Infectious
respiratory diseases spread when a healthy person comes in contact with
virus particles expelled by someone who is sick — usually through a
cough or sneeze. The amount of particles a person is exposed to can
affect how likely they are to become infected and, once infected, how
severe the symptoms become.
The amount of virus necessary to make a person sick is called the
infectious dose. Viruses with low infectious doses are especially
contagious in populations without significant immunity.
The minimum infectious dose of SARS-CoV-2, the virus that causes
Covid-19, is unknown so far, but researchers suspect it is low. “The
virus is spread through very, very casual interpersonal contact,” W.
David Hardy, a professor of infectious disease at Johns Hopkins
University School of Medicine, told STAT.
A high infectious dose may lead to a higher viral load, which can impact the severity of Covid-19 symptoms.
Viral load is a measure of virus particles. It is the amount of virus
present once a person has been infected and the virus has had time to
replicate in their cells. With most viruses, higher viral loads are
associated with worse outcomes.
“The more viral particles that get into the lungs, the more damage to the lungs that is probably happening,” said Hardy.
One study of Covid-19 patients in China found that those with more severe symptoms tended to have higher viral loads.
“It’s not proven, but it would make sense that higher inoculating
doses will lead to higher viral loads, and higher viral loads would
translate into more pathogenic clinical courses,” said Dan Barouch,
director of the Center for Virology and Vaccine Research at Beth Israel
Deaconess Medical Center.
People with higher viral loads may also shed more whole viruses,
which makes them more contagious, compounding the danger of spreading
disease more widely.
If exposure to higher doses, or even frequent low doses, of
SARS-CoV-2 does lead to worse health outcomes, there are significant
implications for health care workers who are routinely exposed to
Covid-19 patients.
“Someone caring for large numbers of patients on the wards, if
they’re not wearing PPE [personal protective equipment], there might be a
high frequency of exposure as well as a high dose of exposure,” Barouch
said.
In Italy, a country particularly hard-hit by the virus, about 9% of reported cases were health care workers. Here in the U.S., 10% of Covid-19 cases in California were health care workers, according to the California Department of Public Health.
New York City will begin manufacturing its own coronavirus test kits,
as well as some personal protection equipment, its mayor announced
Tuesday.
“For the first time, we are going to have a truly reliable, major
supply of testing,” Mayor Bill de Blasio told reporters at City Hall. “A
lot of folks would have said this was impossible, they are making it
possible – and that is what New Yorkers do.”
New York has been the hardest hit U.S. state by the coronavirus, with
nearly 200,000 confirmed infections. More than half are in New York
City. The statewide death toll passed 10,000 this week, and thousands of
people remain hospitalized with the respiratory virus.
De Blasio said starting in early May, the city would begin producing
50,000 test kits per week and he hopes to build that up rapidly, as the
city of 8.6 million will need a huge volume.
The city struggled in the early weeks of the pandemic to acquire
enough test kits from the federal government and from private companies.
While the limited scale of production of test kits will not make the
city self-sufficient, it will be a huge step forward.
“Hopefully, the example New York City is setting will be recognized
in Washington – that if we can do it here, a place that doesn’t produce
tests has figured out a way to do it – then why can’t it be done all
over this country?” De Blasio said. “Why can’t we build up a supply that
can protect all of us?”
But he was quick to say this does not mean that the federal government’s help is no longer necessary.
“If the federal government can’t figure it out, then get out of the
way and let us at the local level get this done,” the New York City
mayor said. “But support us, get us the components, get us the help, so
we can do this rapidly and protect ourselves.
Local manufacturers and 3D printers will produce the swabs used for
collecting the nasal sample, as well as the tubes the specimen is
transported in, while academic and commercial laboratories will produce
the liquid solution the sample is stored in.
The mayor also announced that the city has confirmed the purchase of
an additional 50,000 kits a week from an Indiana company. They will
start arriving on Monday.
The combined production and purchase of test kits means the city
should have about 400,000 testing kits available monthly starting in
May. Testing is an essential part of getting the economy reopened.
