thescientist--2020-08-18--Differences in Antibody Responses Linked to COVID-19 Outcomes

Nearly half a year into the coronavirus pandemic , hospital clinicians still have no good way of knowing how and why some of their COVID-19 patients recover from infection , whereas others take a turn for the worse and die .
A recent study of 22 hospitalized COVID-19 patients provides some clues .
Through an extensive computational analysis of the patients ’ antibody features and functions , researchers report marked differences between those who survived and those who died .
Notably , antibody responses against SARS-CoV-2 ’ s spike protein were stronger among COVID-19 survivors , whereas antibody responses targeting @ @ @ @ @ @ @ elevated in patients who died .
The findings were published last month ( July 30 ) in Immunity .
While it ’ s not clear if these different antibody responses are the reason for the patients ’ different disease trajectories , the research “ provides mechanistic insights into the nature of the immune response to SARS-CoV-2 , ” notes Stanford University immunologist Bali Pulendran , who wasn ’ t involved in the study .
In addition , “ you could [ potentially ] have a means of monitoring these COVID patients to identify @ @ @ @ @ @ @ sense of what the prognosis could be.
” In late February , as COVID-19 tore through nursing homes in Seattle , some patients were seen by University of Washington physician and immunologist Helen Chu at Harborview Medical Center .
Chu puzzled why certain COVID-19 patients , who seemed fine at first , would rapidly deteriorate from one day to the next and die , recalls her collaborator Galit Alter of the Ragon Institute of Massachusetts General Hospital , MIT , and Harvard .
In search of answers , Chu and her colleagues collected @ @ @ @ @ @ @ admission and sent them to Alter , whose group specializes in a branch of immunology called “ systems serology.
” This combines experimental techniques to analyze the features and functions of antibodies with computational approaches to discern , for instance , which ones correlate with immunity .
From previous studies of viral infections including HIV , tuberculosis , and malaria , Alter has learned that it ’ s not the quantity of antibodies that ’ s predictive of immunity , but rather , their different functions and qualities , and , importantly , @ @ @ @ @ @ @ swarm , ” she explains .
Alter and her colleagues profiled the antibodies of the 22 patients ; 12 had recovered from COVID-19 and 10 had died .
The scientists focused on SARS-CoV-2-specific antibodies that target the virus ’ s key proteins , including the spike protein , which it uses to enter human cells , and the nucleocapsid protein , which encloses its genetic material .
For each viral target , the researchers documented a range of antibody characteristics , such as the quantity of specific antibody types and their ability to @ @ @ @ @ @ @ neutrophils .
The team detected no difference in the overall amount of antibodies between survivors and those who died , nor in the antibodies ’ overall capacity to neutralize the virus in vitro .
However , when the team used computational methods to analyze the functional differences between the two groups , they found a combination of five antibody features distinguished them from one another .
Overall , survivors had a much stronger antibody response to the spike protein , whereas antibody responses in those who died were more focused on the nucleocapsid @ @ @ @ @ @ @ survivors have more spike-targeting antibodies , Alter notes , rather , their antibodies are “ targeting [ the spike ] more than they ’ re targeting [ the nucleocapsid ] .
” In fact , in the Seattle cohort , these five features proved even more predictive of a patient ’ s recovery or death than factors such as age or sex .
The team also validated this approach in a larger cohort of COVID-19 patients from a Boston hospital , 20 of whom had recovered and 20 of whom had died .
@ @ @ @ @ @ @ “ laser-focused ” on targeting the spike protein , whereas antibodies tended to focus on the nucleocapsid protein among those who died , Alter says .
“ The survivors really picked different functions than the deceased .
They just leveraged their antibodies in a different way.
” An outstanding question is whether the nature of a patient ’ s antibody response is actually what determines whether they recover or die , or if it ’ s simply a symptom of the overall function of the immune response , Alter says .
That said @ @ @ @ @ @ @ on how antibodies could contribute to the body ’ s defeat of SARS-CoV-2 , she adds .
Spike-focused antibodies might be better at helping the body clear the virus , which could help other components of the immune system drive down inflammation associated with COVID-19 .
The antibodies ’ focus on the nucleocapsid in other patients could have to do with the fact that some people have greater viral loads in the lung , causing the immune system to encounter large quantities of the nucleocapsid protein—which is generally much more abundant than the @ @ @ @ @ @ @ to become “ distracted ” from the right target—the spike protein—and tailor their response towards the nucleocapsid protein .
While preliminary , the findings could offer a path forward in developing a prognostic tool for clinicians to discern relatively early on in the course of disease which patients are likely to fare worse and therefore need more careful attention or should be prioritized for certain types of therapies , Alter suggests .
Other investigators are looking into cytokines as disease severity markers , but the trouble is that those aren ’ t specific @ @ @ @ @ @ @ be useful for vaccine scientists , notes Danny Altmann , an immunologist at Imperial College London who wasn ’ t involved in the research .
“ You need some detailed info on the correlates of protection—otherwise how can you ever know if your vaccine elicits them , ” he writes to The Scientist in an email .
“ Up to now a lot of [ COVID-19 ] findings have been a little general .
With studies like this , we get into some real granularity of what a protective response looks like.
” @ @ @ @ @ @ @ the spike protein , which is probably a good thing , Alter adds .
The authors acknowledge several limitations of the research , including the small size of the Seattle cohort .
However , Alter ’ s group was able to validate the correlations they uncovered in a larger cohort of 170 patients , whose antibody responses were tracked over time , in a soon-to-be published study .
Collectively , the findings are adding to a growing body of research on the interaction between SARS-CoV-2 and the human immune response , Pulendran says @ @ @ @ @ @ @ he and his colleagues investigated the source of higher levels of inflammatory cytokines in severely affected COVID-19 patients .
Surprisingly , the blood-borne monocytes and dendritic cells that usually secrete these cytokines were too “ functionally sluggish ” to respond to viral protein , Palendran says .
Rather , the cytokines appeared to be emanating from the lung , he explains .
How this dysfunctional innate immune response relates to emerging peculiarities of the adaptive immune response—such as T cell and antibody immunity—is still a mystery .
“ The field of COVID immunology @ @ @ @ @ @ @ many exciting observations and insights about one aspect of the immune system or another aspect , ” Pulendran says .
“ The challenge over the coming weeks and months will be [ to figure out ] how to fit these all together.
” C. Atyeo et al.
, “ Distinct early serological signatures track with SARS-CoV-2 survival , ” Immunity , doi:10.1016/j.immuni.2020.07.020 , 2020 .

