Background: A global reduction in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) was observed during the first months of the COVID-19 pandemic. Large-scale studies covering the entire pandemic period are lacking. We investigated hospitalizations for AECOPD and the associated in-hospital mortality at the national level in France during the first two years of the pandemic. Methods: We used the French National Hospital Database to analyse the time trends in (1) monthly incidences of hospitalizations for AECOPD, considering intensive care unit (ICU) admission and COVID-19 diagnoses, and (2) the related in-hospital mortality, from January 2016 to November 2021. Pandemic years were compared with the pre-pandemic years using Poisson regressions. Results: The database included 565,890 hospitalizations for AECOPD during the study period. The median age at admission was 74 years (interquartile range 65-83), and 37% of the stays concerned women. We found: (1) a dramatic and sustainable decline in hospitalizations for AECOPD over the pandemic period (from 8,899 to 6,032 monthly admissions, relative risk (RR) 0.65, 95% confidence interval (CI) 0.65-0.66), and (2) a concomitant increase in in-hospital mortality for AECOPD stays (from 6.2% to 7.6% per month, RR 1.24, 95% CI 1.21-1.27). The proportion of stays yielding ICU admission was similar in the pre-pandemic and pandemic years, 21.5% and 21.3%, respectively. In-hospital mortality increased to a greater extent for stays without ICU admission (RR 1.39, 95% CI 1.35-1.43) than for those with ICU admission (RR 1.09, 95% CI 1.05-1.13). Since January 2020, only 1.5% of stays were associated with a diagnosis of COVID-19, and their mortality rate was nearly 3-times higher than those without COVID-19 (RR 2.66, 95% CI 2.41-2.93). Conclusion: The decline in admissions for AECOPD during the pandemic could be attributed to a decrease in the incidence of exacerbations for COPD patients and/or to a possible shift from hospital to community care. The rise in in-hospital mortality is partially explained by COVID-19, and could be related to restricted access to ICUs for some patients and/or to greater proportions of severe cases among the patients hospitalized during the pandemic.
Background: Routine case surveillance data for SARS-CoV-2 are incomplete, unrepresentative, missing key variables of interest, and may be increasingly unreliable for both timely surge detection and understanding the burden of infection and access to treatment. Methods: We conducted a cross-sectional survey of a representative sample of 1,030 New York City (NYC) adult residents >18 years on May 7-8, 2022, when BA.2.12.1 comprised 47% of reported cases per genomic surveillance. We estimated the prevalence of SARS-CoV-2 infection during the preceding 14-day period (April 23-May 8), weighted to represent the 2020 NYC adult population. Respondents were asked about SARS-CoV-2 testing (including at-home rapid antigen tests), testing outcomes, COVID-like symptoms, and contact with SARS-CoV-2 cases. Based on responses, we classified individuals into three mutually exclusive categories of SARS-CoV-2 infection according to a hierarchical case definition as follows: confirmed (positive test with a provider), probable (positive at home rapid test), and possible (COVID-like symptoms and close contact with a confirmed/probable case). SARS-CoV-2 prevalence estimates were age- and sex-adjusted to the 2020 US population. Individuals with SARS-CoV-2 were asked about awareness/use of antiviral medications. We triangulated survey-based prevalence estimates with NYCs official SARS-CoV-2 metrics on cases, hospitalizations, and deaths, as well as SARS-CoV-2 concentrations in wastewater for the same time period. Results: An estimated 22.1% (95%CI 17.9%-26.2%) of respondents had SARS-CoV-2 infection during the two-week study period, corresponding to ~1.5 million adults (95%CI 1.3-1.8 million). The official SARS-CoV-2 case count during the study period was 51,218. This 22.1% prevalence estimate included 11.4%, 6.5%, and 4.3% who met the confirmed, probable, and possible criteria of our case definition, respectively. Prevalence was estimated at 34.9% (95%CI 26.9%- 42.8%) among individuals with co-morbidities, 14.9% (95% CI 11.0%-18.8%) among those 65+ years, and 18.9% (95%CI 10.2%-27.5%) among unvaccinated persons. Hybrid immunity (i.e., history of both vaccination and prior infection) was 66.2% (95%CI 55.7%-76.7%) among those with COVID and 46.3% (95%CI 40.2-52.2) among those without. Among individuals with COVID, 44.1% (95%CI 33.0%-55.1%) were aware of the antiviral nirmatrelvir/ritonavir (PaxlovidTM), and 15.1% (95%CI 7.1%-23.1%) reported receiving it. Deaths and hospitalizations increased, but remained well below the levels of the BA.1 surge. SARS-CoV-2 virus concentrations in wastewater surveillance showed only a modest signal in comparison to that of the BA.1 surge. Conclusions and Relevance: The true magnitude of NYCs BA.2/BA.2.12.1 surge may have been vastly underestimated by routine SARS-CoV-2 case counts and wastewater surveillance. Hybrid immunity, bolstered by the recent BA.1 surge, likely limited the impact of the BA.2/BA.2.12.1 surge on severe outcomes. Representative surveys are needed as part of routine surveillance for timely surge detection, and to estimate the true burden of infection, hybrid immunity, and uptake of time-sensitive treatments among those most vulnerable to severe COVID.
