The COVID-19 pandemic has shed light on the fractures of healthcare systems around the world, particularly in relation to the healthcare workforce. Frontline staff, in particular, have been exposed to unprecedented strain and delivering care during the pandemic has impacted their safety, mental health and wellbeing. The aim of this paper was to explore the experiences of HCWs delivering care in the UK during the COVID-19 pandemic to understand their wellbeing needs, experiences and strategies used to maintain wellbeing (at individual and organizational levels). We analysed 94 telephone interviews with HCWs and 2000 tweets about HCWs mental health taking place during the first year of the COVID-19 pandemic. Results were grouped under six themes: redeployment; wellbeing support and coping strategies; mental health effects; organisational support; social network and public support. These findings demonstrate a need for open conversations, where staff9s wellbeing needs and strategies can be shared and encouraged, rather than implementing solely top-down psychological interventions. At the macro level, findings also highlighted the impact on HCWs9 wellbeing of public and government support, as well as the need for ensuring protection through PPE, testing, and/or vaccines for frontline workers.
Background: Scarce information exists in relation to the comparison of seroconversion and adverse events following immunization (AEFI) with different SARS-CoV-2 vaccines. Our aim was to correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI. Methods: A multicentric comparative study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured at baseline, 21-28 days after the first and second dose (when applicable) of the following vaccines: BNT162b2 mRNA, mRNA-1273, Gam-COVID-Vac, Coronavac, ChAdOx1-S, Ad5-nCoV and Ad26.COV2. Mixed model and Poisson generalized linear models were performed. Results: We recruited 1867 subjects [52 (SD 16.8) years old, 52% men]. All vaccines enhanced anti-S1 and anti-S2 IgG antibodies over time (p<0.01). The highest increase after the first and second dose was observed in mRNA-1273 (p<0.001). There was an effect of previous SARS-CoV-2 infection; and an interaction of age with SARS-CoV-2, Gam-COVID-Vac and ChAdOx1-S (p<0.01). There was a negative correlation of Severe or Systemic AEFI (AEs) of naive SARS-CoV-2 subjects with age and sex (p<0.001); a positive interaction between the delta of antibodies with Gam-COVID-Vac (p=0.002). Coronavac, Gam-COVID-Vac and ChAdOx1-S had less AEs compared to BNT162b (p<0.01). mRNA-1273 had a higher number of AEFIs. The delta of the antibodies showed an association with AEFIs in previously infected individuals (p<0.001). Conclusions: The magnitude of seroconversion is predicted by age, vaccine type and SARS-CoV-2 exposure. AEs are correlated with age, sex, and vaccine type. The delta of the antibody response is positively correlated with AEs in patients previously exposed to SARS-CoV-2.
Official Covid-19 death tallies have underestimated the mortality impact of the Covid-19 pandemic in the United States. Excess mortality, which compares observed deaths to deaths expected in the absence of the pandemic, is a useful measure for assessing the total effect of the pandemic on mortality levels. In the present study, we produce county- level estimates of excess mortality for 3,127 counties between March 2020 and December 2021. We fit two hierarchical linear models to county-level death rates from January 2015 to December 2019 and predict expected deaths for each month during the pandemic. We compare these estimates with the observed numbers of deaths to obtain excess deaths for each county-month. An estimated 936,911 excess deaths occurred during 2020 and 2021, of which 171,168 were not assigned to Covid-19 on death certificates. Urban counties in the Far West, Great Lakes, Mideast, and New England experienced a substantial urban mortality disadvantage in 2020, whereas rural counties in these regions had higher mortality in 2021. In the Southeast, Southwest, Rocky Mountain, and Plains regions, there was a rural mortality disadvantage in 2020, which was exacerbated in 2021. The proportion of excess deaths assigned to Covid-19 was lower in 2020 (76.3%) than in 2021 (87.0%), suggesting fewer Covid-19 deaths went unassigned later in the pandemic. However, in rural areas and in the Southeast and Southwest a large share of excess deaths were still not assigned to Covid-19 during 2021.
Introduction: Timely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes. Methods: The International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEA’s 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys. Results: The survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposi’s sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate. Conclusion: IeDEA’s approach for site survey development approach has broad relevance for HIV research networks and other priority health conditions.
Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS- CoV-2 mRNA vaccination in a US-based, adult population. Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post- booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively. Results: After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre- vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naive individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years (β=-0.94, p=0.001) and malignancy (β=-0.88, p=0.002) reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p=0.004); (β=-0.66, p=0.014)], diabetes mellitus [(β=-0.57, p=0.032); (β=-0.44, p=0.028)], and systemic steroid use [(β=-0.066, p=0.032); (β=-0.55, p=0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2, but the immune response decreased with malignancy (β =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001). Conclusion: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Prior COVID-19 infection enhances the booster-dose response except in individuals with malignancy, suggesting a need for clinically guiding vaccine dosing regimens.
The SARS-CoV-2 Omicron variant is increasing in prevalence around the world. Accurate estimation of disease severity associated with Omicron is critical for pandemic planning. We found lower risk of accident and emergency (AE) attendance following SARS-CoV-2 infection with Omicron compared to Delta (HR: 0.39 (95% CI: 0.30 to 0.51; P<.0001). For AE attendances that lead to hospital admission, Omicron was associated with an 85% lower hazard compared with Delta (HR: 0.14 (95% CI: 0.09 to 0.24; P<.0001)).
Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial - Condition: COVID-19
Interventions: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2
Sponsors: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University
Not yet recruiting
A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01E; Biological: mRNA-1273
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19 - Condition: COVID-19
Intervention: Drug: AmnioPul-02
Sponsor: Amniotics AB
Not yet recruiting
A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults. - Condition: COVID-19
Interventions: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo
Sponsor:
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Recruiting
Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine - Condition: Covid19
Interventions: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo
Sponsor: Jiangsu Rec-Biotechnology Co., Ltd.
Not yet recruiting
A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years. - Condition: COVID-19
Interventions: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo
Sponsor:
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Recruiting
The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19 - Condition: COVID-19
Intervention: Drug: Chinese herbal medicine
Sponsor:
Hong Kong Baptist University
Not yet recruiting
Home-based Exercise Program in Patients With the Post-COVID-19 Condition - Conditions: Long COVID; Post-acute COVID-19 Syndrome
Intervention: Other: Home- based physical training
Sponsor: University of Sao Paulo
Not yet recruiting
Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients - Condition: COVID-19 Pneumonia
Interventions: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo
Sponsor: Shaperon
Recruiting
Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics) - Conditions: COVID-19; Post Intensive Care Syndrome
Interventions:
Other: Aerobic Exercise Training; Other: Home Plan
Sponsor: Riphah International University
Not yet recruiting
Efficacy and Safety of JT001 (VV116) Compared With Paxlovid - Condition: COVID-19
Interventions: Drug: JT001; Drug: Paxlovid
Sponsor:
Vigonvita Life Sciences
Recruiting
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial - Condition: COVID-19 Acute Respiratory Distress Syndrome
Intervention: Drug: EXOFLO
Sponsor: Direct Biologics, LLC
Not yet recruiting
High Frequency Percussive Ventilation in COVID-19 Patients - Conditions: COVID-19; Acute Respiratory Failure
Intervention:
Device: High frequency Percussive ventilation
Sponsor: University Magna Graecia
Not yet recruiting
Knowledge Mobilization Activities to Support Decision-Making by Youth, Parents and Adults: Study Protocol - Condition: COVID-19
Interventions: Other: Plain Language Recommendation (PLR); Other: Standard Language Version (SLV)
Sponsors: McMaster University; Western University; The Hospital for Sick Children; University of Alberta
Not yet recruiting
Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings - Conditions: Covid19; Diabetes Mellitus
Intervention: Device: continuous glucose monitoring
Sponsor: Tanureet K Arora
Completed
25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 Mpro and RdRp-: an insight from molecular docking and dynamics simulation approaches - The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (M^(pro)) of the virus mediate viral…
Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an in silico perspective - During the past few months, mucormycosis has been associated with SARS-CoV-2 infections. Molecular docking combined with molecular dynamics simulation is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the…
Potential Inhibitors of SARS-CoV-2 from Neocarya macrophylla (Sabine) Prance ex F. White: Chemoinformatic and Molecular Modeling Studies for Three Key Targets - CONCLUSION: The findings of this study have shown that N. macrophylla contains potential leads for SARS-CoV-2 inhibition and thus, should be studied further for development as therapeutic agents against COVID-19.
IL-25 blockade augments antiviral immunity during respiratory virus infection - IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal…
Megakaryocytes in pulmonary diseases - Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are…
Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study - CONCLUSION: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.
Artificial Neural Network-Based Study Predicts GS-441524 as a Potential Inhibitor of SARS-CoV-2 Activator Protein Furin: a Polypharmacology Approach - Furin, a pro-protein convertase, plays a significant role as a biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS-CoV-2, furin has become the center of attraction for researchers as the spike protein contains a polybasic furin cleavage site. In…
Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as “variant of concern” due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous…
Development of an At-home Metal Corrosion Laboratory Experiment for STEM Outreach in Biomaterials During the Covid-19 Pandemic - Due to the coronavirus disease 2019 (COVID-19) pandemic, many universities and outreach programs have switched to online learning platforms, which inhibits students from completing formative hands-on experiments. To address this, we developed a series of at-home experiments for undergraduate engineering students and adapted one of these experiments for outreach purposes. This experiment was well received by middle school students in the Young Eisner Scholars (YES) Program and resulted in…
Building integrated, adaptive and responsive healthcare systems - lessons from paramedicine in Ontario, Canada - CONCLUSIONS: The findings of this study add to the discourse on governing health systems towards being more integrated, adaptive and responsive to population needs. Governance strategies include: supporting networks of local organizational relationships; considering the role of a functionally flexible health workforce; promoting a shared vision and framework for collaboration; and enabling distributed, local control and experimentation.
COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants - As global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension…
Computational study on the affinity of potential drugs to SARS-CoV-2 main protease - Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using Molecular and Quantum Mechanics as well as Molecular Docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the Docking…
Pirfenidone ameliorates early pulmonary fibrosis in LPS-induced acute respiratory distress syndrome by inhibiting endothelial-to-mesenchymal transition via the Hedgehog signaling pathway - Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases….
2’- and 3’-Ribose Modifications of Nucleotide Analogues Establish the Structural Basis to Inhibit the Viral Replication of SARS-CoV-2 - Inhibition of RNA-dependent RNA polymerase (RdRp) by nucleotide analogues with ribose modification provides a promising antiviral strategy for the treatment of SARS-CoV-2. Previous works have shown that remdesivir carrying 1’-substitution can act as a “delayed chain terminator”, while nucleotide analogues with 2’-methyl group substitution could immediately terminate the chain extension. However, how the inhibition can be established by the 3’-ribose modification as well as other 2’-ribose…
The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era - Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α…