COVID-19 thread
Re: COVID-19 thread
First published results of human vaccine trial looks good. Published in the Lancet, which is a few steps up from most sources (notwithstanding autism-vaccine link paper 
).
https://www.thelancet.com/journals/lanc ... 3/fulltext
Still a way off getting something out to to the world and tens of thousands more deaths but have come a long, long way in a short time. Looking forward to profits of gentlemen's bet with "Stewie" come 2021.
).https://www.thelancet.com/journals/lanc ... 3/fulltext
Still a way off getting something out to to the world and tens of thousands more deaths but have come a long, long way in a short time. Looking forward to profits of gentlemen's bet with "Stewie" come 2021.
Re: COVID-19 thread
Summary
Background
A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
Methods
We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Findings
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
Interpretation
The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
Funding
National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in January, 2020. The virus is highly transmissible between humans and has spread rapidly, causing the COVID-19 pandemic.1, 2 Patients infected with SARS-CoV-2, especially older patients and those with pre-existing respiratory or cardiovascular conditions are at greater risk for severe complications, including severe pneumonia, acute respiratory distress syndrome, multiple organ failure, and in some cases, death.3, 4 By May 20, 2020, SARS-CoV-2 had infected more than 4·7 million people across 215 countries or territories and killed more than 316 000 worldwide.5
In the absence of effective prevention measures, current management to control the epidemic is the enforcement of quarantine, isolation, and physical distancing.6, 7 Effective vaccines against COVID-19 are urgently needed to reduce the enormous burden of mortality and morbidity associated with SARS-CoV-2 infection.8 There are more than 100 candidate vaccines in development worldwide,9 among them at least eight have started or will soon start clinical trials. These include Moderna's mRNA COVID-19 vaccine and CanSino's non-replicating adenovirus type-5 (Ad5) vectored COVID-19 vaccine, which both entered phase 1 clinical trials on March 16, 2020; Inovio Pharmaceuticals' DNA vaccine for COVID-19, which entered trials on April 3, 2020; three inactive COVID-19 vaccines manufactured by Sinovac, Wuhan Institute of Biological Products, and Beijing Institute of Biological Products entered clinical trials in April, 2020, successively; University of Oxford's non-replicating chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19, and BioNTech's mRNA COVID-19 vaccine also started trials in recent months.
Here, we report the preliminary assessment at 28 days post-vaccination of the safety, tolerability, and immunogenicity of CanSino's non-replicating Ad5 vectored COVID-19 vaccine in healthy adults in China.
Method
Study design and participants
We did a single-centre, open-label, non-randomised, dose-escalation phase 1 trial of an Ad5 vectored COVID-19 vaccine candidate in a rehabilitation centre in Wuhan, Hubei province, China. Eligible participants were healthy adults aged between 18 and 60 years, who did not have SARS-CoV-2 infection, confirmed by negative results of serum specific IgM and IgG antibodies with a commercial SARS-CoV-2 rapid test kit (Jinwofu, Beijing, China), negative nucleic acid for SARS-CoV-2 in pharyngeal swabs or sputum and anal swabs detected with a nucleic acid diagnostic kit (PCR-fluorescence probing, Sansure Biotech, Changsha, China), and a clear chest CT image with no evidence of lesions in the lungs at the time of screening. Exclusion criteria were a history of seizures or mental illness; allergy to any ingredient included in the vaccine; acute febrile disease on the day of enrolment; receipt of any blood products in the past 4 months; receipt of any research medicines or vaccine in the past month; and being unable to comply with the study schedule. Further details are outlined in the protocol.10 Participants were sequentially enrolled to receive a single intramuscular injection in a dose-escalating manner: the first group of participants were allocated to receive the low dose, followed up for a minimum of 3 days before proceeding to recruit further participants to receive the middle dose, and then after safety observation for 3 days, the last group of participants were recruited and allocated to receive the high dose. The administration of higher dose injections and new enrolment were paused if any criteria for pausing dose escalation were met.