ABOVE: © ISTOCK.COM, SHIVENDU JUAHARI
Nearly half a year into the coronavirus pandemic, hospital clinicians still have no good way of knowing how and why some of their COVID-19 patients recover from infection, whereas others take a turn for the worse and die.
A recent study of 22 hospitalized COVID-19 patients provides some clues. Through an extensive computational analysis of the patients’ antibody features and functions, researchers report marked differences between those who survived and those who died. Notably, antibody responses against SARS-CoV-2’s spike protein were stronger among COVID-19 survivors, whereas antibody responses targeting the virus’s nucleocapsid protein were elevated in patients who died. The findings were published last month (July 30) in Immunity.
While it’s not clear if these different antibody responses are the reason for the patients’ different disease trajectories, the research “provides mechanistic insights into the nature of the immune response to SARS-CoV-2,” notes Stanford University immunologist Bali Pulendran, who wasn’t involved in the study. In addition, “you could [potentially] have a means of monitoring these COVID patients to identify these signatures, and thereby get a sense of what the prognosis could be.”
In late February, as COVID-19 tore through nursing homes in Seattle, some patients were seen by University of Washington physician and immunologist Helen Chu at Harborview Medical Center. Chu puzzled why certain COVID-19 patients, who seemed fine at first, would rapidly deteriorate from one day to the next and die, recalls her collaborator Galit Alter of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard.
The survivors really picked different functions than the deceased. They just leveraged their antibodies in a different way. —Galit Alter, Ragon Institute
In search of answers, Chu and her colleagues collected blood samples from 22 patients upon hospital admission and sent them to Alter, whose group specializes in a branch of immunology called “systems serology.” This combines experimental techniques to analyze the features and functions of antibodies with computational approaches to discern, for instance, which ones correlate with immunity. From previous studies of viral infections including HIV, tuberculosis, and malaria, Alter has learned that it’s not the quantity of antibodies that’s predictive of immunity, but rather, their different functions and qualities, and, importantly, how they act collectively as a “swarm,” she explains.
Alter and her colleagues profiled the antibodies of the 22 patients; 12 had recovered from COVID-19 and 10 had died. The scientists focused on SARS-CoV-2-specific antibodies that target the virus’s key proteins, including the spike protein, which it uses to enter human cells, and the nucleocapsid protein, which encloses its genetic material. For each viral target, the researchers documented a range of antibody characteristics, such as the quantity of specific antibody types and their ability to stimulate other immune cells such as microbe-devouring neutrophils.
The team detected no difference in the overall amount of antibodies between survivors and those who died, nor in the antibodies’ overall capacity to neutralize the virus in vitro. However, when the team used computational methods to analyze the functional differences between the two groups, they found a combination of five antibody features distinguished them from one another. Overall, survivors had a much stronger antibody response to the spike protein, whereas antibody responses in those who died were more focused on the nucleocapsid protein.
It’s not that survivors have more spike-targeting antibodies, Alter notes, rather, their antibodies are “targeting [the spike] more than they’re targeting [the nucleocapsid].” In fact, in the Seattle cohort, these five features proved even more predictive of a patient’s recovery or death than factors such as age or sex.
The team also validated this approach in a larger cohort of COVID-19 patients from a Boston hospital, 20 of whom had recovered and 20 of whom had died. There too, survivors’ antibodies were “laser-focused” on targeting the spike protein, whereas antibodies tended to focus on the nucleocapsid protein among those who died, Alter says. “The survivors really picked different functions than the deceased. They just leveraged their antibodies in a different way.”
An outstanding question is whether the nature of a patient’s antibody response is actually what determines whether they recover or die, or if it’s simply a symptom of the overall function of the immune response, Alter says.
That said, the data do provide plausible hypotheses on how antibodies could contribute to the body’s defeat of SARS-CoV-2, she adds. Spike-focused antibodies might be better at helping the body clear the virus, which could help other components of the immune system drive down inflammation associated with COVID-19. The antibodies’ focus on the nucleocapsid in other patients could have to do with the fact that some people have greater viral loads in the lung, causing the immune system to encounter large quantities of the nucleocapsid protein—which is generally much more abundant than the spike protein. This could cause antibodies to become “distracted” from the right target—the spike protein—and tailor their response towards the nucleocapsid protein.
While preliminary, the findings could offer a path forward in developing a prognostic tool for clinicians to discern relatively early on in the course of disease which patients are likely to fare worse and therefore need more careful attention or should be prioritized for certain types of therapies, Alter suggests. Other investigators are looking into cytokines as disease severity markers, but the trouble is that those aren’t specific to SARS-CoV-2 infections.
The findings could be useful for vaccine scientists, notes Danny Altmann, an immunologist at Imperial College London who wasn’t involved in the research. “You need some detailed info on the correlates of protection—otherwise how can you ever know if your vaccine elicits them,” he writes to The Scientist in an email. “Up to now a lot of [COVID-19] findings have been a little general. With studies like this, we get into some real granularity of what a protective response looks like.” Notably, most vaccinologists are focusing on the spike protein, which is probably a good thing, Alter adds.
The authors acknowledge several limitations of the research, including the small size of the Seattle cohort. However, Alter’s group was able to validate the correlations they uncovered in a larger cohort of 170 patients, whose antibody responses were tracked over time, in a soon-to-be published study.
Collectively, the findings are adding to a growing body of research on the interaction between SARS-CoV-2 and the human immune response, Pulendran says. Just last week in Science, he and his colleagues investigated the source of higher levels of inflammatory cytokines in severely affected COVID-19 patients. Surprisingly, the blood-borne monocytes and dendritic cells that usually secrete these cytokines were too “functionally sluggish” to respond to viral protein, Pulendran says. Rather, the cytokines appeared to be emanating from the lung, he explains.
How this dysfunctional innate immune response relates to emerging peculiarities of the adaptive immune response—such as T cell and antibody immunity—is still a mystery. “The field of COVID immunology is at a stage where there are many exciting observations and insights about one aspect of the immune system or another aspect,” Pulendran says. “The challenge over the coming weeks and months will be [to figure out] how to fit these all together.”
C. Atyeo et al., “Distinct early serological signatures track with SARS-CoV-2 survival,” Immunity, doi:10.1016/j.immuni.2020.07.020, 2020.


thescientist--2020-08-18--Cold-Causing Coronaviruses Don't Seem to Confer Lasting Immunity

Sometime in the late 1980s , in a town in southwest England called Salisbury , 15 volunteers agreed to have a cold-causing coronavirus known as 229E squirted into their noses in a saline solution .
Ten of the volunteers were successfully infected , as determined by viruses recovered from their noses in the days following , although only eight displayed symptoms .
Researchers monitored the levels of antibodies and immune cells in their blood over the ensuing weeks .
A year later , 14 of the same volunteers came back for another round .
Of the nine people who ’ @ @ @ @ @ @ @ , six became infected again , but none developed colds .
Moreover , they only shed virus from their noses for a couple of days , compared with an average of five and a half days the first time around .
As for the five people who ’ d resisted infection the first time around , all became infected this time , but only one developed symptoms .
The researchers struggled to explain the results .
“ These data do not fit any simple model , ” they wrote in their report .
@ @ @ @ @ @ @ amounts of antibody remaining in the original infected group contributed to resistance to reinfection in some volunteers .
It may also have prevented colds and shortened the duration of virus shedding.
” Three decades on , as a pandemic caused by a different coronavirus rages , researchers are still scratching their heads over whether coronaviruses—in particular , SARS-CoV-2—provoke lasting immunity in people they infect .
With no long-term data yet on the immune and other effects of SARS-CoV-2 infection , some scientists are returning to 229E and three other coronaviruses that have been @ @ @ @ @ @ @ and HKU1—in hopes of finding clues to this question .
See “ The Search for Immune Responses that Stop COVID-19 ” One study hoping to shed light on immunity after a coronavirus infection , posted on medRxiv in June and not yet peer-reviewed , drew on blood samples from healthy control subjects in an ongoing HIV project that began in 1985 .
Researchers based at the Amsterdam University Medical Center ( UMC ) and their colleagues at other institutions analyzed stored samples from 10 subjects who had their blood collected every three to @ @ @ @ @ @ @ , looking for antibodies to proteins from the four known cold-causing coronaviruses that would indicate a recent viral infection .
See “ A Brief History of Human Coronaviruses ” The research team knew of the earlier 229E reinfection study , so they weren ’ t surprised to see multiple 229E infections in the same subjects crop up in their own data , as revealed by increases in antibody levels , says Arthur Edridge , a physician and Amsterdam UMC graduate student who is the paper ’ s first author .
“ What was @ @ @ @ @ @ @ ] actually seemed to be a common feature for all the seasonal coronaviruses that we studied , ” he says .
All but one study subject had been infected with a particular coronavirus multiple times over the period of the study , and in some cases the time between infections with the same virus was as little as six months to a year , indicating an “ alarmingly short duration of protective immunity , ” the authors write in their paper .
Edridge cautions that it ’ s not clear whether SARS-CoV-2 will @ @ @ @ @ @ @ familiar coronaviruses—but if it does , then the idea that allowing the virus to spread in order to achieve herd immunity wouldn ’ t be a successful strategy , he adds .
Another recent study to find evidence of coronavirus reinfection was an analysis of data from a respiratory virus monitoring program conducted between 2016 and 2018 .
That study , which included 214 children and adults in New York City and relied on self-reports of symptoms and viral RNA swabbed from the back of the throat , found 12 instances of reinfection @ @ @ @ @ @ @ of these were in children , whose immune systems are less developed than those of adults .
Reinfections were found for three of the four cold-causing coronaviruses ( OC43 , HKU1 , and 229E ) .
Marta Galanti , a postdoc at Columbia University and the study ’ s first author , notes that the reinfections fell into two clusters in terms of timeline : at four to eight weeks after the initial infection , and at 8 to 10 months after the initial infection .
She and her coauthor weren ’ t @ @ @ @ @ @ @ the earlier reinfections were in fact persistent first infections , she says , although they ’ re working on this in a follow-up study .
Like Edridge , Galanti is clear that the reinfection results don ’ t necessarily apply to SARS-CoV-2 .
But , she says , they indicate that “ we have to be prepared [ for ] the possibility that the multiple subsequent infections can happen ” with the novel coronavirus .
“ Maybe it ’ s possible that if you only have these mild respiratory symptoms [ with SARS-CoV-2 @ @ @ @ @ @ @ develop a really strong immune response , and you could get reinfected , ” says Rachel Roper , an immunologist at East Carolina University who was not involved in either of the studies .
But she still thinks there ’ s uncertainty about whether reinfections occur with endemic coronaviruses , and she adds that infection with murine hepatitis virus , a coronavirus that causes serious disease in mice , confers lifelong immunity , as she suspects more severe cases of COVID-19 would .
“ If you had a serious infection the first time @ @ @ @ @ @ @ got a stronger immune response , ” and would either be immune to a second infection or experience only mild symptoms the second time around .
In general , whether a viral infection elicits long-term immunity depends on characteristics of both the virus and the host , says Akiko Iwasaki , an immunologist at Yale University .
She adds that studies have found that the number of antibodies produced by COVID-19 patients varies widely , which may indicate that their protection against future infection also varies .
Other studies have shown that levels @ @ @ @ @ @ @ after a few months .
But Iwasaki adds that antibodies don ’ t reveal the full picture of immunity , as even if antibodies to a virus are at undetectable levels , people who ’ ve been exposed to the pathogen before may be able to mount a quick response thanks to T cells and B cells that “ remember ” the previous infection .
Even if immunity to SARS-CoV-2 does turn out to be short-lived after infection , it might not be bad news for vaccine development , says Roper .
“ @ @ @ @ @ @ @ infect , also do things to turn off the mammalian immune response , ” she says .
“ Hopefully , when we design vaccines , the vaccines won ’ t have those proteins that shut off the host immune response .
So it should be possible to get a better immune response to the vaccine than you do to the virus .
”

