The severe shortfall in testing supplies during the initial COVID-19 outbreak and ensuing struggle to manage the pandemic have affirmed the critical importance of optimal supply-constrained resource allocation strategies for controlling novel disease epidemics. To address the challenge of constrained resource optimization for managing diseases with complications like pre- and asymptomatic transmission, we develop an integro partial differential equation compartmental disease model which incorporates realistic latent, incubation, and infectious period distributions along with limited testing supplies for identifying and quarantining infected individuals. Our model overcomes the limitations of typical ordinary differential equation compartmental models by decoupling symptom status from model compartments to allow a more realistic representation of symptom onset and presymptomatic transmission. To analyze the influence of these realistic features on disease controllability, we find optimal strategies for reducing total infection sizes that allocate limited testing resources between `clinical9 testing, which targets symptomatic individuals, and `non-clinical9 testing, which targets non-symptomatic individuals. We apply our model not only to the original, delta, and omicron COVID-19 variants, but also to generically parameterized disease systems with varying mismatches between latent and incubation period distributions, which permit varying degrees of presymptomatic transmission or symptom onset before infectiousness. We find that factors that decrease controllability generally call for reduced levels of non-clinical testing in optimal strategies, while the relationship between incubation-latent mismatch, controllability, and optimal strategies is complicated. In particular, though greater degrees of presymptomatic transmission reduce disease controllability, they may increase or decrease the role of non-clinical testing in optimal strategies depending on other disease factors like transmissibility and latent period length. Importantly, our model allows a spectrum of diseases to be compared within a consistent framework such that lessons learned from COVID-19 can be transferred to resource constrained scenarios in future emerging epidemics and analyzed for optimality.
Background Vaccines have reduced severe disease and death from COVID-19. However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. Methods and findings We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated SARS-CoV-2 transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both original and variant-adapted vaccine products, in the presence of both continuing transmission of Omicron subvariants and considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is the most efficient strategy, although large numbers of hospitalisations and deaths can be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups is more effective than continuing primary vaccination into younger ages. These findings hold if even if virus drift results in a gradual reduction in vaccine effectiveness over time due to immune escape. In a worst-case scenario where a new variant emerges that is 10% more transmissible, as severe as Delta, and exhibits substantial further immune escape, demand on health services could be similar to that experienced during 2020. Conclusions Regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. The cost-effectiveness of boosting is difficult to assess given the ongoing uncertainty in the likelihood of future variants and their properties but focusing vaccination in the highest-risk cohorts remains the most efficient strategy to reduce morbidity and mortality.
SARS-CoV-2 antibody titers may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody titer and protection from infection was evaluated in 2,323 vaccinated individuals from the National Basketball Association who had antibody levels measured from 9/12/2021 to 12/31/2021. Cox-proportional hazards models were used to estimate risk of infection within 90-days of serologic testing by titer level (<250, 250-800, and >800 AU/mL) and individuals were censored on date of booster receipt. The cohort was 78.2% male, 68.1% aged ≤ 40 years, and 56.4% vaccinated (primary series) with the Pfizer-BioNTech mRNA vaccine. Among the 2,248 individuals not yet boosted at testing, those with titers <250 AU/mL (adj HR: 2.4; 95% CI: 1.5, 3.7) and 250-800 800 AU/mL (adj HR: 1.5; 95% CI: 0.98, 2.4) had greater infection risk compared to those with titers >800 AU/mL. Serologic titers could inform individual COVID-19 risk and booster scheduling.
