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/

Terbium, one of the rarest of the rare earth elements, produces the green color in cell phone displays and is also used in high-efficiency lighting and solid-state devices. However, there are a variety of chemical, environmental, and political challenges to obtaining terbium and other rare earth elements from the environment. Developing new sources of these metals also requires robust detection methods, which poses another challenge. For example, the gold standard method of detecting rare earth elements in a sample — a type of mass spectrometry called ICP-MS — is expensive and not portable. Portable methods, however, are not as sensitive and do not perform well in complex environmental samples, where acidic conditions and other metals can interfere with detection.

“There is not currently a domestic supply chain of rare earth elements like terbium, but they are actually quite abundant in non-traditional sources in the U.S., including coal byproducts, acid mine drainage, and electronic waste,” said Joseph Cotruvo, Jr., assistant professor and Louis Martarano Career Development Professor of Chemistry at Penn State, a member of Penn State’s Center for Critical Minerals, and senior author of the study. “In this study, we developed a luminescence-based sensor that can be used to detect and even quantify low concentrations of terbium in complex acidic samples.”

The new sensor relies on lanmodulin, a protein that the researchers previously discovered that is almost a billion times better at binding to rare earth elements than to other metals. The protein’s selectivity to bind rare earth elements is ideal for a sensor, as it is most likely to bind to rare earths instead of other metals that are common in environmental samples.

To optimize lanmodulin as a sensor for terbium specifically, the researchers altered the protein by adding the amino acid tryptophan to the protein.

“Tryptophan is what is called a ‘sensitizer’ for terbium, which means that light absorbed by tryptophan can be passed to the terbium, which the terbium then emits at a different wavelength,” said Cotruvo. “The green color of this emission is actually one of the main reasons terbium is used in technologies like smart phone displays. For our purposes, when the tryptophan-lanmodulin compound binds to terbium, we can observe the emitted light, or luminescence, to measure the concentration of terbium in the sample.”

The researchers developed many variants of the tryptophan-lanmodulin sensor, optimizing the location of the tryptophan so that it does not interfere with lanmodulin’s ability to bind to rare earth elements. These variants provided important insights into the key features of the protein that enable it to bind rare earths with such high selectivity. Then, they tested the most promising variant to determine the lowest concentration of terbium the sensor could detect in idealized conditions — with no other metals to interfere. Even under highly acidic conditions, like that found in acid mine drainage, the sensor could detect environmentally relevant levels of terbium.

“One challenge with extracting rare earth elements is that you have to get them out of the rock,” said Cotruvo. “With acid mine drainage, nature has already done that for us, but looking for the rare earths is like finding a needle in a haystack. We have existing infrastructure to treat acid mine drainage sites at both active and inactive mines to mitigate their environmental impact. If we can identify the sites with the most valuable rare earth elements using sensors, we can better focus extraction efforts to turn waste streams into revenue sources.”

Next, the researchers tested the sensor in actual samples from an acid mine drainage treatment facility in Pennsylvania, an acidic sample with many other metals present and very low levels of terbium — 3 parts per billion. The sensor determined a concentration of terbium in the sample that was comparable what they detected with the “gold standard” method, suggesting that the new sensor is a viable way to detect low concentrations of terbium in complex environmental samples.

“We plan to further optimize the sensor so that it is even more sensitive and can be used more easily,” said Cotruvo. “We also hope to target other specific rare earth elements with this approach.”

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“We know concussions may have long-term effects on the brain that last beyond getting a doctor’s clearance to return to play,” said study author Tom A. Schweizer, PhD, of St. Michael’s Hospital in Toronto, Canada. “It is unclear, however, to what extent the effects of repeated concussion can be detected among young, otherwise healthy adults. We found even though there was no difference in symptoms or the amount of recovery time, athletes with a history of concussion showed subtle and chronic changes in their brains.”

