blu3bird
Well-Known Member
I hope no one drinks that hand sanitizer lol
Public Health: Tips and information on how to prepare for the epidemic, avoid illness and protect our communities.
- Thread starter DIY-HP-LED
- Start date
blu3bird
Well-Known Member
Yeah but, it might not be all that good of an idea to use regular unleaded as hand sanitizer lolLOL A gallon of gasoline is only $2.
I'll tell you that nothing works as good a gas to get roofing tar off your hands though
Diesel fuel works really good to clean paint off a semi truck bumper if you accidentally bump into a yellow guard rail. Well that's what I've heard, don't tell my boss lol
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DIY-HP-LED
Well-Known Member
The first 12 minutes of this video covers serological testing and issues with 2 recently released studies trying to determine how many have been infected, the remainder of the video deals with technical issues. Links to the papers cited are in the video description on YouTube, these studies are being mentioned in the news and bear on the ongoing public policy discussions about the value of NPIs (Non Pharmaceutical Interventions).
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Coronavirus Pandemic Update 58: Testing; Causes of Hypoxemia in COVID-19 (V/Q vs Shunt vs Diffusion)
Two recent antibody testing studies in the United States may give insight into how widespread COVID-19 actually is - which may also mean the fatality rate is lower than initially thought - but there may be problems with the accuracy of using this data in a prediction model.
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Coronavirus Pandemic Update 58: Testing; Causes of Hypoxemia in COVID-19 (V/Q vs Shunt vs Diffusion)
Two recent antibody testing studies in the United States may give insight into how widespread COVID-19 actually is - which may also mean the fatality rate is lower than initially thought - but there may be problems with the accuracy of using this data in a prediction model.
DIY-HP-LED
Well-Known Member
Some interesting evidence about how many people are asymptomatic in Holland is presented, based on blood donations of 10,000 people, it was found that 3% had antibodies, that means about 15 times the reported cases were asymptomatic, based on this data, covid-19 has estimated mortality rate of of about .66% in developed countries according to these figures. There are some issues concerning the percentage of people who serum converted and this has to be factored into the data.
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International review and new discoveries in the blood-Coronavirus
Dutch study suggests 3% of population may have coronavirus antibodies
1 MIN READ
AMSTERDAM (Reuters) - A study of Dutch blood donors has found that around 3% have developed antibodies against the new coronavirus, health authorities said on Thursday, an indication of what percentage of the Dutch population may have already had the disease.
The head of the National Institute for Health (RIVM), Jaap van Dissel, disclosed the results during a debate with parliament.
“This study shows that about 3% of Dutch people have developed antibodies against the coronavirus,” Van Dissel said. “You can calculate from that, it’s several hundred thousand people” in a country of 17 million.
There are 28,158 confirmed coronavirus cases in the Netherlands, but only the very ill and healthcare workers are currently being tested.
The blood donation service Sanquin announced it would begin testing on 10,000 samples weekly on March 19, but later said it would only disclose results to the RIVM.
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International review and new discoveries in the blood-Coronavirus
Dutch study suggests 3% of population may have coronavirus antibodies
1 MIN READ
AMSTERDAM (Reuters) - A study of Dutch blood donors has found that around 3% have developed antibodies against the new coronavirus, health authorities said on Thursday, an indication of what percentage of the Dutch population may have already had the disease.
The head of the National Institute for Health (RIVM), Jaap van Dissel, disclosed the results during a debate with parliament.
“This study shows that about 3% of Dutch people have developed antibodies against the coronavirus,” Van Dissel said. “You can calculate from that, it’s several hundred thousand people” in a country of 17 million.
There are 28,158 confirmed coronavirus cases in the Netherlands, but only the very ill and healthcare workers are currently being tested.
The blood donation service Sanquin announced it would begin testing on 10,000 samples weekly on March 19, but later said it would only disclose results to the RIVM.
DIY-HP-LED
Well-Known Member
According to this study 37% of people tested positive for covid-19 at a Boston homeless shelter, all were asymptomatic at the time and one has since been hospitalised.
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www.boston25news.com
CDC reviewing ‘stunning’ universal testing results from Boston homeless shelter
BOSTON — The Centers for Disease Control and Prevention is now “actively looking into” results from universal COVID-19 testing at Pine Street Inn homeless shelter.
The broad-scale testing took place at the shelter in Boston’s South End a week and a half ago because of a small cluster of cases there.
Of the 397 people tested, 146 people tested positive. Not a single one had any symptoms.
“It was like a double knockout punch. The number of positives was shocking, but the fact that 100 percent of the positives had no symptoms was equally shocking,” said Dr. Jim O’Connell, president of Boston Health Care for the Homeless Program, which provides medical care at the city’s shelters.
O’Connell said that the findings have changed the future of COVID-19 screenings at Boston’s homeless shelters.
[ Experts: Homeless population vulnerable to coronavirus ]
“All the screening we were doing before this was based on whether you had a fever above 100.4 and whether you had symptoms,” said O’Connell. “How much of the COVID virus is being passed by people who don’t even know they have it?”
The 146 people who tested positive were immediately moved to two different temporary isolation facilities in Boston. According to O’Connell, only one of those patients needed hospital care, and many continue to show no symptoms.
“If we did universal testing among the general population, would these numbers be similar?” said Lyndia Downie, president and executive director at the Pine Street Inn. “I think there are no many asymptomatic people right now. We just don’t know. We don’t have enough data on universal testing to understand how many asymptomatic people are contagious.”
Hundreds of tests are now set to be conducted at additional Boston homeless shelters in the coming days.
“It tells you, you don’t know who’s at risk. You don’t know what you need to do to contain the virus if you don’t actually have the details or facts,” said Marty Martinez, Boston’s chief of Health and Human Services.
About 250 people are expected to be tested on Thursday and Friday at the men’s Southampton Street shelter run by Boston Public Health Commission.
“Our goal within the next three or four days is to test everybody so we have a good understanding of who has it and who doesn’t,” added Martinez.
More than 900 isolation beds have been set up locally for people who are homeless. The majority of those beds have not yet been used, but local and state health officials aren’t sure if that could change after more testing is complete.
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CDC reviewing ‘stunning’ universal testing results from Boston homeless shelter
The Centers for Disease Control and Prevention is now “actively looking into” results from universal COVID-19 testing at Pine Street Inn homeless shelter.
CDC reviewing ‘stunning’ universal testing results from Boston homeless shelter
BOSTON — The Centers for Disease Control and Prevention is now “actively looking into” results from universal COVID-19 testing at Pine Street Inn homeless shelter.
The broad-scale testing took place at the shelter in Boston’s South End a week and a half ago because of a small cluster of cases there.
Of the 397 people tested, 146 people tested positive. Not a single one had any symptoms.
“It was like a double knockout punch. The number of positives was shocking, but the fact that 100 percent of the positives had no symptoms was equally shocking,” said Dr. Jim O’Connell, president of Boston Health Care for the Homeless Program, which provides medical care at the city’s shelters.
O’Connell said that the findings have changed the future of COVID-19 screenings at Boston’s homeless shelters.
[ Experts: Homeless population vulnerable to coronavirus ]
“All the screening we were doing before this was based on whether you had a fever above 100.4 and whether you had symptoms,” said O’Connell. “How much of the COVID virus is being passed by people who don’t even know they have it?”
The 146 people who tested positive were immediately moved to two different temporary isolation facilities in Boston. According to O’Connell, only one of those patients needed hospital care, and many continue to show no symptoms.
“If we did universal testing among the general population, would these numbers be similar?” said Lyndia Downie, president and executive director at the Pine Street Inn. “I think there are no many asymptomatic people right now. We just don’t know. We don’t have enough data on universal testing to understand how many asymptomatic people are contagious.”
