thescientist--2020-11-10--Q&A: Pollution Linked to 15 Percent Increase in COVID-19 Deaths

As the COVID-19 pandemic spread around the globe early in the spring of 2020 , researchers began investigating how air pollution , which has been known for decades to have deleterious effects on human health , could be affecting this respiratory disease .
Inspired by the work of a group of researchers in the US who reported in April that high levels of air pollution correlated to a higher risk of dying from COVID-19 , Jos Lelieveld , an atmospheric chemist at the Max Planck Institute for Chemistry , and others widened their scope , looking at more areas of @ @ @ @ @ @ @ to respiratory health comes from tiny emissions particles that are inhaled .
Fine particulate matter is defined as anything smaller than 2.5 micrometers ( PM ) .
The smaller the particles , the further down the respiratory system they can get , causing big problems by way of oxidative stress and an exuberant inflammatory response .
Some particles can even trigger apoptosis .
Short-term exposure to particle-laden air can cause acute irritation , leading to a cough , while long-term exposure is linked to chronic conditions such as chronic obstructive pulmonary disorder ( @ @ @ @ @ @ @ cancer .
A study published in Cardiovascular Research on October 26 claims that fine particulate matter has increased the risk of deaths from COVID-19 by 15 percent globally , with certain areas such as East Asia reaching a 27 percent increase .
The Scientist talked to Lelieveld to learn more about the relationship between pollution and COVID-19 .
TS : Why do these particles leave people more vulnerable to dying from COVID-19 ?
JL : You have long-term effects [ when people are ] exposed for basically a lifetime to air pollution and @ @ @ @ @ @ @ .
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These diseases are also preconditions for severe development of COVID-19 .
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Many of the lung diseases like pneumonia , COPD , lung cancer , heart disease , strokes , [ are ] the sort of thing that are aggravated by air pollution .
And these are the sorts of things that also make people die from COVID .
A healthy , young subject who has not been developing chronic diseases typically does not die from COVID .
TS : What can someone who lives in a place with @ @ @ @ @ @ @ exposure to these particles ?
JL : We write in our paper that there is no remedy like vaccinations for air pollution , so the only remedy here is that you have to clean the air .
You have to go to cleaner sources of fuels and cleaner fuels and cleaner energy use .
And of course , this also helps the climate .
There are many arguments to do this .
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I ’ m convinced that climate change is a big problem for this planet .
And what I @ @ @ @ @ @ @ the people who think it ’ s not an issue [ that ] carbon dioxide makes the world a bit warmer , maybe I can help convince them by showing that the same sources that create greenhouse gases are also creating pollutants that make you ill. TS : Can you tell me how you collected your data and designed the study ?
JL : We used the data from the paper attached to calculate PM exposure-response functions , plus data from China collected for the SARS epidemic in 2003 .
We tested different @ @ @ @ @ @ @ the same result .
To characterize exposure , we used a combination of satellite data and an atmospheric model , the latter to compute the anthropogenic fraction of PM and the contribution of fossil fuel use .
TS : Are there benchmarks of PM levels that correspond to low or high risk ?
JL : There is a threshold of 2.4 µg/m3 below which the air is considered “ clean ” , precluding health impacts .
TS : Are there certain fine particles that are worse than others ?
JL : There are @ @ @ @ @ @ @ particles are more toxic than most other particles .
But this is not quantitatively known , hence it is common practice to assume that all fine particulates are equally toxic .
TS : How long do fine particles stay with a person after they leave a highly polluted area ?
JL : The atmospheric lifetime of aerosol particles is about one week .
Once inhaled and deposited in the lungs , the damage is done ( much like smoking ) .
The cumulative damage during many years of exposure causes or aggravates chronic @ @ @ @ @ @ @ , which are preconditions that influence the severity of COVID-19 outcomes .
This interview was completed over the phone and via email .
It has been edited for clarity and brevity .

ABOVE: © ISTOCK.COM, FATIDO
As the COVID-19 pandemic spread around the globe early in the spring of 2020, researchers began investigating how air pollution, which has been known for decades to have deleterious effects on human health, could be affecting this respiratory disease. Inspired by the work of a group of researchers in the US who reported in April that high levels of air pollution correlated to a higher risk of dying from COVID-19, Jos Lelieveld, an atmospheric chemist at the Max Planck Institute for Chemistry, and others widened their scope, looking at more areas of the world.
The danger of pollution to respiratory health comes from tiny emissions particles that are inhaled. Fine particulate matter is defined as anything smaller than 2.5 micrometers (PM 2.5 ). The smaller the particles, the further down the respiratory system they can get, causing big problems by way of oxidative stress and an exuberant inflammatory response. Some particles can even trigger apoptosis. Short-term exposure to particle-laden air can cause acute irritation, leading to a cough, while long-term exposure is linked to chronic conditions such as chronic obstructive pulmonary disorder (COPD), heart disease, and cancer.
A study published in Cardiovascular Research on October 26 claims that fine particulate matter has increased the risk of deaths from COVID-19 by 15 percent globally, with certain areas such as East Asia reaching a 27 percent increase. The Scientist talked to Lelieveld to learn more about the relationship between pollution and COVID-19.
Jos Lelieveld COURTESY OF JOS LELIEVELD
TS: Why do these particles leave people more vulnerable to dying from COVID-19?
JL: You have long-term effects [when people are] exposed for basically a lifetime to air pollution and then they develop chronic diseases. . . . These diseases are also preconditions for severe development of COVID-19. . . . Many of the lung diseases like pneumonia, COPD, lung cancer, heart disease, strokes, [are] the sort of thing that are aggravated by air pollution. And these are the sorts of things that also make people die from COVID. A healthy, young subject who has not been developing chronic diseases typically does not die from COVID.
TS: What can someone who lives in a place with more air pollution do to reduce their exposure to these particles?
JL: We write in our paper that there is no remedy like vaccinations for air pollution, so the only remedy here is that you have to clean the air. You have to go to cleaner sources of fuels and cleaner fuels and cleaner energy use. And of course, this also helps the climate. There are many arguments to do this. . . . I’m convinced that climate change is a big problem for this planet. And what I’m hoping is that some of the people who think it’s not an issue [that] carbon dioxide makes the world a bit warmer, maybe I can help convince them by showing that the same sources that create greenhouse gases are also creating pollutants that make you ill.
TS: Can you tell me how you collected your data and designed the study?
JL: We used the data from the paper attached to calculate PM 2.5 exposure-response functions, plus data from China collected for the SARS epidemic in 2003. We tested different types of these functions, leading to the same result. To characterize exposure, we used a combination of satellite data and an atmospheric model, the latter to compute the anthropogenic fraction of PM 2.5 and the contribution of fossil fuel use.
TS: Are there benchmarks of PM 2.5 levels that correspond to low or high risk?
JL: There is a threshold of 2.4 µg/m3 below which the air is considered “clean”, precluding health impacts.
TS: Are there certain fine particles that are worse than others?
JL: There are indications that combustion-related black and organic carbon particles are more toxic than most other particles. But this is not quantitatively known, hence it is common practice to assume that all fine particulates are equally toxic.
TS: How long do fine particles stay with a person after they leave a highly polluted area?
JL: The atmospheric lifetime of aerosol particles is about one week. Once inhaled and deposited in the lungs, the damage is done (much like smoking). The cumulative damage during many years of exposure causes or aggravates chronic cardiopulmonary diseases (much like smoking), which are preconditions that influence the severity of COVID-19 outcomes.
This interview was completed over the phone and via email. It has been edited for clarity and brevity.


thescientist--2020-11-11--Common Cold Coronaviruses Tied to Less Severe COVID-19 Cases