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Sometime in the late 1980s, in a town in southwest England called Salisbury, 15 volunteers agreed to have a cold-causing coronavirus known as 229E squirted into their noses in a saline solution. Ten of the volunteers were successfully infected, as determined by viruses recovered from their noses in the days following, although only eight displayed symptoms. Researchers monitored the levels of antibodies and immune cells in their blood over the ensuing weeks.
A year later, 14 of the same volunteers came back for another round. Of the nine people who’d become infected with the first exposure, six became infected again, but none developed colds. Moreover, they only shed virus from their noses for a couple of days, compared with an average of five and a half days the first time around. As for the five people who’d resisted infection the first time around, all became infected this time, but only one developed symptoms.
The researchers struggled to explain the results. “These data do not fit any simple model,” they wrote in their report. “It may be that the small amounts of antibody remaining in the original infected group contributed to resistance to reinfection in some volunteers. It may also have prevented colds and shortened the duration of virus shedding.”
Three decades on, as a pandemic caused by a different coronavirus rages, researchers are still scratching their heads over whether coronaviruses—in particular, SARS-CoV-2—provoke lasting immunity in people they infect. With no long-term data yet on the immune and other effects of SARS-CoV-2 infection, some scientists are returning to 229E and three other coronaviruses that have been with humans much longer—OC43, NL63, and HKU1—in hopes of finding clues to this question.
Tracking infections
One study hoping to shed light on immunity after a coronavirus infection, posted on medRxiv in June and not yet peer-reviewed, drew on blood samples from healthy control subjects in an ongoing HIV project that began in 1985. [Update: This study has now been peer-reviewed and was published in Nature Medicine on September 14.] Researchers based at the Amsterdam University Medical Center (UMC) and their colleagues at other institutions analyzed stored samples from 10 subjects who had their blood collected every three to six months for at least 10 years, looking for antibodies to proteins from the four known cold-causing coronaviruses that would indicate a recent viral infection.
See “A Brief History of Human Coronaviruses”
The research team knew of the earlier 229E reinfection study, so they weren’t surprised to see multiple 229E infections in the same subjects crop up in their own data, as revealed by increases in antibody levels, says Arthur Edridge, a physician and Amsterdam UMC graduate student who is the paper’s first author. “What was surprising for us is that [reinfection] actually seemed to be a common feature for all the seasonal coronaviruses that we studied,” he says. All but one study subject had been infected with a particular coronavirus multiple times over the period of the study, and in some cases the time between infections with the same virus was as little as six months to a year, indicating an “alarmingly short duration of protective immunity,” the authors write in their paper.
Edridge cautions that it’s not clear whether SARS-CoV-2 will follow the same pattern as these more familiar coronaviruses—but if it does, then the idea that allowing the virus to spread in order to achieve herd immunity wouldn’t be a successful strategy, he adds.
Another recent study to find evidence of coronavirus reinfection was an analysis of data from a respiratory virus monitoring program conducted between 2016 and 2018. That study, which included 214 children and adults in New York City and relied on self-reports of symptoms and viral RNA swabbed from the back of the throat, found 12 instances of reinfection by the same coronavirus, although nine of these were in children, whose immune systems are less developed than those of adults. Reinfections were found for three of the four cold-causing coronaviruses (OC43, HKU1, and 229E).
It’s not clear whether SARS-CoV-2 will follow the same pattern as these more familiar coronaviruses—but if it does, then the idea that allowing the virus to spread in order to achieve herd immunity wouldn’t be a successful strategy.
Marta Galanti, a postdoc at Columbia University and the study’s first author, notes that the reinfections fell into two clusters in terms of timeline: at four to eight weeks after the initial infection, and at 8 to 10 months after the initial infection. She and her coauthor weren’t able to rule out the possibility that the earlier reinfections were in fact persistent first infections, she says, although they’re working on this in a follow-up study.
Like Edridge, Galanti is clear that the reinfection results don’t necessarily apply to SARS-CoV-2. But, she says, they indicate that “we have to be prepared [for] the possibility that the multiple subsequent infections can happen” with the novel coronavirus.
“Maybe it’s possible that if you only have these mild respiratory symptoms [with SARS-CoV-2 infection], you don’t develop a really strong immune response, and you could get reinfected,” says Rachel Roper, an immunologist at East Carolina University who was not involved in either of the studies. But she still thinks there’s uncertainty about whether reinfections occur with endemic coronaviruses, and she adds that infection with murine hepatitis virus, a coronavirus that causes serious disease in mice, confers lifelong immunity, as she suspects more severe cases of COVID-19 would. “If you had a serious infection the first time, all indications are you’ve got a stronger immune response,” and would either be immune to a second infection or experience only mild symptoms the second time around.
Prospects for long-term immunity
In general, whether a viral infection elicits long-term immunity depends on characteristics of both the virus and the host, says Akiko Iwasaki, an immunologist at Yale University. She adds that studies have found that the number of antibodies produced by COVID-19 patients varies widely, which may indicate that their protection against future infection also varies. Other studies have shown that levels of antibodies to SARS-CoV-2 tend to wane after a few months. But Iwasaki adds that antibodies don’t reveal the full picture of immunity, as even if antibodies to a virus are at undetectable levels, people who’ve been exposed to the pathogen before may be able to mount a quick response thanks to T cells and B cells that “remember” the previous infection.
Even if immunity to SARS-CoV-2 does turn out to be short-lived after infection, it might not be bad news for vaccine development, says Roper. “A lot of viruses, when they infect, also do things to turn off the mammalian immune response,” she says. “Hopefully, when we design vaccines, the vaccines won’t have those proteins that shut off the host immune response. So it should be possible to get a better immune response to the vaccine than you do to the virus.”


thescientist--2020-08-18--COVID-19 Outbreaks Occur as Students Return to Campus

As college campuses across the US welcome students back for the start of the semester , numerous universities are faced with isolating individuals who are testing positive for COVID-19 , Inside Higher Ed reports .
For the University of North Carolina at Chapel Hill ( UNC ) , the spread of multiple clusters of COVID-19 cases has caused the school to transition to online-only classes for the duration of the semester , effective Wednesday , August 19 .
After the first week of in-person classes , UNC announced four COVID-19 outbreaks , resulting in the quarantine of three residence halls @ @ @ @ @ @ @ 130 students and five staff members since August 10 .
The Daily Tar Heel , UNC ’ s student newspaper , tweeted Monday afternoon that in the wake of these cases , the university is suspending in-person instruction .
Some of the earliest COVID-19 outbreaks on college campuses involved football players who returned to school up to two months before their peers for summer workouts , The New York Times reported earlier this summer .
In the wake of so many schools experiencing outbreaks , many sports that are high- or moderate-risk for @ @ @ @ @ @ @ soccer , have been postponed until the spring .
Additionally , some schools , including the University of Maryland , have announced limitations on the number of students who can live in their residence halls .
Other universities had anticipated such problems and scrapped in-person instruction from the get-go .
Here are some of the outbreaks that have occurred at college campuses both over the summer and as students have returned for the fall semester : Note : This is a working list and will be updated .
If you have an update @ @ @ @ @ @ @ Winter at lwinter @ the-scientist.com .

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As college campuses across the US welcome students back for the start of the semester, numerous universities are faced with isolating individuals who are testing positive for COVID-19, Inside Higher Ed reports. For the University of North Carolina at Chapel Hill (UNC), the spread of multiple clusters of COVID-19 cases has caused the school to transition to online-only classes for the duration of the semester, effective Wednesday, August 19.
After the first week of in-person classes, UNC announced four COVID-19 outbreaks, resulting in the quarantine of three residence halls and one off-campus fraternity house, totaling 130 students and five staff members since August 10. The Daily Tar Heel, UNC’s student newspaper, tweeted Monday afternoon that in the wake of these cases, the university is suspending in-person instruction.
Some of the earliest COVID-19 outbreaks on college campuses involved football players who returned to school up to two months before their peers for summer workouts, The New York Times reported earlier this summer.
In the wake of so many schools experiencing outbreaks, many sports that are high- or moderate-risk for COVID-19 transmission, such as football and soccer, have been postponed until the spring. Additionally, some schools, including the University of Maryland, have announced limitations on the number of students who can live in their residence halls. Other universities had anticipated such problems and scrapped in-person instruction from the get-go.
Here are some of the outbreaks that have occurred at college campuses both over the summer and as students have returned for the fall semester:
Note: This is a working list and will be updated. If you have an update to this list, please email Lisa Winter at lwinter@the-scientist.com.


thescientist--2020-08-11--Unpacking the Genetic Contribution of Glia to Parkinson’s Disease

Parkinson ’ s disease is the second most common neurodegenerative disorder .
It is characterized by misfolded alpha-synuclein deposits and @ @ @ @ @ lead to progressive motor impairment and disability .
Despite extensive efforts , there are no @ @ @ @ @ ’ s disease or related “ alpha-synucleinopathies.
” Glia may represent a source of untapped @ @ @ @ @ webinar sponsored by BioLegend , Abby Olsen , Associate Neurologist at Brigham and Women ’ @ @ @ @ @ how an innovative Drosophila model helps explore the genetic contribution of glia to Parkinson ’ @ @ @ @ @ will review how forward genetic screens identify novel glial genes and potential therapeutic targets for @ @ @ @ @ and patients .
• The role of alpha-synuclein in glia • The unique transcriptional signature @ @ @ @ @ Parkinson ’ s disease • The pathogenic effects and mechanisms of Parkinson ’ s disease @ @ @ @ @ the glia • Genetic screens to identify novel glial genes and potential therapeutic targets

