Background: Home working rates have increased since the COVID-19 pandemic9s onset, but the health implications of this transformation are unclear. We assessed the association between home working and social and mental wellbeing through harmonised analyses of seven UK longitudinal studies. Methods: We estimated associations between home working and measures of psychological distress, low life satisfaction, poor self-rated health, low social contact, and loneliness across three different stages of the COVID-19 pandemic (T1= Apr-Jun 2020 - first lockdown, T2=Jul-Oct 2020 - eased restrictions, T3=Nov 2020-Mar 2021 - second lockdown), in seven population-based cohort studies using modified Poisson regression and meta-analyses to pool results across studies. Findings: Among 34,131 observations spread over three time points, we found higher rates of home working at T1 and T3 compared with T2, reflecting lockdown periods. Home working was not associated with psychological distress at T1 (RR=0.92, 95%CI=0.79-1.08) or T2 (RR=0.99, 95%CI=0.88-1.11), but a detrimental association was found with psychological distress at T3 (RR=1.17, 95%CI=1.05-1.30). Poorer psychological distress associated with home working was observed for those educated to below degree level at T2 and T3. Men working from home reported poorer self-reported health at T2. Interpretation: No clear evidence of an association between home working and mental wellbeing was found, apart from greater risk of psychological distress associated with home working during the second lockdown, but differences across sub-groups may exist. Longer term shifts to home working might not have adverse impacts on population wellbeing in the absence of pandemic restrictions but further monitoring of health inequalities is required.
Background: Immune protection against SARS-CoV-2 can be induced by natural infection or vaccination or both. The interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied. Methods: We used regression models to evaluate whether the impact of COVID-19 vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for three evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy of the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state. Results: COVID-19 mortality decreased as the coverage of ≥1 dose increased among people ≥65 years of age, and this effect did not vary by seroprevalence or the proportion of the total population ever infected. Seroprevalence and the proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods. Conclusions: COVID-19 vaccination was associated with a sustained reduction in mortality at the state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity.
Introduction: Most studies present a snapshot of hesitant parents9 decisions and thinking concerning COVID-19 vaccination, but for many it is a dynamic rather than a stable process. We examined the considerations of a group of vaccine hesitant parents (VHPs) with respect to COVID-19 vaccinations for their children before, during and after the main vaccination campaign for the 12 to 15-year-old age group in Israel, over a six-month period. Methods: Digital surveys were administered to 1118 Israeli parents. After VHPs were identified, three surveys were conducted to evaluate considerations that discourage or encourage vaccination. A logistic regression was carried out on sixteen models; of these, six were found to be statistically significant. Results: 456 parents9 data were analyzed. Parents9 intentions to vaccinate prior to the vaccination campaign were a good predictor of their actual behavior, (rp=.497, p<.001). We divided the parents into four groups: consistently pro-vaccine (39.4%), consistently anti-vaccine (15.2%), pro-vaccine parents who did not vaccinate (17.6%), and anti-vaccine parents who did vaccinate (27.9%). We identified eight considerations that were significant in VHPs9 vaccination behavior: trust in scientists, doctors and drug companies, children9s preferences, spread of COVID, social responsibility, children9s characteristics, the vaccine9s speed of development and its side effects. Discussion: Greater vaccine uptake for teenagers may depend on the attitudes and perceptions of their parents. We identified encouraging and discouraging considerations that may make potential targets for public health officials when communicating about vaccines.