There are four common cold coronaviruses that we all catch at some stage .
We generate antibodies to them , but our immune memory of them fades over time , and we get re-infected .
Their names are all too easily forgotten—OC43 , HKU1 , 229E , and NL63—but our immune systems may nevertheless remember them for a time .
There have been hints that exposure to these common coronaviruses might offer some protection from COVID-19 , mostly by looking at signs of immune memory in blood samples taken from before the pandemic .
A study in the Journal of @ @ @ @ @ @ @ linking recent endemic coronavirus infections to less severe COVID-19 and even a reduced death rate in patients .
The authors at Boston University School of Medicine found evidence for this by poring over the medical records of thousands of patients who had visited Boston Medical Center as inpatients or outpatients , most probably for respiratory illnesses , between 2015 and 2020 .
Each person had been assessed for infection using a PCR test that screens for bacteria and viruses , including the four endemic coronaviruses .
In total , 15,928 patients had at @ @ @ @ @ @ @ them , 875 tested positive for an endemic coronavirus ( this group was called eCoV+ ) , while the remaining 15,053 people never had a documented coronavirus infection ( termed eCoV- ) .
Of the entire cohort , a total of 1,812 ( 11.4 percent ) later returned for a SARS-CoV-2 test during the initial COVID-19 surge in Boston between March 12 and June 12 .
“ Our study is the first to examine people with known endemic coronavirus infections , and compare them to people who , as far as we know @ @ @ @ @ @ @ documented coronavirus infections , ” says Manish Sagar , the lead author of the study and a virologist at Boston Medical Center .
The infection rate for SARS-CoV-2 was no different between those who had a recently recorded endemic coronavirus infection ( eCoV+ ) and those who did not have a positive test ( eCoV- ) .
This led the authors to conclude that a recent infection with endemic coronaviruses did not keep SARS-CoV-2 at bay—both groups were just as likely to become infected with the pandemic virus .
When the researchers peered @ @ @ @ @ @ @ an important difference between the two groups .
“ The COVID-19 disease is actually much less severe in those patients who had documented endemic coronavirus infections , ” says Sagar .
The odds of intensive care unit ( ICU ) admission were significantly lower in eCoV+ than in eCoV- patients , and there was “ a trend towards lower odds of mechanical ventilation , ” the authors write in their report .
The data also show that among hospitalized patients who had previous positive test results for endemic coronavirus , 4.8 percent of @ @ @ @ @ @ @ those in the group without such a test result .
Local immune memory may help explain these results .
Such “ heterotypic immunity , ” says immunologist Joseph Mizgerd , director of the pulmonary center at Boston University School of Medicine , occurs when immune memory is etched into the lungs and/or nose .
It ’ s common after other types of respiratory infections and might offer protection against SARS-CoV-2 if elicited by endemic coronaviruses .
Although the Boston group did not measure this type of immunity in patients , they now hypothesize @ @ @ @ @ @ @ helps limit lung injury during COVID-19 .
“ We are testing that in ongoing experiments , ” Mizgerd says by email .
He adds that such cross-reactive immunity is often mediated by memory T cells , which can localize in the lung , and he notes that lung-localized heterotypic T cells can prevent severe lung infection during pneumonias caused by other types of respiratory pathogens .
If indeed prior infection does ramp up protection against SARS-CoV-2 , the study could not answer how long it takes for any such benefit to taper off @ @ @ @ @ @ @ on which of the four endemic coronaviruses in particular might be offering protection against the pandemic virus .
The scientists are seeking funding to expand their research and include data from other institutions .
Mizgerd and his team did not look into which immune components may be responsible for an endemic coronavirus influencing a person ’ s immune response to SARS-CoV-2 .
This is something that immunologist Dennis Burton at the Scripps Research Institute in La Jolla , California , and his colleagues have investigated .
Since the start of the pandemic , @ @ @ @ @ @ @ immune responses to seasonal coronaviruses could influence antibody responses to SARS-CoV-2 .
In a study published in September as a preprint on bioRxiv , Burton and colleagues compared serum antibodies and antibody-producing B cells from 36 donors sampled prior to the pandemic to see whether those antibodies reacted with the spike protein from the new pandemic virus .
Very few antibodies from before the pandemic reacted to SARS-CoV-2 , the team found .
The vast majority did not bind strongly to the new virus , although they did identify one antibody that could @ @ @ @ @ @ @ memory B cells in blood samples from before the pandemic that were turned on by the presence of SARS-CoV-2 .
This activation triggered them to make antibodies that reacted against some proteins made by SARS-CoV-2 .
“ That would suggest that there is some cross reactivity there , ” says Burton .
A recent Science study reported that 5 percent of 302 adults and 43 percent of 48 children had antibodies that reacted against certain proteins produced by SARS-CoV-2 .
Children are more prone to common cold coronavirus infections , perhaps explaining why @ @ @ @ @ @ @ why they suffer less severe COVID-19 symptoms .
“ We do not know yet if the presence of such antibodies modifies the risk of becoming infected or the severity of disease , ” senior author George Kassiotis at the Francis Crick Institute in London explains by email .
There are conserved parts of the S2 peptide of the spike protein , such as the fusion peptide , in most coronaviruses “ that are targeted by such cross-reactive and potentially cross-protective antibodies , ” Kassiotis notes .
This “ may hold promise for a @ @ @ @ @ @ @ well as future CoVs , ” the authors write in their Science paper .
Kassiotis says that concerns that “ antibody immunity might be short-lived have now been allayed ” by recent studies and adds that even if antibodies fell below detectable levels , “ the cells that made them will still be there and will respond faster and better to re-infection.
” Antibodies and B cells are part of only one aspect of our immune memory to viruses .
Multiple investigations since the beginning of the pandemic have suggested that between 20 @ @ @ @ @ @ @ had never encountered SARS-CoV-2 had T cells that nevertheless seemed to react against peptides from this virus , as noted recently in a Science paper .
In another study in Nature , researchers in Singapore identified memory T cells in patients who had recovered from SARS back in 2003 .
These were reactive to proteins from SARS-CoV-2 , supporting the idea that T cell memory from infections with human coronaviruses may play a role in the response to an infection with the new pandemic virus .
An additional study recently published in Science @ @ @ @ @ @ @ pandemic to locate parts of SARS-CoV-2 that stimulated existing T cells .
The study found a range of memory T cells that could react to both the new virus but also to the four common cold coronaviruses , again suggesting that existing T cells against common coronaviruses could play a role in the immune response to SARS-CoV-2 in some patients .
Immunologist Stanley Perlman of the University of Iowa who was not involved in any of these studies says that “ everybody should have memory B cells against common cold coronaviruses.
” We @ @ @ @ @ @ @ remember these viruses and perhaps help with fighting SAR-CoV-2 .
However , Perlman emphasized that the implications of this for COVID-19 “ is still a work in progress.
” Burton says he hopes to dig into a molecular understanding of the cross-reactivity of antibodies , which might help design a vaccine against not just SARS-CoV-2 , but common cold coronaviruses too .
These viruses usually cause mild symptoms , but not always .
“ A cross-protective vaccine that protects against SARS-CoV-2 plus the endemic coronaviruses would be a really great boon , ” @ @ @ @ @ @ @ causes of the common cold , but they are also really important causes of pneumonia , pneumonia hospitalizations , and pneumonia deaths .
”

ABOVE: Coronavirus OC43
DR. ERSKINE PALMER, CDC
There are four common cold coronaviruses that we all catch at some stage. We generate antibodies to them, but our immune memory of them fades over time, and we get re-infected.
Their names are all too easily forgotten—OC43, HKU1, 229E, and NL63—but our immune systems may nevertheless remember them for a time. There have been hints that exposure to these common coronaviruses might offer some protection from COVID-19, mostly by looking at signs of immune memory in blood samples taken from before the pandemic. A study in the Journal of Clinical Investigation reports the first clinical evidence linking recent endemic coronavirus infections to less severe COVID-19 and even a reduced death rate in patients.
“The COVID-19 disease is actually much less severe in those patients who had documented endemic coronavirus infections.” —Manish Sagar, Boston Medical Center
The authors at Boston University School of Medicine found evidence for this by poring over the medical records of thousands of patients who had visited Boston Medical Center as inpatients or outpatients, most probably for respiratory illnesses, between 2015 and 2020. Each person had been assessed for infection using a PCR test that screens for bacteria and viruses, including the four endemic coronaviruses.
In total, 15,928 patients had at least one such PCR test. Of them, 875 tested positive for an endemic coronavirus (this group was called eCoV+), while the remaining 15,053 people never had a documented coronavirus infection (termed eCoV-).
Of the entire cohort, a total of 1,812 (11.4 percent) later returned for a SARS-CoV-2 test during the initial COVID-19 surge in Boston between March 12 and June 12.
“Our study is the first to examine people with known endemic coronavirus infections, and compare them to people who, as far as we know, don’t have any recent documented coronavirus infections,” says Manish Sagar, the lead author of the study and a virologist at Boston Medical Center.
The infection rate for SARS-CoV-2 was no different between those who had a recently recorded endemic coronavirus infection (eCoV+) and those who did not have a positive test (eCoV-). This led the authors to conclude that a recent infection with endemic coronaviruses did not keep SARS-CoV-2 at bay—both groups were just as likely to become infected with the pandemic virus.
When the researchers peered closer at the data, they observed an important difference between the two groups. “The COVID-19 disease is actually much less severe in those patients who had documented endemic coronavirus infections,” says Sagar. The odds of intensive care unit (ICU) admission were significantly lower in eCoV+ than in eCoV- patients, and there was “a trend towards lower odds of mechanical ventilation,” the authors write in their report.
The data also show that among hospitalized patients who had previous positive test results for endemic coronavirus, 4.8 percent of them died compared with 17.7 percent among those in the group without such a test result.
Local immune memory may help explain these results. Such “heterotypic immunity,” says immunologist Joseph Mizgerd, director of the pulmonary center at Boston University School of Medicine, occurs when immune memory is etched into the lungs and/or nose. It’s common after other types of respiratory infections and might offer protection against SARS-CoV-2 if elicited by endemic coronaviruses. Although the Boston group did not measure this type of immunity in patients, they now hypothesize that local immunity gained from endemic coronaviruses helps limit lung injury during COVID-19. “We are testing that in ongoing experiments,” Mizgerd says by email. He adds that such cross-reactive immunity is often mediated by memory T cells, which can localize in the lung, and he notes that lung-localized heterotypic T cells can prevent severe lung infection during pneumonias caused by other types of respiratory pathogens.
If indeed prior infection does ramp up protection against SARS-CoV-2, the study could not answer how long it takes for any such benefit to taper off. Nor did the work shed light on which of the four endemic coronaviruses in particular might be offering protection against the pandemic virus. The scientists are seeking funding to expand their research and include data from other institutions.
Mizgerd and his team did not look into which immune components may be responsible for an endemic coronavirus influencing a person’s immune response to SARS-CoV-2. This is something that immunologist Dennis Burton at the Scripps Research Institute in La Jolla, California, and his colleagues have investigated.
Since the start of the pandemic, they have been interested in whether pre-existing immune responses to seasonal coronaviruses could influence antibody responses to SARS-CoV-2. In a study published in September as a preprint on bioRxiv, Burton and colleagues compared serum antibodies and antibody-producing B cells from 36 donors sampled prior to the pandemic to see whether those antibodies reacted with the spike protein from the new pandemic virus. Very few antibodies from before the pandemic reacted to SARS-CoV-2, the team found. The vast majority did not bind strongly to the new virus, although they did identify one antibody that could neutralize SARS-CoV-2.
The group also detected memory B cells in blood samples from before the pandemic that were turned on by the presence of SARS-CoV-2. This activation triggered them to make antibodies that reacted against some proteins made by SARS-CoV-2. “That would suggest that there is some cross reactivity there,” says Burton.
“A cross-protective vaccine that protects against SARS-CoV-2 plus the endemic coronaviruses would be a really great boon.” —Manish Sagar, Boston Medical Center
A recent Science study reported that 5 percent of 302 adults and 43 percent of 48 children had antibodies that reacted against certain proteins produced by SARS-CoV-2. Children are more prone to common cold coronavirus infections, perhaps explaining why they might harbor such antibodies, and why they suffer less severe COVID-19 symptoms.
“We do not know yet if the presence of such antibodies modifies the risk of becoming infected or the severity of disease,” senior author George Kassiotis at the Francis Crick Institute in London explains by email. There are conserved parts of the S2 peptide of the spike protein, such as the fusion peptide, in most coronaviruses “that are targeted by such cross-reactive and potentially cross-protective antibodies,” Kassiotis notes. This “may hold promise for a universal vaccine protecting against current, as well as future CoVs,” the authors write in their Science paper.
Kassiotis says that concerns that “antibody immunity might be short-lived have now been allayed” by recent studies and adds that even if antibodies fell below detectable levels, “the cells that made them will still be there and will respond faster and better to re-infection.”
Antibodies and B cells are part of only one aspect of our immune memory to viruses. Multiple investigations since the beginning of the pandemic have suggested that between 20 percent and 50 percent of people who had never encountered SARS-CoV-2 had T cells that nevertheless seemed to react against peptides from this virus, as noted recently in a Science paper.
In another study in Nature, researchers in Singapore identified memory T cells in patients who had recovered from SARS back in 2003. These were reactive to proteins from SARS-CoV-2, supporting the idea that T cell memory from infections with human coronaviruses may play a role in the response to an infection with the new pandemic virus.
An additional study recently published in Science used human blood samples from before the pandemic to locate parts of SARS-CoV-2 that stimulated existing T cells. The study found a range of memory T cells that could react to both the new virus and to the four common cold coronaviruses, again suggesting that existing T cells against common coronaviruses could play a role in the immune response to SARS-CoV-2 in some patients.
Immunologist Stanley Perlman of the University of Iowa who was not involved in any of these studies says that “everybody should have memory B cells against common cold coronaviruses.” We may also have memory T cells that remember these viruses and perhaps help with fighting SAR-CoV-2. However, Perlman emphasized that the implication of this for COVID-19 “is still a work in progress.”
Burton says he hopes to dig into a molecular understanding of the cross-reactivity of antibodies, which might help design a vaccine against not just SARS-CoV-2, but common cold coronaviruses too. These viruses usually cause mild symptoms, but not always.
“A cross-protective vaccine that protects against SARS-CoV-2 plus the endemic coronaviruses would be a really great boon,” says Sagar. “These coronaviruses are causes of the common cold, but they are also really important causes of pneumonia, pneumonia hospitalizations, and pneumonia deaths.”


