Far UVC Sanitization Kills COVID

 A new type of ultraviolet light that is safe for people took less than five minutes to reduce the level of indoor airborne microbes by more than 98%, a joint study by scientists at Columbia University Vagelos College of Physicians and Surgeons and in the U.K. has found.

…Far-UVC light has a shorter wavelength than conventional germicidal UVC, so it can’t penetrate into living human skin cells or eye cells. But it is equally efficient at killing bacteria and viruses, which are much smaller than human cells.

In the past decade, many studies around the world have shown that far-UVC is both efficient at destroying airborne bacteria and viruses without causing damage to living tissue. But until now these studies had only been conducted in small experimental chambers, not in full-sized rooms mimicking real-world conditions.

…The efficacy of different approaches to reducing indoor virus levels is usually measured in terms of equivalent air changes per hour. In this study, far-UVC lamps produced the equivalent of 184 equivalent air exchanges per hour. This surpasses any other approach to disinfecting occupied indoor spaces, where five to 20 equivalent air changes per hour is the best that can be achieved practically.

“Our trials produced spectacular results, far exceeding what is possible with ventilation alone,” says Kenneth Wood, PhD, lecturer in the School of Physics and Astronomy at the University of St. Andrews and senior author of the study. “In terms of preventing airborne disease transmission, far-UVC lights could make indoor places as safe as being outside on the golf course on a breezy day at St. Andrews.”

Summary here. Study here.

Here and here and here are my previous posts on UV-C sanitization. We are moving slower than I would like but the picture is of a UVC robot being used at Pittsburgh airport so kudos to them.

•  https://marginalrevolution.com/marginalrevolution/2022/03/more-on-uv-c-sanitization.html

Chronic absenteeism in NYC public schools hits alarming 40%

 The citywide rate of chronic absenteeism among NYC public-school students has risen to a staggering 40 percent, The Post has learned.

With 938,000 students enrolled in NYC’s schools, that means some 375,000 kids are missing too much school and falling too far behind.

But that number is likely an undercount because students out with COVID or quarantined could be marked present if they logged in online or had minimal contact with a teacher.

“It seems shocking the number is so high, but it could be even higher because they’re not always marking kids absent,” said education watchdog Leonie Haimson of Class Size Matters. 

It’s a major problem facing cities nationwide. In New York, chronic absenteeism is when a student misses 10 percent or more of the academic year, at least 18 days, for any reason excused or unexcused. The loss often results in low academic achievement, truancy, dropping out, delinquency and substance abuse, child advocates warn.

Chronic absenteeism is when a student misses 10 percent or more of the academic year.

Getty Images

Schools Chancellor David Banks has ordered his deputies to stem the hemorrhage. “It will be 40 percent if no actions are taken. We are taking actions,” a spokesman said.

The 40 percent is up from 26 percent in 2018-19, before the COVID-19 crisis.

The city Department of Education has not posted chronic absenteeism data for the last two years.

The rate is likely worse because principals say schools were told to mark COVID-stricken or quarantined students present if a teacher or administrator simply made contact with the kids or their parents in an email or phone call. 

“We were told they have to be marked present no matter what,” a Brooklyn principal told The Post.

The DOE said kids “may be marked present if they engage in learning remotely.”

Many families worried about safety kept their kids home in the first weeks after NYC schools opened for all in-person classes in September, Haimson and others said. Also, nearly 140,000 students have tested positive since then, staying home sick, while untold thousands of exposed classmates had to quarantine.

The DOE said kids “may be marked present if they engage in learning remotely.”

Shutterstock / Monkey Business I

Heightened anxiety, depression, fear of bullying, and restrictions on fun after-school activities such as sports have also led to lagging attendance, principals say.

​​They also cite the DOE’s policy since early in the pandemic to no longer use attendance as a requirement for students to pass. 

“They know everyone’s going to get promoted,” a principal said. “There’s no fear of not getting promoted, so they don’t have to come in if they don’t want to.’