Importance: The Centers for Disease Control and Prevention (CDC) announced in January 2023 that they were investigating a potential connection between administration of the Pfizer novel coronavirus disease-2019 (COVID-19) bivalent vaccine booster and ischemic stroke (IS). Objective: To explore the relationship between Pfizer bivalent booster administration and IS in older patients in the United States and compare it to other COVID-19 vaccines. Design: A retrospective cohort study was conducted to compare hazard of IS among patients aged 65 years or over who received the Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster vaccine 1-21 and 22-42 days after vaccination. Setting: Patient data were collected from TriNetX, a cloud-based analytics platform that includes electronic health record data from over 90 million unique patients in the United States. Participants: Patients in the United States aged 65 years or over at the time of administration of a Pfizer bivalent (n = 43,216), Moderna bivalent (n = 4,267), or Pfizer/Moderna monovalent (n = 100,583) booster were included for analysis. Cohorts were propensity-score matched by demographic factors and risk factors for IS and severe COVID-19. Exposures: Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster administration. Main outcomes: The hazard ratio (HR) and 95% confidence interval (CI) for IS in the cohorts at 1-21 and 22-42 days after administration. Results: After matching, the Pfizer bivalent cohort included 4,267 patients, with an average age of 73.7 years (44.43% male, 76.59% white). The Moderna bivalent cohort included 4,267 patients, with an average age of 74.0 years (44.08% male, 77.39% white). There was no significant difference in the hazard of IS encounters between the Pfizer bivalent versus Moderna bivalent cohorts at 1-21- or 22-42-days post-administration: HR = 0.59 (0.31, 1.11), 0.73 (0.33, 1.60). The hazard for IS was lower in the Pfizer bivalent cohort than in the Pfizer/Moderna monovalent cohort at both timepoints: HR = 0.24 (0.19, 0.29), 0.25 (0.20, 0.31). Conclusions and relevance: Older adults administered the Pfizer bivalent booster had similar hazard for IS encounters compared to those administered the Moderna bivalent booster vaccine, but lower hazard than those administered the Pfizer/Moderna monovalent boosters.
Background There are limited measures of the impact of the COVID-19 pandemic on tuberculosis (TB) control in high-burden countries like Indonesia. Methods We analysed district-level data of reported TB cases, treatment and deaths, COVID-19 incidence and mortality, health care capacity, economic status, education level, and public health development index from all 514 districts in Indonesia. We compared data before (2016-2019) and during (2020-2021) the pandemic. Findings Compared to the preceding year (2019), in the first pandemic year (2020) the TB case notification declined by 31% (from median 172 [IQR 129-244] in 2019 to 119 [IQR 87-170] in 2020 per 100,000 population; 565,669 vs 393,323 cases, respectively); mortality increased by 8% (from median 4.2 [IQR 2.0-7.4] to 5.0 (IQR 3.1-7.5) per 100,000 population; 13,059 vs 14,148 deaths, respectively); and the overall proportion of cases who started treatment declined by 7% (from 98% to 91%). The second pandemic year (2021) saw a partial recovery of case notifications (median 142 [IQR 99-204]; 473,006) and deaths (4.1 [IQR 2.5-6.8]; 12,016), but a persistently reduced treatment coverage (84%). Reductions in TB notifications between districts were associated with higher COVID-19 incidence and fewer per capita GeneXpert machines for TB diagnosis. Likewise, reduced TB treatment coverage was associated with fewer per capita doctors, and increased reported TB deaths was associated with fewer per capita primary health centres, lower per capita domestic expenditure and higher education. Interpretation The COVID-19 pandemic significantly, yet unevenly, impacted the national TB control programme across Indonesia, with the greatest impacts in districts with the least resilient health systems.
In late 2022, China transitioned from a strict 9zero-COVID9 policy to rapidly abandoning nearly all interventions and data reporting. This raised great concern about the presumably-rapid but undisclosed spread of the SARS-CoV-2 Omicron variant in a very large population of very low pre-existing immunity. A quantitative understanding of the epidemic dynamics of COVID-19 during this period is urgently needed. Here, by modeling a combination of case count and survey data, we show that Omicron spread extremely fast, at a rate of 0.42/day (95% CrI: [0.35, 0.51]/day) after the full exit from zero-COVID policies on Dec. 7, 2022. Consequently, we estimate that the vast majority of the population (97%, 95% CrI: [95%, 99%]) was infected during December, with the nation-wide epidemic peaking on Dec. 23. Overall, our results highlight the extremely high transmissibility of the variant and the importance of proper design of intervention exit strategies to avoid large infection waves.
Rationale: High levels of hyaluronan in lungs and blood associate with COVID-19 severity. However, the effects on systemic hyaluronan concentrations and the mechanisms involved in the pathological overproduction of hyaluronan upon SARS-CoV-2 infection remain incompletely characterized. Objectives: To determine how hyaluronan levels in blood of COVID-19 patients change over time and investigate SARS-CoV-2 impact on hyaluronan metabolism along with the effect of corticosteroid treatment. Methods: The concentrations of hyaluronan were measured in blood plasma from patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS 6-9), both during the acute and convalescent phases. Primary human bronchial epithelial cells isolated from healthy donors were differentiated into an in vitro 3D-lung model and used to study effects of SARS-CoV-2 infection and corticosteroids treatment on hyaluronan metabolism. Measurements and Main results: Compared to healthy controls, both patients with mild and severe COVID-19 showed elevated plasma hyaluronan concentrations, which increased with disease severity. A reduction was observed over time, but hyaluronan levels remained elevated for at least 12 weeks, especially in women. SARS-CoV-2 infection in the 3D-lung model showed upregulation of inflammatory genes, hyaluronan synthases and downregulation of hyaluronidases, which increased the overall hyaluronan concentration. Notably, several of these effects were counteracted by corticosteroid treatment. Conclusions: Overproduction of hyaluronan plays a role in the pathogenesis of COVID-19 and hyaluronan levels in blood remain elevated over time. The in vitro mechanism for the positive effects of corticosteroid treatment in COVID-19 suggests a combined action of reduced inflammation and counteraction of hyaluronan synthesis.