thescientist--2020-11-11--Concerns over Efficacy and Cost of Muscle Wasting Treatments

The US Food and Drug Administration recently approved two drugs that target the genetic error underlying spinal muscular atrophy ( SMA ) , a muscle-wasting disorder , often fatal before the age of two , that was previously untreatable .
The treatments—Zolgensma from Novartis Gene Therapies and Spinraza from Biogen—come with hefty price tags , yet a report in Science Translational Medicine today ( November 11 ) argues that they offer only modest benefits with possible health risks , leaving patients with unmet medical needs and possibly with substantial healthcare bills .
“ This paper highlights the complexity of developing @ @ @ @ @ @ @ those treatments , ” health policy researcher Stacie Dusetzina of Vanderbilt University who was not involved in the research writes in an email to The Scientist .
“ The review of outcomes for SMA treatments are particularly sobering , with small but meaningful gains in motor response outcomes for some infants with SMA .
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but a long list of possible side effects and poor prognosis for many others .
This makes the price very challenging.
” Spinal muscular atrophy , in which mutation of a protein called SMN causes loss of @ @ @ @ @ @ @ affects approximately 500 newborns in the US each year .
The condition is often fatal before the age of two and , until recently , there were no drug treatments .
In 2017 , the FDA approved the drug Spinraza , an antisense oligonucleotide that promotes correct splicing of an SMN-encoding RNA to increase production of the protein .
The drug , which is injected into the spinal canal , costs $ 125,000 dollars per treatment .
With the injection being repeated every four months for life , and assuming the child ’ @ @ @ @ @ @ @ indicate , the cost can quickly run into millions .
See “ FDA Approves First Treatment for Spinal Muscular Atrophy ” In 2019 , the FDA approved Zolgensma , a gene therapy that provides a functional copy via viral vector of the gene encoding SMN .
The one-time treatment , an intravenous infusion , costs $ 2,125,000—the most expensive single treatment ever .
These high prices prompted Jonathan Darrow , a bioethicist at Harvard Medical School , and colleagues to thoroughly investigate the treatments ’ benefits and risks .
( The team did @ @ @ @ @ @ @ risplidam , approved by the FDA this August . )
The authors ’ analysis of trial data and FDA reports show that the administration ’ s approval of Spinraza was granted on the basis of a Phase 3 , placebo-controlled trial involving 78 infants with SMA .
In that trial , 41 percent of the 51 Spinraza-treated infants showed marginal improvements in motor function , compared with no improvements in the placebo group .
This means 59 percent of treated patients showed no improvement , the authors point out .
Additional trials completed @ @ @ @ @ @ @ showed similarly marginal improvements in some treated patients , the authors say .
Darrow and his coauthors also question Zolgensma ’ s efficacy , largely because the FDA ’ s approval of this treatment was based on just 15 patients in an open-label Phase 1 trial .
While treated patients showed improvements , most did not reach the motor milestones of healthy infants .
The authors additionally point to potential safety concerns with the two treatments , including toxicity and infection risk ( because of repeated injections ) in the case of Spinraza @ @ @ @ @ @ @ may indicate inflammation or damage , in the case of Zolgensma .
“ The paper nicely summarizes .
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the inadequacies of the studies ” that supported the drugs ’ approval , says health policy researcher James Chambers of Tufts University who was not involved in the study .
“ It emphasizes that the FDA , not inappropriately , approved these products based upon evidence that healthcare payers would argue maybe is insufficient to really prove that the product works.
” But , he adds , performing the large-scale clinical trials for @ @ @ @ @ @ @ are so few patients .
Chambers also points out that these “ are very important therapies ” and that while the clinical improvements might seem small , “ [ they ] can be huge for a patient who can still maintain some sort of quality of life .
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Those marginal health benefits can be life-changing.
” For a disease where previously a parent could only watch as their child got sicker and died , “ [ Zolgensma ] is a breakthrough , ” writes Jerry Mendell of Nationwide Children ’ @ @ @ @ @ @ @ Scientist .
Mendell studies neuromuscular disorders and was part of the team running the original Zolgensma trial .
He also rebukes Darrow and colleagues ’ safety concerns , saying Zolgensma “ is very safe .
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Risk-benefit is not even close to being an issue.
” Regarding Zolgensma ’ s price tag , he writes , “ the cost is not a factor when it comes to saving lives.
” In justification of Zolgensma ’ s cost , a spokesperson from Novartis Gene Therapies writes in an email to The Scientist @ @ @ @ @ @ @ delivers transformative benefit without the need for add-on therapy .
Gene therapies such as Zolgensma have the potential to reduce the long-term financial burden on patients , families , and the overall healthcare systems by replacing repeat , lifelong therapies with a single treatment.
” And , in justification of Spinraza ’ s price , a Biogen representative writes that “ the prices of our medicines reflect the unique advancements that they bring to patient treatment .
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.
.
SPINRAZA is a major therapeutic advance that can change the course of SMA @ @ @ @ @ @ @ of those affected by the disease , as well as reducing the burden on healthcare systems.
” But , the promise of reduced burdens on healthcare systems and reduced need for further treatment “ isn ’ t guaranteed , ” Dusetzina says .
“ In many cases , we also have these drugs available without understanding the long-term effects .
How long will they work ?
Will the patient need to be treated again in the future ?
” Indeed , some patients that received Zolgensma treatment were later started on Spinraza , @ @ @ @ @ @ @ for Clinical and Economic Review ( ICER ) , possibly “ because their health state started to deteriorate or because they did not improve as much as desired.
” Because “ we allow manufactures to set a price [ for a drug ] unrelated to cost effectiveness .
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our current system of paying for drugs is broken , ” says Marc Rodwin of Suffolk University in Boston who studies health law and politics and was not involved in the report .
The problem is largely a US-specific one , he explains @ @ @ @ @ @ @ such as National Institute for Health and Care Excellence ( NICE ) in the UK and the Transparency Committee in France assess a treatment ’ s cost-effectiveness and negotiate more reasonable prices with drug companies .
But in the US , while ICER informs insurance companies on cost-effectiveness of drugs , it has no regulatory power , explains Darrow .
To establish an administrative body with such power would require significant legislative reform , he says .
Treatments for rare disease , so-called orphan drugs , are always likely to be expensive , @ @ @ @ @ @ @ prices would be unprofitable .
But the “ premiums for health insurance can not just continue to climb to cover these costs , ” Dusetzina says .
“ At some point we have to acknowledge that we are making tradeoffs and decide if we could make better decisions about how much we pay so that we can make sure that we balance innovation and affordability.
” J.J. Darrow et al.
, “ Efficacy and costs of spinal muscular atrophy drugs , ” Sci Transl Med , 12 : eaay9648 , 2020 .

