Abstract In 2015, the Nobel Committee for Physiology or Medicine, in its only award for treatments of infectious diseases since six decades prior, honored the discovery of ivermectin (IVM), a multifaceted drug deployed against some of the world’s most devastating tropical diseases. Since March 2020, when IVM was first used against a new global scourge, COVID-19, more than 20 randomized clinical trials (RCTs) have tracked such inpatient and outpatient treatments. Six of seven meta-analyses of IVM treatment RCTs reporting in 2021 found notable reductions in COVID-19 fatalities, with a mean 31% relative risk of mortality vs. controls. The RCT using the highest IVM dose achieved a 92% reduction in mortality vs. controls (400 total subjects, p<0.001). During mass IVM treatments in Peru, excess deaths fell by a mean of 74% over 30 days in its ten states with the most extensive treatments. Reductions in deaths correlated with extent of IVM distributions in all 25 states with p<0.002. Sharp reductions in morbidity using IVM were also observed in two animal models, of SARS-CoV-2 and a related betacoronavirus. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains.
最新的越南医院工作人员的breakthrough cases的研究结果，注意是preprint，还没有peer review https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3897733 Transmission of SARS-CoV-2 Delta Variant Among Vaccinated Healthcare Workers, Vietnam Abstract Background: Data on breakthrough SARS-CoV-2 Delta variant infections are limited. Methods: We studied breakthrough infections among healthcare workers of a major infectious diseases hospital in Vietnam. We collected demographics, vaccination history and results of PCR diagnosis alongside clinical data. We measured SARS-CoV-2 (neutralizing) antibodies at diagnosis, and at week 1, 2 and 3 after diagnosis. We sequenced the viruses using ARTIC protocol. Findings: Between 11th–25th June 2021 (week 7–8 after dose 2), 69 healthcare workers were tested positive for SARS-CoV-2. 62 participated in the clinical study. 49 were (pre)symptomatic with one requiring oxygen supplementation. All recovered uneventfully. 23 complete-genome sequences were obtained. They all belonged to the Delta variant, and were phylogenetically distinct from the contemporary Delta variant sequences obtained from community transmission cases, suggestive of ongoing transmission between the workers. Viral loads of breakthrough Delta variant infection cases were 251 times higher than those of cases infected with old strains detected between March-April 2020. Time from diagnosis to PCR negative was 8–33 days (median: 21). Neutralizing antibody levels after vaccination and at diagnosis of the cases were lower than those in the matched uninfected controls. There was no correlation between vaccine-induced neutralizing antibody levels and viral loads or the development of symptoms. Interpretation: Breakthrough Delta variant infections are associated with high viral loads, prolonged PCR positivity, and low levels of vaccine-induced neutralizing antibodies, explaining the transmission between the vaccinated people. Physical distancing measures remain critical to reduce SARS-CoV-2 Delta variant transmission.
Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19
Alessandro D.SantinMD1 David E.ScheimPhD2 Peter A.McCulloughMD, MPH3 MorimasaYagisawaPhD4 Thomas J.BorodyMD, PhD, DSc5 1 Department of Obstetrics & Gynecology, Yale University School of Medicine, New Haven, CT, USA 2 Commissioned Officer, US Public Health Service, Inactive Reserve, Blacksburg, VA, USA 3 Texas A & M College of Medicine, Dallas, TX, USA 4 Ōmura Satoshi Memorial Institute, Infection Control Research Center, Kitasato University, Tokyo, Japan 5 Director, Centre for Digestive Diseases, New South Wales, Australia
Abstract In 2015, the Nobel Committee for Physiology or Medicine, in its only award for treatments of infectious diseases since six decades prior, honored the discovery of ivermectin (IVM), a multifaceted drug deployed against some of the world’s most devastating tropical diseases. Since March 2020, when IVM was first used against a new global scourge, COVID-19, more than 20 randomized clinical trials (RCTs) have tracked such inpatient and outpatient treatments. Six of seven meta-analyses of IVM treatment RCTs reporting in 2021 found notable reductions in COVID-19 fatalities, with a mean 31% relative risk of mortality vs. controls. The RCT using the highest IVM dose achieved a 92% reduction in mortality vs. controls (400 total subjects, p<0.001). During mass IVM treatments in Peru, excess deaths fell by a mean of 74% over 30 days in its ten states with the most extensive treatments. Reductions in deaths correlated with extent of IVM distributions in all 25 states with p<0.002. Sharp reductions in morbidity using IVM were also observed in two animal models, of SARS-CoV-2 and a related betacoronavirus. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains.
最新的越南医院工作人员的breakthrough cases的研究结果，注意是preprint，还没有peer review https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3897733 Transmission of SARS-CoV-2 Delta Variant Among Vaccinated Healthcare Workers, Vietnam
Abstract Background: Data on breakthrough SARS-CoV-2 Delta variant infections are limited.
Methods: We studied breakthrough infections among healthcare workers of a major infectious diseases hospital in Vietnam. We collected demographics, vaccination history and results of PCR diagnosis alongside clinical data. We measured SARS-CoV-2 (neutralizing) antibodies at diagnosis, and at week 1, 2 and 3 after diagnosis. We sequenced the viruses using ARTIC protocol.
Findings: Between 11th–25th June 2021 (week 7–8 after dose 2), 69 healthcare workers were tested positive for SARS-CoV-2. 62 participated in the clinical study. 49 were (pre)symptomatic with one requiring oxygen supplementation. All recovered uneventfully. 23 complete-genome sequences were obtained. They all belonged to the Delta variant, and were phylogenetically distinct from the contemporary Delta variant sequences obtained from community transmission cases, suggestive of ongoing transmission between the workers. Viral loads of breakthrough Delta variant infection cases were 251 times higher than those of cases infected with old strains detected between March-April 2020. Time from diagnosis to PCR negative was 8–33 days (median: 21). Neutralizing antibody levels after vaccination and at diagnosis of the cases were lower than those in the matched uninfected controls. There was no correlation between vaccine-induced neutralizing antibody levels and viral loads or the development of symptoms.
Interpretation: Breakthrough Delta variant infections are associated with high viral loads, prolonged PCR positivity, and low levels of vaccine-induced neutralizing antibodies, explaining the transmission between the vaccinated people. Physical distancing measures remain critical to reduce SARS-CoV-2 Delta variant transmission.