Winter break had arrived in Stockholm in late February, and Soo Aleman watched as her fellow Swedes departed the capital city for ski vacations across Europe. Aleman’s colleagues at the Karolinska University Hospital, where she works as a researcher and physician, returned relaxed and invigorated, with stories to tell about their days on the slopes. But a few of the city’s residents also brought back a most unwelcome souvenir: the SARS-CoV-2 coronavirus.
Like much of the rest of the world, Sweden soon found itself in the grips of an outbreak. As Aleman pivoted from her work on the hepatitis B and C viruses to study COVID-19, she began screening patients for the novel infection and for signs of the body’s immune response. And that’s when things got weird.
The body should produce both protective antibodies, which keep the virus from invading, and killer T cells, which tell virus-infected human cells to destroy themselves to keep the virus from spreading. Normally, these immune responses appear in tandem. But in a subset of those who tested positive for COVID-19, Aleman found T cells but no antibodies.
Other scientists around the world also had similar findings. Much of this work is still preliminary, and scientists don’t know what it means in terms of assessing how well a vaccine will work or how well people are protected from severe forms of the disease. But one thing is becoming clear: antibodies might not be telling the whole story when it comes to COVID-19 immunity. “We shouldn’t just look blindly at antibody tests,” Aleman says.
“I don’t know another virus like this,” adds Rory de Vries, a virologist at the Erasmus Medical Center in the Netherlands. “We are living in special times with a special virus.”
The Bs and Ts of immune cells
Wellness gurus may exhort us to treat our bodies like temples, but when it comes to fighting off pathogens, the body is more like a castle under siege. Like any fortress, the body has several lines of defenses to protect it from infectious microbes.
The innate immune system is the first line, and it sets out to discourage any potential intruder by making the body as inhospitable for them as possible by raising the body’s temperature with a fever and assaulting pathogens with toxic chemicals. It acts like an overzealous security guard and reacts against any sign that a cell or protein is not the body’s own.
Even these security forces can be overwhelmed and outmaneuvered by pathogens that have evolved stealth to evade the immune system and counter inflammatory responses dedicated to stopping germs. When that happens, the adaptive immune system kicks in—and that’s when we see things like antibodies and T cells. These defenses emerge after a pathogen has invaded, and the body has learned the type of threat it poses.
B cells produce antibodies, small proteins that recognize certain pieces of a pathogen known as epitopes. If enough antibodies bind to a virus, it can’t enter the body’s cells to make copies of itself, and thus cannot make you sick. Likewise, killer T cells recognize epitopes displayed by virus-infected cells and tell the cells to self-destruct.
It’s a process that has evolved over hundreds of millions of years, and all the different arms of the immune system generally work together seamlessly.
When the body is actively fighting off a pathogen, it mobilizes large numbers of antibodies and T cells. In the following weeks and months, those numbers can slowly decline. That’s normal and even beneficial, said Nicolas Vabret, an immunologist at the Mount Sinai School of Medicine in New York.
“If antibodies didn’t decline, over time, there would only be antibodies in the blood with no room for anything else,” he says.
But the defenses haven’t completely evaporated after this initial siege. A portion of the B cells and T cells form memories of past invaders, while a low level of antibodies keep circulating in the blood. For months or even years, these forces continue to patrol the bloodstream, the spleen, bone marrow, and lymph nodes embedded in various organs long after the infection is over, so if the body ever sees the same pathogen again, it can respond faster.
Sometimes, a reinfected person won’t even have symptoms. Other times, the disease may be very mild. The amount and type of antibodies and T cells present after an infection can tell scientists how well a vaccine might protect people.
More than waning antibodies
Historically during epidemics, scientists have focused on antibody responses rather than T cells, because antibodies are easier to measure in the lab. Antibodies can be detected directly from a blood sample, explains Daniela Weiskopf, an immunologist at the La Jolla Institute for Immunology in California.
When Weiskopf wants to spot a T cell response, however, she has to reenact the series of steps the T cells use to identify a pathogen. First, she synthesizes a library of all the possible tiny epitopes the T cells can recognize. Then she needs to isolate the T cells from the blood and test them against all the different protein epitopes, to see which ones interact with the cells.
For most viruses, antibody and T cell responses usually match up in terms of timing and strength of response, so scientists generally rely on antibody tests alone because they are quicker, cheaper, and easier to administer. Some antibody test kits can provide results in minutes to hours, whereas T cell tests need to be sent to a specialized lab.
“It’s just not practical to test for T cell response in large samples,” says Weiskopf.