ABOVE: ©ISTOCK, JOHNNYGREIG
The US Food and Drug Administration recently approved two drugs that target the genetic error underlying spinal muscular atrophy (SMA), a muscle-wasting disorder, often fatal before the age of two, that was previously untreatable. The treatments—Zolgensma from Novartis Gene Therapies and Spinraza from Biogen—come with hefty price tags, yet a report in Science Translational Medicine today (November 11) argues that they offer only modest benefits with possible health risks, leaving patients with unmet medical needs and possibly with substantial healthcare bills.
“This paper highlights the complexity of developing treatments for rare diseases and paying for those treatments,” health policy researcher Stacie Dusetzina of Vanderbilt University who was not involved in the research writes in an email to The Scientist. “The review of outcomes for SMA treatments are particularly sobering, with small but meaningful gains in motor response outcomes for some infants with SMA . . . but a long list of possible side effects and poor prognosis for many others. This makes the price very challenging.”
Spinal muscular atrophy, in which mutation of a protein called SMN causes loss of motor neurons and consequent muscle wasting, affects approximately 500 newborns in the US each year. The condition is often fatal before the age of two and, until recently, there were no drug treatments.
In 2017, the FDA approved the drug Spinraza, an antisense oligonucleotide that promotes correct splicing of an SMN-encoding RNA to increase production of the protein. The drug, which is injected into the spinal canal, costs $125,000 dollars per treatment. With the injection being repeated every four months for life, and assuming the child’s survival is prolonged as trial results indicate, the cost can quickly run into millions.
See “FDA Approves First Treatment for Spinal Muscular Atrophy”
In 2019, the FDA approved Zolgensma, a gene therapy that provides a functional copy via viral vector of the gene encoding SMN. The one-time treatment, an intravenous infusion, costs $2,125,000—the most expensive single treatment ever.
See “FDA Approves Gene Therapy for Spinal Muscular Atrophy”
These high prices prompted Jonathan Darrow, a bioethicist at Harvard Medical School, and colleagues to thoroughly investigate the treatments’ benefits and risks. (The team did not assess the new oral SMA drug risplidam, approved by the FDA this August.)
The authors’ analysis of trial data and FDA reports show that the administration’s approval of Spinraza was granted on the basis of a Phase 3, placebo-controlled trial involving 78 infants with SMA. In that trial, 41 percent of the 51 Spinraza-treated infants showed marginal improvements in motor function, compared with no improvements in the placebo group. This means 59 percent of treated patients showed no improvement, the authors point out. Additional trials completed after the FDA’s approval have showed similarly marginal improvements in some treated patients, the authors say.
Darrow and his coauthors also question Zolgensma’s efficacy, largely because the FDA’s approval of this treatment was based on just 15 patients in an open-label Phase 1 trial. While treated patients showed improvements, most did not reach the motor milestones of healthy infants.
The authors additionally point to potential safety concerns with the two treatments, including toxicity and infection risk (because of repeated injections) in the case of Spinraza, and elevated liver enzymes, which may indicate inflammation or damage, in the case of Zolgensma.
“The paper nicely summarizes. . . the inadequacies of the studies” that supported the drugs’ approval, says health policy researcher James Chambers of Tufts University who was not involved in the study. “It emphasizes that the FDA, not inappropriately, approved these products based upon evidence that healthcare payers would argue maybe is insufficient to really prove that the product works.” But, he adds, performing the large-scale clinical trials for any rare disease is tricky because there are so few patients.
See “Gene Therapy Finds a Fertile Home in Ohio”
Chambers also points out that these “are very important therapies” and that while the clinical improvements might seem small, “[they] can be huge for a patient who can still maintain some sort of quality of life. . . . Those marginal health benefits can be life-changing.”
For a disease where previously a parent could only watch as their child got sicker and died, “[Zolgensma] is a breakthrough,” writes Jerry Mendell of Nationwide Children’s Hospital in an email to The Scientist. Mendell studies neuromuscular disorders and was part of the team running the original Zolgensma trial. He also rebukes Darrow and colleagues’ safety concerns, saying Zolgensma “is very safe. . . . Risk-benefit is not even close to being an issue.” Regarding Zolgensma’s price tag, he writes, “the cost is not a factor when it comes to saving lives.”
In justification of Zolgensma’s cost, a spokesperson from Novartis Gene Therapies writes in an email to The Scientist, “All available data demonstrate Zolgensma delivers transformative benefit without the need for add-on therapy. Gene therapies such as Zolgensma have the potential to reduce the long-term financial burden on patients, families, and the overall healthcare systems by replacing repeat, lifelong therapies with a single treatment.”
And, in justification of Spinraza’s price, a Biogen representative writes that “the prices of our medicines reflect the unique advancements that they bring to patient treatment. . . . SPINRAZA is a major therapeutic advance that can change the course of SMA and offer meaningful improvements to the lives of those affected by the disease, as well as reducing the burden on healthcare systems.”
But, the promise of reduced burdens on healthcare systems and reduced need for further treatment “isn’t guaranteed,” Dusetzina says. “In many cases, we also have these drugs available without understanding the long-term effects. How long will they work? Will the patient need to be treated again in the future?”
Indeed, some patients that received Zolgensma treatment were later started on Spinraza, according to a report by the Institute for Clinical and Economic Review (ICER), possibly “because their health state started to deteriorate or because they did not improve as much as desired.”
Because “we allow manufactures to set a price [for a drug] unrelated to cost effectiveness. . . our current system of paying for drugs is broken,” says Marc Rodwin of Suffolk University in Boston who studies health law and politics and was not involved in the report.
The problem is largely a US-specific one, he explains. In other countries, regulatory bodies such as National Institute for Health and Care Excellence (NICE) in the UK and the Transparency Committee in France assess a treatment’s cost-effectiveness and negotiate more reasonable prices with drug companies. But in the US, while ICER informs insurance companies on cost-effectiveness of drugs, it has no regulatory power, explains Darrow. To establish an administrative body with such power would require significant legislative reform, he says.
Treatments for rare disease, so-called orphan drugs, are always likely to be expensive, because with limited numbers of patients low prices would be unprofitable. But the “premiums for health insurance cannot just continue to climb to cover these costs,” Dusetzina says. “At some point we have to acknowledge that we are making tradeoffs and decide if we could make better decisions about how much we pay so that we can make sure that we balance innovation and affordability.”
J.J. Darrow et al., “Efficacy and costs of spinal muscular atrophy drugs,” Sci Transl Med, 12:eaay9648, 2020.


Biobanking Best Practices

Researchers often use biobanks to store human specimens of clinical relevance .
While the long-term storage and organization of biological @ @ @ @ @ , biobanking is necessary for many research and clinical applications .
Download this ebook from @ @ @ @ @ about • Using biobanking to further cancer research • How biobanks are instrumental to COVID-19 @ @

Researchers often use biobanks to store human specimens of clinical relevance. While the long-term storage and organization of biological samples is a complicated endeavor, biobanking is necessary for many research and clinical applications.
Download this ebook from Thermo Fisher Scientific to learn about


thescientist--2020-11-11--Beyond Acute Respiration: SARS-CoV-2's Effects on Long-Term Physiology

While primarily a respiratory ailment , COVID-19 also influences other major physiological systems .
In particular , growing evidence shows @ @ @ @ @ effects on cardiovascular and neurological health .
In this webinar from The Scientist , John @ @ @ @ @ discuss SARS-CoV-2 's relationship with the cardiovascular and neurological systems and how these effects influence @ @ @ @ @ Assessment of persistent cognitive dysfunction as a first step in treatment decisions for COVID-19 • @ @ @ @ @ from basic mechanisms to clinical perspectives

FREE Webinar
Tuesday, December 15, 2020
2:30 - 4:00 PM, Eastern Standard Time
Register Now
While primarily a respiratory ailment, COVID-19 also influences other major physiological systems. In particular, growing evidence shows that SARS-CoV-2 infection has pronounced effects on cardiovascular and neurological health. In this webinar from The Scientist, John Connolly and Masataka Nishiga will discuss SARS-CoV-2's relationship with the cardiovascular and neurological systems and how these effects influence diagnosis and treatment.
Topics to be covered
Assessment of persistent cognitive dysfunction as a first step in treatment decisions for COVID-19
COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives
Register Now
Meet the Speakers:
John Connolly, PhD
Professor and Director
ARiEAL Research Centre
McMaster University
Masataka Nishiga, MD, PhD
Postdoctoral Research Fellow
Joseph Wu Laboratory
Cardiovascular Institute
Stanford University School of Medicine


thescientist--2020-11-12--ENZO LAUNCHES PORTABLE MICROPLATE READER FOR USE WITH ITS ELISA AND ASSAY KITS TO SIMPLIFY LABORATOR

ENZO LAUNCHES PORTABLE MICROPLATE READER FOR USE WITH ITS ELISA AND ASSAY KITS TO SIMPLIFY LABORATORY WORKFLOW

Enzo Biochem , Inc. ( NYSE : ENZ ) , a leading biosciences and diagnostics company , announced today the commercial launch of a small portable microplate reader for use with the company ’ s immunoassays and , ultimately , molecular diagnostics , providing new opportunities in point-of-care medicine .
This affordable device enables Enzo to offer a complete solution to academic , CRO , and industrial customers .
Enzo is the provider of over 17,000 ELISA ( enzyme-linked immunosorbent assay ) and assay kits , including hundreds of highly sensitive ELISAs it manufactures .
The advanced design and technology @ @ @ @ @ @ @ makes it possible to deliver precise and accurate results .
Together with Enzo ’ s proprietary software , the device is an option for a wide variety of applications based on the miniaturization of Enzo ’ s assays .
These tests include metabolites , hormones ( e.g .
pregnancy ) , proteins ( e.g .
inflammatory cytokines ) and protein characterization .
With support from an instrument manufacturing company , the Enzo portable reader enables lab work to be executed outside of traditional research facilities ( that rely on shared instrumentation ) .
@ @ @ @ @ @ @ have a dedicated , personal device to fit their space and needs with convenience and accessibility not previously available .
The handheld instrument is about one-tenth the size of the average benchtop plate reader , allowing it to fit into any laboratory setting and saving bench space while providing new levels of flexibility and portability that can be extended to point-of-care facilities to allow physicians to provide molecular testing including assays for viral detection and sexually transmitted diseases .
The compact solid-state technology enables utilization of this instrument in new locations .
With @ @ @ @ @ @ @ from centralized , complex clinical labs closer to patient care .
It simplifies testing procedures and opens up the opportunity to shift testing out of the hands of licensed medical technicians to healthcare professionals operating nearer to patients or , in some instances , even to patients themselves .
“ Access to point-of-care testing continues to grow as technological advances in clinical diagnostic testing drive miniaturization of complex devices .
Now , just as computers moved from mainframes to powerful , portable handheld devices , the same is happening within the clinical diagnostic @ @ @ @ @ @ @ high quality and precise testing capabilities to be available to a broader range of healthcare professionals involved in patient management whether they are sitting at an urgent care facility , a doctor ’ s office or hospital bedside , ” said Kara Cannon , Chief Commercial Officer of Enzo .
“ The point-of-care testing market , currently valued at over $ 18B globally , has the potential to aggressively expand to many testing needs that are now not widely available at point-of-care , including a significant portion of the $ 15B immunoassay testing @ @ @ @ @ @ @ “ Common clinical immunoassay tests , such as vitamin D testing and inflammation analysis , currently are performed regularly in the clinical central testing lab by licensed medical technologists using large , complex instrumentation .
Unlike lateral flow assays , this small yet powerful system does not sacrifice sensitivity for convenience and allows for multi-assay capabilities.
” “ Enzo ’ s corporate vision addresses new opportunities for expansion and growth within both products and services , ” added Ms. Cannon .
“ We are serving markets including laboratories , point-of-care , and direct-to-consumer @ @ @ @ @ @ @ step in extending our offerings beyond the central laboratory , enabling physicians to provide clinical testing at their office , urgent care facility , or other treatment center.
” In the future , Enzo anticipates launching isothermal testing on this platform , enabling constant temperature and eliminating the need for a thermal cycle .