Background. Multiple factors affecting COVID19 vaccine-induced antibody responses in SARS-CoV2 uninfected immunosuppressed solid organ transplant recipients have been reported; however, there is still a lack of information on non-ACE2 competing cross-CoV2 neutralizing functional antibodies induced in these cohorts, and similarly, the vaccine efficacy in prior CoV2-infected immunosuppressed individuals is not well understood. Methods. COVID19 vaccine efficacy was compared in a panel of kidney and heart transplant recipients who were either CoV2 uninfected (n=63) or CoV2 infected (n=13) prior to receiving two or three doses of mRNA vaccines using pseudoviral neutralization assays against eight CoV2 strains (the CoV2_D614G ancestral strain, alpha, beta, gamma, delta, kappa, lambda, and omicron-BA1 variants), while plasma antibody titers were determined by ELISA using recombinant CoV2-RBD-wt proteins. Results. Minimally protective neutralizing plasma antibody titers (IC50 ≥ 1:50) against the variants were recorded 7-14% and 25-35% after the second and third doses respectively, with Omicron being the most resistant. In contrast, all previously infected vaccinees possessed minimal protective plasma titers against D614G after either two or three vaccine doses, with 11/13 exhibiting strong protection (IC50≥ 1:500) and 10/13 exceeding the minimal protective titer against Omicron. Absorption of the selected plasma with immobilized parental RBD removed ≥ 90% of its neutralizing activity, indicating that the dominant neutralization targets were in the RBD. Conclusions. This study showed that CoV2 infection followed by vaccination, but not vaccination alone, induces the presence of potent highly cross-reactive CoV2 neutralizing plasma antibodies that extend to Omicron variants, even in immunosuppressed SOTRs.
Control and mitigation of the COVID-19 pandemic in England has relied on a combination of vac- cination and non-pharmaceutical interventions (NPIs). Some of these NPIs are extremely costly (economically and socially), so it was important to relax these promptly without overwhelming already burdened health services. The eventual policy was a Roadmap of four relaxation steps throughout 2021, taking England from lock-down to the cessation of all restrictions on social interaction. In a series of six Roadmap documents generated throughout 2021, models assessed the potential risk of each relaxation step. Here we show that the model projections generated a reliable estimation of medium-term hospital admission trends, with the data points up to September 2021 generally lying within our 95% prediction intervals. The greatest uncertainties in the modelled scenarios came from vaccine efficacy estimates against novel variants, and from assumptions about human behaviour in the face of changing restrictions and risk.
Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity - Condition: COVID-19
Intervention: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors
Sponsor: Central Hospital, Nancy, France
Not yet recruiting
Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients - Condition: Severe COVID-19
Interventions: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)
Sponsors: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio
Recruiting
A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa - Condition: COVID-19
Intervention: Drug: Molnupiravir 200 mg
Sponsors: University of Witwatersrand, South Africa; Bill and Melinda Gates Foundation
Not yet recruiting
Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) - Condition: COVID-19
Interventions: Drug: FB2001; Drug: FB2001 placebo
Sponsor: Frontier Biotechnologies Inc.
