Now, halfway through 2021, the first official research results are in — and it’s good news: The show can go on.

Published today in the journal ACS Environmental Au, University of Colorado Boulder and University of Maryland researchers have found that while playing musical instruments can emit the same levels of potentially COVID-laden airborne particles as singing, simple safety measures, such as masking instruments, social distancing and implementing time limits, significantly reduce this risk.

“COVID has shown people that aerosol transmission of respiratory diseases is something that happens. But just because it goes into the air doesn’t mean that everyone is going to contract this disease. We found that there are ways to mitigate these aerosols in a space and ways to reduce your risk,” said Tehya Stockman, lead author of the paper and graduate student in mechanical engineering.

This research began in earnest in 2020 at CU Boulder and the University of Maryland to find out if playing musical instruments carried the same risks of COVID-19 transmission as singing is shown to have. While there have been no reported outbreaks from instrumental ensembles, these published findings echo the researchers’ initial hypotheses and recommendations that were eagerly accepted early on in the pandemic by musicians and performing groups worldwide.

“I want to acknowledge the courage of the music directors and the teachers to go ahead and follow our suggestions in the face of all of this adversity, fear and worry,” said Shelly Miller, co-author of the study and professor of mechanical and environmental engineering. “That really meant a lot to us because they trusted our very good research methods, our researchers and the evolution of science as it moves from: we don’t know, to, let’s find out, to OK — now we know this.”

These findings not only apply to the specific musical applications in which they have been tested, they also further validate that masking works as an effective mitigation technique, and ventilation and social distancing are important to reduce transmission, said Miller. Miller said she hopes these findings will further inspire a paradigm shift focused on mitigation measures and ventilation in order to reduce airborne transmission of infectious diseases.

Mitigation matters

The researchers tested three mitigation strategies on a variety of woodwind, reed and brass instruments, as well as with two singers and an actor. They evaluated these strategies, different lengths of performance time and the differences between indoor and outdoor locations by measuring aerosols, carbon dioxide levels and visualizing the flow of the air using various modeling techniques.

First, they found that masks work — even on instruments — and the quality of the filtering material and their fit are important. Masks worn securely over a singer’s mouth and nose, as well as bell covers (made of MERV13 filter material) placed over the ends of instruments significantly decreased the speed and amount of particles produced from both sources.

For woodwind and reed instruments, they found that the amount of air that escapes from the keyholes does not significantly contribute to any increased risk. This means that clarinetists and flautists do not have to place a bag around their entire instrument to play safely.

Second, time together matters. To keep risk low (at 10% chance of transmission), instrumentalists should spend less than 30 minutes indoors and less than 60 minutes outdoors playing together at a time. No matter the amount of social distancing, “infection risk continuously increases with the duration regardless of the distance to the singer or the player,” the researchers found.

They also found that spacing out does pay off: Leaving several feet of distance between players and singers reduces aerosol concentrations, which are highest closest to each person producing them. And while playing outdoors is best, a layered approach with all the other mitigation measures makes it much safer to play indoors.

Finally, no Plexiglass or face shields are needed. The airborne particles that transmit COVID-19 can easily flow around these barriers and mix with the air in a room.

Quantifying carbon dioxide

So how then, can a musician or audience member now know it’s safe to attend a concert?

Carbon dioxide has been shown to be great indicator of how well ventilated — or not — an indoor space is, and therefore its level of risk for catching COVID-19.

But in this study, the researchers showed that when somebody wears a mask, carbon dioxide passes through the mask with the air that a person is exhaling, but the particles which can carry the virus get stuck. This means that when someone puts on a mask or a bell cover, the carbon dioxide emissions continue, but the particle emissions (which could carry the virus) are reduced.

“Carbon dioxide concentration is a measure of the ventilation in the room. But if everybody’s wearing a mask, the carbon dioxide in that room is still going to be high, but the respiratory droplets that may contain the virus are going to be much lower,” Marina Vance, co-author on the study and assistant professor in the Paul M. Rady Department of Mechanical Engineering and the Environmental Engineering Program. “So in that case, it’s not a direct representation of your risk.”