Hundreds of tests are now set to be conducted at additional Boston homeless shelters in the coming days.
“It tells you, you don’t know who’s at risk. You don’t know what you need to do to contain the virus if you don’t actually have the details or facts,” said Marty Martinez, Boston’s chief of Health and Human Services.
About 250 people are expected to be tested on Thursday and Friday at the men’s Southampton Street shelter run by Boston Public Health Commission.
“Our goal within the next three or four days is to test everybody so we have a good understanding of who has it and who doesn’t,” added Martinez.
More than 900 isolation beds have been set up locally for people who are homeless. The majority of those beds have not yet been used, but local and state health officials aren’t sure if that could change after more testing is complete.
DIY-HP-LED
Well-Known Member
Here are some salient remarks from the comments section of the source publication that illustrate the problems with this study, including selection bias. This is the un peer reviewed study that claims the asymptomatic rate using serological testing (for recovered people) is 50 to 85 times the virus test rate for those presenting ill or who are randomly tested, confirmed cases.
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"figureitout1 • a day ago
I am not in the field and have no expertise but I think this study may have measured just the prevalence of the common cold in Santa Clara county. The ELISA assays for IgG and/or IgM antibodies are known to give false-positives due to the other Corona viruses that give us the common cold. It is known from European studies that the common cold in the winter time can cause roughly 3% positive Covid-19 ELISA tests – just about what was measured in this study. In order to get meaningful results a second test (neutralization test that is not sensitive to the common cold viruses) needed to be done on the positive samples. The scientifically correct conclusion of the study would be: the Covid-19 prevalence is between 0% and 4%. It seems irresponsible to put the study on the web and have people, including politicians, jump to hasty and possibly wrong conclusions."
"
John Smith • a day ago
people who thought they have been exposed to covid-19 would want to get a free test. Others who thought they don't have the virus and have been in lockdown for a month would not go out of the house for the free test. This means you're selecting only the people who have been exposed and invalidates the study"
"
Michael A. Kohn, MD, MPP • a day ago
From the 3439 people who showed up for testing, they were able to obtain 3330 valid specimens on which to perform the Premier Biotech serology test. Of these, 50 were positive. That’s 50/3330 = 1.5% . They tried to adjust for the fact that the people who actually showed up were not representative of the county population’s sex, race, and zip code distribution. But the main potential source of error is the accuracy of the test. At a low sero-prevalence like this, a small proportion of false positives can result in a large overestimate. They ran the Premier Biotech test on 30 serum specimens drawn prior to the pandemic and it was negative on all 30. If the error rate on truly uninfected individuals is 0.5%, and the test properly identifies 91.8% of previously infected individuals, then the true sero-prevalence is 1.1%. As the authors say, “Additional validation of the assays used could improve our estimates and those of ongoing serosurveys.” Having reviewed the test accuracy studies of this and other lateral flow immunoassays (http://covid-19-assay.net/ ), I believe we will end up with a true sero-prevalence of about 1% in Santa Clara County. But the authors made a reasonable estimate and did a great job of collecting this data and reporting their results and assumptions."
www.medrxiv.org
COVID-19 Antibody Seroprevalence in Santa Clara County, California
Eran Bendavid, Bianca Mulaney, Neeraj Sood, Soleil Shah, Emilia Ling, Rebecca Bromley-Dulfano, Cara Lai, Zoe Weissberg, Rodrigo Saavedra, James Tedrow, Dona Tversky, Andrew Bogan, Thomas Kupiec, Daniel Eichner, Ribhav Gupta, John Ioannidis, Jay Bhattacharya
doi: https://doi.org/10.1101/2020.04.14.20062463
This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in Santa Clara County. Methods On 4/3-4/4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a representative sample of the county by demographic and geographic characteristics. We report the prevalence of antibodies to SARS-CoV-2 in a sample of 3,330 people, adjusting for zip code, sex, and race/ethnicity. We also adjust for test performance characteristics using 3 different estimates: (i) the test manufacturer's data, (ii) a sample of 37 positive and 30 negative controls tested at Stanford, and (iii) a combination of both. Results The unadjusted prevalence of antibodies to SARS-CoV-2 in Santa Clara County was 1.5% (exact binomial 95CI 1.11-1.97%), and the population-weighted prevalence was 2.81% (95CI 2.24-3.37%). Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases. Conclusions The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases. Population prevalence estimates can now be used to calibrate epidemic and mortality projections.
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"figureitout1 • a day ago
I am not in the field and have no expertise but I think this study may have measured just the prevalence of the common cold in Santa Clara county. The ELISA assays for IgG and/or IgM antibodies are known to give false-positives due to the other Corona viruses that give us the common cold. It is known from European studies that the common cold in the winter time can cause roughly 3% positive Covid-19 ELISA tests – just about what was measured in this study. In order to get meaningful results a second test (neutralization test that is not sensitive to the common cold viruses) needed to be done on the positive samples. The scientifically correct conclusion of the study would be: the Covid-19 prevalence is between 0% and 4%. It seems irresponsible to put the study on the web and have people, including politicians, jump to hasty and possibly wrong conclusions."
"
John Smith • a day ago
people who thought they have been exposed to covid-19 would want to get a free test. Others who thought they don't have the virus and have been in lockdown for a month would not go out of the house for the free test. This means you're selecting only the people who have been exposed and invalidates the study"
"
Michael A. Kohn, MD, MPP • a day ago
From the 3439 people who showed up for testing, they were able to obtain 3330 valid specimens on which to perform the Premier Biotech serology test. Of these, 50 were positive. That’s 50/3330 = 1.5% . They tried to adjust for the fact that the people who actually showed up were not representative of the county population’s sex, race, and zip code distribution. But the main potential source of error is the accuracy of the test. At a low sero-prevalence like this, a small proportion of false positives can result in a large overestimate. They ran the Premier Biotech test on 30 serum specimens drawn prior to the pandemic and it was negative on all 30. If the error rate on truly uninfected individuals is 0.5%, and the test properly identifies 91.8% of previously infected individuals, then the true sero-prevalence is 1.1%. As the authors say, “Additional validation of the assays used could improve our estimates and those of ongoing serosurveys.” Having reviewed the test accuracy studies of this and other lateral flow immunoassays (http://covid-19-assay.net/ ), I believe we will end up with a true sero-prevalence of about 1% in Santa Clara County. But the authors made a reasonable estimate and did a great job of collecting this data and reporting their results and assumptions."
COVID-19 Antibody Seroprevalence in Santa Clara County, California
Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in Santa Clara...
COVID-19 Antibody Seroprevalence in Santa Clara County, California
Eran Bendavid, Bianca Mulaney, Neeraj Sood, Soleil Shah, Emilia Ling, Rebecca Bromley-Dulfano, Cara Lai, Zoe Weissberg, Rodrigo Saavedra, James Tedrow, Dona Tversky, Andrew Bogan, Thomas Kupiec, Daniel Eichner, Ribhav Gupta, John Ioannidis, Jay Bhattacharya
doi: https://doi.org/10.1101/2020.04.14.20062463
This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in Santa Clara County. Methods On 4/3-4/4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a representative sample of the county by demographic and geographic characteristics. We report the prevalence of antibodies to SARS-CoV-2 in a sample of 3,330 people, adjusting for zip code, sex, and race/ethnicity. We also adjust for test performance characteristics using 3 different estimates: (i) the test manufacturer's data, (ii) a sample of 37 positive and 30 negative controls tested at Stanford, and (iii) a combination of both. Results The unadjusted prevalence of antibodies to SARS-CoV-2 in Santa Clara County was 1.5% (exact binomial 95CI 1.11-1.97%), and the population-weighted prevalence was 2.81% (95CI 2.24-3.37%). Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases. Conclusions The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases. Population prevalence estimates can now be used to calibrate epidemic and mortality projections.