On top of that, enrollment has dropped.

Chancellor Banks has made tackling the crisis a priority.

“The chancellor’s office is focusing on reducing chronic absenteeism,” Terrence Paulin, a liaison in the Brooklyn HS superintendent’s office, said in a recent memo to principals and attendance officials leaked on Twitter.

“The Central goal is to reduce the current citywide CA [chronic absenteeism] rate of 40% to 30% by June,” the memo says. 

Each district was given a “target goal,” Paulin said. Schools also have target goals, principals said. Pre-pandemic, chronic absenteeism ranged from less than 10 percent to 50 percent or more in different schools and districts, data show.

Paulin also said he noticed several absences at a school due to COVID back in January “were not coded 65 [present].” He said one student had 16 absences “but it may not be correct.” 

That alarmed David Bloomfield, a Brooklyn College and CUNY Grad Center education professor. He called the chancellor’s goal “well-intentioned,” but blasted the bureaucratic suggestion to fix records retroactively.

“It’s clearly data manipulation, and doesn’t change the experience of any children,” Bloomfield said.

“It’s cooking the books,” a Brooklyn principal said. “You can do your best to make sure they come to school every day, but you can’t change the past unless you change the data. I’m sure that’s why they’re giving that directive.”

The DOE countered that such fixes are routine: “Schools regularly verify attendance records for students to confirm the correct codes were entered,” a spokesman said.

Other cities are also plagued by absenteeism. Last week, the LA  Times reported 46 percent of the city’s public-school students, more than 200,000 kids, have missed at least 9% of the academic year, more than twice the number  pre-pandemic.

“I’ve heard of chronic absenteeism rates of 50% or more since the start of the pandemic,” said Joanna Smith-Griffin, CEO and Founder of AllHere, a Boston-based company that helps districts boost attendance.

Calling it “the canary in the mine,” she said, “Education leaders need to see dropping attendance and, even more alarmingly, enrollment, for what they really mean – a student population still reeling from the physical, social and emotional trauma of a pandemic and an overall breakdown of trust in public institutions, including schools.”

DOE spokesman Nathaniel Styer said officials expect the problem to lessen with more attention to it. “Twenty eight percent of our students will be chronically absent at the end of this year,” he projected.

“We are laser focused on ensuring every student attends school every day. This includes proactively identifying students who are at risk and taking steps to prevent chronic absenteeism. We expect each superintendent to make this a priority and to provide every student facing attendance barriers with the support they and their family need to end the year strong,” Styer said.

https://nypost.com/2022/04/02/chronic-absenteeism-in-nyc-public-schools-hits-alarming-40/

Higher blood fats more harmful than first thought

 Increased levels of blood fats in people with type 2 diabetes and obesity are more harmful than previously thought, a new study has found.

In patients with metabolic diseases, elevated fat levels in the blood create stress in muscle cells -- a reaction to changes outside the cell which damage their structure and function.

University of Leeds researchers have discovered that these stressed-out cells give off a signal which can be passed on to other cells.

The signals, known as ceramides, may have a protective benefit in the short-term, because they are part of a mechanism designed to reduce stress in the cell. But in metabolic diseases, which are long term conditions, the signals can kill the cells, make symptoms more severe, and worsen the illness.

Increased fat in the blood has long been known to damage tissues and organs, contributing to the development of cardiovascular and metabolic diseases including type 2 diabetes. The condition can be caused by obesity, rates of which have nearly tripled worldwide since 1975. In 2016, there were more than 650 million adults aged 18 and above with obesity.

Research supervisor Lee Roberts, Professor of Molecular Physiology and Metabolism in the University of Leeds's School of Medicine, said: "Although this research is at an early stage, our discovery may form the basis of new therapies or therapeutic approaches to prevent the development of cardiovascular and metabolic diseases such as diabetes in people with elevated blood fats in obesity."