Enzo Biochem, Inc. (NYSE:ENZ), a leading biosciences and diagnostics company, announced today the commercial launch of a small portable microplate reader for use with the company’s immunoassays and, ultimately, molecular diagnostics, providing new opportunities in point-of-care medicine. This affordable device enables Enzo to offer a complete solution to academic, CRO, and industrial customers.
Enzo is the provider of over 17,000 ELISA (enzyme-linked immunosorbent assay) and assay kits, including hundreds of highly sensitive ELISAs it manufactures. The advanced design and technology of Enzo’s compact microplate reader makes it possible to deliver precise and accurate results. Together with Enzo’s proprietary software, the device is an option for a wide variety of applications based on the miniaturization of Enzo’s assays. These tests include metabolites, hormones (e.g. pregnancy), proteins (e.g. inflammatory cytokines) and protein characterization.
With support from an instrument manufacturing company, the Enzo portable reader enables lab work to be executed outside of traditional research facilities (that rely on shared instrumentation). Now, researchers and lab professionals can have a dedicated, personal device to fit their space and needs with convenience and accessibility not previously available. The handheld instrument is about one-tenth the size of the average benchtop plate reader, allowing it to fit into any laboratory setting and saving bench space while providing new levels of flexibility and portability that can be extended to point-of-care facilities to allow physicians to provide molecular testing including assays for viral detection and sexually transmitted diseases.
The compact solid-state technology enables utilization of this instrument in new locations. With this technology, point-of-care testing can move from centralized, complex clinical labs closer to patient care. It simplifies testing procedures and opens up the opportunity to shift testing out of the hands of licensed medical technicians to healthcare professionals operating nearer to patients or, in some instances, even to patients themselves.
“Access to point-of-care testing continues to grow as technological advances in clinical diagnostic testing drive miniaturization of complex devices. Now, just as computers moved from mainframes to powerful, portable handheld devices, the same is happening within the clinical diagnostic testing industry. This reduced complexity provides high quality and precise testing capabilities to be available to a broader range of healthcare professionals involved in patient management whether they are sitting at an urgent care facility, a doctor’s office or hospital bedside,” said Kara Cannon, Chief Commercial Officer of Enzo.
“The point-of-care testing market, currently valued at over $18B globally, has the potential to aggressively expand to many testing needs that are now not widely available at point-of-care, including a significant portion of the $15B immunoassay testing market,” added Ms. Cannon. “Common clinical immunoassay tests, such as vitamin D testing and inflammation analysis, currently are performed regularly in the clinical central testing lab by licensed medical technologists using large, complex instrumentation. Unlike lateral flow assays, this small yet powerful system does not sacrifice sensitivity for convenience and allows for multi-assay capabilities.”
“Enzo’s corporate vision addresses new opportunities for expansion and growth within both products and services,” added Ms. Cannon. “We are serving markets including laboratories, point-of-care, and direct-to-consumer. This market launch is an important step in extending our offerings beyond the central laboratory, enabling physicians to provide clinical testing at their office, urgent care facility, or other treatment center.”
In the future, Enzo anticipates launching isothermal testing on this platform, enabling constant temperature and eliminating the need for a thermal cycle.


thescientist--2020-11-12--Jet-printing microfluidic devices on demand

This innovative protocol offers significant benefits to biology and biomedicine , enabling simple , contactless fabrication of microfluidic circuits in minutes – almost as quickly as the circuit pattern can be drawn on paper – using truly cell-friendly materials ; standard Petri dishes and culture media .
The pioneering jet-printing method stems from the recognition that gravity becomes irrelevant at the microscale .
In the everyday world , objects are invariably made with solids ; building complex structures out of liquids , which would collapse into puddles and drain away , is not feasible .
Using microjets to fabricate microfluidic @ @ @ @ @ @ @ that dominate in the microworld .
In this paper , the method was used to successfully clone cells by limiting dilution in a way that beats the Poisson limit , to subculture adherent cells , and to feed arrays of cells continuously for a week in sub-microliter chambers .
Liquid flows were driven through conduits with and without external pumps , and circuits reconfigured to open and close ‘ fluidic valves ’ at will .
The diversity and flexibility of this approach is expected to lead to widespread adoption of the technique for @ @ @ @ @ @ @

This innovative protocol offers significant benefits to biology and biomedicine, enabling simple, contactless fabrication of microfluidic circuits in minutes – almost as quickly as the circuit pattern can be drawn on paper – using truly cell-friendly materials; standard Petri dishes and culture media.
The pioneering jet-printing method stems from the recognition that gravity becomes irrelevant at the microscale. In the everyday world, objects are invariably made with solids; building complex structures out of liquids, which would collapse into puddles and drain away, is not feasible. Using microjets to fabricate microfluidic devices takes advantage of the interfacial forces that dominate in the microworld. In this paper, the method was used to successfully clone cells by limiting dilution in a way that beats the Poisson limit, to subculture adherent cells, and to feed arrays of cells continuously for a week in sub-microliter chambers. Liquid flows were driven through conduits with and without external pumps, and circuits reconfigured to open and close ‘fluidic valves’ at will. The diversity and flexibility of this approach is expected to lead to widespread adoption of the technique for a variety of applications in biomedicine.


thescientist--2020-11-12--Slideshow: Solving A Gray Whale Murder Mystery

ABOVE : Researchers investigate the death of a gray whale that washed up at Angel Island State Park , California , in the spring of 2019 .
CARA FIELD / © THE MARINE MAMMAL CENTER UNDER NOAA FISHERIES MARINE MAMMAL HEALTH AND STRANDING RESPONSE PROGRAM PERMIT 18786-03 More than 360 gray whales have washed ashore in less than two years , leading researchers to ask what might be causing their demise .
Autopsying the dead animals and watching live whales on their migration routes suggest that there may not be a single culprit .
Instead , a combination of interacting @ @ @ @ @ @ @ in fishing gear , killer whale attacks , a balloon in population , and climate change , may be causing the uptick in gray whale deaths .
This stranded dead gray whale washed ashore in early April 2019 at Leadbetter Point State Park in Washington State .
After a necropsy , scientists concluded that it was unusually thin .
Researchers are still trying to determine why many of the whales that have shown up on a beach appear to be underweight .
Data on the whales doesn ’ t only come from dead @ @ @ @ @ @ @ whales gives clues to their health , too .
If a whale has a significant dip behind its head ( top ) , scientists think the whale is skinny and in poor health , but if there is no dip ( bottom ) , the whale is considered healthy .
THE LAGUNA SAN IGNACIO ECOSYSTEM SCIENCE PROGRAM , A PROJECT OF THE OCEAN FOUNDATION Counting the cow-calf pairs helps researchers track and estimate the overall population of gray whales as they migrate from the waters off the west coast of Mexico to the @ @ @ @ @

ABOVE: Researchers investigate the death of a gray whale that washed up at Angel Island State Park, California, in the spring of 2019.
CARA FIELD / © THE MARINE MAMMAL CENTER UNDER NOAA FISHERIES MARINE MAMMAL HEALTH AND STRANDING RESPONSE PROGRAM PERMIT 18786-03
More than 360 gray whales have washed ashore in less than two years, leading researchers to ask what might be causing their demise. Autopsying the dead animals and watching live whales on their migration routes suggest that there may not be a single culprit. Instead, a combination of interacting factors, including ship strikes, entanglement in fishing gear, killer whale attacks, a balloon in population, and climate change, may be causing the uptick in gray whale deaths.
Read the full story.
This stranded dead gray whale washed ashore in early April 2019 at Leadbetter Point State Park in Washington State. After a necropsy, scientists concluded that it was unusually thin. Researchers are still trying to determine why many of the whales that have shown up on a beach appear to be underweight. JOHN WELDON, NORTHERN OREGON/SOUTHERN WASHINGTON MARINE MAMMAL STRANDING PROGRAM UNDER NOAA FISHERIES MARINE MAMMAL HEALTH AND STRANDING RESPONSE PROGRAM PERMIT 18786-03
A necropsy of this gray whale stranded near Long Beach, Washington, showed that it, too, was skinny and malnourished. JOHN WELDON, PORTLAND STATE UNIVERSITY NORTHWEST OREGON/SOUTHERN WASHINGTON MARINE MAMMAL STRANDING PROGRAM UNDER NOAA FISHERIES MARINE MAMMAL HEALTH AND STRANDING RESPONSE PROGRAM PERMIT 18786-03
In April 2019, this female gray whale washed ashore at California’s Point Reyes National Seashore, and researchers were there to investigate. BARBIE HALASKA, THE MARINE MAMMAL CENTER
Data on the whales doesn’t only come from dead animals. The anatomy of the living whales gives clues to their health, too. If a whale has a significant dip behind its head (top), scientists think the whale is skinny and in poor health, but if there is no dip (bottom), the whale is considered healthy. THE LAGUNA SAN IGNACIO ECOSYSTEM SCIENCE PROGRAM, A PROJECT OF THE OCEAN FOUNDATION
At the Piedras Blancas field station near San Simeon, California, a team of scientists uses high-powered binoculars to scan for gray whale cows and their calves. NOAA FISHERIES


