The city-state of Singapore is planning to outfit each of
its 5.7 million residents with a simple wearable device to track people
who have been exposed to the novel coronavirus, according to Reuters.
The massive digital contract-tracing effort, involving
small devices that would fit in pockets or be attached to lanyards,
would follow up on a previous program built on smartphones and apps as
the country aims to loosen its lockdown rules, the report said.
Singapore currently faces over 37,000 confirmed infections
of COVID-19 and has had 24 deaths. The smaller territory has a larger
number of cases compared to its Southeast Asia neighbors, including
Indonesia’s 29,500, the Philippines’ 20,600 and Malaysia’s 8,200,
according to international data collected by Johns Hopkins University.
The technology would be similar in concept to programs
rolled out late last month by Apple and Google, which rely on a
smartphone’s Bluetooth radio to ping nearby devices and record when they
have been in somewhat close physical contact.
If a person tests positive for COVID-19, that data could be
used to trace back interactions and alert people that they may have
been exposed to the disease. The wearable devices, however, would not
need to depend on smartphones.
According to Reuters, Singapore’s previous TraceTogether
app was found to be less effective, as smartphones would turn off the
Bluetooth radio to save power while the app ran in the background.
The country’s government did not say if the new wearables
would be mandatory, the report said. Other governments, such as in Hong
Kong and Bahrain, have used similar devices for monitoring people under
quarantine.
President Donald Trump said in May that he was taking
hydroxychloroquine to guard against COVID-19 infection. But does the
anti-malaria drugwork as preventive measure for the novel coronavirus?
It doesn’t, a new study published in The New England Journal of Medicine
suggests. However, a long list of unanswered questions remains, and one
expert concludes that the drug’s prevention benefits “remain to be
determined.”
In what the study authors called a “pragmatic” clinical trial, 821
adults who had a previous risky COVID-19 exposure were recruited through
social media to receive either hydroxychloroquine (HCQ) or placebo. By
14 days after treatment, 49 of 414 participants on HCQ and 58 of 407 on
placebo developed COVID-19.
The 2.4 percentage points of absolute difference in illness incidence
didn’t cross the statistical significance threshold, the University of
Minnesota-led team said, even though HCQ helped cut the risks of
developing the disease by about 17% on a relative basis.
But Evercore ISI analyst Umer Raffat, who previously estimated HCQ
could show a benefit of around 25% to 30%, raised several questions in a
Wednesday note to clients.
First, evidence of an advantage for HCQ—though small—showed up at day
14 but not at day 5 or day 10. “Would this delta have expanded beyond
day 14? Unclear,” Raffat said.
Secondly, HCQ’s effect appears to be driven by people who had no
additional underlying health conditions. But Raffat noted there was no
explanation for that.
The reason why Raffat previously held higher hopes for HCQ is that
its EC50—the concentration of a drug required to provoke a response
halfway between the baseline and maximum—is similar to that of Gilead
Sciences’ remdesivir, which has proven at least modestly effective
against COVID-19 in several carefully designed clinical trials.
So, why didn’t HCQ live up to its expectations? Were the EC50 data
simply incorrect? Or, is it because this was a prophylaxis study? We
just don’t know, Raffat noted.
On that last point, Myron Cohen, a virologist at the University of
North Carolina at Chapel Hill, raised questions in an NEJM editorial.
Strictly speaking, the study is testing HCQ as a measure of postexposure prophylaxis. Cohen noted that, in a recent mouse study,
prevention of SARS-CoV-2 was achieved only when an experimental drug
was given before or shortly after exposure. Also, in HIV, postexposure
prophylaxis must be used within 72 hours after suspected exposure to
that virus.
However, most participants in the current study started HCQ beyond
that three-day window, suggesting that “what was being assessed was
prevention of symptoms or progression of COVID-19, rather than
prevention of SARS-COV-2 infection,” Cohen wrote.
What’s more, the study authors acknowledged that the trial didn’t
involve consistent proof of exposure, so it’s possible that some
participants never came in contact with the virus in the first place.
That wasn’t the biggest problem, though; after all, the study resembles
that of a phase 3 vaccine efficacy trial, in which participants are
discharged into the real world. For a study this large, we can assume
that the probability of exposure between the two arms was similar.
Perhaps the more important limitation is that only a small number of
COVID-19 cases were confirmed by a lab test. Instead, the
researchers relied on participant-reported symptoms.