In the lab, the team replicated the blood fat levels observed in humans with metabolic disease by exposing skeletal muscle cells to a fatty acid called palmitate. The cells began to transmit the ceramide signal.

When these cells were mixed with others which had not been previously exposed to fats, the researchers found that they communicated with each other, transporting the signal in packages called extracellular vesicles.

The experiment was reproduced in human volunteers with metabolic diseases and gave comparable results. The findings provide a completely new angle on how cells respond to stress, with important consequences for our understanding of certain metabolic diseases including obesity.

Professor Roberts said: "This research gives us a novel perspective on how stress develops in the cells of individuals with obesity, and provides new pathways to consider when looking to develop new treatments for metabolic diseases.

"With obesity an ever-increasing epidemic, the burden of associated chronic disease such as type 2 diabetes necessitates new treatments. We hope the results of our research here open a new avenue for research to help address this growing concern."

The paper, titled 'Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle', is published today in Nature Communications.

The international research team included colleagues from the University of Cambridge, the University of Bonn, University of Bari, Imperial College and AstraZeneca.

Story Source:

Materials provided by University of Leeds. Note: Content may be edited for style and length.

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Journal Reference:

1. Ben D. McNally, Dean F. Ashley, Lea Hänschke, Hélène N. Daou, Nicole T. Watt, Steven A. Murfitt, Amanda D. V. MacCannell, Anna Whitehead, T. Scott Bowen, Francis W. B. Sanders, Michele Vacca, Klaus K. Witte, Graeme R. Davies, Reinhard Bauer, Julian L. Griffin, Lee D. Roberts. Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29363-9

https://www.sciencedaily.com/releases/2022/04/220401094824.htm

New strategy for preventing clogged arteries

 Revving up a process that slows down as we age may protect against atherosclerosis, a major cause of heart attacks and strokes. In findings published online today in Proceedings of the National Academy of Sciences (PNAS), scientists at Albert Einstein College of Medicine led by Ana Maria Cuervo, M.D., Ph.D., successfully minimized artery-narrowing plaque in mice that would otherwise develop those lesions. The researchers did so by boosting chaperone-mediated autophagy (CMA), a cellular housekeeping process that Dr. Cuervo discovered in 1993 and named in 2000.

"We've shown in this research that we need CMA to protect against atherosclerosis, which becomes severe and progresses when CMA declines -- something that also happens when people get older," said Dr. Cuervo, professor of developmental and molecular biology and of medicine, the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases, and co-director of the Institute for Aging Research at Einstein. "But equally important, we've proven that increasing CMA activity can be an effective strategy for curbing atherosclerosis and halting its progression."

An Impressive CMA CV

CMA keeps cells functioning normally by selectively degrading the many proteins that cells contain. In CMA, specialized "chaperone" proteins bind to proteins in the cytoplasm and guide them to enzyme-filled cellular structures called lysosomes to be digested and recycled. Dr. Cuervo has deciphered many of the molecular players involved in CMA and shown that CMA, through its timely degradation of key proteins, regulates numerous intracellular processes including glucose and lipid metabolism, circadian rhythms and DNA repair. She also found that disrupted CMA allows damaged proteins to accumulate to toxic levels, contributing to aging and -- when the toxic buildup occurs in nerve cells -- to neurodegenerative diseases including Parkinson's, Alzheimer's, and Huntington's disease.

Dr. Cuervo's achievements were recognized in 2019 when she was elected to the National Academy of Sciences (NAS). In 1996, the NAS began inviting its newly elected members to submit a special Inaugural Article to PNAS that would underscore the member's scientific contributions. Due to COVID-19 pandemic-related delays, today's paper on CMA's protective role against atherosclerosis is Dr. Cuervo's inaugural PNAS paper and adds to her body of work on the importance of CMA.