thescientist--2020-11-12--Q&A: A New Tool for Ensuring Genetic Privacy

The appetite for data on individuals ’ genetic sequences is growing , both from consumers—the number of testing kits sold by leading companies such as 23andMe and Ancestry.com topped 26 million by the start of 2019—and from scientists looking to amass large datasets for medical research .
In addition to whole genome sequencing and genotyping , in which scientists identify a person ’ s genetic variants , new functional genomics tools such as RNA-seq , ChIP-seq , and single-cell sequencing have led to an exploding number of tests detailing how people ( and their individual cells ) respond to environmental @ @ @ @ @ @ @ But as more and more people volunteer their information , the seemingly anonymized data that results from such tests is becoming a target for hackers looking to glean sensitive medical information .
In particular , the many genetic variants that make each person unique can be used to identify them as surely as a fingerprint , revealing confidential information such as their disease status .
In a process known as a linkage attack , a hacker can use known information about a person from sources such as public records or even discarded objects @ @ @ @ @ @ @ to identify them within an anonymous database compiled by academic researchers .
For example , if someone were to participate anonymously in an AIDS study , it might be possible to uncover their participation—and thus their HIV status—using DNA sequenced from a cigarette .
Bioinformaticians and data scientists are therefore working to develop new ways of storing and analyzing data that protect anonymity while still allowing for the type of collaborative sharing necessary to advance medical science .
The Scientist spoke to Gamze Gursoy and Mark Gerstein , two bioinformaticians at the Yale @ @ @ @ @ @ @ information can be gleaned from genomic data and ways of balancing privacy with utility .
Their paper , published today ( November 12 ) in Cell , details a new method for sanitizing , or removing sensitive information from , functional genomics datasets by separating out identifying variants in a way that does not affect data quality .
See “ Technique to Track Golden State Killer Suspect Could Find You Too ” The Scientist : We hear a lot about genetic privacy in the context of things like 23andMe and Ancestry.com results , @ @ @ @ @ @ @ this paper is a different type of data .
What sets functional genomics apart from something like DNA sequencing or genotyping ?
Gamze Gursoy : The types of data that 23andMe and Ancestry.com [ provide ] when people are interested in looking at ancestry or at their predisposition to diseases are the genetic variants you get from DNA sequencing .
.
.
.
When it comes to functional genomics , you are doing these experiments to understand the activities in the cell nucleus—if genes are expressed , if transcription factors are binding .
@ @ @ @ @ @ @ identify the genetic variants of the individual .
Mark Gerstein : You can only sequence your genome once , but you can do essentially an infinite number of functional genomics experiments on one person .
Inexorably , those human samples will give you variants from the people that donated those samples , but it ’ s utterly irrelevant a lot of times to what you ’ re interested in .
TS : What can our functional genomic data reveal about us as individuals , and why , therefore , should we be concerned @ @ @ @ @ @ @ GG : There are two types of information you can get .
Because these are sequences from a sequencer , you can get [ some of ] the genetic variants of the individual .
That ’ s what we are trying to sanitize , because we don ’ t need them to calculate gene expression , for example .
But there is another thing .
If you figure out who the person is that you have functional genomics data from , you can learn phenotypic information about them .
Because usually , these @ @ @ @ @ @ @ purpose of understanding if a gene is on or off in a disease .
You ’ re trying to protect the genetic variants so that you can not reidentify the person , because once you do , you can get some private , sensitive phenotypic information .
MG : The analogy to think about is what has happened with the internet .
Initially , people thought it was very innocuous to post pictures on Facebook .
Now , there are so many people in the world looking at these things .
I really @ @ @ @ @ @ @ process , because the intent of the biomedical enterprise is to sequence a very large fraction of people ’ s genomes and to build massive databases .
What would be very unfortunate is for people not to think about this stuff ahead of time , for us to build this huge database in the future and find out that it has all these annoying leaks .
That would be extremely damaging to biomedical science .
Even though it might seem academic and kind of silly to be thinking about all this stuff now @ @ @ @ @ @ @ it before it gets to scale .
See “ Hackers Are Breaking into Medical Databases to Protect Patient Data ” TS : What is a linkage attack , and can you share a real life example ?
GG : Let ’ s say you have two data sets .
One of them has information coming from a known individual and the other one is an anonymized data set .
In a linkage attack , you use the known information to deanonymize the anonymized data set .
What we have done , for example @ @ @ @ @ @ @ individual and sequence the DNA we found on the coffee cup .
.
.
.
We know the owner of the coffee cup , and we have a functional genomics database .
We deanonymized the database by linking the genotype that we obtained from the coffee cup to reveal phenotypic information about the owner of the coffee cup .
TS : Do you think that privacy laws are keeping pace with the speed at which we ’ re developing these genomic tools ?
MG : Not exactly .
On one hand , there @ @ @ @ @ @ @ really understand it at all , who essentially share genetic data without understanding the risk .
But I think that ’ s more of a minority .
The mainstream thought process now is that genomic privacy is a big deal .
But what happens is that everything gets locked down .
It ’ s very hard to aggregate lots of studies .
.
.
to get statistical power to find out important genetic correlations .
This thought process , even though we certainly understand it , isn ’ t really a great thought @ @ @ @ @ @ @ point of the data is not the DNA variants .
The point of our paper is that maybe there ’ s a different way of thinking about this .
You could take the results of the experiments and do this type of sanitization , and then be able to share them in a much freer way .
You can sequence someone ’ s DNA once and have the genotypes and lock them away safely .
But then the individual has a lot of tissues , a lot of cells , for functional genomics @ @ @ @ @ @ @ able to sanitize the functional genomics data to shield against these linkage attacks ?
GG : These functional genomics data are shared in certain file formats .
[ During analysis , researchers ] take the sequencing reads and they map them to a human reference genome .
[ The file ] tells us where these reads are mapping in the genome , but it also tells us what the sequence of the reads are .
We look at this data file format , and [ when we find a genetic variant in the @ @ @ @ @ @ @ to a format where [ there ’ s no ] difference between the reference genome and the read .
So , if you have a sequence that is different from that reference genome , we [ overwrite it with ] the reference genome while still preserving where [ the sequence ] maps in the genome .
When you have single nucleotide variants where you have a letter change , it ’ s very easy .
[ For example ] , if you ’ re just changing a letter A to C , the @ @ @ @ @ @ @ and it ’ s not going to affect anything .
But it gets really complicated when you have deletions and insertions .
You could have a region where your genome doesn ’ t have that region , but the reference genome does .
I [ would ] need to add , for example , a few letters to the end of the read so that it still has the same length .
TS : I was curious if either you have done a consumer genetics test , and if you were concerned about @ @ @ @ @ @ @ my family and then I did it .
I was a little concerned , but my curiosity was a little bigger than my concern .
Even though people don ’ t trust companies , in terms of the data abuse I think that there are really good data storage systems that these companies are putting in place .
Of course , it ’ s going to be used for commercial purposes .
But in terms of tracking me down and violating my privacy , I don ’ t see as much of a @ @ @ @ @ @ @ t .
I ’ m very much the worrier character .
Editor ’ s note : The interview was edited for brevity .
G. Gursoy et al.
, “ Data sanitization to reduce private information leakage from functional genomics , ” Cell , doi : 10.1016/j.cell.2020.09.036 , 2020 .