Local companies are also gearing up to produce personal protective
equipment (PPE). Eight companies in Brooklyn and Manhattan will start
making face shields. They can now produce 240,000 each week and are
rapidly scaling up to reach 465,000 a week by April 24. The mayor said
the goal is 620,000 a week.
“It means we will be able to fulfill our entire need for face shields
right here in New York City,” de Blasio said. “We are going to be able
to say New York City is self-sufficient, we will no longer be at the
whim of the federal government or the international markets.”
New York has a large and vibrant garment industry, and several
companies have shifted from making clothes to surgical gowns to help
meet the skyrocketing demand.
The mayor said five companies are already producing 30,000 surgical
gowns a week and will scale up to 100,000 by next week. He said they
hope to reach 250,000 gowns a week soon after, and even go beyond that.
“These are brand new production lines created from scratch by
companies here, by New York City workers, in an atmosphere of crisis,
and they have surpassed any possible expectation we could have and they
are going farther,” he said.
New York Governor Andrew Cuomo said testing has been a challenge from
the beginning and he urged the federal government to take over
responsibility for it.
“You want to talk about an increased federal role, let FEMA do the testing,” he said of the Federal Emergency Management Agency.
A preliminary analysis of late-stage trial data shows thatBeiGene’s investigational checkpoint inhibitor tislelizumab is hitting the mark as a potential first-line treatment in patients with non-squamous non-small cell lung cancer (NSCLC).
This morning, BeiGene said tislelizumab in combination with
pemetrexed and platinum chemotherapy has met the primary endpoint in a
Phase III trial in NSCLC. The treatment has demonstrated a statistically
significant improvement in progression-free survival (PFS) compared to
pemetrexed and platinum chemotherapy alone at the planned interim
analysis. The safety profile of tislelizumab in combination with
pemetrexed and platinum chemotherapy has remained consistent and no new
safety signals were identified, the company said.
The Phase III trial is assessing the combination therapy in patients
with previously untreated stage IIIB or stage IV non-squamous NSCLC and
with no EGFR mutations or ALK translocations. The primary endpoint of
the trial is progression-free survival, with secondary endpoints
including overall survival and safety.
Checkpoint inhibitors have proven to be a valuable tool in combating
various cancers, with Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo
leading the pack. Tislelizumab (BGB-A317) is designed to bind to PD-1, a
cell surface receptor that plays an important role in downregulating
the immune system by preventing the activation of T-cells. It is being
developed as both a monotherapy and as part of a combination treatment
for both solid and hematologic tumors.
Earlier this year, BeiGene announced positive results from a pivotal Phase III trial
of its anti-PD-1 antibody tislelizumab in combination with two
chemotherapy agents in squamous non-small cell lung cancer (NSCLC). In
that study, tislelizumab met the primary endpoint of improved
progression-free survival.
Yong Ben, chief medical officer of immuno-oncology at BeiGene said
the company was excited about the latest Phase III results in NSCLC
following the previous positive trial data in squamous NSCLC.
“These results add to our growing body of evidence demonstrating the
efficacy and safety of tislelizumab for the treatment of advanced
cancers. We look forward to continuing to evaluate tislelizumab in more
than 25 studies, including 15 potentially registration-enabling trials,”
Ben said in a statement.
Non-small cell lung cancer is the most common form of lung cancer in
China. In 2018, there were approximately 770,000 new cases of lung
cancer in China and it is the leading cause of cancer-related death in
both men and women, with approximately 690,500 deaths.
Shun Lu, a professor at Shanghai Chest Hospital and lead investigator
for the Phase III trial, said approximately 60% of lung cancer
diagnoses are made when the disease is in advanced stages and patients
need more treatment options.
“The positive outcome at interim analysis for tislelizumab in this
study and in other clinical trials, including for first-line squamous
NSCLC, demonstrate that it is a promising option for people living with
this advanced cancer,” Lu said in a statement.