Objectives: To report the recovery of patients receiving primary allied healthcare after a COVID-19 infection at a six-month follow-up, and to explore which patient characteristics are associated with the changes in outcomes between the baseline and six-month follow-up. Design: Prospective cohort study. Setting: Allied healthcare in Dutch primary care. Participants: 1,452 adult patients recovering from COVID-19 and receiving treatment from one or more primary care allied health professional(s) (i.e., dietitian, exercise therapist, occupational therapist, physical therapist and/or speech and language therapist). Results: For participation (USER-P range 0 to 100), estimated mean differences of at least 2.3 points were observed after six months. For HRQoL (EQ-VAS range 0 to 100), the mean increase was 12.31 at six months. Furthermore, significant improvements were found for fatigue (FSS range 1 to 7): the mean decrease was -0.7 at six months. For physical functioning (PROMIS-PF range 13.8 to 61.3), the mean increase was 5.9 at six months. Mean differences of -0.8 for anxiety (HADS range 0 to 21), and -1.5 for depression (HADS range 0 to 21), were found after six months. A better baseline score, hospital admission and male sex were associated with a positive change in score between the baseline and six-month follow-up, whereas age, BMI, comorbidities and smoking status were not associated with mean changes in any outcome measure. Conclusions: Patients recovering from COVID-19 who receive primary allied healthcare make progress in recovery, but still experience many limitations in their daily activities after six months. Our findings provide reference values to healthcare providers and healthcare policy-makers regarding what to expect from the recovery of patients who received health care from one or more primary care allied health professionals. Trial registration: Clinicaltrials.gov registry (NCT04735744).
The polyethylene-glycol (PEG)-containing Covid-19 vaccines can cause hypersensitivity reactions (HSRs), or rarely, life-threatening anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet proven in humans. The 191 blood donors in this study included 10 women and 5 men who displayed HSRs to Comirnaty or Spikevax Covid-19 vaccines with 3 anaphylaxis. 118 donors had pre-vaccination anti-PEG IgG/IgM values as measured by ELISA, of which >98% were over background regardless of age, indicating the presence of these Abs in almost everyone. Their values varied over 2-3 orders of magnitude and displayed strong left-skewed distribution with 3-4% of subjects having >15-30-fold higher values than the respective median. First, or booster injections with both vaccines led to significant rises of anti-PEG IgG/IgM with >10-fold rises in about ~10% of Comirnaty, and all Spikevax recipients, measured at different times after the injections. The anti-PEG Ab levels measured within 4-months after the HSRs were significantly higher than those in nonreactors. Serial testing of plasma (n=361 tests) showed the SARS-CoV-2 neutralization IgG to vary over a broad range, with a trend for biphasic dose dependence on anti-PEG Abs. The highest prevalence of anti-PEG Ab positivity in human blood reported to date represents new information which can most easily be rationalized by daily exposure to common PEG-containing medications and/or household items. The significantly higher, HSR-non-coincidental blood level of anti-PEG Abs in hypersensitivity reactor vs. non-reactors, taken together with relevant clinical and experimental data in the literature, suggest that anti-PEG Ab supercarrier people might be at increased risk for HSRs to PEG-containing vaccines, which themselves can induce these Abs via bystander immunogenicity. Our data also raise the possibility that anti-PEG Abs might also contribute to the reduction of these vaccines9 virus neutralization efficacy. Thus, screening for anti-PEG Ab supercarriers may identify people at risk for HSRs or reduced vaccine effectiveness.
Background: COVID-19 and associated controls may be particularly problematic in the context of chronic conditions. This study investigated health management, well-being, and pandemic-related perspectives in these patients in the context of stringent measures, and associated correlates. Methods: A self-report survey was administered via Wenjuanxing in Simplified Chinese between March-June 2022 during the Omicron wave lockdown in Shanghai, China. Items from the Somatic Symptom Scale (SSS) and Symptom Checklist-90 (SCL-90) were administered, as well as pandemic-related items created by a working group of the Chinese Preventive Medical Association. Chronic disease patients in this cross-sectional study were recruited through an associated community family physician group. Results: Overall, 1775 patients, mostly married females with hypertension, participated. Mean SSS scores were 36.1+/-10.5/80, with 41.5% scoring in the elevated range (i.e., above 36). In an adjusted model, female, diagnosis of coronary artery disease and arrhythmia, perceived impact of pandemic on life, duration can tolerate control measures, perception of future & control measures, impact of pandemic on health condition and change to exercise routine due to pandemic were significantly associated with greater distress. Approximately one-quarter (24.5%) perceived the pandemic had a permanent impact on their life, and 44.1% perceived at least a minor impact on their health. One-third (33.5%) discontinued exercise due to the pandemic. While 47.6% stocked up on their medications before the lockdown, their remaining supply was mostly only enough for a couple of weeks and 17.5% of participants discontinued use. Chief among their fears were inability to access healthcare (83.2%), and what they stated they most needed to manage their condition was medication access (65.6%). Conclusions: Since 2020 when we assessed a similar cohort, distress and perceived impact of the pandemic has worsened. Greater access to cardiac rehabilitation in China could address these issues.