The protocol and informed consent were approved by the institutional review board of the Jiangsu Provincial Center of Disease Control and Prevention. Written informed consent from all participants was obtained before screening. This study was undertaken by Jiangsu Provincial Center for Disease Control and Prevention, Hubei Provincial Center for Disease Control and Prevention, and Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in accordance with the Declaration of Helsinki and Good Clinical Practice.
Procedures
The Ad5 vectored COVID-19 vaccine was developed by Beijing Institute of Biotechnology (Beijing, China) and CanSino Biologics (Tianjin, China). The vaccine is a replication defective Ad5 vectored vaccine expressing the spike glycoprotein of SARS-CoV-2. We cloned an optimised full-length spike gene based on Wuhan-Hu-1 (GenBank accession number YP_009724390) with the tissue plasminogen activator signal peptide gene into an E1 and E3 deleted Ad5 vector, and constructed the Ad5 vectored COVID-19 vaccine using the Admax system from Microbix Biosystem (Toronto, ON, Canada). The Ad5 vectored COVID-19 vaccine was manufactured as a liquid formulation containing 5 × 1010 viral particles per 0·5 mL in a vial.
A single shot was allocated intramuscularly in the arm of the participants in the low dose group, with one vial of the Ad5 vectored COVID-19 vaccine (5 × 1010 viral particles per 0·5 mL). The participants in the middle dose group received one shot intramuscularly in the arm with two vials of the Ad5 vectored COVID-19 vaccine (1 × 1011 viral particles per mL). Participants in the high dose group received a double-shot regimen with one vial of the Ad5 vectored COVID-19 vaccine in one arm and two vials of the Ad5 vectored COVID-19 vaccine in the other arm (1·5 × 1011 viral particles per 1·5 mL).
Adverse events were self-reported by the participants, but verified by investigators daily during the first 14 days after vaccination. Subsequently, adverse events were recorded by the participants on diary cards in the following weeks. Laboratory safety tests including white blood cell count, lymphocyte count, neutrophils, platelets, haemoglobin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, fasting blood glucose, and creatinine were measured on day 7 to assess any toxic effects post-vaccination. We graded adverse events and abnormal changes in laboratory tests according to the scale issued by the China State Food and Drug Administration (version 2019).11
Blood samples were taken from participants for serology tests at the scheduled site visits before the vaccination, and on days 14 and 28 after the vaccination. We assessed binding antibody responses against the receptor binding domain (RBD) and spike glycoprotein with ELISA kits manufactured by Beijing Wantai BioPharm (Beijing, China). A dilution of 1:40 was the positivity cutoff value for ELISA. We also measured the neutralising antibody responses induced by vaccination using both live SARS-CoV-2 virus neutralisation (virus strain SARS-CoV-2/human/CHN/Wuhan_IME-BJ01/2020, GenBank number MT291831.1) and pseudovirus neutralisation tests (a vesicular stomatitis virus pseudovirus system expressing the spike glycoprotein).12 Peripheral blood mononuclear cells were isolated from whole blood before the vaccination and at days 14 and 28 post-vaccination. Specific T-cell responses were quantified with an interferon (IFN) γ enzyme-linked immunospot (ELISpot) assay using fresh peripheral blood mononuclear cells stimulated with overlapping spike glycoprotein peptide pools for about 12–24 h before detection, and expressed as the number of spot-forming cells per 100 000 cells. All measurements were subtracted from the unstimulated control values, and minus values were corrected to zero. The results were considered positive if there was at least a two-times increase in the number of IFNγ secreting T cells post-vaccination. We also assessed the CD4+ and CD8+ T-cell responses to vaccination according to the secretion of IFNγ, interleukin-2 (IL-2), and tumour necrosis factor α (TNFα), which were measured by intracellular cytokine staining assays in peripheral blood mononuclear cells after the stimulation with overlapping spike glycoprotein peptide pools for about 6 h and detected by flow cytometry. Similar methods to measure T-cell responses by intracellular cytokine staining assays have been reported previously.13, 14 The pre-vaccination and post-vaccination anti-Ad5 neutralising antibody titres were detected with a serum neutralisation assay.15
Outcomes
We analysed all outcomes in the intention-to-treat cohort. The primary endpoint for safety was the occurrence of adverse reactions within 7 days after the vaccination. Any abnormal changes in laboratory measures at 7 days post-vaccination, and adverse events within 28 days across the treatment groups were also analysed as secondary safety endpoints. The specific ELISA antibody titres to RBD and the spike glycoprotein, and the neutralising antibody amounts against live SARS-CoV-2 and a pseudovirus were measured as humoral immunogenicity endpoints. We defined a positive antibody response (seroconversion) as at least a four-fold increase in post-vaccination titre from baseline. ELISpot IFNγ and positive T-cell responses measured by intracellular cytokine staining assays were compared across the groups as endpoints for cell-mediated responses. Stratified analyses of the immune responses were done based on the pre-existing Ad5 neutralising antibody titres among the participants as low or negative (≤1:200) or high (>1:200).