With the strong data from the interim analysis in hand, BeiGene
intends to discuss a potential filing for regulatory approval for
tislelizumab as a first-line treatment for non-squamous NSCLC in China. https://www.biospace.com/article/beigene-s-checkpoint-inhibitor-hits-the-mark-in-phase-iii-lung-cancer-study/
For some time, there has been speculation that glucose metabolism was
associated with Alzheimer’s disease, with some researchers going so far
as to call Alzheimer’s diabetes type 3. Researchers with the National
Institutes of Health’s National Institute on Aging conducted the largest study
so far on proteins related to Alzheimer’s and identified proteins and
biological processes that regulate glucose metabolism that are
associated with Alzheimer’s. The study was published in the journalNature Medicine.
The study was part of the Accelerating Medicines Partnership for
Alzheimer’s Disease (AMP-AD). The investigators assayed the levels and
analyzed the expression patterns of more than 3,000 proteins in brain
and cerebrospinal fluid samples collected at centers across the U.S.
“This is an example of how the collaborative, open science platform
of AMP-AD is creating a pipeline of discovery for new approaches to
diagnosis, treatment and prevention of Alzheimer’s disease,” said
Richard J. Hodes, NIA director. “This study exemplifies how research can
be accelerated when multiple research groups share their biological
samples and data resources.”
The study involved analyzing protein expression patterns in more than
2,000 human brain and almost 400 cerebrospinal fluid samples taken from
both healthy individuals and Alzheimer’s patients. They analyzed how
the protein modules relate to Alzheimer’s and other neurodegenerative
diseases. They observed changes in proteins related to glucose
metabolism and an anti-inflammatory response in glial cells in brain
tissues from both Alzheimer’s patients and people with documented brain
pathology who were cognitively normal. This also would seem to support
increasing evidence that brain inflammation is involved in the disease
as well.
In Alzheimer’s patients, they found that how cells extract energy
from glucose is increased in both the brains and spinal fluid of
Alzheimer’s patients. The proteins observed were also elevated in
preclinical Alzheimer’s patients, which is to say, people with brain
pathology of the disease who had not shown cognitive decline.
They also noted the importance of their findings that the glucose
metabolism/glial protein module was populated with proteins already
identified as genetic risk factors for Alzheimer’s.
“We’ve been studying the possible links between abnormalities in the
way the brain metabolizes glucose and Alzheimer’s-related changes for a
while now,” said Madhav Thambisetty, investigator and chief of the
Clinical and Translational Neuroscience Section in the NIA’s Laboratory
of Behavioral Neuroscience. “The latest analysis suggests that these
proteins may also have potential as fluid biomarkers to detect the
presence of early disease.”
Earlier research by Thambisetty and colleagues at Emory University
identified a connection between problems in how the brain breaks down
glucose and the amount of amyloid plaques and tangles were in the brain,
as well as memory and cognitive issues.
“This large, comparative proteomic study points to massive changes
across many biological processes in Alzheimer’s and offers new insights
into the role of brain energy metabolism and neuroinflammation in the
disease process,” said Suzana Petanceska, program director of NIA
overseeing the AMP-AD Target Discovery Program. “The data and analyses
from this study has already been made available to the research
community and can be used as a rich source of new targets for the
treatment and prevention of Alzheimer’s or serve as the foundation for
developing fluid biomarkers.”
The research group was led by Erik C.B. Johnson, Nicholas T. Seyfried
and Allan Levey at the Emory School of Medicine in Atlanta. The brain
samples were from autopsies of participants in various Alzheimer’s
research centers, including the Baltimore Longitudinal Study of Aging
(BLSA), Religious Orders Study (ROS) and Memory and Aging Project (MAP),
and Adult Changes in Thought (ACT) initiatives.
Samples from people with six other neurodegenerative disorders and
normal controls were provided by the Emory Goizueta Alzheimer’s Disease
Research Center, with data from the AD Knowledge Portal, the data
repository for the AMP-AD Target Discovery Program, and other NIA
projects. https://www.biospace.com/article/glucose-metabolism-linked-to-alzheimer-s-disease/
President Donald Trump met Tuesday with health-care executives on
what he’s calling the dynamic ventilator reserve, a program aimed at
getting ventilators to coronavirus patients.