Background: In the United States, oral nirmatrelvir-ritonavir (PaxlovidTM) is authorized for use among patients aged ≥12 years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under real-world conditions has not been well established. Methods: We undertook a matched, observational cohort study of non-hospitalized individuals with SARS-CoV-2 infection to compare outcomes between those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Individuals were matched on testing date, age, sex, treatment/care setting, symptoms status (including presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination and SARS-CoV-2 infection, Charlson comorbidity index, and prior-year healthcare utilization. Time to hospital admission was compared between matched COVID-19 cases who received or did not receive nirmatrelvir-ritonavir. Primary analyses evaluated treatment effectiveness against any hospital admission and acute respiratory infection (ARI)-associated hospital admission, with dispense occurring 0-5 days symptom onset. Secondary analyses evaluated effectiveness against the same endpoints for all treatment dispenses. We measured treatment effectiveness as (1-adjusted hazards ratio [aHR])*100%, estimating the aHR via Cox proportional hazards models accounting for match strata and additional patient characteristics. Results: Analyses included 4,329 nirmatrelvir-ritonavir recipients and 20,980 matched non-recipients who were followed ≥30 days after a positive SARS-CoV-2 outpatient test. Overall, 23,603 (93.3%) and 19,564 (78.1%) of 25,039 participants had received ≥2 and ≥3 COVID-19 vaccine doses, respectively. A total of 23,858 (94.2% of 25,039) patients were symptomatic at the point of testing, with a 2.1 day mean time from symptom onset to testing. For patients dispensed nirmatrelvir-ritonavir 0-5 days after symptom onset, effectiveness in preventing all hospital admissions was 88.1% (95% confidence interval: 49.0-97.5%) over 15 days and 71.9% (25.3-90.0%) over 30 days, respectively. Effectiveness in preventing ARI-associated hospital admissions was 88.3% (12.9-98.8%) and 87.3% (18.3-98.5%) over 15 and 30 days, respectively. In expanded analyses that included patients receiving treatment at any point during their clinical course, effectiveness was 86.6% (54.9-96.3%) and 78.0% (46.2-91.4%) in preventing all hospital admissions over 15 and 30 days, respectively, and 93.7% (52.5-99.4%) and 92.8% (53.9-99.1%) in preventing ARI-associated hospital admissions over 15 and 30 days. Subgroup analyses identified similar effectiveness estimates among patients who had received ≥2 COVID-19 vaccine doses. Implications: In a real-world setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvir-ritonavir 0-5 days after symptom onset was associated substantial reductions in risk of hospital admission among individuals testing positive for SARS-CoV-2 infection in outpatient settings.
Background: Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms. Objective: The aim of this scoping review was to investigate if regulatory T cell (Treg) dysregulation is observable beyond the acute illness and if it might be involved in Long COVID immunopathology. Design: A systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science. Results: The literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome9s etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population. Conclusions: Persistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.
