Background: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the United States with mild-to-moderate symptomatic coronavirus disease 2019 (COVID-19) is unknown. Objective: We evaluated the efficacy of ivermectin 400 mcg/kg daily for 3 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial to evaluate repurposed therapies in outpatients with mild-to-moderate COVID-19. Non-hospitalized adults age >=30 years with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for <=7 days were randomized to receive ivermectin 400 mcg/kg daily for 3 days or placebo. The main outcome measure was time to sustained recovery, defined as achieving at least 3 consecutive days without symptoms. Secondary outcomes included a composite of hospitalization or death by day 28. Results: Of the 3457 participants who consented to be evaluated for inclusion in the ivermectin arm, 1591 were eligible for this study arm, randomized to receive ivermectin 400 mcg/kg (n=817) or placebo (n=774), and received study drug. Of those enrolled, 47% reported receiving at least 2 doses of SARS-CoV-2 vaccination. The posterior probability for any improvement in time to recovery was 0.91 (hazard ratio 1.07, 95% credible interval 0.96 to 1.17). The posterior probability of this benefit exceeding 24 hours was less than 0.01, as measured by the difference in mean time unwell. Hospitalizations or deaths were uncommon (ivermectin [n=10]; placebo [n=9]). Ivermectin at 400 mcg/kg was safe and without serious adverse events as compared with placebo (ivermectin [n=10]; placebo [n=9]). Conclusions: Ivermectin dosed at 400 mcg/kg daily for 3 days resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19 in the United States during the delta and omicron variant time periods. Trial registration: ClinicalTrials.gov Identifier: NCT04885530.
Objective This systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants. Methods The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). Results: The eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%). Conclusion There was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
Influenza activity was reported to be below the seasonal levels during the COVID-19 pandemic globally. However, during the SARS-CoV-2 outbreak, the routine real-time surveillance of influenza like illness (ILI) and acute respiratory infection (ARI) was adversely affected due to the changes in priorities, economic constraints, repurposing of hospitals for COVID care and closure of outpatient services. A systematic review and meta-analysis were carried out to assess the pooled proportion of symptomatic cases tested for influenza virus before the COVID-19 pandemic in 2019 and during the pandemic in 2020/2021. The study was designed based on PRISMA guidelines and the meta-analysis was performed to synthesise the pooled proportion of patients sampled for influenza surveillance before the COVID-19 pandemic in 2019 and during the pandemic in 2020/21 with 95% confidence interval (CI). The overall pooled proportion of symptomatic cases undergone influenza surveillance before and during the pandemic was 2.38% (95% CI 2.08%-2.67%) and 4.18% (95% CI 3.8%-4.52%) respectively. However, the pooled proportion of samples tested for influenza before the pandemic was 0.69% (95% CI 0.45-0.92%) and during the pandemic was 0.48% (95% CI 0.28-0.68%) when studies from Canada were excluded. The meta-analysis concludes that globally there was a decline in influenza surveillance during the COVID-19 pandemic except in Canada.
Phase I Clinical Trial of GEN2-Recombinant COVID-19 Vaccine (CHO Cells) in Healthy People Aged 18 and Above - Condition: COVID-19 Pneumonia
Interventions: Biological: Experimental Vaccine 1; Biological: Experimental Vaccine 2; Biological: Experimental Vaccine 3; Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
COVID-19 Algorithm Treatment at Home - Condition: COVID-19
Interventions: Drug: Recommended treatment schedule; Drug: Usual care
Sponsor: Mario Negri Institute for Pharmacological Research
Not yet recruiting
Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19) - Condition: COVID-19
Interventions: Drug: Eucalyptus Oil; Drug: Standard COVID medication
Sponsors: Hasanuddin University; Ministry of Agriculture, Republic of Indonesia
Completed
Study of Oral High/Low-dose Cepharanthine Compared With Placebo in Non Hospitalized Adults With COVID-19 - Condition: Asymptomatic COVID-19
Interventions: Drug: Cepharanthine; Drug: Placebo
Sponsors: Shanghai Jiao Tong University School of Medicine; YUNNAN BAIYAO GROUP CO.,LTD
Not yet recruiting
Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island - Condition: COVID-19
Intervention: Other: telephone interview 24 months after hospitalization for Covid-19
Sponsor: Centre Hospitalier Universitaire de la Réunion
Not yet recruiting
α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19 - Condition: COVID-19
Intervention: Other: Real-time Quaking-Induced Conversion (RT-QuIC)
Sponsor: Medical University Innsbruck
Recruiting
Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults - Condition: COVID-19 Vaccines
Interventions: Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech); Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
Sponsors: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network
Not yet recruiting
Immunogenicity and Safety of a Third Dose of COVID-19 Vaccine(Vero Cell), Inactivated in the Elderly - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine (Vero cell), Inactivated
Sponsor: Sinovac Life Sciences Co., Ltd.