ABOVE: © ISTOCK.COM, JXFZSY
The appetite for data on individuals’ genetic sequences is growing, both from consumers—the number of testing kits sold by leading companies such as 23andMe and Ancestry.com topped 26 million by the start of 2019—and from scientists looking to amass large datasets for medical research. In addition to whole genome sequencing and genotyping, in which scientists identify a person’s genetic variants, new functional genomics tools such as RNA-seq, ChIP-seq, and single-cell sequencing have led to an exploding number of tests detailing how people (and their individual cells) respond to environmental conditions, medications, or disease.
courtesy of gamze gursoy
But as more and more people volunteer their information, the seemingly anonymized data that results from such tests is becoming a target for hackers looking to glean sensitive medical information. In particular, the many genetic variants that make each person unique can be used to identify them as surely as a fingerprint, revealing confidential information such as their disease status. In a process known as a linkage attack, a hacker can use known information about a person from sources such as public records or even discarded objects that contain a person’s DNA to identify them within an anonymous database compiled by academic researchers. For example, if someone were to participate anonymously in an AIDS study, it might be possible to uncover their participation—and thus their HIV status—using DNA sequenced from a cigarette.
Bioinformaticians and data scientists are therefore working to develop new ways of storing and analyzing data that protect anonymity while still allowing for the type of collaborative sharing necessary to advance medical science.
The Scientist spoke to Gamze Gursoy and Mark Gerstein, two bioinformaticians at the Yale School of Medicine, about how sensitive information can be gleaned from genomic data and ways of balancing privacy with utility. Their paper, published today (November 12) in Cell, details a new method for sanitizing, or removing sensitive information from, functional genomics datasets by separating out identifying variants in a way that does not affect data quality.
See “Technique to Track Golden State Killer Suspect Could Find You Too”
The Scientist: We hear a lot about genetic privacy in the context of things like 23andMe and Ancestry.com results, but what you’re describing in this paper is a different type of data. What sets functional genomics apart from something like DNA sequencing or genotyping?
Gamze Gursoy: The types of data that 23andMe and Ancestry.com [provide] when people are interested in looking at ancestry or at their predisposition to diseases are the genetic variants you get from DNA sequencing. . . . When it comes to functional genomics, you are doing these experiments to understand the activities in the cell nucleus—if genes are expressed, if transcription factors are binding. These experiments are not necessarily done to identify the genetic variants of the individual.
Mark Gerstein: You can only sequence your genome once, but you can do essentially an infinite number of functional genomics experiments on one person. Inexorably, those human samples will give you variants from the people that donated those samples, but it’s utterly irrelevant a lot of times to what you’re interested in.
Bioinformaticians are working to remove sensitive, identifying genetic information from functional genomics datasets to allow for public sharing of data while preserving privacy. gamze gursoy and charlotte brannon
TS: What can our functional genomic data reveal about us as individuals, and why, therefore, should we be concerned about the privacy of this information?
GG: There are two types of information you can get. Because these are sequences from a sequencer, you can get [some of] the genetic variants of the individual. That’s what we are trying to sanitize, because we don’t need them to calculate gene expression, for example.
But there is another thing. If you figure out who the person is that you have functional genomics data from, you can learn phenotypic information about them. Because usually, these functional genomics experiments are done for the purpose of understanding if a gene is on or off in a disease. You’re trying to protect the genetic variants so that you cannot reidentify the person, because once you do, you can get some private, sensitive phenotypic information.
MG: The analogy to think about is what has happened with the internet. Initially, people thought it was very innocuous to post pictures on Facebook. Now, there are so many people in the world looking at these things. I really think it’s a very analogous process, because the intent of the biomedical enterprise is to sequence a very large fraction of people’s genomes and to build massive databases. What would be very unfortunate is for people not to think about this stuff ahead of time, for us to build this huge database in the future and find out that it has all these annoying leaks. That would be extremely damaging to biomedical science.
Even though it might seem academic and kind of silly to be thinking about all this stuff now, it is really important to do it before it gets to scale.
See “Hackers Are Breaking into Medical Databases to Protect Patient Data”
courtesy of Mark gerstein
TS: What is a linkage attack, and can you share a real life example?
GG: Let’s say you have two data sets. One of them has information coming from a known individual and the other one is an anonymized data set. In a linkage attack, you use the known information to deanonymize the anonymized data set.
What we have done, for example, is take coffee cups from an individual and sequence the DNA we found on the coffee cup. . . . We know the owner of the coffee cup, and we have a functional genomics database. We deanonymized the database by linking the genotype that we obtained from the coffee cup to reveal phenotypic information about the owner of the coffee cup.
TS: Do you think that privacy laws are keeping pace with the speed at which we’re developing these genomic tools?
MG: Not exactly. On one hand, there’s people who don’t really understand it at all, who essentially share genetic data without understanding the risk. But I think that’s more of a minority. The mainstream thought process now is that genomic privacy is a big deal.
But what happens is that everything gets locked down. It’s very hard to aggregate lots of studies . . . to get statistical power to find out important genetic correlations. This thought process, even though we certainly understand it, isn’t really a great thought process for functional genomics data where the point of the data is not the DNA variants.
The point of our paper is that maybe there’s a different way of thinking about this. You could take the results of the experiments and do this type of sanitization, and then be able to share them in a much freer way. You can sequence someone’s DNA once and have the genotypes and lock them away safely. But then the individual has a lot of tissues, a lot of cells, for functional genomics work.
See “Startups Plan the Health Data Gold Rush”
TS: How are you able to sanitize the functional genomics data to shield against these linkage attacks?
GG: These functional genomics data are shared in certain file formats. [During analysis, researchers] take the sequencing reads and they map them to a human reference genome. [The file] tells us where these reads are mapping in the genome, but it also tells us what the sequence of the reads are.
We look at this data file format, and [when we find a genetic variant in the read], we basically change it to a format where [there’s no] difference between the reference genome and the read. So, if you have a sequence that is different from that reference genome, we [overwrite it with] the reference genome while still preserving where [the sequence] maps in the genome.
When you have single nucleotide variants where you have a letter change, it’s very easy. [For example], if you’re just changing a letter A to C, the read length doesn’t change, and it’s not going to affect anything. But it gets really complicated when you have deletions and insertions. You could have a region where your genome doesn’t have that region, but the reference genome does. I [would] need to add, for example, a few letters to the end of the read so that it still has the same length.
TS: I was curious if either you have done a consumer genetics test, and if you were concerned about privacy.
GG: I talked to my family and then I did it. I was a little concerned, but my curiosity was a little bigger than my concern. Even though people don’t trust companies, in terms of the data abuse I think that there are really good data storage systems that these companies are putting in place. Of course, it’s going to be used for commercial purposes. But in terms of tracking me down and violating my privacy, I don’t see as much of a problem.
MG: I haven’t. I’m very much the worrier character.
Editor’s note: The interview was edited for brevity.
G. Gursoy et al., “Data sanitization to reduce private information leakage from functional genomics,” Cell, doi: 10.1016/j.cell.2020.09.036, 2020.


thescientist--2020-11-12--Harnessing the Most Powerful Cells Crucial to Accelerating Curative Medicines

IsoPlexis has emerged as the gold standard for single-cell functional proteomics through its unique applications of functional immune landscaping , intracellular signaling omics , and high-plex automated immunoassays .
IsoPlexis ’ platform prioritizes function over form to fill the gap missing with traditional technologies .
Historically , researchers have characterized the immune system using protein expression markers , but these expression profiles do not always translate to cellular function .
When developing immunotherapies , a high priority for scientists is to identify polyfunctional cells ( single cells that secrete multiple cytokines ) but these cells can not be characterized when @ @ @ @ @ @ @ platform overcomes this challenge while addressing many of the pain points associated with scaling these types of assays , streamlining the proteomics workflow into one automated hub instrument to advance precision , curative medicines .
The Gold Standard for Functional Single-Cell Proteomics to Advance Curative Medicines Basic , translational , and clinical scientists already use IsoPlexis ’ proteomics technology extensively .
It has helped scientists better understand the mechanisms guiding immune responses to pathogens , inflammation , and therapeutic agents or approaches .
Characterizing immune cell function is essential for understanding the relationship @ @ @ @ @ @ @ improving the therapeutic efficacy of immune-oncology approaches .
IsoPlexis has a proven track record1-4 of helping scientists discover links between immune cell function and therapeutic outcomes .
In a 2018 study published in the journal Blood , Rossi et al .
used IsoPlexis ’ single-cell secretomic analysis to establish a link between polyfunctional chimeric antigen receptor ( CAR ) T cells in pre-infusion CD19 CAR products and patient responses to treatment.1 The same platform used in the Blood study was used by researchers Parisi et al .
to predict the anti-tumor response of @ @ @ @ @ @ @ NKTR-214 , with adoptive cell transfer ( ACT ) compared to the conventional IL-2 combination therapy .
IsoPlexis ’ platform found that ACT with NKTR-214 resulted in increased proliferation , homing , and persistence of anti-tumor T cells in a murine melanoma model .
This resulted in superior anti-tumor activity , and the use of NKTR-214 led to an increase of polyfunctional T cells in murine spleens and tumors .
Enhanced polyfunctionality of T and NK cells in the peripheral blood of human patients suggested that NKTR-214 has the potential to improve the @ @ @ @ @ @ @ These results highlight critical insights of functional immune profiling for uncovering biomarkers that help predict treatment response.5 IsoPlexis ’ functional immune landscaping has been used to investigate the mechanism of COVID-19 inflammation within a variety of cell types .
In a study recently published in Cell , researchers Su et al .
conducted deep functional immune profiling of COVID-19 patients ranging in disease severity compared to healthy samples .
They found that with increasing disease severity as measured by the WHO Ordinal Scale ( WOS ) , CD-4+ T cell , CD-8+ T @ @ @ @ @ @ @ while the proportion of monocytes increased .
Su et al .
noted a surprising similarity between healthy subjects and mild COVID-19 cases , as well as between moderate and severe cases .
IsoPlexis ’ functional immune landscaping was able to shed light on the functional mechanisms behind the differences in disease severity .
The severity of COVID-19 correlated with an increase of polyfunctionality in CD8+ T cells , followed by a significant drop in function at severe stages of the disease , but “ unlike the case of CD8+ and CD4+ T cells @ @ @ @ @ @ @ PSI ) of monocytes ] monotonically increases with disease severity , suggesting that monocytes contribute to the pro-inflammatory condition of moderate or severe COVID-19.6 ” Researchers Su et al .
used IsoPlexis ’ uniquely correlative metrics to assess the relationship between highly functional cell subsets and COVID-19 disease progression .
Monocytes showed a sharp increase in function between the mild and moderate disease stages , while the monocyte population and PSI continued to increase between moderate and severe cases .
These unique findings , enabled by IsoPlexis ’ single-cell functional proteomics suggest that @ @ @ @ @ @ @ that is characteristic of moderate and severe COVID-19 cases .
A New Layer of Multiplexed Proteomic Biology : Intracellular Signaling Omics for Hyper-Powered Targeted Therapies With IsoPlexis ’ intracellular signaling omics , researchers can identify functional pathways driving therapeutic resistance and develop combination therapies to combat resistant cell states and resolve tumor heterogeneity .
IsoPlexis ’ intracellular proteome solutions identify polyfunctional cell subsets to provide a comprehensive picture of altered signal transduction networks in tumors , which allow researchers to identify whether therapies targeting protein signaling networks are effective .
In another study @ @ @ @ @ @ @ al .
utilized IsoPlexis ’ technology to characterize resistance pathways in mutant melanoma cells .
IsoPlexis ’ solutions identified two distinct subpopulations of cells which took different paths to drug resistance .
IsoPlexis ’ intracellular signaling omics provided the insights for researchers to identify combination therapies to combat this resistance that were both effective and low in cytotoxicity.7 In contrast to traditional technologies , IsoPlexis ’ high-plex walk-away immunoassays provide researchers the ability to highly multiplex ( e.g .
30+ cytokines ) and fully automate proteomics for accelerated insights .
The CodePlex family @ @ @ @ @ @ @ 11 μL per sample ) , enabling critical applications across research disciplines from cancer immunology to infectious diseases .
In a study led by Denis Wirtz at Johns Hopkins University , researchers investigated the role of cytokines in promoting or preventing metastatic cancer cell phenotypes .
These researchers used the CodePlex technology to simultaneously measure the concentration of 24 soluble molecules .
Both cytokines IL-6 and IL-8 were secreted at high concentrations in a specific ratio , while proteins typically associated with promoting tumor metastasis and progression were not elevated , suggesting that @ @ @ @ @ @ @ driving the density-dependent cell migration within 3D matrices .
Wirtz ’ s team found a synergistic IL-6 and IL-8 mediated paracrine signaling pathway which may provide a new therapeutic target against metastatic cancer cells.8 The IsoLight system was the first solution to solve numerous instrumentation issues of a typical proteomics workflow by consolidating a multi-faceted and laborious process into one automated , walk-away proteomics system .
This system is most often used by pharmaceutical companies and core facilities at leading institutions worldwide due to its high throughput .
Now the gold standard of @ @ @ @ @ @ @ is available in three different formats : IsoSpark , IsoLight , and IsoSpark Duo .
The introduction of the IsoSpark , a personalized proteomics system for any laboratory , makes unique functional proteomics accessible to every lab , providing an integrated and flexible solution for accelerating curative medicines .
At only 30 % of the size of the IsoLight , the IsoSpark ’ s smaller footprint and lower throughput is perfect for researchers wanting to apply functional immune landscaping , intracellular signaling omics , and high-plex automated immunoassays to their research .
The @ @ @ @ @ @ @ , and both the IsoLight and the IsoSpark Duo run 8 chips for higher throughput .
The IsoSpark Duo is ideal for complete functional immune landscaping with the ability to analyze multiple cell types simultaneously in one run .
IsoPlexis ’ functional proteomics is changing how the world thinks about immune cell characterization , showing how harnessing the most powerful cells is changing immune medicine .
The IsoSpark , the IsoLight , and the IsoSpark Duo , along with functional immune landscaping , intracellular signaling omics , and high-plex automated immunoassays are the @ @ @ @ @ @ @ , introduced on November 11th , is currently available for pre-order in North America and Europe with shipping planned for January 2021 .
Experience the innovation that has unlocked the next generation of personalized medicines with unique functional proteomics .
Bring IsoPlexis ’ gold standard single-cell functional proteomics technology to your laboratory to accelerate the development of curative medicines .
Discover the new era of functional proteomics at IsoPlexis.com/IsoSpark .
• J. Rossi et al.
, “ Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL , @ @ @ @ @ @ @ :804-814 , 2018 .
• D. Li et al.
, “ Persistent polyfunctional chimeric antigen receptor T cells that target glypican 3 eliminate orthotopic hepatocellular carcinomas in mice , ” Gastroenterology , 158 ( 8 ) :2250-2265.e20 , 2020 .
• H. Zhu et al.
, “ Metabolic reprograming via deletion of CISH in human iPSC-derived NK cells promotes in vivo persistence and enhances anti-tumor activity , ” Cell Stem Cell , 27 ( 2 ) :224-237.e6 , 2020 .
• G. Parisi et al.
, “ Persistence of adoptively transferred T cells @ @ @ @ @ @ @ , ” Nat Commun , 11:660 , 2020 .
• Y. Su et al.
, “ Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19 , ” Cell , 2020 .
• Y. Su et al.
, “ Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line , ” Nat Commun , 11:2345 , 2020 .
• H. Jayatilaka et al.
, “ Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration , ” Nat Commun , 8:15584 , @ @