So, if a concert hall requires all audience members to wear masks and that all performers place a bell cover on their instrument, the risk of COVID transmission in that room would be reduced — even if the measured carbon dioxide levels are high. But carbon dioxide is still a great proxy for risk indoors in restaurants, where most people are not masked and are often speaking loudly.

Such direct application of this research to real-life scenarios has been an extremely rewarding experience for Vance and the other researchers.

“The best part of the study was that all of this technical knowledge and all of this scientific understanding was getting translated almost in real-time and getting into the hands of the people that needed it the most. I’ve never been a part of anything like that,” said Vance. “It was nerve-wracking, exciting and important all at once.”

The safe return of music

When lead author Stockman first learned to play clarinet years ago, she didn’t do so with the intent to advance scientific research. But her personal musical experience allowed the work to advance quickly, as she performed calibration tests by herself in the lab during the pandemic.

She understands the frustrations of musicians who may need to follow these protocols. She also knows how important it is to keep people safe.

“What we’ve shown is that there’s easy measures to take that make life still be relatively normal — and you don’t have to fear the air,” said Stockman.

This sentiment is echoed by co-authors Mark Spede, national president of the College Band Directors National Association and director of bands at Clemson University, and James Weaver, director of Performing Arts and Sports for the National Federation of State High School Associations, who point out that the mitigation strategies tested in this study can be implemented not only during the lingering COVID-19 pandemic, but in the face of any future pathogen that may come along.

“Although we may not know how the end of the pandemic will play out, this important study has allowed performing arts educators to advocate for the safe return of live music to the classroom,” said Spede.

This research was conducted in partnership and collaboration with the National Federation of State High School Associations and College Band Directors National Association.

Additional authors on this publication include: Abhishek Kuma, Lingzhe Wang, Sameer Patel, Darin Toohey and Jean Hertzberg of CU Boulder; and Shengwei Zhu, Don Milton and Jelena Srebric of the University of Maryland.

Results from the registry indicated that in addition to more severe or critical infections, pediatric cancer patients were more likely to be hospitalized and die than were other children. The pandemic also disrupted cancer treatment. These effects were observed more significantly in low- and middle-income countries, where the odds of severe or critical disease from COVID-19 were nearly 6 times higher than in high-income countries.

“The results clearly and definitively show that children with cancer fare worse with COVID-19 than children without cancer,” said corresponding author Sheena Mukkada, M.D., St. Jude Departments of Global Pediatric Medicine and Infectious Diseases. “This global collaboration helps clinicians make evidence-based decisions about prevention and treatment, which, unfortunately, remain relevant as the pandemic continues.”

A greater burden for childhood cancer patients

This is the first multinational study to describe the outcomes of a large cohort of children and adolescents with cancer or hematopoietic stem cell transplantation and laboratory diagnosis of COVID-19. The registry remains open and is enrolling children younger than 19 years old.

The analysis looked at 1,500 children from 131 hospitals in 45 countries from April 15, 2020, to February 1, 2021. This is prior to vaccinations becoming available to older children in some areas of the globe, as well as prior to the emergence of certain disease variants, including delta, which are responsible for the new surge and have become a major global concern.

The study found that 65% of patients were hospitalized and 17% required admission or transfer to a higher level of care. It also showed that 4% of patients died due to COVID-19 infections, compared to 0.01-0.7% mortality reported among general pediatric patients. Cancer care was also affected. Cancer therapy was modified in 56% of patients and 45% had chemotherapy withheld while their infections were treated.

“By working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer,” said the paper’s co-author, Professor Kathy Pritchard-Jones, SIOP president. “The results are reassuring that many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”

A global pandemic and a global response

The registry suggests biologic factors that likely influence how children with cancer respond to COVID-19. Those include immune system function and the underlying disease. Analysis also showed that outcomes vary around the world, although the registry does not pinpoint causes. This variation may be due to a multitude of factors, including disruptions from the pandemic, access to care and resources, or delays in infection diagnosis.