Statistical analysis
The sample size was not determined on the basis of statistical power calculations; however, a minimum sample size of 20–30 participants for a pilot vaccine trial has been recommended by the National Medical Products Administration, China. We assessed the number and proportion of participants with adverse reactions post-vaccination and compared safety profiles across the dose groups. The antibodies against SARS-CoV-2 were presented as geometric mean titres with 95% CIs and the cellular responses were shown as a proportion of positive responders. We used the χ2 test or Fisher's exact test to analyse categorical data, ANOVA to analyse the log transformed antibody titres, and Wilcoxon rank-sum test for data that were not normally distributed. When the overall difference across the three groups was significant, pairwise comparisons were made and the differences between groups were estimated with 95% CIs. Multivariable analysis was used to establish the possible effects on the immunogenicity and safety profile of the vaccine candidates. Hypothesis testing was two-sided with an α value of 0·05. Statistical analyses were done by a statistician using SAS (version 9.4) or GraphPad Prism 8·0·1. SPICE (version 6.0) was used for the analysis of data from multicolour flow cytometry experiments.
An independent data and safety monitoring committee, with one independent statistician, one clinician, and one epidemiologist, was established before the start of the trial. Safety data for the first 3 days post-vaccination were assessed and reviewed by the committee to ensure that there was sufficient holding time between dose escalation. This study is registered with ClinicalTrials.gov, NCT04313127.
Role of the funding source
The sponsors of the study participated in study design, but had no role in data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Results
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 were sequentially enrolled and assigned to receive the low dose (n=36 [33%]), middle dose (n=36 [33%]), or high dose (n=36 [33%]) of the Ad5 vectored COVID-19 vaccine (appendix p 2). All participants completed the vaccination and the scheduled visits within 28 days. Baseline characteristics of the participants were similar across the treatment groups (table 1).
Background
A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
Methods
We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Findings
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
Interpretation
The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
Funding
National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in January, 2020. The virus is highly transmissible between humans and has spread rapidly, causing the COVID-19 pandemic.1, 2 Patients infected with SARS-CoV-2, especially older patients and those with pre-existing respiratory or cardiovascular conditions are at greater risk for severe complications, including severe pneumonia, acute respiratory distress syndrome, multiple organ failure, and in some cases, death.3, 4 By May 20, 2020, SARS-CoV-2 had infected more than 4·7 million people across 215 countries or territories and killed more than 316 000 worldwide.5
In the absence of effective prevention measures, current management to control the epidemic is the enforcement of quarantine, isolation, and physical distancing.6, 7 Effective vaccines against COVID-19 are urgently needed to reduce the enormous burden of mortality and morbidity associated with SARS-CoV-2 infection.8 There are more than 100 candidate vaccines in development worldwide,9 among them at least eight have started or will soon start clinical trials. These include Moderna's mRNA COVID-19 vaccine and CanSino's non-replicating adenovirus type-5 (Ad5) vectored COVID-19 vaccine, which both entered phase 1 clinical trials on March 16, 2020; Inovio Pharmaceuticals' DNA vaccine for COVID-19, which entered trials on April 3, 2020; three inactive COVID-19 vaccines manufactured by Sinovac, Wuhan Institute of Biological Products, and Beijing Institute of Biological Products entered clinical trials in April, 2020, successively; University of Oxford's non-replicating chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19, and BioNTech's mRNA COVID-19 vaccine also started trials in recent months.