IsoPlexis has emerged as the gold standard for single-cell functional proteomics through its unique applications of functional immune landscaping, intracellular signaling omics, and high-plex automated immunoassays. IsoPlexis’ platform prioritizes function over form to fill the gap missing with traditional technologies. Historically, researchers have characterized the immune system using protein expression markers, but these expression profiles do not always translate to cellular function. When developing immunotherapies, a high priority for scientists is to identify polyfunctional cells (single cells that secrete multiple cytokines) but these cells cannot be characterized when measuring protein expression markers. IsoPlexis’ platform overcomes this challenge while addressing many of the pain points associated with scaling these types of assays, streamlining the proteomics workflow into one automated hub instrument to advance precision, curative medicines.
The Gold Standard for Functional Single-Cell Proteomics to Advance Curative Medicines
Basic, translational, and clinical scientists already use IsoPlexis’ proteomics technology extensively. It has helped scientists better understand the mechanisms guiding immune responses to pathogens, inflammation, and therapeutic agents or approaches.
Precision Biomarkers for Accelerating & Improving Immune Therapies
Characterizing immune cell function is essential for understanding the relationship between immune cells and cancer cells and improving the therapeutic efficacy of immune-oncology approaches. IsoPlexis has a proven track record1-4 of helping scientists discover links between immune cell function and therapeutic outcomes. In a 2018 study published in the journal Blood, Rossi et al. used IsoPlexis’ single-cell secretomic analysis to establish a link between polyfunctional chimeric antigen receptor (CAR) T cells in pre-infusion CD19 CAR products and patient responses to treatment.1
The same platform used in the Blood study was used by researchers Parisi et al. to predict the anti-tumor response of a novel kinetically engineered IL-2 agonist, NKTR-214, with adoptive cell transfer (ACT) compared to the conventional IL-2 combination therapy. IsoPlexis’ platform found that ACT with NKTR-214 resulted in increased proliferation, homing, and persistence of anti-tumor T cells in a murine melanoma model. This resulted in superior anti-tumor activity, and the use of NKTR-214 led to an increase of polyfunctional T cells in murine spleens and tumors. Enhanced polyfunctionality of T and NK cells in the peripheral blood of human patients suggested that NKTR-214 has the potential to improve the anti-tumor effects of ACT in humans. These results highlight critical insights of functional immune profiling for uncovering biomarkers that help predict treatment response.5
Identifying Key Prognostic Biomarkers of Inflammation in COVID-19
IsoPlexis’ functional immune landscaping has been used to investigate the mechanism of COVID-19 inflammation within a variety of cell types. In a study recently published in Cell, researchers Su et al. conducted deep functional immune profiling of COVID-19 patients ranging in disease severity compared to healthy samples. They found that with increasing disease severity as measured by the WHO Ordinal Scale (WOS), CD-4+ T cell, CD-8+ T cell, and NK cell percentages dropped while the proportion of monocytes increased. Su et al. noted a surprising similarity between healthy subjects and mild COVID-19 cases, as well as between moderate and severe cases. IsoPlexis’ functional immune landscaping was able to shed light on the functional mechanisms behind the differences in disease severity.
The severity of COVID-19 correlated with an increase of polyfunctionality in CD8+ T cells, followed by a significant drop in function at severe stages of the disease, but “unlike the case of CD8+ and CD4+ T cells, the [polyfunctional strength index (PSI) of monocytes] monotonically increases with disease severity, suggesting that monocytes contribute to the pro-inflammatory condition of moderate or severe COVID-19.6” Researchers Su et al. used IsoPlexis’ uniquely correlative metrics to assess the relationship between highly functional cell subsets and COVID-19 disease progression. Monocytes showed a sharp increase in function between the mild and moderate disease stages, while the monocyte population and PSI continued to increase between moderate and severe cases. These unique findings, enabled by IsoPlexis’ single-cell functional proteomics suggest that monocytes may contribute to the pro-inflammatory environment that is characteristic of moderate and severe COVID-19 cases.
A New Layer of Multiplexed Proteomic Biology: Intracellular Signaling Omics for Hyper-Powered Targeted Therapies
With IsoPlexis’ intracellular signaling omics, researchers can identify functional pathways driving therapeutic resistance and develop combination therapies to combat resistant cell states and resolve tumor heterogeneity. IsoPlexis’ intracellular proteome solutions identify polyfunctional cell subsets to provide a comprehensive picture of altered signal transduction networks in tumors, which allow researchers to identify whether therapies targeting protein signaling networks are effective. In another study published in Nature Communications, Su et al. utilized IsoPlexis’ technology to characterize resistance pathways in mutant melanoma cells. IsoPlexis’ solutions identified two distinct subpopulations of cells which took different paths to drug resistance. IsoPlexis’ intracellular signaling omics provided the insights for researchers to identify combination therapies to combat this resistance that were both effective and low in cytotoxicity.7
Highly Multiplexed Automated Proteomics for Identifying Druggable Targets to Treat Cancer Metastasis
In contrast to traditional technologies, IsoPlexis’ high-plex walk-away immunoassays provide researchers the ability to highly multiplex (e.g. 30+ cytokines) and fully automate proteomics for accelerated insights. The CodePlex family of solutions uses ultra-small sample volumes (11 μL per sample), enabling critical applications across research disciplines from cancer immunology to infectious diseases. In a study led by Denis Wirtz at Johns Hopkins University, researchers investigated the role of cytokines in promoting or preventing metastatic cancer cell phenotypes. These researchers used the CodePlex technology to simultaneously measure the concentration of 24 soluble molecules. Both cytokines IL-6 and IL-8 were secreted at high concentrations in a specific ratio, while proteins typically associated with promoting tumor metastasis and progression were not elevated, suggesting that both of these cytokines are responsible for driving the density-dependent cell migration within 3D matrices. Wirtz’s team found a synergistic IL-6 and IL-8 mediated paracrine signaling pathway which may provide a new therapeutic target against metastatic cancer cells.8
Sparking the Next Big Breakthrough
The IsoLight system was the first solution to solve numerous instrumentation issues of a typical proteomics workflow by consolidating a multi-faceted and laborious process into one automated, walk-away proteomics system. This system is most often used by pharmaceutical companies and core facilities at leading institutions worldwide due to its high throughput. Now the gold standard of single-cell functional proteomics IsoPlexis is known for is available in three different formats: IsoSpark, IsoLight, and IsoSpark Duo.
The introduction of the IsoSpark, a personalized proteomics system for any laboratory, makes unique functional proteomics accessible to every lab, providing an integrated and flexible solution for accelerating curative medicines. At only 30% of the size of the IsoLight, the IsoSpark’s smaller footprint and lower throughput is perfect for researchers wanting to apply functional immune landscaping, intracellular signaling omics, and high-plex automated immunoassays to their research.
The IsoSpark runs up to four chips simultaneously, and both the IsoLight and the IsoSpark Duo run 8 chips for higher throughput. The IsoSpark Duo is ideal for complete functional immune landscaping with the ability to analyze multiple cell types simultaneously in one run.
A New Era for Discovery Biology
IsoPlexis’ functional proteomics is changing how the world thinks about immune cell characterization, showing how harnessing the most powerful cells is changing immune medicine.
The IsoSpark, the IsoLight, and the IsoSpark Duo, along with functional immune landscaping, intracellular signaling omics, and high-plex automated immunoassays are the latest innovations from IsoPlexis. The IsoSpark, introduced on November 11th, is currently available for pre-order in North America and Europe with shipping planned for January 2021.
Experience the innovation that has unlocked the next generation of personalized medicines with unique functional proteomics. Bring IsoPlexis’ gold standard single-cell functional proteomics technology to your laboratory to accelerate the development of curative medicines.
Discover the new era of functional proteomics at IsoPlexis.com/IsoSpark.
References