Results from the registry are a call to action to address inequities in access to protective and effective treatment measures against the COVID-19 pandemic worldwide.

“Understanding a global crisis like COVID-19 requires our entire childhood cancer community around the world to come together to respond,” said senior author Carlos Rodriguez-Galindo, M.D., St. Jude Global director. “The impact of this disease has been felt in every corner of the world, but particularly in low- and middle-income countries compared to high-income countries. There are critical differences based on where a child lives. This registry is a tool that is helping us understand what that means for children with cancer everywhere.”

The registry (http://covid19childhoodcancer.org/) is still enrolling patients and continues to add new countries. It includes freely available data-visualization tools so that anyone, anywhere, can access the information.

Learn more about COVID-19 and vaccination

Vaccinations against COVID-19 have been demonstrated to be safe and effective in preventing severe forms of the disease, helping patients avoid hospitalizations and the need for mechanical ventilation. In the United States, vaccines are available and encouraged for children 12 years of age and older. Vaccination is one way to protect not only yourself but your community, including those who are at high risk of severe disease such as children with cancer.

Learn more about how Vaccines Bring Us Closer (https://www.stjude.org/media-resources/special-announcements/get-vaccinated.html) and check out COVID-19 resources from St. Jude (https://www.stjude.org/treatment/patient-resources/covid-19-resources-from-st-jude.html).

Authors and Funding

The study’s other authors are Guillermo Chantada, Hospital San Joan de Deu Barcelona, Spain; Rashmi Dalvi, Bombay Hospital Institute of Medical Sciences Mumbai, India; Laila Hessissen, Mohammed V University Rabat, Morocco; Michael Sullivan, University of Melbourne, Australia; Eric Bouffet, Hospital for Sick Children Toronto, Canada; Nickhill Bhakta, Yichen Chen, Yuvanesh Vedaraju, Lane Faughnan, Maysam Homsi, Hilmarie Muniz-Talavera, Radhikesh Ranadive, Monika Metzger, Paola Friedrich, Asya Agulnik, Sima Jeha, Catherina Lam, Daniel Moreira, Victor Santana, Miguela Caniza and Meenakshi Devidas of St. Jude; and more than 150 members of the Global Registry of COVID-19 in Childhood Cancer.

The study was funded by the National Institutes of Health (Cancer Center Support grant CA21765), and ALSAC, the fundraising and awareness organization of St. Jude.

Although COVID-19 is primarily considered a respiratory disease, experts recognize it also affects the nervous system, sometimes causing severe neurological symptoms. Some COVID-19 survivors also experience long-term mental health problems, including anxiety, depression and post-traumatic stress disorder.

Few studies have examined functional abnormalities in the brain, which might reveal the physiological processes that underlie prolonged mental health symptoms in COVID-19 survivors.

In this paper, published in Neurobiology of Stress, the researchers set out to determine whether survivors experience functional disruption of large-scale brain networks, collections of discrete and widespread regions of the brain that work together to perform complex cognitive tasks. They collected functional MRI (fMRI) data and self-reported post-traumatic stress symptoms from 50 COVID-19 survivors, along with matched control subjects. The COVID-19 survivors were discharged between February and March 2020 from hospitals in Wuhan, China, and were tested about six months after their discharge.

The findings showed COVID-19 survivors self-reported significantly more symptoms of post-traumatic stress than the controls. The study also revealed COVID-19 survivors exhibited abnormal patterns of brain connectivity over time, which were significantly associated with greater post-traumatic stress symptoms.

“Until recently,” said Calhoun, a Georgia Research Alliance Eminent Scholar, “analysis approaches used for fMRI data assumed that the brain’s functional connectivity was static. But we now have approaches that can capture dynamic functional brain connectivity, showing the way brain patterns change over time in fundamental and reoccurring ways.”