Compared with previously prevalent variants of SARS-CoV-2, the Omicron lineages BA.1 and BA.2 are known to be associated with mild clinical courses. In addition, well-established animal models do not develop severe diseases. To address whether the supposedly fatal cases after Omicron-BA.1/2 infection show the known COVID-19 organ alterations, especially in the lungs, 23 full and 3 partial autopsies in the deceased with known Omicron BA.1/2 infections have been consecutively performed. Viral RNA was determined by RT-qPCR and RNA-in situ hybridization. The lineages were analyzed by whole genome sequencing or S-gene analysis. Despite high viral loads in almost all nasopharyngeal swabs and in 13 lung tissue samples, death caused by COVID-19-associated diffuse alveolar damage (DAD) in the acute and organizing stages was found in only eight cases (31%). This rate is significantly lower compared to previous studies, including non-Omicron variants, where rates of 92% and 69% for non-vaccinated and fully vaccinated vaccines were observed. It is of special interest that neither vaccination status nor known risk factors (i.e., age, comorbidities, obesity, immuno-suppression) were significantly associated with a direct cause of death by COVID-19. Only the reason for the hospital admission of the patients due to COVID-19-related symptoms showed a significant correlation with directly COVID-19-caused deaths (P < 0.001). DAD still occurred in the Omicron BA.1/BA.2 era of the SARS-CoV-2 pandemic but at a considerably lower frequency than seen with previous variants of concern. In our study, none of the known risk factors discriminated the cases with COVID-19-caused death from those that had COVID-19 infections but died due to a different disease. Therefore, the host9s genomics might play a key role in this regard. Further studies are urgently needed to elucidate the existence of a genomic mechanism as a risk factor for a fatal course.
Introduction This study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during England9s Delta wave, by age group, dose, and over time. Methods We used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine. Results Compared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18-29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60-69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose. Conclusion Important demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during England9s Delta wave, with evidence of waning predominantly restricted to those aged 70+.
Vaccines induce antigen-specific immunity which provides long-lived protection from the target pathogen. Trials especially from high infectious disease areas indicated that the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) induces in addition non-specific immunity against various pathogens and thereby reduces overall mortality. Although recent trials produced conflicting results, it was suggested that BCG might protect from non-tuberculosis respiratory infections and could be used to bridge time until a specific vaccine against novel respiratory diseases like COVID-19 is available. We performed a systematic search for randomized controlled trials (RCT) published between 2011 and August 5th, 2022 providing evidence about non-specific effects after BCG vaccination, assessed their potential for bias, and meta-analyzed relevant clinical outcomes. We excluded RCTs investigating vaccination with an additional vaccine, unless outcomes from a follow-up period before the second vaccination were reported. Our search identified 15 RCTs including 32160 participants. Vaccination with BCG caused an estimated 49% decrease in risk for respiratory infections (HR 0.51, 95% CI 0.33-0.80) with substantial heterogeneity between trials (I2=80%; p<0.00001). There was evidence for a protective effect on all-cause mortality of 22% if follow-up was restricted to one year (HR 0.78, 95% CI 0.63-0.96); we did not find evidence for an effect when we considered longer follow-up (HR 0.87, 95% CI 0.75-1.02). Infection-related mortality after BCG-vaccination was reduced by 33% (HR 0.67; 95% CI 0.46-0.99), mortality for sepsis by 38% (HR 0.62, 95% CI 0.41-0.93). There was no evidence for a protective effect of BCG vaccination on infections of any origin (HR 0.84, 95% CI 0.71-1.00), COVID-19 (HR 0.83, 95% CI 0.61-1.14), sepsis (HR 0.82, 95% CI 0.62-1.07) or hospitalization (HR 1.02, 95% CI 0.92-1.14). According to these results, depending on the setting, vaccination with BCG provides time-limited partial protection against non-tuberculosis respiratory infections and may reduce mortality. These findings underline BCGs potential 1) in pandemic preparedness against novel pathogens especially in developing countries with established BCG-vaccination programs but limited access to specific vaccines; 2) in reducing microbial infections, antimicrobial prescriptions and thus the development of antimicrobial resistance. There is a need for additional RCTs to clarify the circumstances under which BCGs non-specific protective effects are mediated.
The Efficacy and Safety of TADIOS as an Adjuvant Therapy in Patients Diagnosed With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: TADIOS; Drug: Placebo
Sponsor: Helixmith Co., Ltd.