DIY-HP-LED
Well-Known Member
It appears the R0 went from R0=7 to R0=1 after people were confined to their cabins and avoided direct contact, the ship's AC/ventilation system did not appear to spread the contagion either. NPIs worked spectacularly well in this petri dish of a situation and dropped the infection rate like a stone, so it's all about social discipline, distancing and enforcement.
Also multiply deaths by X20 to get a reasonable estimate of the true number of cases:
"The group also estimates that the infection fatality rate (IFR) in China — the proportion of all infections, including asymptomatic ones, that result in death — is even lower, at roughly 0.5%. The IFR is especially tricky to calculate in the population, because some deaths go undetected if the person didn’t show symptoms or get tested".
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www.nature.com
nature
NEWS
26 MARCH 2020
What the cruise-ship outbreaks reveal about COVID-19
Close confines help the virus to spread, but closed environments are also an ideal place to study how the new coronavirus behaves.
When COVID-19 was detected among passengers on the cruise ship Diamond Princess, the vessel offered a rare opportunity to understand features of the new coronavirus that are hard to investigate in the wider population. Some of the first studies from the ship — where some 700 people were infected — have revealed how easily the virus spreads, provided estimates of the disease’s severity and allowed researchers to investigate the share of infections with no symptoms.
Information gleaned from such outbreaks is crucial for people making decisions on how to manage the epidemic, say researchers.
“Cruise ships are like an ideal experiment of a closed population. You know exactly who is there and at risk and you can measure everyone,” says John Ioannidis, an epidemiologist at Stanford University in California. This is very different from trying to study the spread in a wider population, where only some people, typically those with severe symptoms, are tested and monitored.
Diamond Princess
On 1 February, a passenger who had disembarked from the Diamond Princess days earlier in Hong Kong tested positive for the COVID-19 coronavirus. The ship was quarantined immediately after it arrived in Japanese waters on 3 February, with 3,711 passengers and crew members on board. Over the next month, more than 700 people on board were infected — including a nurse — and for weeks the ship was the site of the largest outbreak outside China.
Outbreaks seed easily on the vessels because of the close confines and high proportions of older people who tend to be more vulnerable to the disease. Since the Diamond Princess, at least 25 other cruise ships have confirmed COVID-19 cases — including 78 cases on the Grand Princess, which was quarantined off the coast of California. Returned passengers have also seeded outbreaks in countries including the United States.
Japanese officials performed more than 3,000 tests on the Diamond Princess, starting with older passengers and those with symptoms. Some passengers were tested more than once, offering insight into the virus’s spread over time. Testing almost all of the passengers and crew helped researchers to understand a key blind spot in many infectious-disease outbreaks — how many people are actually infected, including those who have mild symptoms or none at all. These cases often go undetected in the general population.
Using the Diamond Princess data, a team reports in Eurosurveillance1 that by 20 February, 18% of all infected people on the ship had no symptoms. “That is a substantial number,” says co-author Gerardo Chowell, a mathematical epidemiologist at Georgia State University in Atlanta. But the passengers included a large number of elderly people, who are most likely to develop severe disease if infected, so the share of asymptomatic people in the general population is likely to be higher, he says.
Disease severity
Another team used data from the ship to estimate2 that the proportion of deaths among confirmed cases in China, the case fatality rate (CFR), was around 1.1% — much lower than the 3.8% estimated by the World Health Organization (WHO).
The WHO simply divided China’s total number of deaths by the total number of confirmed infections, says Timothy Russell, a mathematical epidemiologist at the London School of Hygiene and Tropical Medicine. That method does not take into account that only a fraction of infected people are actually tested, and so it makes the disease seem more deadly than it is, he says.
By contrast, Russell and his colleagues used data from the ship — where almost everyone was tested, and all seven deaths recorded — and combined it with more than 72,000 confirmed cases in China, making their CFR estimate more robust. The results have been posted on the biomedical preprint server medRxiv, and have not been peer-reviewed yet.
The group also estimates that the infection fatality rate (IFR) in China — the proportion of all infections, including asymptomatic ones, that result in death — is even lower, at roughly 0.5%. The IFR is especially tricky to calculate in the population, because some deaths go undetected if the person didn’t show symptoms or get tested.
more...
Also multiply deaths by X20 to get a reasonable estimate of the true number of cases:
"The group also estimates that the infection fatality rate (IFR) in China — the proportion of all infections, including asymptomatic ones, that result in death — is even lower, at roughly 0.5%. The IFR is especially tricky to calculate in the population, because some deaths go undetected if the person didn’t show symptoms or get tested".
--------------------------------------------------------------------------------------------------------------------------------------
What the cruise-ship outbreaks reveal about COVID-19
Close confines help the virus to spread, but closed environments are also an ideal place to study how the new coronavirus behaves.
www.nature.com
nature
NEWS
26 MARCH 2020
What the cruise-ship outbreaks reveal about COVID-19
Close confines help the virus to spread, but closed environments are also an ideal place to study how the new coronavirus behaves.
When COVID-19 was detected among passengers on the cruise ship Diamond Princess, the vessel offered a rare opportunity to understand features of the new coronavirus that are hard to investigate in the wider population. Some of the first studies from the ship — where some 700 people were infected — have revealed how easily the virus spreads, provided estimates of the disease’s severity and allowed researchers to investigate the share of infections with no symptoms.
Information gleaned from such outbreaks is crucial for people making decisions on how to manage the epidemic, say researchers.
“Cruise ships are like an ideal experiment of a closed population. You know exactly who is there and at risk and you can measure everyone,” says John Ioannidis, an epidemiologist at Stanford University in California. This is very different from trying to study the spread in a wider population, where only some people, typically those with severe symptoms, are tested and monitored.
Diamond Princess
On 1 February, a passenger who had disembarked from the Diamond Princess days earlier in Hong Kong tested positive for the COVID-19 coronavirus. The ship was quarantined immediately after it arrived in Japanese waters on 3 February, with 3,711 passengers and crew members on board. Over the next month, more than 700 people on board were infected — including a nurse — and for weeks the ship was the site of the largest outbreak outside China.
Outbreaks seed easily on the vessels because of the close confines and high proportions of older people who tend to be more vulnerable to the disease. Since the Diamond Princess, at least 25 other cruise ships have confirmed COVID-19 cases — including 78 cases on the Grand Princess, which was quarantined off the coast of California. Returned passengers have also seeded outbreaks in countries including the United States.
Japanese officials performed more than 3,000 tests on the Diamond Princess, starting with older passengers and those with symptoms. Some passengers were tested more than once, offering insight into the virus’s spread over time. Testing almost all of the passengers and crew helped researchers to understand a key blind spot in many infectious-disease outbreaks — how many people are actually infected, including those who have mild symptoms or none at all. These cases often go undetected in the general population.
Using the Diamond Princess data, a team reports in Eurosurveillance1 that by 20 February, 18% of all infected people on the ship had no symptoms. “That is a substantial number,” says co-author Gerardo Chowell, a mathematical epidemiologist at Georgia State University in Atlanta. But the passengers included a large number of elderly people, who are most likely to develop severe disease if infected, so the share of asymptomatic people in the general population is likely to be higher, he says.
Disease severity
Another team used data from the ship to estimate2 that the proportion of deaths among confirmed cases in China, the case fatality rate (CFR), was around 1.1% — much lower than the 3.8% estimated by the World Health Organization (WHO).
The WHO simply divided China’s total number of deaths by the total number of confirmed infections, says Timothy Russell, a mathematical epidemiologist at the London School of Hygiene and Tropical Medicine. That method does not take into account that only a fraction of infected people are actually tested, and so it makes the disease seem more deadly than it is, he says.