FREE Webinar
Thursday, September 17, 2020
12:00 - 1:00 PM, Eastern Standard Time
Register Now
Parkinson’s disease is the second most common neurodegenerative disorder. It is characterized by misfolded alpha-synuclein deposits and dopaminergic neuron death, which lead to progressive motor impairment and disability. Despite extensive efforts, there are no disease-modifying therapies available for Parkinson’s disease or related “alpha-synucleinopathies.” Glia may represent a source of untapped therapeutic potential.
In this webinar sponsored by BioLegend, Abby Olsen, Associate Neurologist at Brigham and Women’s Hospital, will discuss how an innovative Drosophila model helps explore the genetic contribution of glia to Parkinson’s disease pathogenesis. She will review how forward genetic screens identify novel glial genes and potential therapeutic targets for downstream investigation in mammalian systems and patients.
Topics to be covered


thescientist--2020-08-19--Influenza Aboard Dust Particles Infects Guinea Pigs

The current pandemic has shown how viruses such as SARS-CoV-2 can be shed while breathing , coughing , or sneezing , even when wearing a mask .
Now , a new study using guinea pigs hints at an additional transmission mechanism : the animals spread influenza to their neighbors via airborne dust , dander , and fur , and the vast majority of airborne particulates emitted from the guinea pigs came not from their breath , but from dust they kicked up , the authors reported August 18 in Nature Communications .
The experiments did not assess whether the coronavirus @ @ @ @ @ @ @ ’ s really shocking to most virologists and epidemiologists that airborne dust , rather than expiratory droplets , can carry influenza virus capable of infecting animals , ” William Ristenpart , a chemical engineer at the University of California , Davis , and a coauthor on the study , says in a press release .
“ The implicit assumption is always that airborne transmission occurs because of respiratory droplets .
.
.
.
Transmission via dust opens up whole new areas of investigation.
” See “ Coronavirus Found on Food Packaging , but @ @ @ @ @ @ @ , airborne fomites , surfaces that can harbor viruses , might come from used tissues , sheets , clothing , or the personal protective equipment ( PPE ) worn by medical professionals , Science News reports .
The team carried out several experiments to determine how many particles the animals were generating , whether virus-laden dust could move to other cages , and once there , if the viral particles were capable of infecting other guinea pigs .
First , the researchers used an aerodynamic particle sizer to monitor the microscopic dust released @ @ @ @ @ @ @ The number of particles depended on how active the animals were , Ristenpart tells Popular Science , and the most energetic rodents released up to 1,000 particles per second .
Later , after the same animals had been infected with influenza , the team found the virus on their fur , ears , and paws .
Because guinea pigs don ’ t sneeze when they have the flu , researchers say the virus may end up on different parts of the animals as they walk and groom .
Lisa Marr , an environmental @ @ @ @ @ @ @ involved in the study , tells Popular Science that this “ personal cloud of aerosols ” is sometimes referred to as the “ Pigpen Effect , ” named after the Charlie Brown character .
She adds that humans too kick up dust in this way , in addition to breathing out respiratory particles .
To filter out the proportion of aerosols produced by breathing , Ristenpart next created what he calls “ guinea pig burritos , ” wrapping anesthetized animals in a small aluminum sleeve to block dust particles .
The team measured @ @ @ @ @ @ @ a small hole left for their noses .
The captured particles were much less abundant than in the previous experiment , showing that airborne fomites are responsible for most of the particles given off by guinea pigs .
Lastly , Ristenpart and his colleagues needed to show that these particles were capable of infecting other animals at a distance—many viruses , including SARS-CoV-2 , can reside on contaminated surfaces , but may not remain infectious for long outside of a host .
Once the infected guinea pigs had recovered and become immune to @ @ @ @ @ @ @ onto their fur and placed the animals in cages separated from , but near , cages with an uninfected guinea pig inside .
In three of the 12 pairs , the second rodent fell ill , indicating that the virus was moving through the air , potentially from dust and dander .
Taken together , this work “ suggests that there is a mode of [ virus ] transmission that is underappreciated ” for influenza , Ristenpart tells Science News , adding that only “ dust liberated from a virus-laden surface ” is @ @ @ @ @ @ @ is needed to determine whether these findings apply to COVID-19 , although they are in line with observations from previous studies .
For example , work published in Nature in April found that in two hospitals in Wuhan , the concentration of the virus was higher in the rooms where medical professionals changed out of their PPE than in patients ’ rooms , Popular Science reports .
The authors suggested this might be due to dust and microscopic fibers shed by the clothing .
In addition , Ristenpart tells Science News about another @ @ @ @ @ @ @ review , in which he analyzed the fibers shed by cotton face masks .
Not everyone agrees the results of the current study will translate into humans .
Julian Tang , a virologist and fluid dynamicist at the University of Leicester who was not involved in the study , tells Science News it may be that dust kicked up from guinea pig bedding simply aerosolizes more easily than human sources such as clothing or bedding .
“ I ’ m really not convinced that in humans , this aerosolized fomite route will play @ @ @ @ @ @ @ Tang says .
See “ How Our Exhalations Help Spread Pathogens Such as SARS-CoV-2 ”

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The current pandemic has shown how viruses such as SARS-CoV-2 can be shed while breathing, coughing, or sneezing, even when wearing a mask. Now, a new study using guinea pigs hints at an additional transmission mechanism: the animals spread influenza to their neighbors via airborne dust, dander, and fur, and the vast majority of airborne particulates emitted from the guinea pigs came not from their breath, but from dust they kicked up, the authors reported August 18 in Nature Communications. The experiments did not assess whether the coronavirus can be transmitted similarly.
“It’s really shocking to most virologists and epidemiologists that airborne dust, rather than expiratory droplets, can carry influenza virus capable of infecting animals,” William Ristenpart, a chemical engineer at the University of California, Davis, and a coauthor on the study, says in a press release. “The implicit assumption is always that airborne transmission occurs because of respiratory droplets. . . . Transmission via dust opens up whole new areas of investigation.”
In humans, airborne fomites, surfaces that can harbor viruses, might come from used tissues, sheets, clothing, or the personal protective equipment (PPE) worn by medical professionals, Science News reports.
The team carried out several experiments to determine how many particles the animals were generating, whether virus-laden dust could move to other cages, and once there, if the viral particles were capable of infecting other guinea pigs.
First, the researchers used an aerodynamic particle sizer to monitor the microscopic dust released by guinea pigs in their cage. The number of particles depended on how active the animals were, Ristenpart tells Popular Science, and the most energetic rodents released up to 1,000 particles per second. Later, after the same animals had been infected with influenza, the team found the virus on their fur, ears, and paws. Because guinea pigs don’t sneeze when they have the flu, researchers say the virus may end up on different parts of the animals as they walk and groom.
Lisa Marr, an environmental engineer at Virginia Tech who was not involved in the study, tells Popular Science that this “personal cloud of aerosols” is sometimes referred to as the “Pigpen Effect,” named after the Charlie Brown character. She adds that humans too kick up dust in this way, in addition to breathing out respiratory particles.
To filter out the proportion of aerosols produced by breathing, Ristenpart next created what he calls “guinea pig burritos,” wrapping anesthetized animals in a small aluminum sleeve to block dust particles. The team measured the particles the animals breathed out of a small hole left for their noses. The captured particles were much less abundant than in the previous experiment, showing that airborne fomites are responsible for most of the particles given off by guinea pigs.
See “Simple Tool Evaluates Mask Performance at Blocking Droplets”
Lastly, Ristenpart and his colleagues needed to show that these particles were capable of infecting other animals at a distance—many viruses, including SARS-CoV-2, can reside on contaminated surfaces, but may not remain infectious for long outside of a host.
Once the infected guinea pigs had recovered and become immune to the flu, the researchers painted influenza onto their fur and placed the animals in cages separated from, but near, cages with an uninfected guinea pig inside. In three of the 12 pairs, the second rodent fell ill, indicating that the virus was moving through the air, potentially from dust and dander.
Taken together, this work “suggests that there is a mode of [virus] transmission that is underappreciated” for influenza, Ristenpart tells Science News, adding that only “dust liberated from a virus-laden surface” is likely to be infectious.
Further research is needed to determine whether these findings apply to COVID-19, although they are in line with observations from previous studies. For example, work published in Nature in April found that in two hospitals in Wuhan, the concentration of the virus was higher in the rooms where medical professionals changed out of their PPE than in patients’ rooms, Popular Science reports. The authors suggested this might be due to dust and microscopic fibers shed by the clothing. In addition, Ristenpart tells Science News about another of his studies, currently undergoing peer review, in which he analyzed the fibers shed by cotton face masks.
Not everyone agrees the results of the current study will translate into humans. Julian Tang, a virologist and fluid dynamicist at the University of Leicester who was not involved in the study, tells Science News it may be that dust kicked up from guinea pig bedding simply aerosolizes more easily than human sources such as clothing or bedding. “I’m really not convinced that in humans, this aerosolized fomite route will play any [major] role,” Tang says.