“We’re going to have a big discussion today having to do with costs
and hospitals and obviously how it relates to the hidden enemy,” Trump
said at the beginning of the meeting at the White House. “I look forward
to discussing our new partnership to establish the dynamic ventilator
reserve,” he said.
The researchers said the findings “warrant deeper epidemiological
scrutiny and prospective evaluation in individually randomized trials.”
The World Health Organization said this week
that there is currently “no evidence” that the BCG vaccine can protect
people from the coronavirus, but two clinical trials are underway.
The WHO will “evaluate the evidence when it is available,” and does
not currently recommend the vaccination for the prevention of COVID-19,
it said.
Studies like the Johns Hopkins one, which has yet to be
peer-reviewed, “are prone to significant bias from many confounders,
including differences in national demographics and disease burden,
testing rates for COVID-19 virus infections, and the stage of the
pandemic in each country,” the organization said.
Researchers at the Murdoch Children’s Research Institute in Melbourne, Australia, are probing whether the vaccine could protect health care workers on the front line from the deadly bug.
“I think BCG vaccine is a bit of the equivalent of a Hail Mary pass,”
Dr. William Schaffner, an infectious disease specialist at the
Vanderbilt University School of Medicine, told WBZ-TV this week. “It’s such an outside-the-box concept that one would like to be optimistic, but we’ll have to wait and see.” https://nypost.com/2020/04/14/coronavirus-death-rates-lower-in-countries-using-tb-vaccine/
Johnson & Johnson (JNJ.N)
on Tuesday said it expects its medical device business to begin
recovering in the fourth quarter as elective medical procedures delayed
by the coronavirus pandemic start to resume.
The U.S. healthcare conglomerate lowered its full-year 2020 forecast
due to the hit to that business, with procedures like hip and knee
replacements on hold. The division accounts for nearly 30% of total
sales.
However, investors appeared to take heart that J&J did not simply
withdraw its 2020 forecasts over coronavirus uncertainty as the
pandemic causes massive business disruptions around the world. It also
raised the quarterly dividend to $1.01 per share, and its shares rose
4.4% to $145.87.
J&J’s 2020 adjusted earnings forecast of $7.50 to $7.90 per share
– down from its prior view of $8.95 to $9.10 – assumes any return of
the coronavirus outbreak in the fall will look much different than the
current global health crisis.
“If the virus does return, the world should be much better prepared
to test, identify and isolate it. There may also be therapeutic options
available,” Chief Financial Officer Joseph Wolk said on a conference
call.
Wolk said he expected elective procedures and doctor visits to
largely resume in the second half of the year, with the business seeing a
lingering impact but starting to stabilize in the third quarter.
Drugmakers and medical researchers are racing to develop treatments
and vaccines for the novel coronavirus, which has infected some 2
million people globally and killed over 123,000.
J&J plans to start human trials of its vaccine candidate by
September. It signed a vaccine deal with the U.S. government to jointly
invest $1 billion and hopes to be able to manufacture more than 1
billion doses.
J&J said it is developing the vaccine on a “not-for-profit” basis.
“Being part of the solution to conquer the pandemic is good for all
businesses, not just the business of Johnson & Johnson,” Wolk told
Reuters in a phone interview.
The company was not looking to recoup research and development costs
and plans to price the vaccine to offset costs related to its
manufacturing and distribution, Wolk said.
J&J, the first major U.S. drugmaker to report earnings since the
outbreak, said medical device sales in the first quarter fell 8.2% to
$5.93 billion, with products used in high-margin orthopedic procedures
and vision correction hit particularly hard.
Consumer health sales jumped 9.2% to $3.63 billion, driven by a surge
in demand for products like Tylenol and Motrin as consumers faced with
an illness that causes fever and cough stocked up on essentials.
