This study addresses the following policy questions: What forms of debt relief and additional financing are most effective in mitigating the fiscal impact of the COVID-19 pandemic in countries that are at risk of or facing debt distress? What would the subsequent impact be on government health and HIV financing up until 2030? To answer these questions, five debt relief and additional financing options are hypothetically applied to seven Sub-Saharan African countries using a macro-fiscal programming framework and debt scenario modelling. Aggregate impacts demonstrate that, on average, the COVID-19 period has had a significant impact on government health and HIV-related expenditure. Each of the five presented options studied are shown to have an iteratively greater impact in mitigating the effects of the pandemic on government health and HIV-related expenditure. However, none of the debt relief and additional financing options succeed in offsetting the loss of health and HIV fiscal space that has occurred during the COVID-19 pandemic. Adequate solutions to make up for this shortfall require the consideration of options beyond the current policy dialogue.
Background: Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with SARS-CoV-2. Methods: We collected saliva specimens from working-age adults receiving SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. Following bacterial culture enrichment, we tested for pneumococci by quantitative polymerase chain reaction (qPCR) targeting the lytA and piaB genes, and measured associations with SARS-CoV-2 infection via conditional logistic regression. Results: Analyses included 1,278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. Prevalence of pneumococcal carriage was 9.2% (117/1,278) among all participants (11.2% [63/564] clinic-based testing; 7.6% [54/714] outreach testing). Prevalence of SARS-CoV-2 infection was 27.4% (32/117) among pneumococcal carriers and 9.6% (112/1,161) among non-carriers (adjusted odds ratio [aOR]: 2.73; 95% confidence interval: 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR=4.01 [2.08-7.75]) and among symptomatic participants (aOR=3.38 [1.35-8.40]), when compared to findings within the outreach-based sample and among asymptomatic participants. Adjusted odds of SARS-CoV-2 co-infection increased 1.24 (1.00-1.55)-fold for each 1-unit decrease in piaB qPCR CT value among pneumococcal carriers. Last, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected COVID-19 case (aOR=7.64 [1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and non-carriers, respectively). Conclusions: Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.
Background: Given the low levels of COVID-19 vaccine coverage in Sub-Saharan Africa, despite high levels of natural SARS-CoV-2 exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of natural immunity. Methods: We used ELISA to measure whole-spike IgG and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients. We measured antibody neutralizing potency against the wild-type (Wuhan) SARS-CoV-2 pseudo-virus in a subset of 51 patients over three successive time points. Binding and neutralizing antibody levels and potencies were then tested for correlations with COVID-19 severities, graded according to the National Institute of Health (NIH), USA criteria. Results: Rates of sero-conversion increased from Day 0 (day of PCR testing) to Day 180 (six months) (63.6% to 100 %) and (69.3 % to 97%) for anti-spike IgG and anti-spike-RBD binding Igs, respectively. Levels of these binding antibodies peaked at Day 28 (P<0.0001) and were subsequently maintained for six months without significant decay (p>0.99). Similarly, antibody neutralizing potencies peaked at Day 28 (p<0.0001) but had decreased by three-folds, six months after COVID-19 diagnosis (p<0.0001). Binding antibodies levels were highly correlated with neutralizing antibody potencies at all the time points analyzed (r>0.6, P<0.0001). Levels and potencies of binding and neutralizing antibodies increased with disease severity. Conclusion: Most COVID-19 patients from Sub-Saharan Africa generate SARS-CoV-2 specific binding antibodies that remain stable during the first six months of infection. Although antibody binding levels and neutralizing potencies were directly correlated, the respective neutralizing antibodies decayed three-fold by the sixth month of COVID-19 diagnosis suggesting that they are short-lived, consistent with what has been observed elsewhere. Thus, just like for other populations, regular vaccination boosters will be required to broaden and sustain the high levels of predominantly naturally acquired anti-SARS-CoV-2 neutralizing antibodies.
Oral antivirals can potentially reduce the burden of COVID-19. However, low SARS-CoV-2 clinical testing rates in many low- and middle-income countries (LMICs) (mean <10 tests/100,000 people/day, July 2022) makes the development of effective test-and-treat programs challenging. Here, we used an agent-based model to investigate how testing rates and strategies could affect development of test-and-treat programs in three representative LMICs. We find that at <10 tests/100,000 people/day, test-and-treat programs are unlikely to have any impact on the public health burden of COVID-19. At low effective transmission rates (R_t≤1.2), increasing to 100 tests/100,000 people/day and allowing uncapped distribution of antivirals to LMICs (estimate = 26,000,000-90,000,000 courses/year for all LMICs), could avert up to 65% of severe cases, particularly in countries with older populations. For higher R_t, significant reductions in severe cases are only possible by substantially increasing testing rates or restricting clinical testing to those with higher risk of severe disease.
