The antiviral drug Paxlovid has been shown to rapidly reduce viral load. Coupled with vaccination, timely administration of safe and effective antivirals could provide a path towards managing COVID-19 without restrictive non-pharmaceutical measures. Here, we estimate the population-level impacts of expanding treatment with Paxlovid in the US using a multi-scale mathematical model of SARS-CoV-2 transmission that incorporates the within-host viral load dynamics of the Omicron variant. We find that, under a low transmission scenario (Re~1.2) treating 20% of symptomatic cases with Paxlovid would be life and cost saving, leading to an estimated 0.26 (95% CrI:0.03, 0.59) million hospitalizations averted, 30.61 (95% CrI:1.69, 71.15) thousand deaths averted, and US$52.16 (95% CrI:2.62, 122.63) billion reduction in the US. Rapid and broad use of the antiviral Paxlovid could substantially reduce COVID-19 morbidity and mortality, while averting socioeconomic hardship.
Objectives. To assess the association of Long COVID with housing insecurity in the United States. Methods. To compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms > 3 months) and COVID-19 survivors who don9t report long-term symptoms, we used survey-weighted regression models on 203,807 responses from the Household Pulse Survey, a representative survey of US households collected September 2022 - April 2023. Among people with Long COVID, we assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-to-day life were associated with a higher prevalence of housing insecurity. Results. During the study period, 54,446 (27.2%) respondents with COVID-19 experienced symptoms lasting 3 months or longer, representing an estimated 27 million US adults. People with Long COVID were nearly twice as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.85, 95% CI 1.74-1.96), be behind on housing payments (PR 1.76, 95% CI 1.57-1.99), and face likely eviction or foreclosure (PR 2.12, 95% CI 1.58-2.86). Functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity. Conclusions. Compared with COVID-19 survivors who don9t experience long-term symptoms, people with Long COVID are more likely to report indicators housing insecurity, particularly those with functional limitations and long-term COVID-19 related symptoms impacting day-to-day life. Policies are needed to support people living with chronic illnesses following SARS-CoV-2 infection.
National opinion on a wide variety of public health topics can change over time or have highly contextual nuisances. As the COVID-19 pandemic has progressed, we aimed to see how public perceptions have changed regarding the acceptance of using wastewater for community health monitoring in the metropolitan United States. This study is an annual update of prior inquiry into knowledge of wastewater-based epidemiology, privacy concerns surrounding the collection of wastewater samples and the use of data acquired along with privacy awareness from an online survey administered in the winter of 2023. We found public support for monitoring of toxins (90.8%), disease (90.6%), terror (86.8%), gun residue (59.8%), alcohol (49%), illicit drugs (70.5%), and prescription medications (68.6%) remained high. Most respondents supported monitoring of the entire city (77.6%). This longitudinal research has shown year-upon-year only slight increases in public support of wastewater monitoring for public health protection and continues to show an absence of significant nationwide privacy concerns as long as catchment population sizes ensure fully anonymous households. This support is conditional and is probably best understood through the lens of the COVID-19 pandemic where the value proposition of public protection was popularized. The survey also consistently showed the public would support expansion of wastewater monitoring as a standard complement of public health tools into other areas of public health protection.
Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.
OBJECTIVES Three years following the start of the COVID-19 pandemic, the World Health Organization (WHO) declared COVID-19 a global health emergency of international concern. As immunity levels in the population acquired through past infections and vaccinations have been decreasing, booster vaccinations have become necessary to control new outbreaks. This study aimed to determine the most suitable vaccination strategy to control the COVID-19 surge. METHODS A mathematical model was developed to simultaneously consider the immunity levels induced by vaccines and infections, and employed to analyze the possibility of future resurgence and control using vaccines and antivirals. RESULTS As of May 11, 2023, a peak in resurgence is predicted to occur around mid-October of the same year if the current epidemic trend continues without additional vaccinations. In the best scenario, the peak number of severely hospitalized patients can be reduced by 43% (480) compared to the scenario without vaccine intervention (849). Depending on the outbreak trends and vaccination strategies, the best timing for vaccination in terms of minimizing the said peak varies from May to August 2023. CONCLUSIONS Our results indicate that if the epidemic continues, the best timing for vaccinations must be earlier than specified by the current plan in Korea. Further monitoring of outbreak trends is crucial for determining the optimal timing of vaccinations to manage future surges.
Background: cSCC (cutaneous squameous cell carcinom) and its precursors are a major cause of morbidity especially in immunosuppressed patients and are frequently associated with human papilloma virus (HPV) infections. Objective: The purpose of this study is to investigate the therapeutically potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors. Methods: In this retrospective study, all patients who received Gardasil-9, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors. Results: The hazard ratio for major dermatologic interventions was 0.27 (CI 0.14-0.51, p <0.001) between pre- and post Gardasil-9 intervention. Gardasil-9 vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 case loads during the observational period. Limitation: The retrospective study design and the rather low number of patients may influence study results. Furthermore, analysis of HPV types and data collection on vaccine-specific HPV antibody measurements was not possible. Conclusion: Alpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions in immunosuppressed patients with high skin tumor burden.