Completed
A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir - Condition: COVID-19
Interventions: Drug: nirmatrelvir; Drug: ritonavir; Drug: placebo for nirmatrelvir
Sponsor: Pfizer
Not yet recruiting
COVID-19 iCura SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Device: iCura COVID-19 Antigen Rapid Home Test; Diagnostic Test: RT-PCR Test
Sponsors: EDP Biotech; Paragon Rx Clinical, Inc.; iCura Diagnostics, LLC
Recruiting
Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia - Condition: COVID-19
Intervention: Drug: DILTIAZEM TEVA 60 mg or placebo
Sponsors: Hospices Civils de Lyon; Signia Therapeutics
Not yet recruiting
FMT for Post-acute COVID-19 Syndrome - Conditions: Post-Acute COVID19 Syndrome; COVID-19
Intervention: Procedure: Faecal Microbiota Transplantation
Sponsor: Chinese University of Hong Kong
Recruiting
Research on Community Based ATK Test Study to Control Spread of COVID-19 in Migrant Community - Condition: COVID-19 Pandemic
Intervention: Device: STANDARD Q COVID-19 Ag Test
Sponsor: University of Oxford
Active, not recruiting
Safety and Immunogenicity of COVID-19 Vaccine in Population Aged 18 Years and Above - Condition: COVID-19
Interventions: Biological: low-dose LYB001; Biological: Recombinant COVID-19 Vaccine (CHO Cell); Biological: high-dose LYB001
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.
Recruiting
The Efficacy and Safety of BioBlock® Intranasally Administered Virus-Neutralizing Bovine Colostrum Nasal Spray in Preventing of COVID-19 (Coronavirus Disease-19) Infection in Healthy Volunteer Individuals - Condition: SARS CoV 2 Infection
Intervention: Biological: BioBlock® antiviral nasal spray
Sponsor: Chemi-Pharm AS
Recruiting
Safety, Tolerability, and Immunogenicity of Trivalent Coronavirus Vaccine Candidate VBI-2901a - Conditions: COVID-19; Coronavirus Infections
Intervention: Biological: VBI-2901a
Sponsor: VBI Vaccines Inc.
Not yet recruiting
3EO Health SARS-CoV-2 OTC At Home Test - Condition: COVID-19 Pandemic
Intervention: Diagnostic Test: In Vitro
Sponsor: 3EO Health
Not yet recruiting
Understanding the Impact of Death Conditions Linked to the COVID-19 Crisis on the Grieving Process in Bereaved Families - Condition: Psychological Disorder
Intervention: Other: Qualitative research interview
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting
Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial - Conditions: HIV; Organ Transplantation; Lymphoma, Non-Hodgkin; Chronic Lymphocytic Leukemia; Multiple Myeloma; COVID-19 Vaccines
Interventions: Biological: BNT162b2; Biological: mRNA-1273; Biological: NVX-COV2373
Sponsors: Bayside Health; Monash University
Not yet recruiting
PAPR: PAP + MBSR for Front-line Healthcare Provider COVID-19 Related Burnout - Conditions: Depression; Burnout, Professional
Interventions: Drug: Psilocybin; Behavioral: Mindfulness-Based Stress Reduction (MBSR)
Sponsors: University of Utah; Heffter Research Institute; Usona Institute
Not yet recruiting
Physiology of Long COVID and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity - Condition: Post-acute Sequelae of SARS-CoV-2 Infection
Intervention: Behavioral: Exercise
Sponsor: University of Colorado, Denver
Not yet recruiting
Phase 3 Study to Evaluate Immunogenicity and Safety of BBV154 Booster Dose - Condition: COVID-19 Respiratory Infection
Interventions: Biological: BBV154 Intranasal Vaccine; Biological: Intramuscular vaccine COVAXIN; Biological: Covishield
Sponsor: Bharat Biotech International Limited
Completed
Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV - CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs.