The researchers identified three distinct, reoccurring states of functional connectivity in the subjects’ brains. The COVID-19 survivors showed an increased occurrence of a particular state marked by patterns of connections between brain networks involving sensorimotor functions and visual networks.

“When we looked within the COVID-19 survivor group, we also found a significant relationship between the severity of their post-traumatic stress symptoms and how often their brain patterns are in that state,” said Calhoun. “If they spend more time in that state, they tend to have higher values on those symptom scales.”

“Our findings provide evidence that COVID might affect transient brain dynamics rather than its ongoing activity,” said Zening Fu, the study’s first author and a research scientist at TReNDS.

The results highlight the importance of evaluating transient, time-varying functional network changes among COVID-19 survivors, although Calhoun notes there are still many unanswered questions, including why this one brain state is linked to post-traumatic stress. The research team is also interested in replicating the study using other data and looking at changes within subjects before and after contracting COVID-19.

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The study is the first to comprehensively quantify the overall burden and characteristics of COVID-19 in the U.S. during 2020. The researchers simulated the transmission of SARS-CoV-2 within and between all 3,142 U.S. counties using population, mobility, and confirmed case data.

Infections were more widespread in some areas of the country

In areas of the upper Midwest and Mississippi valley, including the Dakotas, Minnesota, Wisconsin and Iowa, more than 60 percent of the population is estimated to have been infected by the end of 2020. In five metropolitan areas the researchers examined, 48 percent of residents of Chicago, 52 percent of Los Angeles, 42 percent of Miami, 44 percent of New York City, and 27 percent of people in Phoenix, had been infected in the same timeframe.

Testing picked up on a growing number of infections but offered an incomplete picture

The portion of confirmed cases reflected in the study’s estimates, i.e. the ascertainment rate, rose from 11 percent in March to 25 percent in December, reflecting improved testing capacity, a relaxation of initial restrictions on test usage, and increasing recognition, concern, and care-seeking among the public. However, the ascertainment rate remained well below 100 percent, as individuals with mild or asymptomatic infections, who could still spread the virus, were less likely to be tested.

“The vast majority of infectious were not accounted for by the number of confirmed cases,” says Jeffrey Shaman, PhD, professor of environmental health sciences at Columbia University Mailman School of Public Health. “It is these undocumented cases, which are often mild or asymptomatic infectious, that allow the virus to spread quickly through the broader population.”

One in 130 Americans was contagious at year’s end

Roughly 1 in 130 Americans (0.77%) was contagious with SARS-CoV-2 on December 31, 2020. A similar percentage (0.83%) was estimated to be latently infected, i.e. infected but not yet contagious. In some metropolitan areas, the percentage of individuals who was contagious at year’s end was much higher.

Fatality rates fell with strengthening treatments and public health measures

The percentage of people with infections who died from COVID-19 fell from 0.8 percent during the spring wave to 0.3 percent by year’s end. Urban areas like New York City that peaked in the spring saw the worst numbers for reasons that include delays in testing availability and masking mandates, overwhelmed hospitals, and lack of effective treatments.

Cities peaked at different times of the year

New York and Chicago experienced strong spring and fall/winter waves but little activity during summer; Los Angeles and Phoenix underwent summer and fall/winter waves; and Miami experienced all three waves. Los Angeles County, the largest county in the U.S. with a population of more than 10 million people, was particularly hard-hit during the fall and winter and had a community infection rate of 2.4 percent on December 31.

A new pandemic landscape for 2021

Looking ahead, the authors write that several factors will alter population susceptibility to infection. The virus will continue to spread to those who haven’t yet been infected. While vaccines protect against severe and fatal disease, breakthrough infections, including those that are mild or asymptomatic, will contribute to the spread of the virus. The current study does account for the possibility of reinfection, although there is evidence of waning antibodies and reinfection. New more contagious variants make reinfection and breakthrough infections more likely.