Background Surrogates of antiviral efficacy are needed for COVID-19. We investigated the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in unvaccinated outpatients treated for mild to moderate COVID-19. Methods We searched PubMed, Scopus and medRxiv from inception to 27th September 2022, for randomised controlled trials (RCTs) which tested potential treatments for COVID-19 in non-hospitalized patients. We included studies that reported both clinical and virological outcomes. Clinical outcomes were the rate of disease progression (generally hospitalization or death within 28 days of commencing treatment) and virological outcomes were viral load (viral RNA copies in upper respiratory tract swabs) within the first 7 days of treatment. Studies were excluded if they did not report on the outcome of a primary randomised controlled trial, or if results were reported in a more complete form in another publication. Risk of Bias assessment was performed using the RoB 2.0 tool. We used generalised linear models with random effects to assess the association between outcomes and account for study heterogeneity. Findings We identified 1372 unique studies of which 14 (with a total of 9257 participants) met inclusion criteria. Larger virological treatment effects at both day 3 and day 5 were associated with decreased odds of progression to hospitalisation or death in unvaccinated ambulatory subjects. The odds ratio (OR) for each extra two-fold reduction in viral load in treated compared to control subjects was 0.54 on both days 3 and 5 post treatment (day 3 95% CI 0.38 to 0.74, day 5 95%CI 0.41 to 0.72). There was no relationship between the odds of hospitalisation or death and virological treatment effect at day 7 (OR 0.91, 95%CI 0.74 to 1.13). Interpretation Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy. Funding The authors were supported by the Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council and the University of New South Wales.
Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19 - Condition: COVID-19 Pneumonia
Interventions: Other: manual therapy; Other: breathing exercise and prone position alone
Sponsor: Cairo University
Completed
Safety Study of COVID19 Vaccine on the Market - Condition: COVID-19
Intervention: Biological: Recombinant new coronavirus vaccine (CHO cell)
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention
Recruiting
Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences - Conditions: COVID-19; COVID-19 Pandemic
Interventions: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines
Sponsors: University of California, San Diego; San Ysidro Health Center
Not yet recruiting
Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: SHEN26 capsule; Drug: SHEN26 placebo
Sponsor: Shenzhen Kexing Pharmaceutical Co., Ltd.
Recruiting
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast) - Condition: Covid19
Interventions: Other: Placebo; Drug: Montelukast
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Recruiting
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine) - Condition: Covid19
Interventions: Drug: Fluvoxamine; 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 D (Ivermectin 600) - Condition: Covid19
Interventions: Drug: Ivermectin; 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 E (Fluvoxamine 100) - Condition: Covid19
Interventions: Drug: Fluvoxamine; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
A Study to Investigate the Safety, Immunogenicity of a Bivalent mRNA Vaccine RQ3025 as a Booster Dose in Healthy Adults - Condition: COVID-19
Interventions: Biological: RQ3013; Biological: RQ3025
Sponsors: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical University
Recruiting
Pycnogenol® in Post-COVID-19 Condition - Conditions: Post COVID-19 Condition; Long COVID
Interventions: Drug: Pycnogenol®; Drug: Placebo
Sponsor: University of Zurich
Recruiting
Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19 - Conditions: Pulmonary Fibrosis; COVID-19 Pneumonia
Intervention: Drug: Bailing capsule
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Not yet recruiting
To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2 - Condition: COVID-19
Intervention: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)
Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Completed
A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation - Conditions: COVID-19; Hematopoietic Stem Cell Transplantation
Intervention: Biological: COVID Convalescent Plasma
Sponsor: Institute of Hematology & Blood Diseases Hospital
Recruiting
Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV) - Condition: COVID-19
Intervention: Biological: SARS-CoV-2 DNA Vaccine (ICCOV)
Sponsors: Immuno Cure 3 Limited; The University of Hong Kong
Recruiting
Cupping Therapy on Immune System in Post Covid -19 - Condition: Covid-19 Patients
Interventions: Combination Product: Cupping therapy with convential medical treatment; Drug: Convential medical treatment
Sponsor: Cairo University
Completed
Targeting the cGAS-STING pathway as an inflammatory crossroad in coronavirus disease 2019 (COVID-19) - Context and objective: The emerging pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has imposed significant mortality and morbidity on the world. An appropriate immune response is necessary to inhibit SARS-CoV-2 spread throughout the body.Results: During the early stages of infection, the pathway of stimulators of interferon genes (STING), known as the cGAS-STING pathway, has a significant role in the induction of the…
Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis - CONCLUSIONS: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.