All considered, the study’s results are “more provocative than
definitive, suggesting that the potential prevention benefits of
hydroxychloroquine remain to be determined,” Cohen said in the
editorial.
But one thing is clear: HCQ led to more than twice as many side effects than placebo, although none of them were serious.
Much controversy has been swirling around the antimalaria drug since Trump publicly touted it as a game-changer for COVID-19.
Previously, the World Health Organization temporarily halted its
large-scale trial of HCQ to treat COVID-19 patients after a study in The Lancet
found patients getting the drug appeared to have a higher risk of
death. However, that study itself inspired backlash, as nearly 150
doctors signed an open letter blasting the observational research for
relying solely on registry analysis rather than on a randomized,
placebo-controlled clinical trial.
Now, the WHO study has resumed; after reviewing available data, a
safety monitoring board decided there was no reason to discontinue the
global trial, the health body said Wednesday. https://www.fiercepharma.com/pharma/study-suggests-hydroxychloroquine-doesn-t-prevent-covid-19-but-questions-remain
All eyes are on a handful of drug
companies after news that the U.S. is prioritizing five COVID-19 vaccine
programs. But since the selections went public, experts have been
raising questions about the process and the drugmakers that were left
off.
Earlier this week, The New York Times reported
that AstraZeneca, Pfizer, Merck, Johnson & Johnson and Moderna had
scored “finalist” status at Operation Warp Speed, an aggressive program
to deliver COVID-19 vaccines to Americans this year. Four of the
companies have already received federal funding for their programs, and
the finalists will have access to additional resources, NYT reports.
Among those resources is priority access to clinical trial facilities, former FDA chief Scott Gottlieb said
on CNBC. With limited testing capacity nationwide and many vaccines in
development, that’s set to hinder companies that weren’t picked.
The former FDA chief pointed out
two absences that struck him—Sanofi and Novavax. Of the five vaccines
selected, only one platform—from Merck—has ever been used in an approved
shot.
“There’s no sort
of old-style technology in this mix,” Gottleib said. “I’m surprised that
either Sanofi or Novavax, someone who is developing [a
vaccine using] an older approach … wasn’t selected. If you want to
spread your bets, you probably want to spread your bets across different
platforms.”
Sanofi and Novavax “appear to be pretty
far along,” Gottlieb added, or at least “close enough that they could
have been included if in fact the government wanted to include a
protein-based approach in this initial mix.”
In late-stage testing,
each COVID-19 vaccine will need to be tested in 10,000 to 15,000
participants against a control arm of about 15,000 patients, Gottlieb
said. He predicted that clinical trial access will be a “critical issue”
this fall.
Meanwhile, a source linked to the project told Science the selection process has been “chaotic” and that it wasn’t “transparent to those of us who are trying to help out.”
The latest move is “typical Operation
Warp Speed, where everything is sort of cryptic and it’s unclear what
they’re actually saying,” Baylor College of Medicine vaccine expert
Peter Hotez told Science. Hotez, who is part of a public-private group
formed to assist with COVID-19 drug and vaccine development, said the
process has not been transparent so far. He also wondered why Sanofi had
been left out of the finalists.
About six months into the pandemic, 10
vaccines are in human testing and more than 120 are in preclinical
stages, according to an update this week from the World Health
Organization. Even as researchers move their projects through research
stages, teams are also working on the manufacturing end to prepare for a
massive scale-up in the event the vaccines succeed in testing.
On May 25, 2020, George Floyd, 46, died following his arrest and
restraint, handcuffed and prone, at the hand of Minneapolis Police
Department officers. Eyewitness video of Officer Derek Michael Chauvin
kneeling on Floyd’s neck went viral on social media. I’m first going to
take you through the videos of George Floyd’s death so you can see them
through the eyes of a forensic pathologist. I currently perform forensic
autopsies in California, and I analyze videos of officer-involved
deaths as a part of that job. I played no part in this death
investigation.
Autopsy means “see for yourself” — but sometimes the autopsy doesn’t
show you everything. A forensic pathologist cannot accurately determine
the cause of death and the manner of death
by looking at the autopsy findings alone. That’s because there are
several ways to kill people without causing devastating injury to the
internal organs. Asphyxia from neck and chest compression is one of
those ways.