Fighting Back Against Plaque

Cardiovascular disease (CVD) is the world's leading cause of death, with more than 80% of those CVD deaths due to heart attacks and strokes. CVD, in turn, is usually associated with atherosclerosis: the buildup of plaque (a sticky material consisting of fat, cholesterol, calcium, and other substances) within the walls of arteries. Accumulating plaque hardens and narrows arteries, preventing them from delivering oxygenated blood to heart muscle (leading to heart attacks), the brain (strokes), and to the rest of the body.

To investigate CMA's role in atherosclerosis, Dr. Cuervo and colleagues promoted atherosclerosis in mice by feeding them a fatty Western diet for 12 weeks and monitoring CMA activity in plaque-affected aortas of the animals. CMA activity initially increased in response to the dietary challenge; after 12 weeks, however, plaque buildup was significant, and virtually no CMA activity could be detected in the two types of cells -- macrophages and arterial smooth muscle cells -- that are known to malfunction in atherosclerosis, leading to the buildup of plaque within arteries.

"CMA seemed to be very important in protecting macrophages and smooth muscle cells -- helping them function normally despite the pro-atherosclerotic diet -- at least for a while, until their CMA activity basically came to a halt," said Dr. Cuervo. She noted that feeding the high-fat diet to mice totally lacking in CMA activity produced even stronger evidence of CMA's importance: plaques nearly 40% larger than those in control animals that were also on the high-fat diet.

Of Mice and Also Men

The researchers found evidence that weak CMA activity correlates with atherosclerosis in people too. Some patients who have had strokes undergo a surgical procedure, known as carotid endarterectomy, that removes plaque-affected segments of their carotid arteries to reduce the risk of a second stroke. Dr. Cuervo and her colleagues analyzed CMA activity in carotid artery segments from 62 first-stroke patients who were followed for three years after their surgery.

"Those patients with higher levels of CMA following their first strokes never got a second one, while second strokes occurred in nearly all the patients with low CMA activity," said Dr. Cuervo. "This suggests that your CMA activity level post-endarterectomy could help in predicting your risk for a second stroke and in guiding treatment, especially for people with low CMA."

Turning Up CMA, Tuning Out Atherosclerosis

The study is the first to show that turning up CMA could be an effective way to prevent atherosclerosis from becoming severe or progressing. The researchers genetically "upregulated" CMA in mice that were fed a pro-atherosclerotic, high-fat Western diet and later compared them with control mice fed the same diet for 12 weeks. The CMA-boosted mice had greatly improved blood lipid profiles, with markedly reduced levels of cholesterol compared with the control mice. Plaque lesions that formed in the genetically altered mice were significantly smaller and milder in severity compared with plaques in control mice. Fortunately, people won't need genetic alteration to benefit from this finding.

"My colleagues and I have developed drug compounds that have shown promise for safely and effectively increasing CMA activity in most mouse tissues and in human-derived cells," said Dr. Cuervo. Einstein has filed intellectual property on this underlying technology.

The PNAS paper is titled "Protective role of chaperone-mediated autophagy against atherosclerosis." Other Einstein authors were Julio Madrigal-Matute, Ph.D., Dario F. Riascos-Bernal, Antonio Diaz, M.D., Ph.D., Inmaculada Tasset, Ph.D., Adrian Martin-Segura, Ph.D., Susmita Kaushik, Ph.D., Simoni Tiano, M.D., Matthieu Bourdenx, Ph.D., Gregory J. Krause, M.S., Nicholas Sibinga, M.D., Fernando Macian, M.D., Ph.D., and Rajat Singh, M.D. The paper's other co-corresponding author is Judith C. Sluimer, Ph.D., of Maastricht University Medical Centre in The Netherlands and the University of Edinburgh in the United Kingdom.

Story Source:

Materials provided by Albert Einstein College of Medicine. Note: Content may be edited for style and length.