This study focused on changes within two areas in the middle of the brain that are especially vulnerable to concussion. Researchers focused on blood flow in the cingulate cortex and white matter microstructure in the corpus callosum. Changes in blood flow and microstructure that show up on brain scans can indicate underlying brain injury. The cingulate cortex is a layer of gray matter that coordinates sensory and motor skills. Below it is the corpus callosum, a broad band of nerve fibers linking the two hemispheres of the brain.

The study looked at 228 athletes with an average age of 20. This included 61 with a recent concussion and 167 without. Within the first group, 36 had a history of concussion. Within the second group, 73 had a history of concussion.

Researchers took up to five brain scans of each recently concussed athlete, from time of injury to one year after returning to play.

Researchers found that one year after a recent concussion, athletes with a history of concussion had sharper declines in blood flow within one area of the cingulate compared to those without a history of concussions. Those with a history of concussion had an average cerebral blood flow of 40 milliliters (mL) per minute, per 100 grams (g) of brain tissue. Those without a history of concussion had an average cerebral blood flow of 53 mL per minute, per 100g of brain tissue.

In athletes with a history of concussion, in the weeks after a new concussion, researchers also found microstructural changes in a region of the brain called the splenium, which is part of the corpus callosum.

“Our findings suggest that an athlete with a history of concussion should be watched closely, as these subtle brain changes may be worsened by repeated injury,” said Schweizer. “Additionally, our results should raise concern about the cumulative effects of repeated head injuries later in life.”

A limitation of the study is that athletes reported their own histories of concussion and could be inaccurate. Further research is needed that would follow athletes over time.

The study was supported by Canadian Institutes of Health Research, the Canadian Institute for Military and Veterans Health Research and Siemens Healthineers Canada.

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“Dementia risk scores might be useful to help identify people at higher risk of dementia earlier, so that potential lifestyle factors can be addressed earlier and monitored more closely,” said study author Sebastian Köhler PhD, of Maastricht University, the Netherlands. “Our study found that a substantial proportion of brain changes might be attributable to risk factors that can be modified.”

The study involved 4,164 people with an average age of 59. All participants took a test called the “Lifestyle for Brain Health” (LIBRA). The total score reflects a person’s potential for developing dementia. This study took into account 11 out of 12 lifestyle factors on the test, including high blood pressure, heart disease, smoking, diet and physical activity. Higher scores reflect higher dementia risk, with scores ranging from -2.7 to +12.7. Overall, the study group had an average score of 1.19. Researchers divided the participants into three groups: those with low risk of dementia, with an average score of -1.47, those with medium risk, with an average score of 1.20, and those with high risk, with an average score of 4.6.

Participants in the study took tests of memory and other thinking skills, such as information processing speed, executive function and attention. Researchers also looked at brain scans for signs of cerebral small vessel disease, which are signs of vascular brain damage often seen in patients who have dementia. They also looked for changes in volumes of white matter and gray matter.

Researchers found that people who were in the high-risk group on the LIBRA test, indicating a less brain-healthy lifestyle, had higher volumes of brain lesions, 1.27 ml compared to 0.48 ml for those in the lowest risk group. The high-risk group also had lower scores on two tests of thinking: information processing speed and executive function and attention.

Only in men, however, did researchers find associations between higher scores on the LIBRA test and lower volumes of grey matter, as well as lower scores on tests of memory.

“More research is needed to confirm these findings and determine why there were differences between men and women,” Köhler said. “It’s exciting that a simple test score may indeed be an index of brain health. We need to learn whether people can improve their scores by making changes in their diet, increasing physical activity or limiting alcohol to low-to-moderate use.”

The study does not prove that lifestyle test scores predict dementia, it only shows an association.

The study was supported by the European Regional Development Fund, the Province of Limburg, the Dutch Ministry of Economic Affairs and Climate Policy, the Weijerhorst Foundation, the Pearl String Diabetes Initiative, Maastricht University, the Annadal Foundation and Health Foundation Limburg, all in the Netherlands.

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