The Washington Post has video from a restaurant pointed at the street
that captured George Floyd’s first interactions with the police. In it,
you can see two police officers. One talks to Floyd for over two
minutes before he tries to remove him from the vehicle. Floyd then
briefly struggles with both officers and appears to nearly collapse at
03:14- 03:17. As an officer walks Floyd, who is handcuffed behind his
back, over to the wall, Floyd’s gait is uneven. He is talking to the
officer, and they appear to continue the dialogue as the officer assists
Floyd in sitting down against the wall. The officer even makes some
notes in his notepad. The officer lifts Floyd back to his feet by
pulling up on his arms, which causes Floyd to grimace and turn his face
toward the officer. His gait is again lurching and uneven as the two
officers walk him across the road to their patrol vehicle. When they
reach it, he falls to the ground for a moment. Bystander video of police kneeling on George FloydGeorge Floyd’s interaction with police
The fact that Floyd appears to be talking to the officer and the
officer is taking notes suggests that Floyd is engaging in dialogue. The
gait disturbance suggests that Floyd may have been under the influence
of alcohol or some other drug that could affect his balance. The grimace
as he is being handled suggests that the cuffs are on too tight or that
he is in pain during this encounter as the officer pulls up on his
cuffed arms. Here’s what I don’t see: I don’t see someone who appears to
be suffering from excited delirium when drugs of abuse can cause
agitation, hyperthermia, and sudden death. Floyd is not naked or dressed
inappropriately for the weather. He does not appear to be sweating
profusely. He does not appear to be agitated or violent.
Bystander video of police kneeling on George Floyd
A short bystander video from another perspective
shows three police officers kneeling on Floyd while another stands at
his head. They appear to be exerting pressure on his neck, torso, left
(still handcuffed) arm, and legs. Pressure on the torso can limit chest
rise, and added pressure on other parts of the body can decrease cardiac
return (the volume of blood coming back from the limbs).
Looking at a longer, unedited bystander video
posted on Facebook, the first thing I notice is that Floyd’s voice
sounds gravelly, and he repeatedly says, “I can’t breathe.” EMS and
police are sometimes trained that anyone who says “I can’t breathe” is
lying — because if you can speak, you can breathe. This is not true, and
there are many reasons why people might say “I can’t breathe” and still
be in medical distress. These reasons include increasing fatigue of
respiratory muscles; blockage of pulmonary blood flow; incomplete airway
obstruction; and acidosis, a buildup of acid in the blood which
triggers an increased breathing rate and causes the sensation of
shortness of breath.
At the start of the video, Floyd has already appeared to have lost
bladder function. This can be a sign of medical distress. Floyd
specifically mentions “the knee in my neck,” a coherent statement and
not the grunting and screaming we typically hear in deaths from excited
delirium. As this video starts, Officer Chauvin already has his knee
pressed on Floyd’s neck, and you can see that pressure is being applied
to the part of his anatomy that contain the carotid arteries and jugular
veins. Floyd first appears to become unresponsive at 4:01. He stops
talking, his eyes close, and his face is still. Bystanders start
noticing this at 4:45. At 6:58 an officer checks his pulse. Officer
Chauvin’s knee doesn’t come off Floyd’s neck until 7:55, over 3 minutes
after Floyd first seems to have gone unconscious.
The district attorney’s charging documents
in the case stated, “The autopsy revealed no physical findings that
support a diagnosis of traumatic asphyxia or strangulation,” and that
“Floyd had underlying health conditions including coronary artery
disease and hypertensive heart disease. The combined effects of Floyd
being restrained by the police, his underlying health conditions, and
any potential intoxicants in his system likely contributed to his
death.” In contrast, the medical examiner’s first press release stated that “the cause and manner of death is currently pending further testing.”
Why the difference?
Charging documents are usually written by attorneys based on
information obtained from police officers and a representative of the
medical examiner’s office. They should not be interpreted as the
definitive result of the autopsy, and they are frequently inaccurate.
The headlines that suggested that asphyxia had been ruled out by the
medical examiner were wrong.