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Journal Reference:

1. Julio Madrigal-Matute, Jenny de Bruijn, Kim van Kuijk, Dario F. Riascos-Bernal, Antonio Diaz, Inmaculada Tasset, Adrián Martín-Segura, Marion J. J. Gijbels, Bianca Sander, Susmita Kaushik, Erik A. L. Biessen, Simoni Tiano, Mathieu Bourdenx, Gregory J. Krause, Ian McCracken, Andrew H. Baker, Han Jin, Nicholas E. S. Sibinga, Jose Javier Bravo-Cordero, Fernando Macian, Rajat Singh, Patrick C. N. Rensen, Jimmy F. P. Berbée, Gerard Pasterkamp, Judith C. Sluimer, Ana Maria Cuervo. Protective role of chaperone-mediated autophagy against atherosclerosis. Proceedings of the National Academy of Sciences, 2022; 119 (14) DOI: 10.1073/pnas.2121133119

https://www.sciencedaily.com/releases/2022/03/220328150520.htm

Novel nuclear microRNA ibeing developed for treatment of cardiovascular disease

 A novel angiogenic microRNA drug can be a new option for the treatment of ischemic cardiovascular disease, according to a new study published in PLOS ONE by researchers from the University of Eastern Finland together with international collaborators. In the study, the researchers describe a novel nuclear acting microRNA.

MicroRNAs are small RNA molecules, which regulate gene expression. Their canonical role is gene silencing by targeting messenger RNAs in cell cytoplasm. However, this novel microRNA, miR-466c, has a different mechanism of action. It upregulates the vascular endothelial growth factor A (VEGFA) by targeting the gene promoter in the cell nucleus.

In addition to expanding the academic understanding of microRNA biology, these findings have commercial relevance for the development of novel RNA drugs. Increasing the expression of VEGFA by using small RNAs offers novel options for the treatment of ischemic cardiovascular disease, where the blood supply in the tissue is compromised.

"RNA activation as a phenomenon has been known for 16 years already, but its commercial potential has been recognised only recently," says Adjunct Professor Mikko Turunen, Chair of the newly founded RNatives company, which will be commercialising the patented microRNA drug.

"Our patented microRNA drug has several advantages over traditional means of increasing gene expression. First of all, by activating the cell's own therapeutic gene (e.g., VEGFA), all the different spliceforms of the gene are correctly produced. Also, being a small RNA, it is much less immunogenic and more stable than longer RNAs, such as mRNA based drugs," Turunen says.

In addition to RNA drugs, RNatives is developing engineered exosomes for the delivery of these RNAs into the patients.

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Story Source:

Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.

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Journal Reference:

1. Pia Laitinen, Mari-Anna Väänänen, Ida-Liisa Kolari, Petri I. Mäkinen, Minna U. Kaikkonen, Marc S. Weinberg, Kevin V. Morris, Paula Korhonen, Tarja Malm, Seppo Ylä-Herttuala, Thomas C. Roberts, Mikko P. Turunen, Tiia A. Turunen. Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia. PLOS ONE, 2022; 17 (3): e0265948 DOI: 10.1371/journal.pone.0265948

https://www.sciencedaily.com/releases/2022/04/220401094845.htm

Omicron 'less severe' than Delta for children ages 4 and younger, study suggests

 New research from the Case Western Reserve University (CWRU) School of Medicine suggests that the children younger than age 5 who are infected with the COVID-19 Omicron variant have less risk of severe health outcomes than those infected with the Delta variant.

The study, published Friday in JAMA Pediatrics, is the first large-scale research effort to compare the health outcomes of coronavirus infection from Omicron to Delta in children 4 and younger -- the age group not yet able to be vaccinated.

The findings show that the Omicron variant is 6-8 times more infectious than the Delta variant. The severe clinical outcomes ranged from a 16% lower risk for emergency room visits to 85% less risk for mechanical ventilation. And about 1.8% of children infected with Omicron were hospitalized, compared to 3.3% with Delta.

