICU). Of the 5,788 children admitted and tested for RSV, 41.8% of the overall study cohort, and 48.7% of those 0-11 months of age, were positive. Risk factors for hospital admission included prematurity and congenital cardiac disease. Patients with these risk factors were also more likely to receive oxygen therapy, or be admitted to a HDU or PICU. However, 84.5% of those admitted to an observation unit, 78.1% of those admitted to a ward, 67.7% of those admitted to HDU and 50.0% of those admitted to PICU had no identified comorbidity. Using admissions data for England and Scotland we estimate that every year 12,167 infants with RSV infection receive low flow oxygen, 4,998 high flow oxygen and 6,198 a course of antibiotic therapy in secondary care. Interpretation Although RSV was the major pathogen in this cohort, 51.3% of admissions for serious respiratory viral infections in those aged <1 year of age were not associated with the virus. Whilst prematurity and congenital cardiac disease were risk factors for admission to hospital, HDU and PICU, the majority of these admissions, for all levels of care except PICU, were in previously healthy term born infants.
MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance - Condition: COVID-19
Intervention: Drug: Manzi Guben granules
Sponsors: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine
Not yet recruiting
Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial - Condition: COVID-19
Intervention: Procedure: Pilates Exercises
Sponsor: Michele de Aguiar Zacaria
Recruiting
Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age - Condition: COVID-19
Intervention: Biological: SARS-CoV-2 subunit protein recombinant vaccine
Sponsors: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran
Not yet recruiting
Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome - Condition: COVID-19 Pneumonia
Intervention: Other: Aerobic exercise and strength training
Sponsor: Ukbe Sirayder
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone) - Condition: Covid19
Interventions: Drug: Fluticasone; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400) - Condition: Covid19
Interventions: Drug: Ivermectin; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages - Condition: COVID-19
Intervention: Behavioral: Persuasive Appeal
Sponsor: University of Calgary
Completed
Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19 - Condition: COVID-19
Intervention: Diagnostic Test: Blood sampling
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Completed
Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19 - Condition: COVID-19
Interventions: Drug: N-Acetylcysteine; Drug: Placebo
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Active, not recruiting
A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients - Condition: COVID-19
Intervention: Diagnostic Test: miRNA analysis in plasma
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Completed
Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis - Condition: COVID-19
Interventions: Drug: Double-Stranded RNA sodium salt; Drug: Placebo
Sponsor: Promomed, LLC
Completed
CONFIDENCE: a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents - Condition: COVID-19 Vaccination
Intervention: Behavioral: CONFIDENCE
Sponsors: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health
Not yet recruiting
Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection - Condition: COVID-19
Interventions: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator
Sponsor: Hebei Medical University
Recruiting
Cognitive Rehabilitation for People With Cognitive Covid19 - Condition: Long Covid19
Intervention: Behavioral: Cognitive rehabilitation
Sponsors: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust
Recruiting
MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study - Conditions: COVID-19; Influenza A; Influenza B
Interventions: Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test; Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)
Sponsors: Medical Group Care, LLC; CSSi Life Sciences
Recruiting
Nuclear export inhibitor Selinexor targeting XPO1 enhances coronavirus replication - Nucleocytoplasmic transport of proteins using XPO1 (exportin 1) plays a vital role in cell proliferation and survival. Many viruses also exploit this pathway to promote infection and replication. Thus, inhibiting XPO1-mediated nuclear export with selective inhibitors activates multiple antiviral and anti-inflammatory pathways. The XPO1 inhibitor, Selinexor, is an FDA-approved anticancer drug predicted to have antiviral function against many viruses, including SARS-CoV-2. Unexpectedly, we…
Use of the particle agglutination/particle agglutination inhibition test for antigenic analysis of SARS-CoV-2 - CONCLUSIONS: The PAI test is an easy and rapid method to analyze the antigenicity of SARS-CoV-2.
Machine learning combines atomistic simulations to predict SARS-CoV-2 Mpro inhibitors from natural compounds - To date, the COVID-19 pandemic has still been infectious around the world, continuously causing social and economic damage on a global scale. One of the most important therapeutic targets for the treatment of COVID-19 is the main protease (Mpro) of SARS-CoV-2. In this study, we combined machine-learning (ML) model with atomistic simulations to computationally search for highly promising SARS-CoV-2 Mpro inhibitors from the representative natural compounds of the National Cancer Institute (NCI)…
Relapse of acquired hemophilia A following COVID-19 - Acquired hemophilia A (AHA) is a rare disease in which an autoantibody causes bleeding by interacting with and inhibiting the coagulation activity of endogenous factor VIII (FⅧ). Most cases of AHA are idiopathic, and other causes include autoimmune diseases, malignant tumors, pregnancy, drugs, and viral infections. An 86-year-old man was diagnosed with AHA based on the following results: activated partial thromboplastin time (aPTT) extension of 130.7 seconds, inhibitor pattern by mixing study,…
HLA-E01:01 + HLA-E01:01 genotype confers less susceptibility to COVID-19, while HLA-E01:03 + HLA-E01:03 genotype is associated with more severe disease - BACKGROUND: HLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8^(+) T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have…
DiDang decoction improves mitochondrial function and lipid metabolism via the HIF-1 signaling pathway to treat atherosclerosis and hyperlipidemia - CONCLUSION: DDD exerts therapeutic effects on AS and HLP through multiple targets and pathways, and improves mitochondrial function, reduces ROS content, inhibits ferroptosis and apoptosis by activating the HIF-1 signaling pathway, which provides reliable theoretical and experimental support for DDD treatment of AS and HLP.