So were the ones that said that Michael Baden, MD, did an
“independent autopsy.” Baden is a retained expert and is being paid for
his services by Floyd’s family. He is not independent. The Hennepin
County Medical Examiner, which is paid by taxpayer money, is the only
independent agency here. They did the first, legally-mandated autopsy,
and collected the evidence. The medical examiner’s office is not an arm
of law enforcement. If a retained expert finds something at autopsy that
is not favorable to the client’s legal case, the client doesn’t have to
disclose that expert at all. Everything the medical examiner does and
all the evidence they collect is a public record. None of their
findings, no matter what they reveal, can be suppressed.
Furthermore, a “second autopsy” is always fraught with problems. The
process of performing the first autopsy causes “autopsy artifact” —
severed blood vessels, dissected organs, and even broken bones — that
the second autopsy pathologist may not be able to distinguish from
inflicted injury. When I perform a forensic autopsy on someone we
suspect might have died of asphyxia, I will frequently keep the entire
neck block (the windpipe, blood vessels, and surrounding organs and
structures of the throat) in a stock jar in the morgue, as evidence. I
may even save large sections of the heart and brain for specialized
testing. These materials would not be available to a private-practice
pathologist hired to perform a second autopsy.
If Baden looked at Floyd’s corpse after a thorough forensic autopsy,
there would have been little left for him to examine. Keep in mind that
he also does not have access to all the evidence in the case, such as
the medical records, witness statements, body camera videos, or police
reports.
Following a press conference on June 1 about the second autopsy,
Baden admitted that portions of Floyd’s organs were indeed missing, and
that he didn’t have access to the results from toxicology testing. Soon
after, the Hennepin County Medical Examiner issued a press release, and
subsequent to that, the full autopsy report, which indicated that the
cause of death was “cardiopulmonary arrest complicating law enforcement
subdual, restraint, and neck compression,” and that the manner of death
was homicide. They listed arteriosclerotic and hypertensive heart
disease, fentanyl intoxication, and recent methamphetamine use as other
significant conditions contributing to death.
This means that Floyd stopped breathing and his heart stopped beating
(cardiopulmonary arrest) because of the injury caused by his restraint
in the custody of law enforcement officers, to include asphyxia from
neck compression. Asphyxia means that there is a lack of oxygen going to
the brain. It can happen from obstruction of the airway, restriction of
breathing from compression of the neck or chest, or the prevention of
blood flow to the brain by collapsing the blood vessels in the neck. It
can also happen from the replacement of oxygen in the blood by carbon
monoxide, or depletion of oxygen in the atmosphere, like in a fire.
“Cardiopulmonary arrest” is not a heart attack. Online sources that
imply that the medical examiner is covering up George Floyd’s death by
calling it a “heart attack” are wrong.
The death certificate’s “other significant conditions” — Floyd’s
natural heart disease and the presence of drugs of abuse in his tested
blood — do not excuse the officers, nor should they cause anyone to
blame the victim. They are there on the death certificate because those
findings, in the opinion of the medical examiner, would have made his
death more likely. They are not the cause of death. The cause of death
is police restraint.
At the end of their press release, the Hennepin County Medical
Examiner adds the following important reminder: “Under Minnesota state
law, the Medical Examiner is a neutral and independent office and is
separate and distinct from any prosecutorial authority or law
enforcement agency.” Regardless of whether experts agree with their
interpretation of the evidence, they were the first to collect it, and
because they did their job, that evidence is now available for public
scrutiny in a court of law.
Japan aims to put coronavirus vaccines into use by June 2021, the
health minister said on Friday, as the country strives to be fully ready
to host the Tokyo Olympics, originally planned for this summer but
postponed by one year due to the pandemic.
Drugmakers around the world are scrambling to develop a treatment or
vaccine for COVID-19, the respiratory disease caused by the highly
infectious new coronavirus which has so far killed nearly 400,000 people
worldwide.
“We will be securing production facilities in parallel with expedited
vaccine development,” Japan’s Health Minister Katsunobu Kato told
reporters as he outlined plans to bring vaccines into use by the end of
the first half of 2021.
Usually, plants for actual vaccine production are arranged only after the successful completion of development.
The Japanese government has earmarked 146 billion yen ($1.34 billion)
for vaccine production and distribution in the second extra budget that
Prime Minister Shinzo Abe’s cabinet approved last month.
Japanese pharmaceutical firms developing coronavirus vaccines include Shionogi & Co (4507.T) and AnGes Inc (4563.T).