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
Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages - Condition: COVID-19
Intervention: Behavioral: Persuasive Appeal
Sponsor: University of Calgary
Completed
Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2 - Condition: COVID-19
Intervention: Drug: AZD 1222
Sponsors: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health
Completed
Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19 - Condition: COVID-19
Interventions: Drug: GS-5245; Drug: GS-5245 Placebo
Sponsor: Gilead Sciences
Not yet recruiting
A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19 - Condition: COVID-19
Interventions: Drug: HH-120 nasal spray; Drug: Placebo Comparator
Sponsor: Huahui Health
Recruiting
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
Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection - Condition: COVID-19
Interventions: Drug: VV116+SOC; Drug: SOC
Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd
Recruiting
Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19) - Condition: COVID-19
Interventions: Drug: STI-1558; Drug: STI-1558 placebo
Sponsor: Zhejiang ACEA Pharmaceutical Co. Ltd.
Not yet recruiting
Pirfenidone in Adult Hospitalized Patients With COVID-19 - Condition: COVID-19 Pneumonia
Interventions: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo
Sponsor: Capital Medical University
Active, not recruiting
Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19 - Condition: Long COVID-19
Intervention: Biological: UC-MSCs
Sponsor: Shanghai East Hospital
Not yet recruiting
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
The Effectiveness of a Health Education Intervention to Reduce Anxiety in Quarantined COVID-19 Patients - Condition: Health Education, COVID-19, Quarantine, Anxiety, Pandemic
Intervention: Other: health education intervention
Sponsor: University of Monastir
Completed
Exercise Intervention Using mHealth in Patients With Post-Acute COVID-19 Syndrome: a Randomized Clinical Trial - Conditions: Post-Acute COVID19 Syndrome; Long COVID; Post COVID-19 Condition
Interventions: Device: COVIDReApp Group; Other: Control Group
Sponsor: University of Cadiz
Recruiting
In silico anti-SARS-CoV-2, antiplasmodial, antioxidant, and antimicrobial activities of crude extracts and homopterocarpin from heartwood of Pterocarpus macrocarpus Kurz - Natural products play an essential role in new drug discovery. In the present study, we determined the anti-SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2), antioxidant, antiplasmodial, and antimicrobial activities of Pterocarpus macrocarpus Kurz. heartwood and structurally characterized the bioactive compounds. P. macrocarpus Kurz. heartwood was macerated with n-hexane, ethyl acetate, and ethanol, respectively, for 7 days, three times. The compounds were isolated by…
A novel antiviral formulation containing caprylic acid inhibits SARS-CoV-2 infection of a human bronchial epithelial cell model - A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an…
Virtual screening of bioactive anti-SARS-CoV natural products and identification of 3β,12-diacetoxyabieta-6,8,11,13-tetraene as a potential inhibitor of SARS-CoV-2 virus and its infection related pathways by MD simulation and network pharmacology - Since the first prevalence of COVID-19 in 2019, it still remains the most devastating pandemic throughout the world. The current research aimed to find potential natural products to inhibit the novel coronavirus and associated infection by MD simulation and network pharmacology approach. Molecular docking was performed for 39 natural products having potent anti-SARS-CoV activity. Five natural products showed high binding interaction with the viral main protease for the SARS-CoV-2 virus, where…
Inhibition of the SARS-CoV-2 main protease by a thiadiazolidinone derivative - No abstract
Nanozyme-Based Colorimetric SARS-CoV-2 Nucleic Acid Detection by Naked Eye - Fluorescence-based PCR and other amplification methods have been used for SARS-CoV-2 diagnostics, however, it requires costly fluorescence detectors and probes limiting deploying large-scale screening. Here, a cut-price colorimetric method for SARS-CoV-2 RNA detection by iron manganese silicate nanozyme (IMSN) is established. IMSN catalyzes the oxidation of chromogenic substrates by its peroxidase (POD)-like activity, which is effectively inhibited by pyrophosphate ions (PPi). Due to the large…