The Case Western Reserve-led team analyzed the electronic health records of more than 651,640 children in the United States who had medical encounter with healthcare organizations between 9/2021-1/2022-including more than 22,772 children infected with Omicron in late December and late January -- to more than 66,000 children infected when Delta was prevalent in the fall. The study also compared the records of more than 10,000 children immediately before the detection of Omicron in the U.S., but when Delta was still predominant.

Children younger than 5 are not yet eligible for COVID-19 vaccines and have a low rate of previous SARS-CoV-2 infections, which also limits their pre-existing immunity.

The team examined clinical health outcomes for pediatric patients during a 14-day window following SARS-CoV-2 infection. Among the factors they reviewed were: emergency room visits, hospitalizations, ICU admissions and mechanical ventilation use.

Further demographic data analysis found that children infected with Omicron were on average younger-1.5 years of age versus 1.7 years-and had fewer comorbidities.

"The major conclusion to our research was that many more children were infected with Omicron when compared to Delta, but the children who are infected are not impacted as severely as were children infected with the Delta variant," said Pamela Davis, the Arline H. and Curtis F. Garvin Research Professor at the Case Western Reserve School of Medicine. "However, because there are so many more children infected, our hospitals were affected over the winter months by an influx of young children."

"We saw the number of hospitalizations within this age group skyrocket in January of this year because the infection rate of Omicron is about 10 to 15 times compared to that of the Delta variant," said Rong Xu, professor of biomedical infomatics and director of the Center for AI in Drug Discovery at the School of Medicine. "Omicron is less severe than Delta, however, the reduction of the severity range in clinical outcomes is only 16 to 85%. Furthermore, since so many un-vaccinated children were infected, the long-term effects of COVID-19 infections on the brain, heart, immune systems and other organs of children remains unknown and worrisome. "

The CDC recommends those age 5 and older receive a COVID-19 vaccine, and fully vaccinated people 12 and older receive a booster shot. According to updated guidance by the CDC, Americans no longer need to mask indoors in counties with low or medium "Covid-19 Community Level."

Story Source:

Materials provided by Case Western Reserve University. Note: Content may be edited for style and length.

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Journal Reference:

1. Lindsey Wang, Nathan A. Berger, David C. Kaelber, Pamela B. Davis, Nora D. Volkow, Rong Xu. Incidence Rates and Clinical Outcomes of SARS-CoV-2 Infection With the Omicron and Delta Variants in Children Younger Than 5 Years in the US. JAMA Pediatrics, 2022; DOI: 10.1001/jamapediatrics.2022.0945

https://www.sciencedaily.com/releases/2022/04/220401182946.htm

Hospitals bet big on venture capital amid COVID-19 revenue flux

 When the coronavirus first hit the U.S. two years ago, hospitals quickly realized that the pandemic would play havoc not only with their care capabilities, but also with their bottom lines.

As hospital systems became overwhelmed with patients sick with COVID-19, lucrative inpatient volumes plummeted, and many operators have yet to fully recover. To compensate for oscillating revenue, some hospitals have shifted their focus to outpatient service lines and alternative revenue sources, including investments.

In fact, more hospitals — especially large nonprofit systems with substantial cash pools — are acting more like venture capitalists as they ramp up investments in companies with products they can use and scale, all with an eye toward what might generate a return on investment down the line, according to an analysis conducted by Healthcare Dive.

"They're really doing this because they want to diversify revenue," said Rick Gundling, senior vice president of healthcare financial practices for the Healthcare Financial Management Association, a professional group for health finance staff.

Shifting market sentiment could throw cold water on what was previously a red-hot funding arena for digital health startups. But many expect hospital venture activity to only increase as technology becomes more woven into everyday medical delivery and administration.

"There still in 2021 was an unprecedented amount of money raised in healthcare venture capital to yet be deployed. And that money's going to get deployed somewhere," said Matthew Warrens, managing director of UnityPoint Health Ventures, the corporate venture capital arm of Iowa-based nonprofit UnityPoint Health.

While the pandemic hasn't changed the types of startups and solutions that hospitals are investing in, the pace has picked up in the past two years, data show.