But when Aleman and other virologists and immunologists began turning their attention to COVID-19, a different story started emerging. Aleman and her colleagues began to study how immunity developed in people who had tested positive for SARS-CoV-2, as well as their close contacts, some of whom were presumably exposed to the virus, even if they didn’t get sick. As expected, hospitalized individuals developed strong antibody and T cell responses to SARS-CoV-2. But two-thirds of the close contacts who were asymptomatic showed a subsequent T cell response, even though tests didn’t detect any antibodies.
“It was very strange and very surprising,” Aleman says. The study results, released June 29 without peer review via the medical pre-print service medRxiv, didn’t reveal whether these individuals never developed antibodies or whether they rapidly declined to undetectable levels. Regardless, the report immediately raised concerns about a vaccine, since stimulating antibody production is a key strategy by which immunizations protect against disease.
This apparent decline in antibodies was reported again on July 21, in 34 individuals with mild COVID-19 infections. If some people infected with SARS-CoV-2 don’t produce antibodies, it could mean they might not respond to a vaccine.
T cells to the rescue?
Immunologist Adrian Hayday at King’s College London is less worried. Even though T cells are harder to measure and may not prevent a second infection, they play a major role in the body’s ability to remember past infections and protect someone from severe disease.
“It kind of looks like T cells could be really useful to you in this infection,” Hayday says, pointing to several new papers on SARS-CoV-2 and other coronaviruses as proof.
SARS-CoV-2 is one of seven known coronaviruses that can infect humans. The original SARS virus vanished after creating large outbreaks in 2003, and the Middle Eastern Respiratory Syndrome (MERS) virus has only infected a small number of people in the Middle East and North Africa. Four other coronaviruses circulate widely and cause the common cold.
Immunity to the common cold coronaviruses only lasts a year or two, which is why sniffles and stuffiness remain a pervasive part of life. However, patients infected with the original SARS virus still possessed memory T cells that responded to the virus’ proteins 17 years later, immunologist Antonio Bertoletti at Duke-NUS Medical School in Singapore recently reported in Nature. These same memory T cells also reacted to SARS-CoV-2. It’s something Bertoletti says bodes well for COVID-19.
“Even if the T cells don’t prevent a second infection, you might not get as sick,” he says.
A Science paper published August 4 by Weiskopf and colleagues supports this hypothesis and hints that preexisting immunity to these common cold coronaviruses may help explain why some people have no symptoms. Since COVID-19 has some similarity to these viruses, some T cells may respond to both pathogens. However, it’s still early days for this idea.
“We really don’t know how T cells relate to disease severity,” he says.
Weiskopf, fellow La Jolla Institute immunologist Alessandro Sette, and de Vries also conducted an in-depth analysis of the immune response from 20 adults who had recovered from COVID-19. They found that although antibodies developed primarily to the spike protein that coated the virus, T cells could respond to epitopes from inside and outside of the virus. Their results were published in Cell.
That’s good news for a vaccine, de Vries says, because it means that even if the outer spike proteins mutate over time, T cells will still be able to provide some protection, since they recognize other parts of the virus that are less prone to change.
What no one can say yet is what these T cell responses mean in terms of preventing and infection, or how long they might last. Potential preexisting T cell responses may yet affect how well a vaccine protects people, Sander says.
“We’ve been dealing with this virus for six months,” Weiskopf says, “so we cannot know about what might happen 12 months out.”
Nearly 100,000 children tested positive for the coronavirus in the last two weeks of July, a new report from the American Academy of Pediatrics finds. Just over 97,000 children tested positive for the coronavirus from July 16 to July 30, according to the association.
Out of almost 5 million reported COVID-19 cases in the U.S., CBS News’ Michael George reports that the group found that more than 338,000 were children.
Vanderbilt University’s Dr. Tina Hartert hopes increased testing of children will help determine what role they play in transmission, as school districts around the country return to some form of school. She is leading a government-funded study that saw DIY testing kits sent to some 2,000 families.
“The kits are shipped to the families, they are taught how to collect these samples, and then the samples are sent back by the families to a central repository,” she said.
In New York City, home to the nation’s largest school district, Mayor Bill de Blasio announced a return to in-person schooling in the fall and pledged officials “have worked incessantly to get this right.”
“They’ve looked at examples from all over the world of what will keep the school community safe, and they’ve made a series of choices of how to do things from the health and safety lens first, while also making sure we can educate our kids,” he said in a Friday press conference.
De Blasio gave parents until Friday night to register students for in-person instruction, remote learning or a hybrid.