Body Weight is Inversely Associated with Anti-SARS-CoV-2 Antibody Levels after BNT162b2 mRNA Vaccination in Young and Middle Aged Adults - CONCLUSION: Anti-SARS-CoV-2 antibody was inversely correlated with weight and BMI, which may be used as a marker to predict immune response of BNT162b2 mRNA vaccination in young and middle aged adults.
A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo - “Pan-coronavirus” antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations….
Assessment of Practices Affecting Racial and Ethnic COVID-19 Vaccination Equity in 10 Large US Cities - CONCLUSIONS: Lack of consistent public reporting and transparency of COVID-19 vaccination data has likely hindered public health responses by impeding the ability to track the effectiveness of strategies that target vaccine equity.
SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376 - Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first protease inhibitor against the SARS-CoV-2 protease 3CL^(pro) that has been licensed for clinical use. To identify mutations that confer resistance to this protease inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a polyprotein composed of the VSV glycoprotein G, the SARS-CoV-2 3CL^(pro), and the VSV polymerase L. Viral replication was thus dependent on the autocatalytic…
Reducing delayed transfer of care in older people: A qualitative study of barriers and facilitators to shorter hospital stays - CONCLUSION: Poor quality and availability of information, and poor communication, inhibit effective transfer of care. Communication is fundamental to patient-centred care and even more important in discharge models characterized by limited assessments and quicker discharge. Interventions at the service level and targeted patient information about what to expect in discharge assessments and after discharge could help to address poor communication and support for improving discharge of older…
RNA-dependent RNA polymerase (RdRp) natural antiviral inhibitors: a review - Viral diseases are the cause of many global epidemics, leading to deaths, affecting the quality of life of populations, and impairing public health. The limitations in the treatment of viral diseases and the constant resistance to conventional antiviral treatments encourage researchers to discover new compounds. In this perspective, this literature review presents isolated molecules and extracts of natural products capable of inhibiting the activity of the nonstructural protein that acts as the…
Novel α-aminophosphonate derivates synthesis, theoretical calculation, Molecular docking, and in silico prediction of potential inhibition of SARS-CoV-2 - Using the Density Functional Theory approach and in silico docking, the current study analyzes the inhibitory role of a novel α-aminophosphonate derivative against SARS-CoV-2 major protease (Mpro) and RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. FT-IR, UV-Vis, and NMR (1H, 13C, 31P) approaches were used to produce and confirm the novel α-aminophosphonate derivative. The quantum chemical parameters were detremined, and the reactivity of the synthesized molecule was discussed using DFT at…
Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients - The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2^(nd) dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6…
Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2 - Three directly acting antivirals (DAAs) demonstrated substantial reduction in COVID-19 hospitalizations and deaths in clinical trials. However, these agents did not completely prevent severe illness and are associated with cases of rebound illness and viral shedding. Combination regimens can enhance antiviral potency, reduce the emergence of drug-resistant variants, and lower the dose of each component in the combination. Concurrently targeting virus entry and virus replication offers…
Correction for Zhao et al., “Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon” - No abstract
Crystal structure of the Rho-associated coiled-coil kinase 2 inhibitor belumosudil bound to CK2α - The small molecule belumosudil was initially identified as a selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2) and has recently been approved for the treatment of graft-versus-host disease. However, recent studies have shown that many of the phenotypes displayed upon treatment with belumosudil were due to CK2α inhibition. CK2α is in itself a very promising therapeutic target for a range of conditions and has recently been put forward as a potential treatment for COVID-19….
IL-4 receptor blockade is a global repressor of naïve B cell development and responses in a dupilumab-treated patient - Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naïve B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in…
Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines - SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth…
Case report: Refractory intestinal Behçet’s syndrome successfully treated with tofacitinib: A report of four cases - Behçet’s syndrome (BS) is a chronic form of relapsing multisystem vasculitis, characterized by recurrent oral and genital ulcers. Intestinal BS is a special type of BS. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BS, and punched-out ulcers can be observed in the intestine or esophagus. At present, there is no recognized radical treatment for intestinal BS. Glucocorticoids and immunosuppressants are currently the main drugs used to improve the condition. Although it…