thescientist--2020-08-19--Revealing the Complexities of Cancer with Single-cell RNA Analysis

Solid tumors are comprised of a variety of cell types that affect tumor growth and treatment success .
Bulk RNA @ @ @ @ @ unique gene expression profiles of individual cells , allowing researchers to overlook rare but interesting @ @ @ @ @ Using single-cell RNA-sequencing , researchers can begin to tease apart different cell types ’ contributions @ @ @ @ @ resistance .
Download this eBook from The Scientist and BD Biosciences to discover more about

Solid tumors are comprised of a variety of cell types that affect tumor growth and treatment success. Bulk RNA sequencing of tumors masks the unique gene expression profiles of individual cells, allowing researchers to overlook rare but interesting subpopulations of malignant cells. Using single-cell RNA-sequencing, researchers can begin to tease apart different cell types’ contributions to cancer progression and treatment resistance.
Download this eBook from The Scientist and BD Biosciences to discover more about


thescientist--2020-08-19--Immune Biomarkers Tied to Severe COVID-19: Study

A study of COVID-19 patients at two London hospitals has identified blood-based immunological changes that are linked to the disease and , in some cases , to symptom severity .
The results , reported in Nature Medicine on Monday ( August 17 ) join a growing body of data on how the human immune system responds to SARS-CoV-2 that will hopefully lead to prognostic tools and potential treatments .
“ The study is a nice comprehensive characterization of the different trajectories of host response against SARS-CoV-2 [ and ] technically well performed , ” Antonio Bertoletti an emerging infectious disease @ @ @ @ @ @ @ was not involved in the research , writes in an email to The Scientist .
It provides “ some specific findings , like the severe drop of dendritic cells and the inflammatory cytokine profile , ” he adds , “ [ that ] might predict the worsening of the disease.
” Microbiologist and immunologist Stanley Perlman of the University of Iowa who also was not a part of the research team is less optimistic about the potential for prediction .
“ They came up with parameters that seem to define the different [ @ @ @ @ @ @ @ , “ but for an individual [ patient ] it ’ s very hard ” to make a prediction because “ there is so much overlap ” between the groups .
He nonetheless praises the efforts of the authors of the paper and similar endeavors , saying such studies provide “ a sense for what seems to be happening in people who do worse , which in itself is useful , if not for prognosis .
.
.
it can help you in management [ of the disease ] .
” Since late @ @ @ @ @ @ @ been relentlessly and rampantly spreading from person to person across the globe .
While in many people the virus causes no ill effects , in others it ravages the lungs , leaving them hospitalized for weeks , and in some the infection is fatal .
More than 780,000 people have died from the disease worldwide to date .
For a disease with such diversity of symptoms and outcomes , and in patients of different ages and sexes with different underlying conditions , finding a common immune signature for COVID-19—a set of immune proteins @ @ @ @ @ @ @ like an impossibility , but immunologist Adrian Hayday of King ’ s College London and the Francis Crick Institute was not discouraged by the odds .
Despite “ extraordinary heterogeneity ” within patient populations , he says , “ immune responses against potentially lethal pathogens can have very dominant effects that rise above the background and therefore provide you with an immune signature.
” Discovering such a signature would be of great value , he explains .
For one thing , “ you might find things that are unique to COVID-19 and that @ @ @ @ @ @ @ to target therapeutically , ” he says .
And , it might identify “ changes that actually could give the doctors a very early indication of which way a patient was going to go.
” For Hayday and his colleagues ’ study , the team collected blood samples from 63 patients with mild , moderate , and severe COVID-19 who were admitted to Guys and St. Thomas ’ s hospitals in London from March to May this year , and from 55 control individuals , including healthy people who had previously tested positive @ @ @ @ @ @ @ or mild symptoms ) , people with other respiratory tract infections , and healthy individuals with no recent respiratory infections .
The researchers performed flow cytometry experiments and protein assays on the blood samples to analyze the presence and characteristics of various immune cell types and to measure antibodies and other immune factors .
Among the results , the team found that almost all COVID-19 patients had robust production of anti–SARS-CoV-2 antibodies—which raises questions about the general usefulness of convalescent plasma treatment , which supplies antibodies from recovered donors , says clinician scientist @ @ @ @ @ @ @ London who coauthored the study .
Indeed , the FDA ’ s plan to approve the treatment is now on hold due to lack of evidence of efficacy .
A report in Immunity , however , suggests antibody quality , not quantity , is linked to outcome and therefore that plasma from survivors might be qualitatively better than that of very sick patients .
There were also three patients in Haday and Shankar-Hari ’ s study in whom no antibodies were detected and all three died , suggesting select individuals may benefit .
@ @ @ @ @ @ @ also enriched for plasmablasts ( antibody secreting cells ) , markers of T cell exhaustion , and the cytokines IL-8 , IL-6 , IL-10 , and IP-10 , while lacking in basophils and certain subpopulations of dendritic cells and monocytes compared with healthy controls .
Some of these immune features were also seen in patients with other respiratory tract infections .
Others , such as low basophils and dendritic cells and high IP-10 , were particular to COVID-19 .
Some features correlated with the severity of disease .
Through a longitudinal study of @ @ @ @ @ @ @ during the hospital stay—the team showed that those patients who had high levels of IL-6 , IL-10 , and especially IP-10 when their first blood sample was taken were more likely to have a poorer outcome than patients in whom these cytokine levels were lower .
The trio of cytokines was “ quite an extraordinary predictor that could discern whether a patient at admission with respiratory difficulties would actually improve or worsen , ” says Hayday .
IP-10 levels in a patient ’ s first blood sample could even predict the length of @ @ @ @ @ @ @ It ’ s a great paper , ” says Michael Betts of the University of Pennsylvania who was not involved in the work , and “ it certainly agrees with a lot of the literature that has accumulated already.
” He notes that while some differences exist between the new results and other COVID-19 signature studies , for the most part they are similar .
Hayday ’ s group has made the raw data available here .
It remains to be seen—in longitudinal validation studies with a larger cohort of patients—whether the trio @ @ @ @ @ @ @ severity , says Shankar-Hari , and whether they might be worthy targets for therapy .
For now , “ we still know little about why different infected individuals [ have ] such diversity of symptoms and outcomes , ” writes Bertoletti , “ but at least we start to understand what is occurring in such different manifestations and this is important to clinical management .
”

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A study of COVID-19 patients at two London hospitals has identified blood-based immunological changes that are linked to the disease and, in some cases, to symptom severity. The results, reported in Nature Medicine on Monday (August 17) join a growing body of data on how the human immune system responds to SARS-CoV-2 that will hopefully lead to prognostic tools and potential treatments.
“The study is a nice comprehensive characterization of the different trajectories of host response against SARS-CoV-2 [and] technically well performed,” Antonio Bertoletti an emerging infectious disease researcher at Duke-National University of Singapore who was not involved in the research, writes in an email to The Scientist. It provides “some specific findings, like the severe drop of dendritic cells and the inflammatory cytokine profile,” he adds, “[that] might predict the worsening of the disease.”
Microbiologist and immunologist Stanley Perlman of the University of Iowa who also was not a part of the research team is less optimistic about the potential for prediction. “They came up with parameters that seem to define the different [severity] groups,” he says, “but for an individual [patient] it’s very hard” to make a prediction because “there is so much overlap” between the groups.
He nonetheless praises the efforts of the authors of the paper and similar endeavors, saying such studies provide “a sense for what seems to be happening in people who do worse, which in itself is useful, if not for prognosis . . . it can help you in management [of the disease].”
There have been a number of recent papers describing immune signatures of COVID-19, including ones in Science, Science Immunology, Nature and Immunity. Read The Scientist’s coverage of the Immunity paper here.
Since late 2019, the novel coronavirus SARS-CoV-2 has been relentlessly and rampantly spreading from person to person across the globe. While in many people the virus causes no ill effects, in others it ravages the lungs, leaving them hospitalized for weeks, and in some the infection is fatal. More than 780,000 people have died from the disease worldwide to date.
For a disease with such diversity of symptoms and outcomes, and in patients of different ages and sexes with different underlying conditions, finding a common immune signature for COVID-19—a set of immune proteins and cells that define the disease—may seem like an impossibility, but immunologist Adrian Hayday of King’s College London and the Francis Crick Institute was not discouraged by the odds.
Despite “extraordinary heterogeneity” within patient populations, he says, “immune responses against potentially lethal pathogens can have very dominant effects that rise above the background and therefore provide you with an immune signature.”
Discovering such a signature would be of great value, he explains. For one thing, “you might find things that are unique to COVID-19 and that might give you some very important things to target therapeutically,” he says. And, it might identify “changes that actually could give the doctors a very early indication of which way a patient was going to go.”
For Hayday and his colleagues’ study, the team collected blood samples from 63 patients with mild, moderate, and severe COVID-19 who were admitted to Guys and St. Thomas’s hospitals in London from March to May this year, and from 55 control individuals, including healthy people who had previously tested positive for coronavirus (and had had no or mild symptoms), people with other respiratory tract infections, and healthy individuals with no recent respiratory infections.
The researchers performed flow cytometry experiments and protein assays on the blood samples to analyze the presence and characteristics of various immune cell types and to measure antibodies and other immune factors.
IP-10 levels in a patient’s first blood sample could even predict the length of hospital stay
Among the results, the team found that almost all COVID-19 patients had robust production of anti–SARS-CoV-2 antibodies—which raises questions about the general usefulness of convalescent plasma treatment, which supplies antibodies from recovered donors, says clinician scientist Manu Shankar-Hari of King’s College London who coauthored the study. Indeed, the FDA’s plan to approve the treatment is now on hold due to lack of evidence of efficacy. A report in Immunity, however, suggests antibody quality, not quantity, is linked to outcome and therefore that plasma from survivors might be qualitatively better than that of very sick patients. There were also three patients in Haday and Shankar-Hari’s study in whom no antibodies were detected and all three died, suggesting select individuals may benefit.
As a whole, patient samples were also enriched for plasmablasts (antibody secreting cells), markers of T cell exhaustion, and the cytokines IL-8, IL-6, IL-10, and IP-10, while lacking in basophils and certain subpopulations of dendritic cells and monocytes compared with healthy controls.
Some of these immune features were also seen in patients with other respiratory tract infections. Others, such as low basophils and dendritic cells and high IP-10, were particular to COVID-19.
Some features correlated with the severity of disease. Through a longitudinal study of individual patients—taking blood samples on different days during the hospital stay—the team showed that those patients who had high levels of IL-6, IL-10, and especially IP-10 when their first blood sample was taken were more likely to have a poorer outcome than patients in whom these cytokine levels were lower.
The trio of cytokines was “quite an extraordinary predictor that could discern whether a patient at admission with respiratory difficulties would actually improve or worsen,” says Hayday. IP-10 levels in a patient’s first blood sample could even predict the length of hospital stay, he adds.
“It’s a great paper,” says Michael Betts of the University of Pennsylvania who was not involved in the work, and “it certainly agrees with a lot of the literature that has accumulated already.” He notes that while some differences exist between the new results and other COVID-19 signature studies, for the most part they are similar.
Hayday’s group has made the raw data available here.
It remains to be seen—in longitudinal validation studies with a larger cohort of patients—whether the trio of cytokines will be reliable predictors of severity, says Shankar-Hari, and whether they might be worthy targets for therapy.
For now, “we still know little about why different infected individuals [have] such diversity of symptoms and outcomes,” writes Bertoletti, “but at least we start to understand what is occurring in such different manifestations and this is important to clinical management.”
A.G. Laing et al., “A dynamic COVID-19 immune signature includes associations with poor prognosis,” Nat Med, doi:10.1038/s41591-020-1038-6, 2020.