More than 25 children died of the coronavirus in July alone. Pressure to get kids back into the classroom has left superintendents in more than 13,000 different school districts across the country to figure out how to keep children safe amid a myriad of public health advisories, and handle learning differences.
Niles, Michigan Superintendent Dan Applegate is hoping Plexiglas could be a solution for children with speech impediments to be able to participate in class.
He demonstrated by speaking behind a transparent slate at a press conference.
“As I’m sitting here and I can articulate,” Applegate said. “The student on the other side will be wearing a mask. Then I can put my mask on, and that student can drop their mask and articulate as well.”
Indiana’s Lawrence Township is cleaning school buses with a hospital-grade disinfectant spray for students still needing rides to school.
“You’re going to see a very clean and disinfected bus,” Transportation Director Matt Miles said. “We actually have fogging machines.”
However, they are not expecting many students to get on the bus — 35% of children in the area are expected to learn remotely, while other school districts in the U.S. will not open at all.
Roche Holding AG ROG, -0.27% said Friday that the Food and Drug Administration had approved Evrysdi, a treatment for spinal muscular atrophy in adults and most children. It’s the second drug to be approved by the regulator to treat the rare disease. The therapy was developed by PTC Therapeutics Inc. PTCT, +1.72% and will be marketed by Genentech, a division of Roche. “We believe Evrysdi, with its favorable clinical profile and oral administration, may offer meaningful benefits for many living with this rare neurological disease,” Roche’s Levi Garraway said in a news release. A spokesperson said in an email that the treatment will cost about $340,000 per year, which is a lower price point than Biogen’s BIIB, +10.10% Spinraza and AveXis Inc.’s Zolgensma; however the lower-than-expected price “could help increase market share and rapidity of adoption, though will produce lower revenue per patient than we had estimated,” RBC Capital Markets’ Brian Abrahams wrote in a note to investors. Since the start of the year, PTC’s stock is down 0.4%, shares of Roche have gained 6.2%, and the S&P 500 SPX, +0.06% is up 3.7%.
An immunocompromised New York City Councilman who underplayed the severity of his COVID-19 diagnosis in April now says that it was actually much worse, and hydroxychloroquine saved his life.
Paul Vallone, a Democrat who represents Queens, says he took the drug along with a ‘Z-pack’ antibiotic and drastically improved within days.
“I couldn’t breathe, very weak, couldn’t get out of bed. My doctor prescribed it. My pharmacy had it. Took it that day and within two to three days I was able to breathe,” Vallone told the New York Post, adding “Within a week I was back on my feet.”
Though Vallone went public with his coronavirus diagnosis in an April 1 Twitter post, saying he was experiencing “mild symptoms,” his actual condition was considerably more severe. Vallone’s initial prognosis was particularly grim, as he also suffers from sarcoidosis, an auto-immune disease that attacks his lungs.
“We were in panic mode when I went down because I didn’t have a lot of immune response,” he said. “I needed something to stay alive.” –New York Post
Vallone’s brother, former City Councilman Peter who currently serves as a civil court judge in Queens, is now a believer in the drug.
“I guess all those doctors who are prescribing it are right. This drug is already on the market and the patent is up so it’s cheap. A new drug won’t be. So big money does not want this drug to be used. Always follow the money,” Peter said in a May 12 Facebook post.
Paul, responding in the comments section, said “[It] saved my life.”
Hydroxychloroquine, or HCQ, is a commonly used anti-malaria drug also used for decades to treat lupus and arthritis. It became covid-19 treatment non-grata, however, after President Trump touted the inexpensive drug earlier this year – admitting to taking a course as a prophylactic against the disease.
“You’d be surprised at how many people are taking it, especially the frontline workers before you catch it. The frontline workers — many, many are taking it,” Trump said in May.
Studies on the drug have been mixed but mostly positive, with recent evidence pointing to significant results against COVID-19 when used earlyin the disease’s progression.
Paul Vallone reflected on his April diagnosis, saying “At that time, there was only fear and panic, he offered hope in a possible treatment when there was none. With my sarcoidosis and then my COVID symptoms, It basically saved me. For that my family will always be thankful.”
Dealing with the social and economic upheaval from the coronavirus pandemic will require the skills and talents of many types of professions – medical personnel, public health experts, parents, students, educators, legislators, enforcement authorities and many others. Until now, though, the U.S. has struggled to mounta coordinated national response to effectively stamp out COVID-19, even as other countries in Europe and East Asia have shown that the disease can be controlled.
In the past, the United States has successfully mobilized to address deeply complex challenges and I believe one of those – sending astronauts to the Moon – can be instructive today, even though a pandemic is a very different challenge.