Inovio Pharmaceuticals
was one of the earlier companies to identify a potential vaccine
candidate against COVID-19, but the company has run into manufacturing
problems that have stymied its development plans, while other biopharma
groups have pushed ahead in their own development programs.
Inovio’s development issues for its vaccine candidate have become
mired in a conflict with the contract manufacturing organization it has
worked with on previous projects. Because of the issues with the CMO,
Korea-based VGXI, Inc., Inovio has filed a lawsuit
seeking to break the impasse and transfer an existing supply agreement
to another agency. VGXI, according to the company’s lawsuit, is unable
or unwilling to manufacture its vaccine candidate in large quantities.
Inovio has been pushing to develop its vaccine candidate, INO-4800, but
without the large-scale manufacturing necessary, the company’s efforts
have been slowed down considerably. Inovio had a goal of producing one
million doses of INO-4800 by the end of 2020 to support its clinical
trials and emergency use. VGXI could not meet that demand.
Inovio and VGXI have been partners since 2008. VGXI produces and
supplies the DNA plasmids for Inovio’s research and early clinical
trials for its product candidates. Inovio has no purchase commitments
under this supply agreement. The company said purchase agreements are
determined on an individual purchase order basis. Under the Supply
Agreement, Inovio said it agreed to treat VGXI as its most favored
supplier for DNA plasmids, and VGXI agreed to treat Inovio as its most
favored customer.
As COVID-19 took gripped the world, Inovio began to develop its vaccine candidate and in April, received permission
from the U.S. Food and Drug Administration to initiate a Phase I study.
As the company eyes a potential Phase II, VGXI informed Inovio that is
does not have the capacity to manufacture the company’s full order of
DNA plasmids on the requested timeline, nor would it be able to
manufacture plasmids for the commercial sale of INO-4800, if it achieved
regulatory approval.
On June 3, Inovio filed a complaint in the Court of Common Pleas of
Montgomery County in Pennsylvania seeking emergency relief to compel
VGXI to “facilitate the transfer of manufacturing methods, using VGXI’s
technology, under the parties’ existing supply agreement,” the company
said in a filing with the U.S. Securities and Exchange Commission. The
technology transfer is permitted under the existing supply agreement
and, if it goes through, would allow Inovio to find another manufacturer
who can meet its needs. When VGXI told the company it did not have the
capabilities to meet its demands, Inovio said it began discussions with
other third-party contract manufacturers, as permitted by the Supply
Agreement. Inovio struck a deal with Ology Bioservices Inc. and
Richter-Helm BioLogics GmbH & Co. KG to support large-scale
manufacturing of INO-4800 and sought to have VGXI turn over the
technology required. VGXI refused, which prompted the lawsuit.
In its filing,
Inovio said it believes the widespread availability of INO-4800 is
essential in quest to develop a medication against the disease that has
been linked to the deaths of more than 390,000 people across the globe,
including 108,000 in the United States. https://www.biospace.com/article/inovio-files-complaint-to-break-ties-with-cmo-over-covid-19-vaccine-production-issues/
Aimed squarely at the prestige from being first in
the global race for a SARS-CoV-2 vaccine, China’s government, including
the military and several state-backed companies, has committed “hundreds of millions” of dollars and cleared regulatory barriers to accelerate R&D.
Domestic drugmakers have already been ramping up
production as Chairman Xi Jinping has committed to share a domestically
developed vaccine with the world.
Five Chinese companies are behind five of 10
vaccine candidates being testing in humans according to WHO. Two are
being developed by state-run China National Biotec Group Co.
Another group, tied to China’s military, has received the nod to run a late-stage study in Canada.
Tianjin-based CanSino Biologics, together with the
military, was the first to publish study results (Phase 1) in an
established medical journal (The Lancet).
China is a step behind with vaccine-making
technologies, however. Four of the candidates in clinical trials were
produced by an older method using inactivated viruses, the same approach
long-used for flu, hepatitis A, polio and rabies vaccines. Moderna’s
top candidate, currently in a Phase 2 trial, is an RNA vaccine.
Privately held Sinovac Biotech Ltd., along with
several government entities, is conducting Phase 1 & 2 studies on
its candidate in Jiangsu province.
Regardless of who wins the race, Chinese companies
should play a key role in vaccine manufacturing considering their
capacities. The country is already one of the top producers in the
world.
Both the China and the U.S. expect to have a vaccine available by year-end.