Investigating the competition between ACE2 natural molecular interactors and SARS-CoV-2 candidate inhibitors - The SARS-CoV-2 pandemic still poses a threat to the global health as the virus continues spreading in most countries. Therefore, the identification of molecules capable of inhibiting the binding between the ACE2 receptor and the SARS-CoV-2 spike protein is of paramount importance. Recently, two DNA aptamers were designed with the aim to inhibit the interaction between the ACE2 receptor and the spike protein of SARS-CoV-2. Indeed, the two molecules interact with the ACE2 receptor in the region…
Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19 - The relationship between diabetes and COVID-19 is bi-directional: while individuals with diabetes and high blood glucose (hyperglycemia) are predisposed to severe COVID-19, SARS-CoV-2 infection can also cause hyperglycemia and exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network of SARS-CoV-2 infection, hyperglycemia, and hyper-inflammation, all factors that drive COVID-19 pathophysiology, are urgently needed. Here, we show that genetic ablation or…
Arabincoside B isolated from Caralluma arabica as a potential anti-pneumonitis in LPS mice model - Acute lung injury (ALI) is a life-threatening condition usually associated with poor therapeutic outcomes and a high mortality rate. Since 2019, the situation has worsened due to the COVID-19 pandemic. ALI had approximately 40% of deaths before COVID-19, mainly due to the dysfunction of the blood-gas barrier that led to lung edema, failure of gas exchange, and dyspnea. Many strategies have been taken to mitigate the disease condition, such as diuretics, surfactants, antioxidants,…
Azapeptide activity-based probes for the SARS-CoV-2 main protease enable visualization of inhibition in infected cells - The COVID-19 pandemic has revealed the vulnerability of the modern, global society. With expected waves of future infections by SARS-CoV-2, treatment options for infected individuals will be crucial in order to decrease mortality and hospitalizations. The SARS-CoV-2 main protease is a validated drug target, for which the first inhibitor has been approved for use in patients. To facilitate future work on this drug target, we designed a solid-phase synthesis route towards azapeptide activity-based…
Plant-derived Ren’s oligopeptide has antiviral effects on influenza virus and SARS-CoV-2 - Influenza virus and SARS-CoV-2 virus are two important viruses that cause respiratory tract diseases. The high-frequency mutation of the two types of viruses leads to failure of the durable immune protection of vaccines, meanwhile it also poses continuous challenges to the development of antiviral drugs. Traditional Chinese medicine contains large number of biologically active compounds, and some of them contain broad-spectrum antiviral ingredients. In this study, we extracted antiviral active…
Exploring epidemic voluntary vaccinating behavior based on information-driven decisions and benefit-cost analysis - A complex dynamic interplay exists between epidemic transmission and vaccination, which is significantly influenced by human behavioral responses. We construct a research framework combining both the function modeling of the cumulative global COVID-19 information and limited individuals’ information processing capacity employing the Gompertz model for growing processes. Meanwhile, we built a function representing the decision to get vaccinated following benefit-cost analysis considered the…
Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus - Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N-benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC(50) = 1.56±0.55 µmol L^(-1)). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2-c]pyrazole fragment showed moderate activity…
Synthesis of conjugates of (aR,7S)-colchicine with monoterpenoids and investigation of their biological activity - Conjugates of the natural alkaloid (aR,7S)-colchicine with bicyclic monoterpenoids and their derivatives were synthesized for the first time. Molecular docking of the synthesized agents in the active site of the main viral protease of the SARS-CoV-2 virus was carried out. The cytotoxic properties of the agents against different cell lines and the ability to inhibit the main viral protease 3CLPro were studied.
Identification of natural compounds as SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation - CONCLUSION: To sum up, the study concluded that four phytochemicals (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) had significant effects on the binding sites of the SARS-CoV-2 S protein. This study needs further in vitro and in vivo experimental validation of these major phytochemicals to assess their potential anti-SARS-CoV-2. Graphical abstract.