Twelve years after the famed Project Apollo to land men on the Moon in 1969, General Motors hired former NASA Administrator Robert Frosch to bring space-age technology to car manufacturing. He commissioned a small task force to incorporate Apollo’s engineering process into the design of vehicles. I began my systems engineering career in this task force and now work on integrating the statistical and management sciences into future moonshots.
Today, this systems engineering approach is central to the automotive “moonshot” to create driverless vehicles. And I believe the Apollo method could be applied to some of the pandemic’s thornier issues. Let’s look at the challenge of educating U.S. children as an example.
The Centers for Disease Control and Prevention guidelines recommend reopening school buildings in the fall – with various safety precautions. But unlike other nations which have dictated specific protocols, the U.S. has delegated those decisions to individual districts. This is where the Apollo engineering system could help: by determining the appropriate division of responsibility based on expertise.
Systems engineering includes six key steps:
Define requirements. The first step in planning to return students to classrooms or teach online is identifying stakeholders – including parents, students, teachers, neighbors and employers – to hear their concerns. Then, planners must itemize the key benefits that school provides in addition to education, such as: child care for working parents, meals for hungry children, discipline and socialization.
Create the relevant committees and assign responsibilities. Coordinating a wide range of experts is critical to safely educating children in person. To do so, a small task force must outline an overarching approach breaking down the overall effort into its component parts, such as transportation to schools, school ventilation and sanitation, curriculum development and serving meals. The task force then creates a committee for each “sub-problem,” such as an on-site education committee, testing and tracing, a remote education committee and a medical committee. To ensure that each individual group contributes to a successful overall solution, the task force develops committee requirements to guide and evaluate their efforts, while giving each committee as much flexibility as possible in leveraging its expertise.
Create the relevant subcommittees and assign responsibilities. Each committee outlines its approach to its sub-problem and creates subcommittees to provide more detail on different elements of the approach. For example, the on-site education committee might break off into smaller groups that address safety enforcement, classroom design and building ventilation. Each subcommittee is given “subcommittee requirements” to guide its efforts.
If necessary, work can be further specialized within sub-subcommitees: The Space Shuttle program involved more than a dozen levels of responsibility.
Work the plan. As each subcommittee tackles its assignment, coordinators orchestrate their efforts to avert missteps and enhance synergies between other groups. For example, if the safety subcommittee concludes that some children will not keep masks on in class, the coordinator might create more aggressive requirements for those working on classroom design and ventilation. When a subcommittee finishes its assignment, the solution is evaluated against that subcommittee’s requirements.
Integrate proposals from every committee. Once all issues facing on-site education have been addressed, individual solutions – on masks, building ventilation, classroom design, testing and more – are evaluated as a whole before being approved as the committee’s integrated, overall solution. The committee solution is then evaluated against the committee’s requirements. Each of the committee solutions are then evaluated as a whole before becoming the task force’s plan. The task force’s plan is then evaluated against its requirements. Stakeholder representatives then evaluate whether the plan ensures that schools can, indeed, open safely.
Support rollout Initially, these protocols are implemented at a small scale and then ramped up slowly as all are trained to understand their responsibilities: teachers, administrators and other staff, parents, students, employers, police, doctors, families and government authorities.
Constant maintenance and nimble adaptation will be needed to deal with unforeseen events like schools running out of masks or from students and school staff getting sick. Once an effective vaccine is available and the pandemic dissipates, the plan must detail how some protocols can be safely dismantled.
This exercise in systems engineering is not meant to be an actual school opening plan but instead a perspective on how people can organize to address complex problems that involve many groups of people.
The U.S. has successfully completed moonshots before. We can do it again.
Children who suffer trauma from abuse or violence early in life show biological signs of aging faster than children who have never experienced adversity, according to research published by the American Psychological Association. The study examined three different signs of biological aging — early puberty, cellular aging and changes in brain structure — and found that trauma exposure was associated with all three.
“Exposure to adversity in childhood is a powerful predictor of health outcomes later in life — not only mental health outcomes like depression and anxiety, but also physical health outcomes like cardiovascular disease, diabetes and cancer,” said Katie McLaughlin, PhD, an associate professor of psychology at Harvard University and senior author of the study published in the journal Psychological Bulletin. “Our study suggests that experiencing violence can make the body age more quickly at a biological level, which may help to explain that connection.”