By contrast, Russell and his colleagues used data from the ship — where almost everyone was tested, and all seven deaths recorded — and combined it with more than 72,000 confirmed cases in China, making their CFR estimate more robust. The results have been posted on the biomedical preprint server medRxiv, and have not been peer-reviewed yet.
The group also estimates that the infection fatality rate (IFR) in China — the proportion of all infections, including asymptomatic ones, that result in death — is even lower, at roughly 0.5%. The IFR is especially tricky to calculate in the population, because some deaths go undetected if the person didn’t show symptoms or get tested.
more...
Last edited:
DIY-HP-LED
Well-Known Member
There's More to Gilead Sciences' Remdesivir Data Than Meets the Eye | The Motley Fool
Contextual analysis of leaked data from Gilead's remdesivir clinical trial shows we may be closer than we think to developing an effective treatment for the COVID-19.
There's More to Gilead Sciences' Remdesivir Data Than Meets the Eye
Contextual analysis of leaked data from Gilead's remdesivir clinical trial shows we may be closer than we think to developing an effective treatment for the COVID-19.
Zhiyuan Sun
(ZhiyuanSun)
Apr 20, 2020 at 1:33PM
The ongoing COVID-19 pandemic has caused significant disruptions to the global economy, as well as grievances for families witnessing their loved ones die from the virus. Fortunately, there's finally a light at the end of the tunnel as one investigative treatment has revealed potential efficacy for combating the outbreak.
Last week, clinical data from Gilead Sciences (NASDAQ:GILD) shared with STAT News point to a potential respite in the COVID-19 crisis and possibly significant upside for Gilead investors.
IMAGE SOURCE: GETTY IMAGES
The good news
Currently, Gilead is investigating remdesivir in multiple phase 3 clinical trials involving over 2,400 participants from 152 clinical sites, including the University of Chicago Medical Center. At this location, 125 patients diagnosed with COVID-19 were treated with daily infusions of remdesivir and had their symptoms monitored over five to 10 days.
Out of this subgroup, only two deaths have been reported with the vast majority of patients already discharged. In other words, the fatality rate (the number of deaths attributable to a disease in a given sample) of the cohort is 1.6%. So far, the results seem superb, as the case fatality rate for COVID-19 in America, calculated via data from John Hopkins University, stands at 4.69%. The case fatality rate represents the number of deaths attributable to the number of confirmed cases of a disease. As of April 19, this amounted to 33,903 deaths per 722,621 diagnosed cases.
At this point, however, skeptical investors may point to the fact that data from the University of Chicago does not have a placebo cohort to compare to, making efficacy claims inconclusive. Currently, no treatments for the COVID-19 have demonstrated efficacy in placebo controlled studies and hence can only be prescribed via either emergency use authorization of compassionate-use.
What the devil's advocates are saying
One counterargument against remdesivir is this: the Centers for Disease Control and Prevention simply does not have enough resources to test everyone for COVID-19. If the number of positive but undiagnosed cases in America was 3 million as compared to 722,621, then the infection fatality ratio of the virus can be as low as 0.91% (33,903 deaths per 3,722,621 infected). Here, the infection fatality ratio is more representative of the true fatality rate of the virus, because it accounts for all possible patients who are infected with COVID-19, not just the ones who were tested.
If used as a benchmark, data from Gilead's treatment cohort will indicate the drug has no effect in improving patients' survival, and may actually be harming them. The point is, without a placebo arm in the trial, we cannot know for sure whether or not remdesivir is working.
What their analysis is missing
Luckily, there is one critical detail in the trial which is extremely likely to point to remdesivir's efficacy. Out of the 125 patients treated, 113 had severe symptoms. As we know, the vast majority of patients with severe symptoms are the elderly and immunocompromised. In one estimate, the infection fatality rate of patients in this category lies between 1.93% to 7.8%.
Given this context, remdesivir may be significantly improving the odds of patients' survival. This is further supported by observations from another study, where a tremendous improvement exists between survival rates (percentage of patients in a study still alive after a given period of time post diagnosis) of patients on invasive ventilators who took remdesivr versus those who didn't.
Those who are not convinced of the drug's economic potential, however, may argue that since infection curves are exhibiting signs of flattening across the world, there will be a lack of demand for remdesivir as the number of new cases drop. There is just one problem with this argument.
In previous respiratory epidemics such as H1N1 in 2009 to 2010 and the 1918 Spanish Flu, there were resurgences of the virus via second and third wave outbreaks after the initial spread was contained. Together, these epidemics infected 24% to 33% of the entire global population before subsiding for good.
Hence, if the COVID-19 was to reemerge, the demand for remdesivir will no doubt be enormous, should it be approved by that time.
What this means for investors
The company's multi-center, placebo controlled phase 3 clinical trials on remdesivir are set to release top-line results by the end of April and is highly likely to be successful. An approval by the Food and Drug Administration can take as little as a couple of months due to the agency's Coronavirus Treatment Acceleration Program. The drug could see over $1 billion in sales over the course of the entire coronavirus outbreak, due to the sheer number of patients infected and potentially at risk for the virus. This is assuming the drug can treat up to 500,000 patients and cost little over $2,000 for one course of treatment.
DIY-HP-LED
Well-Known Member
More information on remdesivir and other treatments. Looking at the data from 12 monkeys, 6 who were treated, it appears to be highly effective, when compared to the controls. I can see human clinical trials being halted for ethical reasons over this apparently high efficacy rate, it would be unethical to allow the control patients to progress in their illness after a certain point. Do you let the controls die for data, if close to 100% of those who are treated recover? I'm sure they worked something ethical out, I wouldn't want to be in the control group if they did not.
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www.fiercebiotech.com
COVID-19: New animal data back up Gilead's remdesivir as other treatment candidates emerge
Gilead Sciences’ COVID-19 hopeful remdesivir has kicked up plenty of controversy as the company speeds up R&D amid questions about whether early human trials of the drug have adequately proven it works. Now, scientists at the National Institutes of Health and Gilead have published results from an animal trial of remdesivir that they believe will help the scientific community better assess the drug’s power to combat the virus.
In a trial involving 12 rhesus macaques, early treatment of COVID-19 with remdesivir reduced symptoms of the disease and lung damage, they reported in a study posted on bioRxiv. Six macaques were treated with the drug, while the others were untreated. Seven days after the start of the study, the macaques treated with remdesivir were significantly healthier than those in the control group, according to the study (PDF).
The animal trial was designed to replicate the remdesivir dosing schedule that’s being tested in the ongoing clinical trial. So the macaques received an intravenous dose of the drug 12 hours after being infected with COVID-19, followed by one booster dose per day for six days. At the end of the week, all six untreated animals were showing breathing difficulties. Only one of the treated macaques had breathing problems, which were mild, they reported.
“Data from clinical trials in humans are pending, but our data in rhesus macaques indicate that remdesivir treatment should be considered as early as clinically possible to prevent progression to severe pneumonia in COVID-19 patients,” the researchers wrote.
RELATED: Gilead turbocharges production of COVID-19 hopeful remdesivir
It’s not just the medical community that’s watching remdesivir closely, but also Gilead investors. They ratcheted up the company’s share price last week after positive results from a small trial of the drug in COVID-19 patients at the University of Chicago Medical Center were leaked.
Problem is, no one will be able to say for certain whether remdesivir will be the panacea everyone is hoping for until Gilead reports data from phase 3 trials, one of which is designed to compare the drug to the standard of care in treating COVID-19. Those data aren’t expected until late May.
Meanwhile, several other research groups are searching for additional drugs that could be deployed against COVID-19. One such group, led by the Sanford Burnham Prebys Medical Discovery Institute, reported over the weekend it's identified four drugs the researchers believe could enter human trials for COVID-19 because they have already been shown to be safe in trials for other diseases.