Remdesivir Use in Low Weight, Premature, and Renally Impaired Infants With SARS-CoV-2 Infection in Sheikh Khalifa Medical City, UAE: Case Series - Remdesivir possesses in vitro inhibitory effect against severe acute respiratory syndrome coronavirus 2 and the Middle East respiratory syndrome. It works by inhibiting severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase that is essential for viral replication. Remdesivir is approved by Food and Drug Administration for treating COVID-19 in hospitalized adult and pediatric patients aged 28 days and more and weighing 3 kg and more. This case series is describing two cases…
Can Internet penetration curb the spread of infectious diseases among regions?-Analysis based on spatial spillover perspective - Based on the outbreak of COVID-19, this paper empirically studied the impact of internet penetration on the incidence of class A and B infectious diseases among regions in spatial Dubin model, by using health panel data from 31 provinces in China from 2009 to 2018. The findings showed that: (1) The regional spillover effect of incidence of class A and B infectious diseases was significantly positive, and that is most obvious in the central regions. (2) Internet penetration not only has a…
A comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic - Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all…
Stress adaptation signature into the functional units of spike, envelope, membrane protein and ssRNA of SARS-CoV-2 - Pandemic coronavirus causes respiratory, enteric and sometimes neurological diseases. Proteome data of individual coronavirus strains were already reported. Here we investigated of SARS-CoV-2 ssRNA and protein of spike, envelope and membrane to determine stress adaptation profile. Thermodynamic properties, Physicochemical behaviour and, amino acid composition along with their RMSD value was analysed. Thermodynamic index of SARS-CoV2 spike, envelope and membrane ssRNA is unstable in higher…
Extensive blood transcriptome analysis reveals cellular signaling networks activated by circulating glycocalyx components reflecting vascular injury in COVID-19 - CONCLUSIONS: Circulating glycocalyx components in COVID-19 have distinct biologic feedback effects on immune and endothelial cells and result in upregulation of key regulatory transcripts leading to further immune activation and more severe systemic inflammation. These consequences are most pronounced during the early hospital phase of COVID-19 before pulmonary failure develops. Elevated levels of circulating glycocalyx components may early identify patients at risk for microvascular injury and…
The evaluation of in vitro antichagasic and anti-SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone - The compound 3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their in vitro anti-SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to…
A review article on neuroprotective, immunomodulatory, and anti-inflammatory role of vitamin-D3 in elderly COVID-19 patients - Vitamin D3 is a secosteroid, broad-spectrum immunomodulatory, antioxidant, and anti-inflammatory hormone produced either by the internal subcutaneous pathway in the presence of ultraviolet B (UVB) rays or by the external pathway in the form of supplements. Vitamin D3 deficiency is a common and reversible contributor to mortality and morbidity among critically ill patients, including Coronavirus Disease 2019 (COVID-19) and other viral infections. The major functions of vitamin D3 are inhibiting…
Multigenerational effects of microplastic fragments derived from polyethylene terephthalate bottles on duckweed Lemna minor: Size-dependent effects of microplastics on photosynthesis - The 2019 global coronavirus disease pandemic has led to an increase in the demand for polyethylene terephthalate (PET) packaging. Although PET is one of the most recycled plastics, it is likely to enter the aquatic ecosystem. To date, the chronic effects of PET microplastics (MPs) on aquatic plants have not been fully understood. Therefore, this study aimed to investigate the adverse effects of PET MP fragments derived from PET bottles on the aquatic duckweed plant Lemna minor through a…
Structural basis of nirmatrelvir and ensitrelvir activity against naturally occurring polymorphisms of the SARS-CoV-2 Main Protease - SARS-CoV-2 is the causative agent of COVID-19. The main viral protease (M^(pro)) is an attractive target for antivirals. The clinically approved drug nirmatrelvir, and the clinical candidate ensitrelvir have so far showed great potential for treatment of viral infection. However, the broad use of antivirals is often associated with resistance generation. Herein, we enzymatically characterized 14 naturally occurring M^(pro) polymorphisms that are close to the binding site of these antivirals….
Comparison study of Beninese and Chinese herbal medicines in treating COVID-19 - CONCLUSIONS: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.