Active, not recruiting
Efficacy, Safety and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell)(Recov) - Condition: COVID-19
Interventions: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: Placebo
Sponsor: Jiangsu Rec-Biotechnology Co., Ltd.
Not yet recruiting
Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain
Sponsor: Sinovac Biotech (Hong Kong) Limited
Not yet recruiting
A Phase 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19 - Condition: COVID-19
Interventions: Biological: RQ3013; Biological: Comirnaty
Sponsors: Walvax Biotechnology Co., Ltd.; Shanghai RNACure Biopharma Co., Ltd.
Not yet recruiting
Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb) - Conditions: COVID-19 Acute Respiratory Distress Syndrome; COVID-19
Interventions: Drug: Plerixafor 20 MG/ML [Mozobil]; Other: Placebo
Sponsor: 4Living Biotech
Not yet recruiting
Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19 - Conditions: COVID-19; Type 2 Diabetes Mellitus
Intervention: Other: Aerobic and Relaxation Exercises
Sponsor: Bozyaka Training and Research Hospital
Active, not recruiting
Inhibition of Bradykinin in COVID-19 Infection With Icatibant - Condition: SARS CoV 2 Infection
Interventions: Drug: Icatibant; Drug: 0.9% Sodium Chloride Injection
Sponsors: Belfast Health and Social Care Trust; Queen’s University, Belfast
Recruiting
Effect of Prone Positioning on the Severity of COVID-19 Pneumonia and Acute Respiratory Distress Syndrome. - Conditions: COVID-19 Acute Respiratory Distress Syndrome; COVID-19 Pneumonia; Prone Positioning
Intervention: Other: Prone Positioning Maneuver
Sponsors: Ayub Medical College, Abbottabad; Ayub Teaching Hospital
Completed
The use of ivermectin for the treatment of COVID-19: Panacea or enigma? - The outbreak of SARS-CoV-2 pandemic has triggered unprecedented social, economic and health challenges. To control and reduce the infection rate, countries employed non-pharmaceutical measures such as social distancing, isolation, quarantine, and the use of masks, hand and surface sanitisation. Since 2021 a global race for COVID-19 vaccination ensued, mainly due to a lack of equitable vaccine production and distribution. To date, no treatments have been demonstrated to cure COVID-19. The…
Sewage surveillance for SARS-CoV-2: Molecular detection, quantification, and normalization factors - The presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in wastewater systems provides a primary indication of the coronavirus disease 2019 (COVID-19) spread throughout communities worldwide. Droplet digital polymerase chain reaction (dd-PCR) or reverse transcription-polymerase chain reaction (RT-PCR) administration of SARS-CoV-2 in wastewaters provides a reliable and efficient technology for gathering secondary local-level public health data. Often the accuracy of…
C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus - Porcine epidemic diarrhea virus (PEDV) is an emerging coronavirus which causes acute diarrhea and destroys gastrointestinal barrier function in neonatal pigs. Trefoil factor 1 (TFF1) is a protective peptide for maintaining the integrity of gastrointestinal mucosa and reducing intestinal inflammation. However, its role in protecting intestinal epithelium against PEDV infection is still unclear. In this study, we discovered that TFF1 expression was activated in the jejunum of pigs with PEDV…
Impact of Thermal Pretreatment of Saliva on the RT-PCR Detection of SARS-CoV-2 - The use of saliva directly as a specimen to detect viral RNA by RT-PCR has been tested for a long time as its advantages are relevant in terms of convenience and costs. However, as other body fluids, its proven inhibition effect on the amplification reaction can be troublesome and compromise its use in the detection of viral particles. The aim of the present work is to demonstrate that saliva pretreatment may influence the RT-PCR amplification of three gene targets of SARS-CoV-2 significantly. A…
Pralatrexate for Peripheral T-cell lymphoma (PTCL): Chance only supports the prepared mind. Systematic review - CONCLUSION: While there are manageable side effects such as thrombocytopenia, neutropenia, and mucositis, it is critical to explore new approaches, targeted agents, novel cellular therapies, and immunotherapies to determine optimal pretreatment in the rare but heterogeneous disease PTCL, and future studies and experienced haematologists are needed.