Reprobing Immunoassay Samples

Protein expression drives many biological and pathological processes .
Identifying and quantifying changes in protein levels is therefore critical for @ @ @ @ @ health and disease .
However , disease research is plagued by limited sample sizes , @ @ @ @ @ used to assess protein expression require relatively large amounts of sample to generate each data @ @ @ @ @ a solution to this problem by offering highly reproducible quantitative data while consuming miniscule sample @ @ @ @ @ probe the same sample with multiple antibodies without disrupting epitope integrity .
Download this application @ @ @ @ @ , a complete protein analysis solution from ProteinSimple , automates multiplexed protein detection and quantification @

Protein expression drives many biological and pathological processes. Identifying and quantifying changes in protein levels is therefore critical for understanding the underlying mechanisms behind health and disease. However, disease research is plagued by limited sample sizes, and the most common assays used to assess protein expression require relatively large amounts of sample to generate each data point.
Capillary-based immunoassays present a solution to this problem by offering highly reproducible quantitative data while consuming miniscule sample amounts. Capillary-based immunoassays can probe the same sample with multiple antibodies without disrupting epitope integrity.
Download this application note to explore how JessTM, a complete protein analysis solution from ProteinSimple, automates multiplexed protein detection and quantification.


thescientist--2020-08-19--Combating COVID-19 with Cell-Free Expression

Imagine the ability to rewire , reshape , and use parts of a living system to build something new .
It is not science fiction , nor is it Frankenstein ’ s monster .
It is synthetic biology , a relatively nascent field that is making a profound impact on society and healthcare .
As the world continues to grapple with the ongoing effects of the COVID-19 pandemic , researchers are turning to synthetic biology , and in particular , to cell-free expression systems to develop new rapid diagnostic tools , vaccines , and treatments .
“ It ’ s @ @ @ @ @ @ @ all do that every day in our cell phones ; we program information in zeros and ones .
Synthetic biology takes that to a totally new dimension .
Rather than just being able to control information , I now get to control information that builds atoms , ” said Michael Jewett , a professor of chemical and biological engineering at Northwestern University .
Synthetic biologists such as Jewett combine engineering principles , computer programming , and molecular biology to design and build synthetic gene circuits and other molecular components that rewire living cells @ @ @ @ @ @ @ including biological sensors and diagnostic tests .
Rewiring a living system is tricky .
Cells are already biologically programmed to achieve their own functional goals , not the goals of the researcher .
To circumvent this problem , synthetic biologists remove the cell wall and extract the cell ’ s molecular machinery , including the core factors needed for transcription and translation .
This cell-free expression system can then be coerced to produce and even detect proteins of interest .
“ It 's like if you took a car , you lift up @ @ @ @ @ @ @ , and you repurpose it for something else .
We 're repurposing the molecular machinery to do some objective function , ” said Jewett .
Working outside a cellular system prevents the cell from responding and changing its gene expression profile , ensuring a reproducible and stable molecular expression system .
“ The complexities itself are much lower than that of the living cells , and it 's easier to control the different features in that you can dictate , at least at the outset , what [ compounds ] are there and @ @ @ @ @ @ @ James Collins a professor of biological engineering at the Massachusetts Institute of Technology .
Scientists have used cell-free expression systems for two decades as a basic research tool to make discoveries about the living world .
In fact , scientists used cell-free systems to uncover the genetic code in the 1960s .
However , many of these early systems were small-scale , did not last very long , and could not make complex proteins .
Within the last 20 years , researchers have addressed each of these problems , transforming cell-free expression systems @ @ @ @ @ @ @ technology platform .
“ The systems now , instead of lasting five minutes , last 15 to 20 hours in batch reactions .
They can make really complex proteins all the way up to full-length antibodies , which are used in medicine .
They can carry out pretty complex integrated circuitry that can basically detect , sense , and respond to something just like a cell , ” said Jewett .
Researchers also developed better ways to support cell-free expression systems by supplying the system with glucose as a source of energy and @ @ @ @ @ @ @ needed to produce proteins .
Scientists even solved the problem of scalability .
“ If you imagine running a PCR reaction , which is typically two or five microliters , in a 1000-liter scale , that 's what we 're doing economically , which is crazy .
In fact , many people kind of deemed that impossible 10 years ago , but it 's happening , ” said Jewett .
Cell-free expression systems can be rapidly pre-assembled and stored in a laboratory freezer , or freeze-dried in a powdered form .
This eliminates @ @ @ @ @ @ @ .
“ The problems then reduce to automated liquid handling , ” said Jewett .
Automated liquid handling robots enable researchers to run more samples at a time for rapid library screening or analyzing genetic parts and gene circuits .
Making cell-free expression systems is an art that , much like any other laboratory technique , takes skill , practice , and time .
Some researchers make their own cell-free expression systems , but others purchase commercial ready-to-use master mixes .
These mixes , such as the myTXTL® Cell-Free Expression System from Arbor @ @ @ @ @ @ @ molecular components for a given reaction so that the researcher only has to add their DNA sample for reliable and robust high-yield protein expression .
“ The homebrew has some really nice efforts by Michael Jewett and his team to get them highly functional , but when we make our own , we 're not as good and so it often doesn ’ t have the functionality level that we need , ” said Collins .
“ My team has used Arbor Biosciences ; they have very good products .
In the cell-free @ @ @ @ @ @ @ go-to [ companies ] .
” Like homebrewed systems , purchased premixed cell-free systems can also be paired with automated liquid handling for high-throughput and efficient library screening or analysis .
These advances made it possible for synthetic biologists to develop practical technologies that mitigate disease and impact society .
When the COVID-19 pandemic struck , synthetic biologists pivoted the cell-free expression technology that they were using for other diseases to develop new diagnostics , materials , and treatments specifically for COVID-19 .
Keith Pardee , a synthetic biologist at the University of @ @ @ @ @ @ @ to send Zika virus diagnostic testing kits to low- and middle-income countries .
“ When the COVID-19 outbreak happened , we thought this is obviously a natural thing for us to do .
So , we basically are taking that platform for Zika and applying it to SARS-CoV-2 , ” said Pardee .
Pardee extracts enzymes needed for transcription and translation from Escherichia coli to create a cell-free expression system that senses parts of the SARS-CoV-2 genome and triggers a molecular switch to produce a reporter protein .
It also eliminates the need @ @ @ @ @ @ @ can replace RT-PCR for more rapid diagnostic testing .
“ Because we didn ’ t have that black box of working with a cell , we were able to get sensors very quickly , maybe within two days of having the synthetic DNA arrive in the lab , we had sensors working , ” said Pardee .
Pardee will send COVID-19 diagnostic kits in two waves to the same countries that he was planning to send the Zika kits , only now he has added Toronto , Canada to the list .
The @ @ @ @ @ @ @ a day for two weeks .
The second wave will contain a “ lab-in-a-box , ” that could convert a common microbiology lab into a diagnostic testing lab to maintain a sustained testing capacity .
Similarly , James Collins was developing a suite of clothing-based sensors for healthcare workers , first responders , and military personnel to detect the presence of viruses or compounds .
“ The idea would be like a lab coat of the future , ” said Collins .
He conceived the idea during the Ebola outbreak of 2014 .
@ @ @ @ @ @ @ systems and locked them onto a piece of paper , and later into fabric .
They then showed that the system could be rehydrated and transcription and translation activated by adding liquid .
“ We were revising this publication when the pandemic hit , and realized that we could embody the same technology into facemasks by having an insert that can be added .
If a person is infected , they 'll give out particles in water vapor—that is coughing , sneezing , talking—and that itself could activate these freeze-dried components , ” @ @ @ @ @ @ @ infected , the mask would produce a fluorescent signal that could be detected using a handheld fluorometer .
Collins ’ s previous discoveries in synthetic biology also contributed to the technology behind the Moderna vaccine for COVID-19 , which is in the late-stages of development .
Ten years ago , with George Daly and Derek Rossi , Collins developed a stable synthetic mRNA system to express proteins directly in cells .
They used the technology to efficiently reprogram induced pluripotent stem cells , but mentioned in the paper that the technology could be @ @ @ @ @ @ @ I 've been so motivated by so many scientists , by how much we 're all redirecting ; we 're pivoting , ” said Jewett .
Four months ago , Jewett ’ s research focused primarily on developing water-based diagnostics for identifying toxins .
Using the same cell-free expression approaches , Jewett is now developing CRISPR-based diagnostics for rapid COVID-19 detection and working on antiviral frontline approaches to stop COVID-19 infection .
Using cell-free expression systems , Jewett ’ s team identifies proteins that could cloak the COVID-19 spike protein and prevent its @ @ @ @ @ @ @ clones using classic mammalian cell-culture can take 12 -18 months .
“ We need two months .
We need four weeks .
We need to have technologies that can meet the pace of this pandemic , ” said Jewett .
Instead of growing cells , Jewett and his team thaw pre-built , frozen cell-free expression stocks , add DNA , and identify good candidates within a day .
If other laboratories are interested in pivoting but are unable to pre-assemble frozen stocks or lack the technical experience needed , they can reach out @ @ @ @ @ @ @ Biosciences for reliable cell-free expression systems .
Arbor Biosciences is adept at developing robust cell-free systems that can be immediately implemented in COVID-19 research or in other disease-based research for rapid , efficient , and dependable discovery .
“ In this era of emergent and reemerging pandemic outbreaks , what we need is speed .
Cell-free systems really offer this exciting component , and the technology is well suited to address that need , ” said Jewett .
Cell-free expression systems alone will not solve the COVID-19 pandemic , but it can complement @ @ @ @ @ @ @ developing .
We , like many others , have been conceiving ideas and schemes and now 's the time , ” said Jewett .
“ We have to make an impact with whatever we can.
” Arbor Biosciences is a development and manufacturing company founded by scientists to serve our peers in molecular biology applications .