Two of the drugs had entered early trials in autoimmune diseases: apilimod, which was once tested by Synta (now Madrigal Pharmaceuticals), and Millennium’s MLN-3897. A third, VBY-825, has been studied in pancreatic cancer, and the fourth, ONO 5334, in osteoporosis. The study was also posted (PDF) on bioRxiv.
RELATED: COVID-19: Bio researchers race to repurpose everything from antiviral to anticancer discoveries
The Sanford Burnham Prebys-led team started by screening a library of 12,000 existing compounds that have been shown to be safe for use in people. They searched specifically for drugs that could halt the replication of the virus that causes COVID-19, SARS-CoV-2.
They found 30 drugs that were able to prevent the virus from copying itself—including remdesivir and the antimalarial chloroquine derivatives that have also generated interest during the pandemic. They suggested that the additional four options they uncovered should also enter human trials. That’s because they all work differently than remdesivir and the antimalarials do, and their safety profiles have been well characterized already, they said.
“Many drugs identified in this study—most of which are new to the COVID-19 research community—can begin clinical trials immediately or in a few months after additional testing,” said senior author Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys, in a statement.
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COVID-19: New animal data back up Gilead's remdesivir as other treatment candidates emerge
Gilead Sciences’ COVID-19 hopeful remdesivir has kicked up plenty of controversy as the company speeds up R&D amid questions about whether early human trials of the drug have adequately proven | Is Gilead's remdesivir the COVID-19 panacea everyone is hoping for, and should four experimental...
COVID-19: New animal data back up Gilead's remdesivir as other treatment candidates emerge
Gilead Sciences’ COVID-19 hopeful remdesivir has kicked up plenty of controversy as the company speeds up R&D amid questions about whether early human trials of the drug have adequately proven it works. Now, scientists at the National Institutes of Health and Gilead have published results from an animal trial of remdesivir that they believe will help the scientific community better assess the drug’s power to combat the virus.
In a trial involving 12 rhesus macaques, early treatment of COVID-19 with remdesivir reduced symptoms of the disease and lung damage, they reported in a study posted on bioRxiv. Six macaques were treated with the drug, while the others were untreated. Seven days after the start of the study, the macaques treated with remdesivir were significantly healthier than those in the control group, according to the study (PDF).
The animal trial was designed to replicate the remdesivir dosing schedule that’s being tested in the ongoing clinical trial. So the macaques received an intravenous dose of the drug 12 hours after being infected with COVID-19, followed by one booster dose per day for six days. At the end of the week, all six untreated animals were showing breathing difficulties. Only one of the treated macaques had breathing problems, which were mild, they reported.
“Data from clinical trials in humans are pending, but our data in rhesus macaques indicate that remdesivir treatment should be considered as early as clinically possible to prevent progression to severe pneumonia in COVID-19 patients,” the researchers wrote.
RELATED: Gilead turbocharges production of COVID-19 hopeful remdesivir
It’s not just the medical community that’s watching remdesivir closely, but also Gilead investors. They ratcheted up the company’s share price last week after positive results from a small trial of the drug in COVID-19 patients at the University of Chicago Medical Center were leaked.
Problem is, no one will be able to say for certain whether remdesivir will be the panacea everyone is hoping for until Gilead reports data from phase 3 trials, one of which is designed to compare the drug to the standard of care in treating COVID-19. Those data aren’t expected until late May.
Meanwhile, several other research groups are searching for additional drugs that could be deployed against COVID-19. One such group, led by the Sanford Burnham Prebys Medical Discovery Institute, reported over the weekend it's identified four drugs the researchers believe could enter human trials for COVID-19 because they have already been shown to be safe in trials for other diseases.
Two of the drugs had entered early trials in autoimmune diseases: apilimod, which was once tested by Synta (now Madrigal Pharmaceuticals), and Millennium’s MLN-3897. A third, VBY-825, has been studied in pancreatic cancer, and the fourth, ONO 5334, in osteoporosis. The study was also posted (PDF) on bioRxiv.
RELATED: COVID-19: Bio researchers race to repurpose everything from antiviral to anticancer discoveries
The Sanford Burnham Prebys-led team started by screening a library of 12,000 existing compounds that have been shown to be safe for use in people. They searched specifically for drugs that could halt the replication of the virus that causes COVID-19, SARS-CoV-2.
They found 30 drugs that were able to prevent the virus from copying itself—including remdesivir and the antimalarial chloroquine derivatives that have also generated interest during the pandemic. They suggested that the additional four options they uncovered should also enter human trials. That’s because they all work differently than remdesivir and the antimalarials do, and their safety profiles have been well characterized already, they said.
“Many drugs identified in this study—most of which are new to the COVID-19 research community—can begin clinical trials immediately or in a few months after additional testing,” said senior author Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys, in a statement.
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DIY-HP-LED
Well-Known Member
My opinion is that the leak was caused by excitement over the preliminary scientific results which were spectacular, not an attempt to jack the stock price.
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www.fiercebiotech.com
Congressman calls on SEC to look into leaked remdesivir data: report
ast Thursday, analysts urged caution when reading into leaked data for Gilead’s COVID-19 hopeful remdesivir, stressing that the numbers came from a single site participating in a study with no control group. Now, a congressman is asking the Securities and Exchange Commission (SEC) to investigate.
The experimental drug swiftly relieved fever and respiratory symptoms in patients with severe COVID-19, said Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital, in leaked video. She made her comments in a discussion of the results with other university faculty members that was recorded. Stat obtained a copy of the video and reported the results Thursday.
The leak was “so significant” at a time that the world is “so desperate to find a cure,” said Rep. Lloyd Doggett, a Texas Democrat who chairs the House Ways and Means Health Subcommittee, CNN reported on Friday.
Although the source of the leak is unclear, “providing information that’s designed to impact the stock market is not something that is permitted under federal securities law,” Doggett said.
“That’s why we need a thorough SEC investigation,” he said.
RELATED: Gilead's remdesivir looks promising in leaked early results, but don't jump to conclusions: analysts
Remdesivir isn’t supposed be a moneymaker for Gilead, which “will work to ensure affordability and access so that remdesivir is available to patients with the greatest need,” according to an open letter penned by CEO Daniel O’Day last month. But the program did move the needle on the company’s stock, sending it up more than 15% in after-hours trading Thursday.
“We calculate remdesivir has already been responsible for ~$15bn in market cap to Gilead, and the move today and in the after-market increases that to a total value of ~$35bn,” wrote SVB Leerink analyst Geoffrey Porges in an investor note Thursday. “This seems a generous amount of credit for a product that the company has specifically stipulated will not be sold for a profit, but investors may be discounting that commentary, or simply looking to buy any positive COVID news.”
Gilead told CNN that the company was not involved in the leak.
The University of Chicago is participating in a study of remdesivir in patients who had severe disease but who were not sick enough to need a ventilator. The study is testing a five-day and a 10-day course of remdesivir in those patients but does not have a control arm. Of the 125 patients recruited by the hospital for two phase 3 studies, 113 had severe disease.
RELATED: Gilead CEO says coronavirus hopeful remdesivir will be 'affordable,' but it could still rake in revenue
“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” said Mullane.
Gilead is sponsoring two phase 3 studies of remdesivir, including one in patients with moderate disease, as well as the trial in patients with severe disease. The former does have a control arm, testing a five- or 10-day course of remdesivir against standard of care. And since the studies kicked off in late February, the company has expanded the latter trial to include thousands more patients with severe disease, including those on ventilators. Gilead expects preliminary data from the “severe” study by the end of April and data from the “moderate” study in May.