Antivirals and the Potential Benefits of Orally Inhaled Drug Administration in COVID-19 Treatment - Coronavirus Disease 2019 (COVID-19) pandemic has been on the agenda of humanity for more than 2 years. In the meantime, the pandemic has caused economic shutdowns, halt of daily lives and global mobility, overcrowding of the healthcare systems, panic, and worse, more than 6 million deaths. Today, there is still no specific therapy for COVID-19. Research focuses on repurposing of antiviral drugs that are licensed or currently in the research phase, with a known systemic safety profile. However,…
Conserved coronavirus proteins as targets of broad-spectrum antivirals - Coronaviruses are a class of single-stranded, positive-sense RNA viruses that have caused three major outbreaks over the past two decades: Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All outbreaks have been associated with significant morbidity and mortality. In this study, we have identified and explored conserved binding sites in the key coronavirus…
Combined exploration of the mechanism of Sang Xing Decoction in the treatment of smoke-induced acute bronchitis from protein and metabolic levels - Sang Xing decoction (SXD) is a typical prescription for treating “warm dryness” in traditional Chinese medicine (TCM), which is equivalent to respiratory diseases such as acute bronchitis in modern medicine. However, its mechanism of action remains unclear. In this study, the representative components of SXD were characterized using liquid chromatography-tandem mass spectrometry (LC-MS). The key targets, signaling pathways, and metabolic pathways associated with SXD in the treatment of acute…
GMI, a protein from Ganoderma microsporum, induces ACE2 degradation to alleviate infection of SARS-CoV-2 Spike-pseudotyped virus - CONCLUSIONS: GMI prevents SARS-CoV-2 pseudovirus infection via induction of ACE2 degradation in host cells. Our findings suggest that GMI will be a potential prevention agent to alleviate SARS-CoV-2 infection.
Prevalence of alcohol-tolerant and antibiotic-resistant bacterial pathogens on public hand sanitizer dispensers - CONCLUSION: HSDs serve as potential breeding grounds for dissemination of pathogens and antibiotic resistance across unknowing users. Proper HSD maintenance will ensure protection of public health and sustainable use of sanitizing alcohols, to prevent emergence of alcohol-resistant pathogens.
Risk stratification models for stroke in patients hospitalized with COVID-19 infection - CONCLUSIONS: We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.
The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition - Highly pathogenic human coronaviruses (CoV) including SARS-CoV, MERS-CoV and SARS-CoV-2 have emerged over the past two decades, resulting in infectious disease outbreaks that have greatly affected public health. The CoV surface spike (S) glycoprotein mediates receptor binding and membrane fusion for cell entry, playing critical roles in CoV infection and evolution. The S glycoprotein is also the major target molecule for prophylactic and therapeutic interventions, including neutralizing…
Inhibition of SARS-CoV-2 pathogenesis by potent peptides designed by the mutation of ACE2 binding region - The outbreak of COVID-19 has resulted in millions of deaths. Despite all attempts that have been made to combat the pandemic, the re-emergence of new variants complicated SARS-CoV-2 eradication. The ongoing global spread of COVID-19 demands the incessant development of novel agents in vaccination, diagnosis, and therapeutics. Targeting receptor-binding domain (RBD) of spike protein by which the virus identifies host receptor, angiotensin-converting enzyme (ACE2), is a promising strategy for…
Discovery of novel SARS-CoV-2 inhibitors targeting the main protease Mpro by virtual screenings and hit optimization - Two years after its emergence, SARS-CoV-2 still represents a serious and global threat to human health. Antiviral drug development usually takes a long time and, to increase the chances of success, chemical variability of hit compounds represents a valuable source for the discovery of new antivirals. In this work, we applied a platform of variably oriented virtual screening campaigns to seek for novel chemical scaffolds for SARS-CoV-2 main protease (M^(pro)) inhibitors. The study on the…
Breaking boundaries: Pan BETi disrupt 3D chromatin structure, BD2-selective BETi are strictly epigenetic transcriptional regulators - BACKGROUND: Bromodomain and extraterminal proteins (BETs) are more than just epigenetic regulators of transcription. Here we highlight a new role for the BET protein BRD4 in the maintenance of higher order chromatin structure at Topologically Associating Domain Boundaries (TADBs). BD2-selective and pan (non-selective) BET inhibitors (BETi) differentially support chromatin structure, selectively affecting transcription and cell viability.