Here, we report the preliminary assessment at 28 days post-vaccination of the safety, tolerability, and immunogenicity of CanSino's non-replicating Ad5 vectored COVID-19 vaccine in healthy adults in China.
Method
Study design and participants
We did a single-centre, open-label, non-randomised, dose-escalation phase 1 trial of an Ad5 vectored COVID-19 vaccine candidate in a rehabilitation centre in Wuhan, Hubei province, China. Eligible participants were healthy adults aged between 18 and 60 years, who did not have SARS-CoV-2 infection, confirmed by negative results of serum specific IgM and IgG antibodies with a commercial SARS-CoV-2 rapid test kit (Jinwofu, Beijing, China), negative nucleic acid for SARS-CoV-2 in pharyngeal swabs or sputum and anal swabs detected with a nucleic acid diagnostic kit (PCR-fluorescence probing, Sansure Biotech, Changsha, China), and a clear chest CT image with no evidence of lesions in the lungs at the time of screening. Exclusion criteria were a history of seizures or mental illness; allergy to any ingredient included in the vaccine; acute febrile disease on the day of enrolment; receipt of any blood products in the past 4 months; receipt of any research medicines or vaccine in the past month; and being unable to comply with the study schedule. Further details are outlined in the protocol.10 Participants were sequentially enrolled to receive a single intramuscular injection in a dose-escalating manner: the first group of participants were allocated to receive the low dose, followed up for a minimum of 3 days before proceeding to recruit further participants to receive the middle dose, and then after safety observation for 3 days, the last group of participants were recruited and allocated to receive the high dose. The administration of higher dose injections and new enrolment were paused if any criteria for pausing dose escalation were met.
The protocol and informed consent were approved by the institutional review board of the Jiangsu Provincial Center of Disease Control and Prevention. Written informed consent from all participants was obtained before screening. This study was undertaken by Jiangsu Provincial Center for Disease Control and Prevention, Hubei Provincial Center for Disease Control and Prevention, and Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in accordance with the Declaration of Helsinki and Good Clinical Practice.
Procedures
The Ad5 vectored COVID-19 vaccine was developed by Beijing Institute of Biotechnology (Beijing, China) and CanSino Biologics (Tianjin, China). The vaccine is a replication defective Ad5 vectored vaccine expressing the spike glycoprotein of SARS-CoV-2. We cloned an optimised full-length spike gene based on Wuhan-Hu-1 (GenBank accession number YP_009724390) with the tissue plasminogen activator signal peptide gene into an E1 and E3 deleted Ad5 vector, and constructed the Ad5 vectored COVID-19 vaccine using the Admax system from Microbix Biosystem (Toronto, ON, Canada). The Ad5 vectored COVID-19 vaccine was manufactured as a liquid formulation containing 5 × 1010 viral particles per 0·5 mL in a vial.
A single shot was allocated intramuscularly in the arm of the participants in the low dose group, with one vial of the Ad5 vectored COVID-19 vaccine (5 × 1010 viral particles per 0·5 mL). The participants in the middle dose group received one shot intramuscularly in the arm with two vials of the Ad5 vectored COVID-19 vaccine (1 × 1011 viral particles per mL). Participants in the high dose group received a double-shot regimen with one vial of the Ad5 vectored COVID-19 vaccine in one arm and two vials of the Ad5 vectored COVID-19 vaccine in the other arm (1·5 × 1011 viral particles per 1·5 mL).