The company has also made the drug available to studies run by other sponsors, such as the National Institutes of Health, as well as to more than 1,700 people on a compassionate use basis. Last week, The New England Journal of Medicine published data from 53 patients with severe disease, but that data set also lacked a control group.
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Congressman calls on SEC to look into leaked remdesivir data: report
Last Thursday, analysts urged caution when reading into leaked data for Gilead’s COVID-19 hopeful remdesivir, stressing that the numbers came from a single site participating in a study with no con | Last Thursday, analysts urged caution when reading into leaked data for Gilead’s COVID-19...
Congressman calls on SEC to look into leaked remdesivir data: report
ast Thursday, analysts urged caution when reading into leaked data for Gilead’s COVID-19 hopeful remdesivir, stressing that the numbers came from a single site participating in a study with no control group. Now, a congressman is asking the Securities and Exchange Commission (SEC) to investigate.
The experimental drug swiftly relieved fever and respiratory symptoms in patients with severe COVID-19, said Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital, in leaked video. She made her comments in a discussion of the results with other university faculty members that was recorded. Stat obtained a copy of the video and reported the results Thursday.
The leak was “so significant” at a time that the world is “so desperate to find a cure,” said Rep. Lloyd Doggett, a Texas Democrat who chairs the House Ways and Means Health Subcommittee, CNN reported on Friday.
Although the source of the leak is unclear, “providing information that’s designed to impact the stock market is not something that is permitted under federal securities law,” Doggett said.
“That’s why we need a thorough SEC investigation,” he said.
RELATED: Gilead's remdesivir looks promising in leaked early results, but don't jump to conclusions: analysts
Remdesivir isn’t supposed be a moneymaker for Gilead, which “will work to ensure affordability and access so that remdesivir is available to patients with the greatest need,” according to an open letter penned by CEO Daniel O’Day last month. But the program did move the needle on the company’s stock, sending it up more than 15% in after-hours trading Thursday.
“We calculate remdesivir has already been responsible for ~$15bn in market cap to Gilead, and the move today and in the after-market increases that to a total value of ~$35bn,” wrote SVB Leerink analyst Geoffrey Porges in an investor note Thursday. “This seems a generous amount of credit for a product that the company has specifically stipulated will not be sold for a profit, but investors may be discounting that commentary, or simply looking to buy any positive COVID news.”
Gilead told CNN that the company was not involved in the leak.
The University of Chicago is participating in a study of remdesivir in patients who had severe disease but who were not sick enough to need a ventilator. The study is testing a five-day and a 10-day course of remdesivir in those patients but does not have a control arm. Of the 125 patients recruited by the hospital for two phase 3 studies, 113 had severe disease.
RELATED: Gilead CEO says coronavirus hopeful remdesivir will be 'affordable,' but it could still rake in revenue
“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” said Mullane.
Gilead is sponsoring two phase 3 studies of remdesivir, including one in patients with moderate disease, as well as the trial in patients with severe disease. The former does have a control arm, testing a five- or 10-day course of remdesivir against standard of care. And since the studies kicked off in late February, the company has expanded the latter trial to include thousands more patients with severe disease, including those on ventilators. Gilead expects preliminary data from the “severe” study by the end of April and data from the “moderate” study in May.
The company has also made the drug available to studies run by other sponsors, such as the National Institutes of Health, as well as to more than 1,700 people on a compassionate use basis. Last week, The New England Journal of Medicine published data from 53 patients with severe disease, but that data set also lacked a control group.
DIY-HP-LED
Well-Known Member
Better living through chemistry:
Here is what the availability of remdesivir looks like and how quickly they expect to scale up production. If this drug works as indicated by the preliminary data, it will be a game changer and the higher the production rate, the more the economy can be opened up. Treatment might factor in the immune response, in other words they might want people to get just sick enough to induce a natural immune response, but not to the point where difficulties arise. Those who have mild to moderate cases will not get the drug since there would be no need. Looking at these numbers the production rate could exceed the serious illness rate (ICU beds /ventilators) in America, with a controlled reopening of society until herd immunity or a vaccine becomes a factor. If remdesivir and convalescent plasma treatments can lower the mortality rates to flu like levels, America might have a shot at getting out of this jamb by fall.
"In a public communication in early April, CEO Daniel O’Day outlined a series of measures Gilead was taking to increase access to remdesivir. At the time, the company said it had on hand enough active ingredient to create about 1.5 million doses, enough for roughly 140,000 treatment courses, based on a 10-day regimen. The company has been working to increase both internal capacity and external partnerships to generate an additional 500,000 courses by October, 1 million courses by the end of the year, and, if needed, several million courses in 2021".
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cen.acs.org
Scaling up remdesivir amid the coronavirus crisis
Manufacturing experts weigh in on Gilead’s challenge in making its potential COVID-19 treatment
by Lisa M. Jarvis
APRIL 20, 2020
With society clamoring for something—anything—that can stem the rapidly rising death toll of the COVID-19 pandemic, Gilead Sciences’ antiviral remdesivir has emerged as a closely-watched treatment option. Laboratory studies of other coronaviruses suggested it might be able to take down this one, and as the outbreak took hold in China in January, it was among the first treatments that doctors tried.
Credit: C&EN
Remdesivir
Now, with cases worldwide at nearly 2.5 million, scrutiny of data coming out of clinical trials of the drug has reached fever pitch. When the health-focused news site Stat posted a story based on leaked video of a University of Chicago clinician talking optimistically about remdesivir’s possible effectiveness, it didn’t just prop up Gilead’s stock price; it lifted the entire stock market.
With each new anecdote, whether about an individual patient or a hunch from a doctor running a trial, the pressure on Gilead mounts. If any of the five late-stage clinical studies underway show that remdesivir works, Gilead will need to make a lot of it, and fast.
Gilead declined interview requests, but C&EN talked with manufacturing experts with experience in scaling up drugs amid crises to understand the challenge Gilead faces and how fast the firm—or any company developing a drug that might be effective against COVID-19—could reasonably meet demand. Past situations provide some guidance, though all concede that none of them matches the level of urgency being felt now.
Drug manufacturing today is like a bucket brigade, explains Princeton University chemist Paul Reider, who previously held chemistry leadership positions at Amgen and Merck & Co. One supplier sends raw materials to another, which uses those basic chemicals to do the first step in the synthesis of a molecule—say, creating a simple side chain. The result gets passed on to another company in the brigade, which performs the next step, and so on. Two or more of those bucket lines might converge to put together the now-complex pieces into the final molecule.
The efficiency of the brigade varies from drug to drug. One variable is the complexity of the molecule. The antimalarial hydrochloroquine, also being tested in COVID-19, is at the easy end of the spectrum. Making it in large quantities, if the need arises, will require little more than high-quality manufacturing capacity. Remdesivir, with its six chiral centers, is “a medium complexity project,” says Ian Davies, director of internal and external scientific relationships for the Princeton Catalysis Initiative.
But beyond the molecule itself, ease of scale-up has much to do with a company’s manufacturing design philosophy, Davies notes. While all firms design a safe route, “most companies approach this on sufficiency,” rather than efficiency, says Davies, who previously led Merck & Co.’s process chemistry group. They estimate a drug’s market size and likely price tag, and weigh that against how much manufacturing the active ingredient will cost. If the margins look good enough, many companies won’t invest much in making a process more efficient, he says.
continued...
Here is what the availability of remdesivir looks like and how quickly they expect to scale up production. If this drug works as indicated by the preliminary data, it will be a game changer and the higher the production rate, the more the economy can be opened up. Treatment might factor in the immune response, in other words they might want people to get just sick enough to induce a natural immune response, but not to the point where difficulties arise. Those who have mild to moderate cases will not get the drug since there would be no need. Looking at these numbers the production rate could exceed the serious illness rate (ICU beds /ventilators) in America, with a controlled reopening of society until herd immunity or a vaccine becomes a factor. If remdesivir and convalescent plasma treatments can lower the mortality rates to flu like levels, America might have a shot at getting out of this jamb by fall.