ABSTRACT Importance: Recent sublineages of the SARS–CoV–2 Omicron variant, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID–19 following vaccination. Objective: To evaluate the association between COVID–19 mRNA vaccination with 2, 3, or 4 doses among immunocompetent adults and the risk of medically attended COVID–19 illness during a period of BA.4/BA.5 predominant circulation; to evaluate the relative severity of COVID–19 in hospitalized cases across Omicron BA.1, BA.2/BA.2.12.1, and BA.4/BA.5 sublineage periods. Setting, Design and Participants: Test-negative study of adults with COVID–19–like illness (CLI) and molecular testing for SARS–CoV–2 conducted in 10 states from December 16, 2021, to August 20, 2022. Exposure: mRNA COVID–19 vaccination. Main Outcomes and Measures: Emergency department/urgent care encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. The adjusted odds ratio (OR) for the association between prior vaccination and medically attended COVID-19 was used to estimate VE, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as reference group). Among hospitalized case-patients, demographic and clinical characteristics and in-hospital outcomes including ICU admission and death were compared across sublineage periods. Results: Between June 19 – August 20, 2022, 82,229 ED/UC and 21,007 hospital encounters were included for the BA.4/BA.5 vaccine effectiveness analysis. Among adults hospitalized with CLI, the adjusted odds ratio (OR) was 0.75 (95% CI: 0.68-0.83) for receipt of 2 vaccine doses at ≥150 days after receipt, 0.32 (95% CI: 0.20–0.50) for a third dose 7–119 days after receipt, and 0.64 (95% CI: 0.58–0.71) for a third dose ≥120 days (median 235 days) after receipt for cases vs controls. For COVID-19-associated hospitalization, among patients ages ≥65 years 7-59 and ≥60 days (median 88 days) after a fourth dose, ORs were 0.34 (95% CI: 0.25–0.47) and 0.43 (95% CI: 0.34–0.56), respectively. Among hospitalized cases, ICU admission and/or in-hospital death occurred in 21.4% during the BA.1 vs 14.7% during the BA.4/BA.5 period (standardized mean difference: 0.17). Conclusion: VE against medically attended COVID-19 illness decreased over time since last dose; receipt of one or two booster doses increased effectiveness over a primary series alone.
Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of interferon gamma and interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID. We propose immune exhaustion as the driver of long-COVID, with the complete absence of interferon gamma; and IL-8 preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.
The SARS-CoV-2 pandemic has highlighted the need for devices capable of carrying out rapid differential detection of viruses that may manifest similar physiological symptoms yet demand tailored treatment plans. Seasonal influenza may be exacerbated by COVID-19 infections, increasing the burden on healthcare systems. In this work, we demonstrate a technology, based on liquid-gated graphene field-effect transistors, for rapid and ultraprecise detection and differentiation of influenza and SARS-CoV-2 surface protein. The device consists of 4 onboard graphene field-effect electrolyte-gated transistors arranged in a quadruple architecture, where each quarter is functionalized with either antigen-specific antibody or chemically passivated control. The antigen-antibody interaction is dependent on uniform diffusion of virus delivered in low ionic strength phosphate buffer solution, entailing a facile operating procedure, where the user adds a drop of the viral surface protein solution onto the device. Our sensor platform was tested against a range of concentrations of viral surface proteins from both viruses with the lowest tested and detected concentration at ~50 ag/mL, or 88 zM for COVID-19 and 227 zM for Flu, 5-fold lower than the values reported previously on a similar platform. Unlike the contemporary standard, RT-PCR test, which have a turnaround time of a few hours, the reported graphene biosensor technology has a fast response time of ~10 seconds enabling rapid diagnosis. Furthermore, the antibodies tested were confirmed to be antigen-specific through cross-reactivity tests. Thus, we have developed a multi-virus, highly sensitive and specific detection tool for rapid diagnostic applications for contemporary, emerging, and future viruses.
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
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
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
VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination - Conditions: Immunization; Infection; Pregnancy Related; COVID-19
Interventions: Behavioral: VAX-MOM COVID-19 Intervention; Other: Standard of Care
Sponsors: University of Rochester; Centers for Disease Control and Prevention; University of California, Los Angeles
Not yet 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
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
3EO Health SARS-CoV-2 OTC At Home Test - Condition: COVID-19 Pandemic
Intervention: Diagnostic Test: In Vitro
Sponsor: 3EO Health
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
Sequential Enhanced Safety Study of a Novel Coronavirus Messenger RNA (mRNA) Vaccine in Adults Aged 18 Years and Older. - Condition: Corona Virus Disease 2019(COVID-19)
Intervention: Biological: 0.3ml of mRNA vaccine
Sponsor: Yu Qin
Enrolling by invitation
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
Two Cases of Acute Myocarditis in Young Male Adults After mRNA Vaccines Against COVID-19: Similarities and Differences - CONCLUSION: The benefits of vaccination against Covid-19 outweigh possible untoward effects and especially myocarditis. Health workers must close monitor the vaccinated patients for possible future cardiovascular complications.
Therapeutic Approaches in COVID-19 Patients: The Role of the Renin-Angiotensin System - Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the…
The Integral Membrane Protein ZMPSTE24 Protects Cells from SARS-CoV-2 Spike-Mediated Pseudovirus Infection and Syncytia Formation - COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on global public health, emphasizing the importance of understanding innate immune mechanisms and cellular restriction factors that cells can harness to fight viral infections. The multimembrane-spanning zinc metalloprotease ZMPSTE24 is one such restriction factor. ZMPSTE24 has a well-characterized proteolytic role in the maturation of prelamin A, precursor of the nuclear…
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….