Adverse events were self-reported by the participants, but verified by investigators daily during the first 14 days after vaccination. Subsequently, adverse events were recorded by the participants on diary cards in the following weeks. Laboratory safety tests including white blood cell count, lymphocyte count, neutrophils, platelets, haemoglobin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, fasting blood glucose, and creatinine were measured on day 7 to assess any toxic effects post-vaccination. We graded adverse events and abnormal changes in laboratory tests according to the scale issued by the China State Food and Drug Administration (version 2019).11
Blood samples were taken from participants for serology tests at the scheduled site visits before the vaccination, and on days 14 and 28 after the vaccination. We assessed binding antibody responses against the receptor binding domain (RBD) and spike glycoprotein with ELISA kits manufactured by Beijing Wantai BioPharm (Beijing, China). A dilution of 1:40 was the positivity cutoff value for ELISA. We also measured the neutralising antibody responses induced by vaccination using both live SARS-CoV-2 virus neutralisation (virus strain SARS-CoV-2/human/CHN/Wuhan_IME-BJ01/2020, GenBank number MT291831.1) and pseudovirus neutralisation tests (a vesicular stomatitis virus pseudovirus system expressing the spike glycoprotein).12 Peripheral blood mononuclear cells were isolated from whole blood before the vaccination and at days 14 and 28 post-vaccination. Specific T-cell responses were quantified with an interferon (IFN) γ enzyme-linked immunospot (ELISpot) assay using fresh peripheral blood mononuclear cells stimulated with overlapping spike glycoprotein peptide pools for about 12–24 h before detection, and expressed as the number of spot-forming cells per 100 000 cells. All measurements were subtracted from the unstimulated control values, and minus values were corrected to zero. The results were considered positive if there was at least a two-times increase in the number of IFNγ secreting T cells post-vaccination. We also assessed the CD4+ and CD8+ T-cell responses to vaccination according to the secretion of IFNγ, interleukin-2 (IL-2), and tumour necrosis factor α (TNFα), which were measured by intracellular cytokine staining assays in peripheral blood mononuclear cells after the stimulation with overlapping spike glycoprotein peptide pools for about 6 h and detected by flow cytometry. Similar methods to measure T-cell responses by intracellular cytokine staining assays have been reported previously.13, 14 The pre-vaccination and post-vaccination anti-Ad5 neutralising antibody titres were detected with a serum neutralisation assay.15
Outcomes
We analysed all outcomes in the intention-to-treat cohort. The primary endpoint for safety was the occurrence of adverse reactions within 7 days after the vaccination. Any abnormal changes in laboratory measures at 7 days post-vaccination, and adverse events within 28 days across the treatment groups were also analysed as secondary safety endpoints. The specific ELISA antibody titres to RBD and the spike glycoprotein, and the neutralising antibody amounts against live SARS-CoV-2 and a pseudovirus were measured as humoral immunogenicity endpoints. We defined a positive antibody response (seroconversion) as at least a four-fold increase in post-vaccination titre from baseline. ELISpot IFNγ and positive T-cell responses measured by intracellular cytokine staining assays were compared across the groups as endpoints for cell-mediated responses. Stratified analyses of the immune responses were done based on the pre-existing Ad5 neutralising antibody titres among the participants as low or negative (≤1:200) or high (>1:200).
Statistical analysis
The sample size was not determined on the basis of statistical power calculations; however, a minimum sample size of 20–30 participants for a pilot vaccine trial has been recommended by the National Medical Products Administration, China. We assessed the number and proportion of participants with adverse reactions post-vaccination and compared safety profiles across the dose groups. The antibodies against SARS-CoV-2 were presented as geometric mean titres with 95% CIs and the cellular responses were shown as a proportion of positive responders. We used the χ2 test or Fisher's exact test to analyse categorical data, ANOVA to analyse the log transformed antibody titres, and Wilcoxon rank-sum test for data that were not normally distributed. When the overall difference across the three groups was significant, pairwise comparisons were made and the differences between groups were estimated with 95% CIs. Multivariable analysis was used to establish the possible effects on the immunogenicity and safety profile of the vaccine candidates. Hypothesis testing was two-sided with an α value of 0·05. Statistical analyses were done by a statistician using SAS (version 9.4) or GraphPad Prism 8·0·1. SPICE (version 6.0) was used for the analysis of data from multicolour flow cytometry experiments.
An independent data and safety monitoring committee, with one independent statistician, one clinician, and one epidemiologist, was established before the start of the trial. Safety data for the first 3 days post-vaccination were assessed and reviewed by the committee to ensure that there was sufficient holding time between dose escalation. This study is registered with ClinicalTrials.gov, NCT04313127.
Role of the funding source
The sponsors of the study participated in study design, but had no role in data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Results
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 were sequentially enrolled and assigned to receive the low dose (n=36 [33%]), middle dose (n=36 [33%]), or high dose (n=36 [33%]) of the Ad5 vectored COVID-19 vaccine (appendix p 2). All participants completed the vaccination and the scheduled visits within 28 days. Baseline characteristics of the participants were similar across the treatment groups (table 1).