Imagine the ability to rewire, reshape, and use parts of a living system to build something new. It is not science fiction, nor is it Frankenstein’s monster. It is synthetic biology, a relatively nascent field that is making a profound impact on society and healthcare. As the world continues to grapple with the ongoing effects of the COVID-19 pandemic, researchers are turning to synthetic biology, and in particular, to cell-free expression systems to develop new rapid diagnostic tools, vaccines, and treatments.
“It’s a way to program information. We all do that every day in our cell phones; we program information in zeros and ones. Synthetic biology takes that to a totally new dimension. Rather than just being able to control information, I now get to control information that builds atoms,” said Michael Jewett, a professor of chemical and biological engineering at Northwestern University.
Synthetic biologists such as Jewett combine engineering principles, computer programming, and molecular biology to design and build synthetic gene circuits and other molecular components that rewire living cells for a variety of new applications, including biological sensors and diagnostic tests.
Going Cell-Free
Rewiring a living system is tricky. Cells are already biologically programmed to achieve their own functional goals, not the goals of the researcher. To circumvent this problem, synthetic biologists remove the cell wall and extract the cell’s molecular machinery, including the core factors needed for transcription and translation. This cell-free expression system can then be coerced to produce and even detect proteins of interest.
“It's like if you took a car, you lift up the hood, pull out the engine, and you repurpose it for something else. We're repurposing the molecular machinery to do some objective function,” said Jewett. Working outside a cellular system prevents the cell from responding and changing its gene expression profile, ensuring a reproducible and stable molecular expression system.
“The complexities itself are much lower than that of the living cells, and it's easier to control the different features in that you can dictate, at least at the outset, what [compounds] are there and how much is there,” said James Collins a professor of biological engineering at the Massachusetts Institute of Technology.
Scientists have used cell-free expression systems for two decades as a basic research tool to make discoveries about the living world. In fact, scientists used cell-free systems to uncover the genetic code in the 1960s. However, many of these early systems were small-scale, did not last very long, and could not make complex proteins. Within the last 20 years, researchers have addressed each of these problems, transforming cell-free expression systems from a basic tool into a useable technology platform.
“The systems now, instead of lasting five minutes, last 15 to 20 hours in batch reactions. They can make really complex proteins all the way up to full-length antibodies, which are used in medicine. They can carry out pretty complex integrated circuitry that can basically detect, sense, and respond to something just like a cell,” said Jewett.
Researchers also developed better ways to support cell-free expression systems by supplying the system with glucose as a source of energy and other biological compounds such as amino acids needed to produce proteins. Scientists even solved the problem of scalability. “If you imagine running a PCR reaction, which is typically two or five microliters, in a 1000-liter scale, that's what we're doing economically, which is crazy. In fact, many people kind of deemed that impossible 10 years ago, but it's happening,” said Jewett.
Cell-free expression systems can be rapidly pre-assembled and stored in a laboratory freezer, or freeze-dried in a powdered form. This eliminates the need for researchers to regrow cells. “The problems then reduce to automated liquid handling,” said Jewett. Automated liquid handling robots enable researchers to run more samples at a time for rapid library screening or analyzing genetic parts and gene circuits.
Making cell-free expression systems is an art that, much like any other laboratory technique, takes skill, practice, and time. Some researchers make their own cell-free expression systems, but others purchase commercial ready-to-use master mixes. These mixes, such as the myTXTL® Cell-Free Expression System from Arbor Biosciences, come pre-loaded with all the molecular components for a given reaction so that the researcher only has to add their DNA sample for reliable and robust high-yield protein expression.
“The homebrew has some really nice efforts by Michael Jewett and his team to get them highly functional, but when we make our own, we're not as good and so it often doesn’t have the functionality level that we need,” said Collins. “My team has used Arbor Biosciences; they have very good products. In the cell-free world, they're one of the go-to [companies].” Like homebrewed systems, purchased premixed cell-free systems can also be paired with automated liquid handling for high-throughput and efficient library screening or analysis.
Pivoting
These advances made it possible for synthetic biologists to develop practical technologies that mitigate disease and impact society. When the COVID-19 pandemic struck, synthetic biologists pivoted the cell-free expression technology that they were using for other diseases to develop new diagnostics, materials, and treatments specifically for COVID-19.
Keith Pardee, a synthetic biologist at the University of Toronto was working on a three-year project to send Zika virus diagnostic testing kits to low- and middle-income countries. “When the COVID-19 outbreak happened, we thought this is obviously a natural thing for us to do. So, we basically are taking that platform for Zika and applying it to SARS-CoV-2,” said Pardee.
Pardee extracts enzymes needed for transcription and translation from Escherichia coli to create a cell-free expression system that senses parts of the SARS-CoV-2 genome and triggers a molecular switch to produce a reporter protein. It also eliminates the need to purify RNA from the sample and can replace RT-PCR for more rapid diagnostic testing. “Because we didn’t have that black box of working with a cell, we were able to get sensors very quickly, maybe within two days of having the synthetic DNA arrive in the lab, we had sensors working,” said Pardee.
Pardee will send COVID-19 diagnostic kits in two waves to the same countries that he was planning to send the Zika kits, only now he has added Toronto, Canada to the list. The first wave will supply 1000 test kits a day for two weeks. The second wave will contain a “lab-in-a-box,” that could convert a common microbiology lab into a diagnostic testing lab to maintain a sustained testing capacity.
Similarly, James Collins was developing a suite of clothing-based sensors for healthcare workers, first responders, and military personnel to detect the presence of viruses or compounds. “The idea would be like a lab coat of the future,” said Collins. He conceived the idea during the Ebola outbreak of 2014. Collins and his team freeze-dried cell-free expression systems and locked them onto a piece of paper, and later into fabric. They then showed that the system could be rehydrated and transcription and translation activated by adding liquid.
“We were revising this publication when the pandemic hit, and realized that we could embody the same technology into facemasks by having an insert that can be added. If a person is infected, they'll give out particles in water vapor—that is coughing, sneezing, talking—and that itself could activate these freeze-dried components,” said Collins. If a person were infected, the mask would produce a fluorescent signal that could be detected using a handheld fluorometer.
Collins’s previous discoveries in synthetic biology also contributed to the technology behind the Moderna vaccine for COVID-19, which is in the late-stages of development. Ten years ago, with George Daly and Derek Rossi, Collins developed a stable synthetic mRNA system to express proteins directly in cells. They used the technology to efficiently reprogram induced pluripotent stem cells, but mentioned in the paper that the technology could be used for RNA-based vaccine development.
“I've been so motivated by so many scientists, by how much we're all redirecting; we're pivoting,” said Jewett. Four months ago, Jewett’s research focused primarily on developing water-based diagnostics for identifying toxins. Using the same cell-free expression approaches, Jewett is now developing CRISPR-based diagnostics for rapid COVID-19 detection and working on antiviral frontline approaches to stop COVID-19 infection.
Using cell-free expression systems, Jewett’s team identifies proteins that could cloak the COVID-19 spike protein and prevent its connection to cell receptors. Identifying good clones using classic mammalian cell-culture can take 12 -18 months. “We need two months. We need four weeks. We need to have technologies that can meet the pace of this pandemic,” said Jewett. Instead of growing cells, Jewett and his team thaw pre-built, frozen cell-free expression stocks, add DNA, and identify good candidates within a day.
If other laboratories are interested in pivoting but are unable to pre-assemble frozen stocks or lack the technical experience needed, they can reach out to commercial providers, such as Arbor Biosciences for reliable cell-free expression systems. Arbor Biosciences is adept at developing robust cell-free systems that can be immediately implemented in COVID-19 research or in other disease-based research for rapid, efficient, and dependable discovery.
“In this era of emergent and reemerging pandemic outbreaks, what we need is speed. Cell-free systems really offer this exciting component, and the technology is well suited to address that need,” said Jewett. Cell-free expression systems alone will not solve the COVID-19 pandemic, but it can complement existing technologies. “Research is just developing. We, like many others, have been conceiving ideas and schemes and now's the time,” said Jewett. “We have to make an impact with whatever we can.”
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Connecting the DOTS