Previous research found mixed evidence on whether childhood adversity is always linked to accelerated aging. However, those studies looked at many different types of adversity — abuse, neglect, poverty and more — and at several different measures of biological aging. To disentangle the results, McLaughlin and her colleagues decided to look separately at two categories of adversity: threat-related adversity, such as abuse and violence, and deprivation-related adversity, such as physical or emotional neglect or poverty.
The researchers performed a meta-analysis of almost 80 studies, with more than 116,000 total participants. They found that children who suffered threat-related trauma such as violence or abuse were more likely to enter puberty early and also showed signs of accelerated aging on a cellular level-including shortened telomeres, the protective caps at the ends of our strands of DNA that wear down as we age. However, children who experienced poverty or neglect did not show either of those signs of early aging.
In a second analysis, McLaughlin and her colleagues systematically reviewed 25 studies with more than 3,253 participants that examined how early-life adversity affects brain development. They found that adversity was associated with reduced cortical thickness — a sign of aging because the cortex thins as people age. However, different types of adversity were associated with cortical thinning in different parts of the brain. Trauma and violence were associated with thinning in the ventromedial prefrontal cortex, which is involved in social and emotional processing, while deprivation was more often associated with thinning in the frontoparietal, default mode and visual networks, which are involved in sensory and cognitive processing.
These types of accelerated aging might originally have descended from useful evolutionary adaptations, according to McLaughlin. In a violent and threat-filled environment, for example, reaching puberty earlier could make people more likely to be able to reproduce before they die. And faster development of brain regions that play a role in emotion processing could help children identify and respond to threats, keeping them safer in dangerous environments. But these once-useful adaptations may have grave health and mental health consequences in adulthood.
The new research underscores the need for early interventions to help avoid those consequences. All of the studies looked at accelerated aging in children and adolescents under age 18. “The fact that we see such consistent evidence for faster aging at such a young age suggests that the biological mechanisms that contribute to health disparities are set in motion very early in life. This means that efforts to prevent these health disparities must also begin during childhood,” McLaughlin said.
There are numerous evidence-based treatments that can improve mental health in children who have experienced trauma, McLaughlin said. “A critical next step is determining whether these psychosocial interventions might also be able to slow down this pattern of accelerated biological aging. If this is possible, we may be able to prevent many of the long-term health consequences of early-life adversity,” she says.
Natalie Colich, Eileen S. Williams, Maya Rosen and Katie McLaughlin. Biological Aging in Childhood and Adolescence Following Experiences of Threat and Deprivation: A Systematic Review and Meta-Analysis. Psychological Bulletin, 2020 DOI: 10.1037/bul0000270
It is said that adversity doesn’t build character; it reveals it. When the sh*t hits the fan and everything is going against us, we learn a lot about ourselves.
When power went down in our region and we were left without telephone, internet, or cable service, I wondered how I would work with traders. Everyone was working from home, which meant that my only ways of connecting with them had been taken away. A fleeting thought went through my mind that I could cancel all my meetings. As soon as the thought entered, I rejected it. I was not going to give up. I drove my car to various towns in the area until I found a spot with a solid internet connection. I kept my phone charged with the car battery and downloaded an app that allowed me to do face-to-face meetings with minimal bandwidth demands. Instead of working from home, I discovered work-from-car!
Similarly, when everything went down in the recent storm, I received encouragement from Margie and together we figured out how to use a portable generator and connect it to major portions of our house. I have minimal mechanical skills–I actually tested as learning disabled with respect to performance tasks as a child–but I was not going to be a victim of the storm, and I was not going to let Margie down.
In both cases, adversity brought out a latent strength, a quality I have, but do not always draw upon: persistence in the face of challenge. I refuse to let circumstances control me. That refusal gives energy and leads to creative solutions I would have not pursued otherwise.
Recently, I’ve noticed significant differences in how traders handle adversity, whether it’s a losing trade, a missed opportunity, a drawdown, etc. The really good traders refuse to let the setback control them. They view and re-view their trading and they make sure they drill the learning lessons in their head. They miss an entry, but they don’t give up on the idea. They don’t simply place a revenge trade; they become even more focused as a result of the missed trade–and that allows them to find another way to participate.
That’s really it: adversity can disrupt us, or it can focus us. It can lead us to withdraw and seek comfort, or it can push us to dig deep and draw upon our latent strengths. The concept of sisu suggests that each of us possesses a second wind of energy that we can access during periods of challenge. Might it be the case that the winners in life’s race are those with the greatest capacity to draw upon that second wind? Perhaps by continually placing ourselves in challenging circumstances, we can cultivate the sisu–the access to hidden strengths–needed to perform at our best when we most need to perform.