Re: COVID-19 thread
Boston marathon is going virtual.
Charles next ?
Charles next ?
Re: COVID-19 thread
Let's talk reopening and COVID 19 with USA Rowing team Dr Kate Ackerman. Can we row team boats soon? What will the Olympics look like ? What will college and junior rowing look like? What mask is best to train in ?
https://traffic.libsyn.com/secure/rowin ... .08_AM.mp3
Don't forget to subscribe on iTunes and Google Play
https://traffic.libsyn.com/secure/rowin ... .08_AM.mp3
Don't forget to subscribe on iTunes and Google Play
Re: COVID-19 thread
Big 10.
First a cancellation of fall football and now a possible rescheduling to spring.
https://amp.detroitnews.com/amp/3334804001
First a cancellation of fall football and now a possible rescheduling to spring.
https://amp.detroitnews.com/amp/3334804001
Problems worthy of attack prove their worth by fighting back - Piet Hein
Re: COVID-19 thread
With zero new Covid-19 cases and deaths recently in many Australian States (less than 20 new cases nationally), Australia is now easing restrictions and crew rowing commences on Wednesday. Summer is just over a month away and regattas are already being planned. Australia & New Zealand have proven to the rest of the world that the only way to beat this virus, without a vaccine, is by enduring tough lock downs. After 7 months of the toughest lock down restrictions in the world (Melbourne, I can't wait to get back to some form of normal life again.)
-
Stewie Griffin Should Cox
- Old timer
- Posts: 3668
- Joined: Mon Feb 11, 2008 10:28 pm
Re: COVID-19 thread
At what cost ? To GDP? And to mental health and suicide rates ?platypus wrote:With zero new Covid-19 cases and deaths recently in many Australian States (less than 20 new cases nationally), Australia is now easing restrictions and crew rowing commences on Wednesday. Summer is just over a month away and regattas are already being planned. Australia & New Zealand have proven to the rest of the world that the only way to beat this virus, without a vaccine, is by enduring tough lock downs. After 7 months of the toughest lock down restrictions in the world (Melbourne, I can't wait to get back to some form of normal life again.)
Re: COVID-19 thread
"At what cost ? To GDP? And to mental health and suicide rates ?"
Two interesting points:
1) Cost to GDP??? Well, just before going into the Covid-19 crisis, Australia posted a substantial economic budget surplus. Therefore, unlike many other countries in the world, it was well placed economically, to throw money at this thing. Money was poured into Health Services and small business job keeper schemes. Australia did go into an economic recession. However, this was only for a short period of time and has now ended, with the economy poised to come back strong.
2) Mental health and suicide rates ??? The people of Melbourne, Australia's second largest city, had to endure without a doubt, the harshest and longest lock down imposed by any city in the world. It was extended for a longer period, totalling about 7 months, due to major stuff ups in hotel quarantine, aged care and contact tracing, caused by the government. Consequently, unreasonably strict social distancing laws were set in place with heavy $5,000 penalties for breaches. Curfew was imposed from 8pm to 5am. Other than essential services, everything was closed down and many lost their jobs, other than those that could work from home. Outside of curfew hours, you could only leave home to exercise for one hour or go food shopping. Plus everyone had to wear a mask. Furthermore, a ring of steel was placed around the city and travel restrictions allowed you to travel a maximum of 5km from home. Only one person in the household was allowed to go shopping with no partners or children. It was so tough being locked away inside for so long. But, nevertheless, it may surprise you that the suicide rate remained the same. Yes, official figures show that the numbers remained the same but the reasons for suicide changed. Those with suicidal tendencies, that would normally commit suicide for job loss or marriage break up reasons, were instead recorded with Covid-19 as the reason beside their names.