A few months before SARS sparked major outbreaks in several countries in early 2003 , there were a series of small clusters of infection in Guangdong province , in southern China .
Between November 2002 and January 2003 , seven clusters were reported in Guangdong , ranging from one to nine cases in size .
Based on the scope of these outbreaks , researchers later estimated that the reproduction number—R , which is defined as the average number of new infectious caused by a typical case—may have been around 0.8 during this period .
However , by the time the @ @ @ @ @ @ @ a couple of months later , SARS had an R of more than 2 .
There are several reasons the R of an infection may increase , and we can understand them better by breaking transmission down into four main components .
Consider the steps that lead an infectious person to spread the infection to others .
It depends on A ) the duration of time someone is infectious , B ) the opportunities for transmission during this period ( such as social interactions ) , C ) the transmission probability during each @ @ @ @ @ @ @ or sneezes ) , and D ) the probability that the person on the other end of the interaction is susceptible to that infection .
I like to call these four things the DOTS for short , and if we multiply them together we get the value of the reproduction number : For example , if a case is infectious for a week on average ( i.e .
duration ) , interacts with around five new people per day ( i.e .
opportunities ) , has a 5 percent chance of infecting each @ @ @ @ @ @ @ i.e .
transmission probability ) , and everyone is susceptible , we ’ d expect 7 x 5 x 0.05 x 1 = 1.75 secondary cases on average .
As I explain in my latest book , The Rules of Contagion , for infectious diseases , each of the DOTS can influence the extent of contagion .
One 2016 study estimated that viruses that transmitted successfully among humans tended to cause longer infections ( that is , larger duration value ) and spread directly from one person to another , rather than via @ @ @ @ @ @ @ more opportunities ) .
Transmission probability can also make a difference ; avian influenza viruses , such as H5N1 , have struggled to gain a foothold in people because they can ’ t latch onto the cells in our airway as easily as human viruses can .
That ’ s why there was concern in 2011 , when teams at Erasmus Medical Center and the University of Wisconsin–Madison announced that they had each created new strains of H5N1 .
Among other changes , mutations in these viruses could make them more capable of @ @ @ @ @ @ @ mammalian airway .
Unlike circulating avian influenza viruses—which had only spread between humans who ’ d come into close contact with each other—these mutant versions could go airborne , successfully spreading between ferrets in the lab .
An increase in susceptibility can also nudge the reproduction number higher , such as when vaccination coverage falls for diseases such as measles , which means outbreaks may follow .
As well as understanding how infections spread , the DOTS can provide insights into how we might control them .
In the case of HIV , @ @ @ @ @ @ @ duration of time someone is infectious , and fewer sexual partners can reduce the number of opportunities for transmission .
The latter generally isn ’ t an appealing option for most people , so health agencies have instead encouraged people to use condoms , which reduces the transmission probability during sexual encounters .
In recent years , there have also been successful programs of pre-exposure prophylaxis , whereby HIV-negative individuals take anti-HIV drugs to reduce their susceptibility to infection .
For SARS-CoV-2 , there isn ’ t yet a way to reduce susceptibility @ @ @ @ @ @ @ with infection , the duration of subsequent immunity remains unclear .
This means control measures have focused on decreasing the effective duration of infectiousness ( by isolating people with symptoms and quarantining their contacts ) , the number of opportunities ( by reducing social interactions ) , or limiting the probability of transmission with personal protective equipment .
Just as there ’ s not a single component of transmission that made the COVID-19 pandemic take off , there won ’ t be a simple solitary measure that will keep SARS-CoV-2 under control in @ @ @ @ @ @ @ future outbreaks , countries will have to connect together measures that can target several of the DOTS .
Adam Kucharski is an associate professor in the department of infectious disease epidemiology at the London School of Hygiene and Tropical Medicine .

A few months before SARS sparked major outbreaks in several countries in early 2003, there were a series of small clusters of infection in Guangdong province, in southern China. Between November 2002 and January 2003, seven clusters were reported in Guangdong, ranging from one to nine cases in size. Based on the scope of these outbreaks, researchers later estimated that the reproduction number—R, which is defined as the average number of new infectious caused by a typical case—may have been around 0.8 during this period. However, by the time the first major outbreak occurred in Hong Kong a couple of months later, SARS had an R of more than 2.
There are several reasons the R of an infection may increase, and we can understand them better by breaking transmission down into four main components. Consider the steps that lead an infectious person to spread the infection to others. It depends on A) the duration of time someone is infectious, B) the opportunities for transmission during this period (such as social interactions), C) the transmission probability during each opportunity (such as whether someone coughs or sneezes), and D) the probability that the person on the other end of the interaction is susceptible to that infection. I like to call these four things the DOTS for short, and if we multiply them together we get the value of the reproduction number:
R = duration x opportunities x transmission probability x susceptibility
For example, if a case is infectious for a week on average (i.e. duration), interacts with around five new people per day (i.e. opportunities), has a 5 percent chance of infecting each of these contacts during an interaction (i.e. transmission probability), and everyone is susceptible, we’d expect 7 x 5 x 0.05 x 1 = 1.75 secondary cases on average.
As I explain in my latest book, The Rules of Contagion, for infectious diseases, each of the DOTS can influence the extent of contagion. One 2016 study estimated that viruses that transmitted successfully among humans tended to cause longer infections (that is, larger duration value) and spread directly from one person to another, rather than via a secondary source (that is, more opportunities). Transmission probability can also make a difference; avian influenza viruses, such as H5N1, have struggled to gain a foothold in people because they can’t latch onto the cells in our airway as easily as human viruses can. That’s why there was concern in 2011, when teams at Erasmus Medical Center and the University of Wisconsin–Madison announced that they had each created new strains of H5N1. Among other changes, mutations in these viruses could make them more capable of infecting the easy-to-access upper portion of the mammalian airway. Unlike circulating avian influenza viruses—which had only spread between humans who’d come into close contact with each other—these mutant versions could go airborne, successfully spreading between ferrets in the lab. An increase in susceptibility can also nudge the reproduction number higher, such as when vaccination coverage falls for diseases such as measles, which means outbreaks may follow.
As well as understanding how infections spread, the DOTS can provide insights into how we might control them. In the case of HIV, for example, treatment can reduce the duration of time someone is infectious, and fewer sexual partners can reduce the number of opportunities for transmission. The latter generally isn’t an appealing option for most people, so health agencies have instead encouraged people to use condoms, which reduces the transmission probability during sexual encounters. In recent years, there have also been successful programs of pre-exposure prophylaxis, whereby HIV-negative individuals take anti-HIV drugs to reduce their susceptibility to infection.
For SARS-CoV-2, there isn’t yet a way to reduce susceptibility other than through natural infection. Even with infection, the duration of subsequent immunity remains unclear. This means control measures have focused on decreasing the effective duration of infectiousness (by isolating people with symptoms and quarantining their contacts), the number of opportunities (by reducing social interactions), or limiting the probability of transmission with personal protective equipment. Just as there’s not a single component of transmission that made the COVID-19 pandemic take off, there won’t be a simple solitary measure that will keep SARS-CoV-2 under control in the long term. To prevent large future outbreaks, countries will have to connect together measures that can target several of the DOTS.
Adam Kucharski is an associate professor in the department of infectious disease epidemiology at the London School of Hygiene and Tropical Medicine.
Correction (January 4, 2021): In a previous version of this story, R0 was mistakenly used instead of R in some instances. This has been corrected. The Scientist regrets the error.