"In a public communication in early April, CEO Daniel O’Day outlined a series of measures Gilead was taking to increase access to remdesivir. At the time, the company said it had on hand enough active ingredient to create about 1.5 million doses, enough for roughly 140,000 treatment courses, based on a 10-day regimen. The company has been working to increase both internal capacity and external partnerships to generate an additional 500,000 courses by October, 1 million courses by the end of the year, and, if needed, several million courses in 2021".
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Scaling up remdesivir amid the coronavirus crisis
Manufacturing experts weigh in on Gilead’s challenge in making its potential COVID-19 treatment
Scaling up remdesivir amid the coronavirus crisis
Manufacturing experts weigh in on Gilead’s challenge in making its potential COVID-19 treatment
by Lisa M. Jarvis
APRIL 20, 2020
With society clamoring for something—anything—that can stem the rapidly rising death toll of the COVID-19 pandemic, Gilead Sciences’ antiviral remdesivir has emerged as a closely-watched treatment option. Laboratory studies of other coronaviruses suggested it might be able to take down this one, and as the outbreak took hold in China in January, it was among the first treatments that doctors tried.
Credit: C&EN
Remdesivir
Now, with cases worldwide at nearly 2.5 million, scrutiny of data coming out of clinical trials of the drug has reached fever pitch. When the health-focused news site Stat posted a story based on leaked video of a University of Chicago clinician talking optimistically about remdesivir’s possible effectiveness, it didn’t just prop up Gilead’s stock price; it lifted the entire stock market.
With each new anecdote, whether about an individual patient or a hunch from a doctor running a trial, the pressure on Gilead mounts. If any of the five late-stage clinical studies underway show that remdesivir works, Gilead will need to make a lot of it, and fast.
Gilead declined interview requests, but C&EN talked with manufacturing experts with experience in scaling up drugs amid crises to understand the challenge Gilead faces and how fast the firm—or any company developing a drug that might be effective against COVID-19—could reasonably meet demand. Past situations provide some guidance, though all concede that none of them matches the level of urgency being felt now.
Drug manufacturing today is like a bucket brigade, explains Princeton University chemist Paul Reider, who previously held chemistry leadership positions at Amgen and Merck & Co. One supplier sends raw materials to another, which uses those basic chemicals to do the first step in the synthesis of a molecule—say, creating a simple side chain. The result gets passed on to another company in the brigade, which performs the next step, and so on. Two or more of those bucket lines might converge to put together the now-complex pieces into the final molecule.
The efficiency of the brigade varies from drug to drug. One variable is the complexity of the molecule. The antimalarial hydrochloroquine, also being tested in COVID-19, is at the easy end of the spectrum. Making it in large quantities, if the need arises, will require little more than high-quality manufacturing capacity. Remdesivir, with its six chiral centers, is “a medium complexity project,” says Ian Davies, director of internal and external scientific relationships for the Princeton Catalysis Initiative.
But beyond the molecule itself, ease of scale-up has much to do with a company’s manufacturing design philosophy, Davies notes. While all firms design a safe route, “most companies approach this on sufficiency,” rather than efficiency, says Davies, who previously led Merck & Co.’s process chemistry group. They estimate a drug’s market size and likely price tag, and weigh that against how much manufacturing the active ingredient will cost. If the margins look good enough, many companies won’t invest much in making a process more efficient, he says.
continued...
DIY-HP-LED
Well-Known Member
continued from above:
And when it comes to remdesivir, experts say Gilead might not have been inclined, or even had the time, to make the process as efficient as it could be. Gilead developed the compound during the 2014 Ebola virus outbreak in West Africa and sped it along with the goal of testing it before the outbreak waned. The process likely reflects the anticipated demand for an Ebola treatment: the 2014 Ebola outbreak saw 29,000 cases over 2.5 years; the current coronavirus pandemic is approaching 2.5 million cases in under 5 months.
As the scope of the pandemic widens, Gilead has been open about the challenges of manufacturing the drug. The firm says it typically takes 9 to 12 months to make an antiviral like remdesivir, but that since January it has shrunk the timeline to 6 to 8 months. “We continue to work on optimizing the chemical synthesis processes,” the company states.
In a public communication in early April, CEO Daniel O’Day outlined a series of measures Gilead was taking to increase access to remdesivir. At the time, the company said it had on hand enough active ingredient to create about 1.5 million doses, enough for roughly 140,000 treatment courses, based on a 10-day regimen. The company has been working to increase both internal capacity and external partnerships to generate an additional 500,000 courses by October, 1 million courses by the end of the year, and, if needed, several million courses in 2021.
The ramp up is significant. But global demand, which could include both treatment for the ongoing pandemic and government stockpiling, could dwarf those figures if the drug proves to be beneficial in treating COVID-19.
Manufacturing experts point to the astronomical demand for government stockpiles of the influenza treatment Tamiflu amid the H1N1 outbreak, which began in 2004. The situations have important differences—Tamiflu is oral, while remdesivir is intravenous, meaning its utility, if proven, would be more limited—but the thought exercise for how to tackle the problem is probably similar.
Indeed, David LaPre, who led the team at Roche that scaled up Tamiflu production, says the first question for companies with promising COVID-19 treatments is how many doses they will need. “There were a lot of debates as to what’s the right number, and I’m sure that’s the problem people are facing today as they think about antivirals as a weapon in our arsenal against COVID-19,” says LePre, who is now a pharmaceutical consultant. “I sense that now, like then, there’s not going to be a precise number—you basically have to pick one that makes sense between your own thinking and the thinking of health authorities. That becomes the target.”
In 2005, Roche based its Tamiflu target on several case studies that pegged demand at more than 1 billion doses, LaPre says.
Another layer of complexity is the vast network of partners—the bucket brigade—involved in taking a drug from raw materials to a finished product delivered to a hospital or pharmacy. Decades ago, big pharma firms performed many of those steps in-house across a handful of manufacturing sites. During the late 1990s, when Merck was preparing for a surge in demand for the HIV treatment Crixivan, “we picked up every available piece of equipment we needed” from sites in several states, Reider, who worked on Crixivan, recalls.
Roche, which licensed Tamiflu from Gilead in 1996, also was able to expand its internal capacity while at the same time building an external supply chain. Between 2005 and 2007, Roche ended up providing roughly 200 million courses of Tamiflu for government stockpiles around the globe.
But over the past 15 years, drug companies have scaled back their internal capacity. “People don’t recognize how many pieces are touched” by a vast network of contract manufacturing partners around the globe, says James Bruno, president of the consulting firm Chemical and Pharmaceutical Solutions. And “if one of those pieces fails,” it creates a bottleneck that is felt down the entire bucket brigade.
Gilead typically outsources the synthesis of its drugs through late-stage intermediates, performing the last critical steps in-house. And while it says it is trying to increase its own capacity, its first step was likely “to quickly scan the globe as to who has the right capability that can be brought to bear,” LaPre says.
And when it comes to remdesivir, experts say Gilead might not have been inclined, or even had the time, to make the process as efficient as it could be. Gilead developed the compound during the 2014 Ebola virus outbreak in West Africa and sped it along with the goal of testing it before the outbreak waned. The process likely reflects the anticipated demand for an Ebola treatment: the 2014 Ebola outbreak saw 29,000 cases over 2.5 years; the current coronavirus pandemic is approaching 2.5 million cases in under 5 months.
As the scope of the pandemic widens, Gilead has been open about the challenges of manufacturing the drug. The firm says it typically takes 9 to 12 months to make an antiviral like remdesivir, but that since January it has shrunk the timeline to 6 to 8 months. “We continue to work on optimizing the chemical synthesis processes,” the company states.