However, the important thing is that eventually the extended and severe lock down worked. We are now getting zero to 3 new cases per day and have less than 100 active cases remaining in the whole of the country. Life is getting back to normal, while we watch the new covid-19 numbers in Europe, India & USA sky rocket. Over 50,000 in some countries per day. Only the countries with strong political leaders, prepared to sacrifice popularity for the health of the people, will beat this virus. But of course, Trump says that the virus is going away. No need to wear a mask. Keep the country open. The economy, social freedom and political votes is more important than people dying from covid-19. I guess we won't know for sure until the USA election results are out.
Two interesting points:
1) Cost to GDP??? Well, just before going into the Covid-19 crisis, Australia posted a substantial economic budget surplus. Therefore, unlike many other countries in the world, it was well placed economically, to throw money at this thing. Money was poured into Health Services and small business job keeper schemes. Australia did go into an economic recession. However, this was only for a short period of time and has now ended, with the economy poised to come back strong.
2) Mental health and suicide rates ??? The people of Melbourne, Australia's second largest city, had to endure without a doubt, the harshest and longest lock down imposed by any city in the world. It was extended for a longer period, totalling about 7 months, due to major stuff ups in hotel quarantine, aged care and contact tracing, caused by the government. Consequently, unreasonably strict social distancing laws were set in place with heavy $5,000 penalties for breaches. Curfew was imposed from 8pm to 5am. Other than essential services, everything was closed down and many lost their jobs, other than those that could work from home. Outside of curfew hours, you could only leave home to exercise for one hour or go food shopping. Plus everyone had to wear a mask. Furthermore, a ring of steel was placed around the city and travel restrictions allowed you to travel a maximum of 5km from home. Only one person in the household was allowed to go shopping with no partners or children. It was so tough being locked away inside for so long. But, nevertheless, it may surprise you that the suicide rate remained the same. Yes, official figures show that the numbers remained the same but the reasons for suicide changed. Those with suicidal tendencies, that would normally commit suicide for job loss or marriage break up reasons, were instead recorded with Covid-19 as the reason beside their names.
However, the important thing is that eventually the extended and severe lock down worked. We are now getting zero to 3 new cases per day and have less than 100 active cases remaining in the whole of the country. Life is getting back to normal, while we watch the new covid-19 numbers in Europe, India & USA sky rocket. Over 50,000 in some countries per day. Only the countries with strong political leaders, prepared to sacrifice popularity for the health of the people, will beat this virus. But of course, Trump says that the virus is going away. No need to wear a mask. Keep the country open. The economy, social freedom and political votes is more important than people dying from covid-19. I guess we won't know for sure until the USA election results are out.
Re: COVID-19 thread
Ppus: I'm testing negative every week and winter's coming. Can I DHL myself to the Yarra? No matter the election, this next few months will be brutal.platypus wrote:"At what cost ? To GDP? And to mental health and suicide rates ?"
However, the important thing is that eventually the extended and severe lock down worked. We are now getting zero to 3 new cases per day and have less than 100 active cases remaining in the whole of the country. Life is getting back to normal, while we watch the new covid-19 numbers in Europe, India & USA sky rocket. Over 50,000 in some countries per day. Only the countries with strong political leaders, prepared to sacrifice popularity for the health of the people, will beat this virus. But of course, Trump says that the virus is going away. No need to wear a mask. Keep the country open. The economy, social freedom and political votes is more important than people dying from covid-19. I guess we won't know for sure until the USA election results are out.
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Stewie Griffin Should Cox
- Old timer
- Posts: 3668
- Joined: Mon Feb 11, 2008 10:28 pm
Re: COVID-19 thread
I agree the Melbourne lockdown was hard but effective. I have a member of my team there are it was tough. The countries that have done well with covid have been brutally tough in this regard. China, south Korea etc. the problem in the the UK and US people see it as an afront to theirs rights and won’t do itplatypus wrote:"At what cost ? To GDP? And to mental health and suicide rates ?"
Two interesting points:
1) Cost to GDP??? Well, just before going into the Covid-19 crisis, Australia posted a substantial economic budget surplus. Therefore, unlike many other countries in the world, it was well placed economically, to throw money at this thing. Money was poured into Health Services and small business job keeper schemes. Australia did go into an economic recession. However, this was only for a short period of time and has now ended, with the economy poised to come back strong.