2’,3’ cyclic-nucleotide 3’-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly by blocking infection-induced mitochondria depolarization - The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world’s healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus replication cycle have been developed however, effective late-stage therapeutical targets have yet to be identified. To that end, our lab identified 2’,3’ cyclic-nucleotide 3’-phosphodiesterase (CNP) as a late-stage inhibitor of SARS-CoV-2 replication….
An evolutionarily conserved strategy for ribosome binding and inhibition by β-coronavirus non-structural protein 1 - An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Nsp1, which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs through an unknown mechanism. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-CoV inhibits translation through ribosome binding. The C-terminal domain of all β-CoV…
Green and rapid and instrumental one-pot method for the synthesis of imidazolines having potential anti-SARS-CoV-2 main protease activity - The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is responsible for ongoing epidemics in humans and some other mammals and has been declared a public health emergency of international concern. In this project, several small non-peptide molecules were synthesized to inhibit the major proteinase (M^(pro)) of SARS-CoV-2 using rational strategies of drug design and medicinal chemistry. M^(pro) is a key enzyme of coronaviruses and plays an essential role in mediating viral replication…
Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients - CONCLUSIONS: This analysis shows that vilobelimab efficiently inhibits C5a in critically ill COVID-19 patients. There was no evidence of immunogenicity associated with vilobelimab treatment. Trial registration ClinicalTrials.gov, NCT04333420. Registered 3 April 2020, https://clinicaltrials.gov/ct2/show/NCT04333420.
Covalent-reversible peptide-based protease inhibitors. Design, synthesis, and clinical success stories - Dysregulated human peptidases are implicated in a large variety of diseases such as cancer, hypertension, and neurodegeneration. Viral proteases for their part are crucial for the pathogens’ maturation and assembly. Several decades of research were devoted to exploring these precious therapeutic targets, often addressing them with synthetic substrate-based inhibitors to elucidate their biological roles and develop medications. The rational design of peptide-based inhibitors offered a rapid…
Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation - CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.
Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2 - COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles’ inherent…
Tocilizumab for the treatment of COVID-19 - INTRODUCTION: Since the beginning of the COVID-19 pandemic, the repurposing of medicines has been pursued to find interventions effective in preventing fatal outcome of the disease. One of these drugs was tocilizumab, an interleukin-6 inhibiting monoclonal antibody, previously used to treat several immune-related disorders.
Preventative and therapeutic potential of animal milk components against COVID-19: A comprehensive review - The global pandemic of COVID-19 is considered one of the most catastrophic events on earth. During the pandemic, food ingredients may play crucial roles in preventing infectious diseases and sustaining people’s general health and well-being. Animal milk acts as a super food since it has the capacity to minimize the occurrence of viral infections due to inherent antiviral properties of its ingredients. SARS-CoV-2 virus infection can be prevented by immune-enhancing and antiviral properties of…
COVID-19 PCR: frequency of internal control inhibition in clinical practice - CONCLUSIONS: This study showed a low percentage of inhibition using RNase P as an internal control in COVID-19 PCRs using the CDC protocol, thus proving the effectiveness of this protocol for identification of SARS-CoV-2 in clinical samples. Re-extraction was efficacious for samples that showed little or no fluorescence for the RNase P gene.
A suitable drug structure for interaction with SARS-CoV-2 main protease between boceprevir, masitinib and rupintrivir; a molecular dynamics study - In recent years, more than 200 countries of the world have faced a health crisis due to the epidemiological disease of COVID-19 caused by the SARS-CoV-2 virus. It had a huge impact on the world economy and the global health sector. Researchers are studying the design and discovery of drugs that can inhibit SARS-CoV-2. The main protease of SARS-CoV-2 is an attractive target for the study of antiviral drugs against coronavirus diseases. According to the docking results, binding energy for…
Combining virtual screening with cis-/trans-cleavage enzymatic assays effectively reveals broad-spectrum inhibitors that target the main proteases of SARS-CoV-2 and MERS-CoV - The main protease (M^(pro)) of SARS-CoV-2 is essential for viral replication, which suggests that the M^(pro) is a critical target in the development of small molecules to treat COVID-19. This study used an in-silico prediction approach to investigate the complex structure of SARS-CoV-2 M^(pro) in compounds from the United States National Cancer Institute (NCI) database, then validate potential inhibitory compounds against the SARS-CoV-2 M^(pro) in cis- and trans-cleavage proteolytic assays….
Structure-Based Drug Design of RdRp Inhibitors against SARS-CoV-2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since 2019, spreading rapidly and posing a significant threat to human health and life. With over 6 billion confirmed cases of the virus, the need for effective therapeutic drugs has become more urgent than ever before. RNA-dependent RNA polymerase (RdRp) is crucial in viral replication and transcription, catalysing viral RNA synthesis and serving as a promising therapeutic target for developing…