“While the landscape has changed with the availability of vaccines and the spread of new variants, it is important to recognize just how dangerous the pandemic was in its first year,” concludes Sen Pei, PhD, assistant professor of environmental health sciences at Columbia University Mailman School of Public Health.

Additional authors include Teresa K. Yamana, Sasikiran Kandula, and Marta Galanti at Columbia Mailman School.

The study was supported by funding from the National Science Foundation (DMS-2027369) and a gift from the Morris-Singer Foundation. Human mobility data was provided by SafeGraph. Shaman and Columbia University disclose partial ownership of SK Analytics. Shaman discloses consulting for Business Network International (BNI).

With these findings, researchers have constructed a genetic risk score — a number reflecting a person’s overall genetic propensity based on how many risk variants they carry — that predicts a range of behavioral, medical and social outcomes, including education levels, obesity, opioid use disorder, suicide, HIV infections, criminal convictions and unemployment.

“[This study] illustrates that genes don’t code for a particular disorder or outcome; there are no genes ‘for’ substance use disorder, or ‘for’ behavior problems,” said joint senior author Danielle Dick, Ph.D., Commonwealth Professor of Psychology and Human and Molecular Genetics at Virginia Commonwealth University. “Instead, genes influence the way our brains are wired, which can make us more at risk for certain outcomes. In this case, we find that there are genes that broadly influence self-control or impulsivity, and that this predisposition then confers risk for a variety of life outcomes.”

The study, “Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction,” was published today in the journal Nature Neuroscience and was conducted by a consortium of 26 researchers at 17 institutions in the United States and the Netherlands.

It was led by Dick; Philipp Koellinger, Ph.D., professor of social science genetics at the University of Wisconsin Madison and Vrije Universiteit Amsterdam; Kathryn Paige Harden, Ph.D., professor of psychology at the University of Texas at Austin; and Abraham A. Palmer, Ph.D., professor of psychiatry at the University of California, San Diego.

The study is one of the largest genome-wide association studies ever conducted, pooling data from an effective sample size of 1.5 million people of European descent. The researchers’ genetic risk score has one of the largest effect sizes — a measurement of the prediction power — of any genetic risk score for a behavioral outcome to date.

“It demonstrates the far-reaching effects of carrying a genetic liability toward lower self-control, impacting many important life outcomes,” said Dick, a professor in the Department of Psychology in the College of Humanities and Sciences and the Department Human and Molecular Genetics in the School of Medicine at VCU. “We hope that a greater understanding of how individual genetic differences contribute to vulnerability can reduce stigma and blame surrounding many of these behaviors, such as behavior problems in children and substance use disorders.”

The identification of the more than 500 genetic loci is important, the researchers said, because it provides new insight into our understanding of behaviors and disorders related to self-regulation, collectively referred to as “externalizing” and that have a shared genetic liability.

“We know that regulating behavior is a critical component of many important life outcomes — from substance use and behavioral disorders, like ADHD, to medical outcomes ranging from suicide to obesity, to educational outcomes like college completion,” Dick said.

Characterizing the genetic contributions to self-regulation can be helpful in myriad ways, she said.

“It allows us to better understand the biology behind why some people are more at risk, which can assist with medication development, and it can allow us to know who is more at risk, so we can put early intervention and prevention programs in place,” she said. “Identifying genetic risk factors is a critical component of precision medicine, which has the goal of using information about an individual’s genetic and environmental risk factors to deliver more tailored, effective intervention specific to that individual’s risk profile.”

The researchers noted, however, that having a higher risk profile isn’t necessarily a bad thing.

“For example, CEOs, entrepreneurs and fighter pilots are often higher on risk taking,” Dick said. “DNA is not destiny. We all have unique genetic codes, and we’re all at risk for something; but understanding one’s predisposition can be empowering — it can help individuals understand their strengths, and their potential challenges, and act accordingly.”

For more information about the study and its findings, please visit this FAQ: https://externalizing.org/faqs/