2) Mental health and suicide rates ??? The people of Melbourne, Australia's second largest city, had to endure without a doubt, the harshest and longest lock down imposed by any city in the world. It was extended for a longer period, totalling about 7 months, due to major stuff ups in hotel quarantine, aged care and contact tracing, caused by the government. Consequently, unreasonably strict social distancing laws were set in place with heavy $5,000 penalties for breaches. Curfew was imposed from 8pm to 5am. Other than essential services, everything was closed down and many lost their jobs, other than those that could work from home. Outside of curfew hours, you could only leave home to exercise for one hour or go food shopping. Plus everyone had to wear a mask. Furthermore, a ring of steel was placed around the city and travel restrictions allowed you to travel a maximum of 5km from home. Only one person in the household was allowed to go shopping with no partners or children. It was so tough being locked away inside for so long. But, nevertheless, it may surprise you that the suicide rate remained the same. Yes, official figures show that the numbers remained the same but the reasons for suicide changed. Those with suicidal tendencies, that would normally commit suicide for job loss or marriage break up reasons, were instead recorded with Covid-19 as the reason beside their names.
However, the important thing is that eventually the extended and severe lock down worked. We are now getting zero to 3 new cases per day and have less than 100 active cases remaining in the whole of the country. Life is getting back to normal, while we watch the new covid-19 numbers in Europe, India & USA sky rocket. Over 50,000 in some countries per day. Only the countries with strong political leaders, prepared to sacrifice popularity for the health of the people, will beat this virus. But of course, Trump says that the virus is going away. No need to wear a mask. Keep the country open. The economy, social freedom and political votes is more important than people dying from covid-19. I guess we won't know for sure until the USA election results are out.
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oneofthorsboys
- JV
- Posts: 88
- Joined: Sat Sep 15, 2018 10:33 pm
Re: COVID-19 thread
In this world of ours we have folks who believe the world is flat, that the moon landings were faked, that climate change is not caused primarily by man and that Donald Trump is a good president. Throughout history people have believed those who shout loudest, who promise most, those who blame societies ills on others, never themselves and who claim that (insert empire, Reich, States here) is the greatest country in the world and that God saves their Queen, blesses their country, or in the case of a fairly notorious lot back in the early to mid 20th century who proudly engraved on their armed forces belt buckles that "Gott mit uns".
The fact is that a large minority of people are and always have been fundamentally ignorant, uneducated and frankly stupid. There has never been any point talking logic to the illogical, sense to the senseless or compassion to the heartless. All you can do right now is vote them out, send them packing and maybe pump all that money your country spends on its military into real factual, scientific based education.
The fact is that a large minority of people are and always have been fundamentally ignorant, uneducated and frankly stupid. There has never been any point talking logic to the illogical, sense to the senseless or compassion to the heartless. All you can do right now is vote them out, send them packing and maybe pump all that money your country spends on its military into real factual, scientific based education.
Re: COVID-19 thread
So men's varsity collegiate rowing is doomed, eh?oneofthorsboys wrote:In this world of ours we have folks who believe the world is flat, that the moon landings were faked, that climate change is not caused primarily by man and that Donald Trump is a good president. Throughout history people have believed those who shout loudest, who promise most, those who blame societies ills on others, never themselves and who claim that (insert empire, Reich, States here) is the greatest country in the world and that God saves their Queen, blesses their country, or in the case of a fairly notorious lot back in the early to mid 20th century who proudly engraved on their armed forces belt buckles that "Gott mit uns".
The fact is that a large minority of people are and always have been fundamentally ignorant, uneducated and frankly stupid. There has never been any point talking logic to the illogical, sense to the senseless or compassion to the heartless. All you can do right now is vote them out, send them packing and maybe pump all that money your country spends on its military into real factual, scientific based education.
Re: COVID-19 thread
With nobody currently "in charge" in the USA, new daily cases have surged past 100,000. In contrast, Australia's heavy handed strict approach to combating the virus, is now paying dividends with currently zero daily cases for the whole of the country. Manufacture of the Oxford vaccine begins next week in Australia.There has also been a 1.5 billion dollar investment in four other vaccines, so not all its eggs are put in the one basket. If Biden takes control, the whole world will be watching to see how he deals with this virus.