Not yet recruiting
Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities - Condition: COVID-19
Interventions: Behavioral: Full Intervention; Other: Enhanced Usual Care
Sponsors: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
Recruiting
A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection - Condition: COVID-19
Interventions: Drug: PanCytoVir™ (probenecid); Drug: Placebo
Sponsor: TrippBio, Inc.
Not yet recruiting
Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough - Condition: Post COVID-19
Intervention: Drug: Montelukast Sodium Tablets
Sponsor: Assiut University
Completed
Topical Antibacterial Agents for Prevention of COVID-19 - Conditions: COVID-19; SARS-CoV2 Infection
Interventions: Drug: Neosporin; Other: Vaseline
Sponsors: Yale University; Bill and Melinda Gates Foundation
Not yet recruiting
**NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - Condition: COVID-19 Pandemic
Interventions: Drug: Placebo; Drug: Experimental drug
Sponsor: Medesis Pharma SA
Recruiting
Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study - Condition: Post-COVID19 Condition
Interventions: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure
Sponsors: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits
Not yet recruiting
Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection - Conditions: COVID-19; Rehabilitation
Interventions: Other: Respiratory training with the use of resistance set on respiratory muscle trainer; Other: Respiratory training without resistance set on respiratory muscle trainer
Sponsor: Medical University of Bialystok
Recruiting
Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention - Condition: Post-acute COVID-19 Syndrome
Intervention: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention
Sponsor: VA Office of Research and Development
Not yet recruiting
Mineralocorticoid Use in COVID-19 Patients - Conditions: COVID-19; ARDS
Intervention: Drug: Fludrocortisone Acetate 0.1 MG
Sponsor: Ain Shams University
Completed
Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients - Conditions: COVID-19; Dysglycemia
Interventions: Drug: Insulin; Drug: Subcutaneous Insulin
Sponsor: Benha University
Completed
A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects - Condition: COVID-19
Intervention: Combination Product: Delcetravir dry powder inhaler
Sponsor: Esfam Biotech Pty Ltd
Not yet recruiting
Surface Display of Peptides Corresponding to the Heptad Repeat 2 Domain of the Feline Enteric Coronavirus Spike Protein on Bacillus subtilis Spores Elicits Protective Immune Responses Against Homologous Infection in a Feline Aminopeptidase-N-Transduced Mouse Model - Although feline coronavirus (FCoV) infection is extremely common in cats, there are currently few effective treatments. A peptide derived from the heptad repeat 2 (HR2) domain of the coronavirus (CoV) spike protein has shown effective for inhibition of various human and animal CoVs in vitro, but further use of FCoV-HR2 in vivo has been limited by lack of practical delivery vectors and small animal infection model. To overcome these technical challenges, we first constructed a recombinant…
Corona versus Dengue: Distinct Mechanisms for Inhibition of Polyprotein Processing by Antiviral Drugs - Inhibitors interfering with processing of the viral polyprotein are used successfully for the control of extremely important viral pathogens, such as HIV and most recently SARS-CoV-2. This Viewpoint provides a mechanistic evaluation of a promising antiviral lead compound against dengue virus, JNJ-A07, 4-(3-((1-(4-chlorophenyl)-2-oxo-2-(6-(trifluoromethoxy)indolin-1-yl)ethyl)amino)-5-methoxyphenoxy)butanoic acid. The antiviral effect of JNJ-A07 appears, in our opinion, to be connected to an…
The Impact on COVID-19 by Intravenous Bevacizumab Used for Hereditary Hemorrhagic Telangiectasia: A Case Report - Coronavirus disease 2019 (COVID-19) continues as an infectious pandemic. With emphasis on mitigating its impact globally, strategies have been emphasized on prevention to treatment in severe cases. As for pharmacotherapies, many have been researched, with a few being recommended for patients with COVID-19 depending upon their severity. Bevacizumab, a recombinant monoclonal antibody often used for oncological disease and rare genetic disorders, has gained attention in combatting COVID-19 due to…
Evaluation of Clove Phytochemicals as Potential Antiviral Drug Candidates Targeting SARS-CoV-2 Main Protease: Computational Docking, Molecular Dynamics Simulation, and Pharmacokinetic Profiling - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause a sudden respiratory disease spreading with a high mortality rate arising with unknown mechanisms. Still, there is no proper treatment available to overcome the disease, which urges the research community and pharmaceutical industries to screen a novel therapeutic intervention to combat the current pandemic. This current study exploits the natural phytochemicals obtained from clove, a traditional natural therapeutic…
Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2 - CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.
Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies - Patients with hematological malignancies (HMs) are at a higher risk of developing severe form and protracted course of COVID-19 disease. We investigated whether the combination of viral replication inhibition with remdesivir and administration of anti-SARS-CoV-2 immunoglobulins with convalescent plasma (CP) therapy might be sufficient to treat B-cell-depleted patients with COVID-19. We enrolled 20 consecutive patients with various HMs with profound B-cell lymphopenia and COVID-19 pneumonia…
Multi-target mechanisms against coronaviruses of constituents from Chinese Dagang Tea revealed by experimental and docking studies - CONCLUSION: This study proposes E. chinensis and its triterpenoids and flavonoids as promising potential treatments for coronaviruses.
Allosteric inhibitors of the main protease of SARS-CoV-2 - SARS-CoV-2 has raised the alarm to search for effective therapy for this virus. To date several vaccines have been approved but few available drugs reported recently still need approval from FDA. Remdesivir was approved for emergency use only. In this report, the SARS-CoV-2 3CLpro was expressed and purified. By using a FRET-based enzymatic assay, we have screened a library consisting of more than 300 different niclosamide derivatives and identified three molecules JMX0286, JMX0301, and JMX0941…
Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold - Rubella, a viral disease characterized by a red skin rash, is well-controlled due to an effective vaccine, but outbreaks are still occurring in the absence of available antiviral treatments. The rubella virus (RUBV) papain-like protease (RubPro) is crucial for RUBV replication, cleaving the non-structural polyprotein p200 into two multi-functional proteins, p150 and p90. This protease could represent a potential drug target, but structural and mechanistic details important for the inhibition of…
Investigation of potential inhibitor properties of violacein against HIV-1 RT and CoV-2 Spike RBD:ACE-2 - A violacein-producing bacterium was isolated from a mud sample collected near a hot spring on Kümbet Plateau in Giresun Province and named the GK strain. According to the phylogenetic tree constructed using 16S rRNA gene sequence analysis, the GK strain was identified and named Janthinobacterium sp. GK. The crude violacein pigments were separated into three different bands on a TLC sheet. Then violacein and deoxyviolacein were purified by vacuum liquid column chromatography and identified by NMR…
Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2’-O-ribose methyltransferases - The SARS-CoV-2 infection cycle is a multi-stage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2’-O-ribose cap needed for viral immune escape. We find that the host cap 2’-O-ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16…
Opaganib in Coronavirus Disease 2019 Pneumonia: Results of a Randomized, Placebo-Controlled Phase 2a Trial - CONCLUSIONS: In this proof-of-concept study, hypoxic, hospitalized patients receiving oral opaganib had a similar safety profile to placebo-treated patients, with preliminary evidence of benefit for opaganib as measured by supplementary oxygen requirement and earlier hospital discharge. These findings support further evaluation of opaganib in this population.
Piperlongumin Improves Survival in the Mouse Model of Sepsis: Effect on Coagulation Factors and Lung Inflammation - Excessive inflammation and coagulation contribute to high morbidity and mortality in sepsis. Many studies have indicated the role of piperlongumine (PL) in anti-inflammation, but its effect on coagulation remains uncertain. Here, we explore whether PL could moderate coagulation indicators and alleviate lung inflammation during sepsis. RAW264.7 cells were induced by lipopolysaccharide (LPS) and treated with PL. Inflammatory and coagulation indicators, cell function and signaling, were evaluated…
Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients - The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although…
Epigallocatechin gallate (EGCG) attenuates severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection by blocking the interaction of SARS-CoV-2 spike protein receptor-binding domain to human angiotensin-converting enzyme 2 - The outbreak of the coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 triggered a global pandemic where control is needed through therapeutic and preventive interventions. This study aims to identify natural compounds that could affect the fusion between the viral membrane (receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein) and the human cell receptor angiotensin-converting enzyme 2. Accordingly, we performed the…