In a public communication in early April, CEO Daniel O’Day outlined a series of measures Gilead was taking to increase access to remdesivir. At the time, the company said it had on hand enough active ingredient to create about 1.5 million doses, enough for roughly 140,000 treatment courses, based on a 10-day regimen. The company has been working to increase both internal capacity and external partnerships to generate an additional 500,000 courses by October, 1 million courses by the end of the year, and, if needed, several million courses in 2021.
The ramp up is significant. But global demand, which could include both treatment for the ongoing pandemic and government stockpiling, could dwarf those figures if the drug proves to be beneficial in treating COVID-19.
Manufacturing experts point to the astronomical demand for government stockpiles of the influenza treatment Tamiflu amid the H1N1 outbreak, which began in 2004. The situations have important differences—Tamiflu is oral, while remdesivir is intravenous, meaning its utility, if proven, would be more limited—but the thought exercise for how to tackle the problem is probably similar.
Indeed, David LaPre, who led the team at Roche that scaled up Tamiflu production, says the first question for companies with promising COVID-19 treatments is how many doses they will need. “There were a lot of debates as to what’s the right number, and I’m sure that’s the problem people are facing today as they think about antivirals as a weapon in our arsenal against COVID-19,” says LePre, who is now a pharmaceutical consultant. “I sense that now, like then, there’s not going to be a precise number—you basically have to pick one that makes sense between your own thinking and the thinking of health authorities. That becomes the target.”
In 2005, Roche based its Tamiflu target on several case studies that pegged demand at more than 1 billion doses, LaPre says.
Another layer of complexity is the vast network of partners—the bucket brigade—involved in taking a drug from raw materials to a finished product delivered to a hospital or pharmacy. Decades ago, big pharma firms performed many of those steps in-house across a handful of manufacturing sites. During the late 1990s, when Merck was preparing for a surge in demand for the HIV treatment Crixivan, “we picked up every available piece of equipment we needed” from sites in several states, Reider, who worked on Crixivan, recalls.
Roche, which licensed Tamiflu from Gilead in 1996, also was able to expand its internal capacity while at the same time building an external supply chain. Between 2005 and 2007, Roche ended up providing roughly 200 million courses of Tamiflu for government stockpiles around the globe.
But over the past 15 years, drug companies have scaled back their internal capacity. “People don’t recognize how many pieces are touched” by a vast network of contract manufacturing partners around the globe, says James Bruno, president of the consulting firm Chemical and Pharmaceutical Solutions. And “if one of those pieces fails,” it creates a bottleneck that is felt down the entire bucket brigade.
Gilead typically outsources the synthesis of its drugs through late-stage intermediates, performing the last critical steps in-house. And while it says it is trying to increase its own capacity, its first step was likely “to quickly scan the globe as to who has the right capability that can be brought to bear,” LaPre says.
greg nr
Well-Known Member
We have to temper all of this with the knowledge that FEMA will likely seize all shipments of this drug in this country and do what it has been doing with ppe and ventilators. Mainly, rewarding trump allies and punishing his critics. Many states won't see more than a dribble of the drug at enormous cost while others will get all they want.
No treatment or vaccine that is in limited supplies will help the vast majority of this country recover. Period.
DIY-HP-LED
Well-Known Member
I figure as soon as it's proven to work that Donald will seize the supply and use the power of life and death to control the states, he will probably ban exports and hord the drug, even if its not required, it will be power and Donald will want it. Poor countries will be shown no consideration and given nothing, unless they have dirt on Biden. The smart move would be, that if efficacy was proven for remdesivir, to have a manhattan project and produce billions of doses free for the world, it's the world economy that has to improve for the American economy to do well.
From what I've seen thus far, it is my opinion, that using both remdesivir and convalescent plasma transfusions, even the most vulnerable can be successfully treated. If we do NPI's properly, test, isolate and contact trace, we could have an ethical plan for herd immunity. This also will greatly diminish the requirements for ICU beds and ventilators. Most people will tolerate being sick, but not being fucked for life or dead! Remove the fear and the economy will open up, but without mass gatherings for a while.
hanimmal
Well-Known Member
Or he will just say he is going to do that because he is uber aware that he can say anything to the press and it doesn't matter in a court of law.
It's why he has lost virtually everyone with any credibility from his administration/executive branch, when they drew a line, or got caught, he dumped them. He only gets press because he is the POTUS.
DIY-HP-LED
Well-Known Member
As long as Mitch and the GOP can get it themselves, fuck everybody else, I believe access to the therapies mentioned above and confidence in them by the elites is driving the opening up agenda forward, their fear is being diminished, but not yours. This drug alone has the same potential in fighting this viral infection, that penicillin had in fighting bacterial ones. From the animal studies and limited human trial information I've seen, it appears to be extremely effective. Production and the abuse of distribution by Trump appear to be the only issues that I can see. We will need to wait for further data and studies, but I'm pretty optimistic as are most experts.
I'm watching it closely because it can have the biggest quickest impact on the crises and save many lives, probably over a million in America alone over the next year, while helping the economy get back on its feet. Remdesivir and convalescent plasma transfusion might make all the difference in how this pandemic is dealt with. We will see in a week or so, I figure, the pressure is immense and nobody doing this study is taking the weekends off, the data has been "locked" last week on one clinical trial and that usually means an announcement is imminent.
hanimmal
Well-Known Member
My fear is not being diminished? I try to be respectful mostly, but this really sounds like you are just talking shit about me.
The rest is just the informercial, I get it. But I am sure we will see Dear Leader pushing it soon enough.
Luckily scientists and doctors are working around the world on this, that is who is going to get us out of this mess, not talking points and spin aimed to make enough noise about this issue that nobody knows what is real or fake and become highly manipulatable to the propaganda that needs to get pushed for Dear Leader to have a shot in hell at winning.
DIY-HP-LED
Well-Known Member
Eh? This is a potential way out of this mess, not a political talking point and not an insult to you! If these treatments can lower the infection rate to flu levels it will make a difference, a big fucking difference. I'm not here on this topic with a political agenda, but with a humanitarian one. You seem to conflate everything into some hidden agenda and if Donald breaths a word of it it must be false.
Read the studies that I've posted, if you are not at least cautiously optimistic you don't understand the implications of either threarapy. I'm looking for ways out of this mess and sitting on our asses at home is only part of the solution. Sometimes people post stuff because they actually believe it, unless you think I'm a Russian with a nefarious purpose. This is about finding the truth not about winning arguments, I stick to science and just layer on some hope and optimism. Don't bother with giving me bullshit about selling false hope either, all the facts are on this thread for any adult to make up their own mind about it. It requires a clear and unbiased mind though.
I'm selling hope, Trump and that bunch are selling bullshit, destruction and despair. I'm not talking shit about you or anybody else, its not my game, unless they are Trumpers and I have no clue how you came to such a conclusion. Reading people here try to talk about science is amusing sometimes because many are emotional basket cases who sprinkle almost every conversation with paranoia, ad hominem attacks and personal insults.
I can't fix your fear only you can do that.
hanimmal
Well-Known Member
I don't claim to know what you are or why you post the things you do.
DIY-HP-LED
Well-Known Member
Those who bother to check this thread might have noticed a lot more science papers on it, since science is being discussed on several threads, in so far as it relates to public policy and the pandemic. This thread is now a place where papers or links to them that are relevant to the discussion can be posted and quickly referenced. Part of that epidemiological discussion are emerging treatments that will have an impact on public policy, among other things, like saving hundreds of thousand or millions of lives, important shit. These treatment studies will be posted here when released and most likely be discussed on the new threads that will be created for that purpose by myself or others. I have no problem with anybody who wants to talk about them here.