A Healthcare Dive analysis of CB Insights data found that taken as a whole, the amount of large health systems' venture investments jumped significantly from 2019 to 2020, and again from 2020 to 2021, even though deal size contracted slightly.

View more details on the analysis.

Venture funds maintained by large hospitals were ratcheting up their investments even before the pandemic. But the overall pace has accelerated over the past two years

Dollar total and amount of rounds participated in by major hospital VCs, 2010-2021

"We were already on a path to make more and larger investments prior to the pandemic. I think what the pandemic did was allow us to really crystallize and focus on what our themes would be, and how we internally leverage support for our companies," said Akhil Saklecha, managing director of Cleveland Clinic Ventures, the VC arm of academic medical giant Cleveland Clinic.

Jumping on the digital health revolution

Even before COVID-19, venture capital was becoming a more attractive investment option to many operators than real estate or the stock market for a handful of reasons, including low interest rates. Then came the financial volatility of the pandemic, resulting in hospital lobbies calling for billions in federal aid and many smaller and rural facilities facing closure.

Large health systems with better cash reserves and stronger assets were able to pivot better than some of their peers, and increased their investments at a time of acute financial uncertainty. The biggest venture deals in 2020 and 2021 have been from those systems, which took advantage of low interest rates and the acceleration of health tech spurred by COVID-19.

"They poised themselves to be able to take care of that," Gundling said, noting the timing of higher investments despite COVID-19's economic uncertainty actually makes sense. "It seems counterintuitive but it's actually quite intuitive. It's very strategic."

Hospital VCs funneled more dollars to startups during the pandemic — especially nonprofits

Annual venture round activity by large hospital funds, 2010-2021

Hospitals have several paths to fund venture capital. Some invest internally within their own organization, while others partner with venture capital firms. Still, a growing number of systems have begun rolling out their own venture subsidiaries that can focus wholly on venture opportunities, with their own set of governance models and processes allowing them to jump more quickly on potential forward-looking opportunities.

Iowa-based system UnityPoint launched its own $100 million venture capital fund, UnityPoint Ventures, in May 2019.

Though many operators have been doing venture investing through limited partnerships or other vehicles for a couple of decades, the purpose of UnityPoint's fund is the strategic value its portfolio companies provide — "though we absolutely are underwriting and expect strong financial returns," Warrens said.

"The difference between the two is that when you're doing that internally, with your internal lens, and linking it directly to the organization's overall strategy, you are going to be much more likely to pair financial investment opportunity with the companies that are going to bring that strategic value," Warrens said.

The pandemic stoked the digital health investment landscape into a frenzy, resulting in record funding in 2021 that many expect will spill over into 2022. Unsurprisingly, digital health is a major focus area for hospital VCs, as hospitals almost overnight ramped up their telehealth and remote care operations early 2020 and since then, have worked to manage a large, sustained volume of patients clamoring for virtual care.

"There's a much more increased focus on digital health. It's been a very fast-growing part of the industry," Gundling said. "That's probably the biggest numbers and the shift in priorities."

UnityPoint Ventures' Warrens noted the pandemic added more fuel on ever-increasing valuations, which changes venture opportunities.

"What we saw was that early on in our portfolio, we'd made some really good investments in what I would describe as point solutions, like remote monitoring and digital behavioral health. In my opinion, the pandemic expedited the scaling of those solutions, right? It just became obvious that these were things that we had to do as an organization. And so those things got deployed faster," Warrens said.

In addition to digital health, systems are also targeting areas like hospital-at-home technology, autonomously or remotely operated medical devices and tools to streamline the consumer experience and back-end administrative functions. Cybersecurity, specialty pharmacy and mental and behavioral health also rank high on the priority list for hospital investors.

The pandemic has also spurred interest in identifying and combating emerging pathogens, leading some hospital VCs to zero in on new methods of therapeutic and diagnostic discovery.

Academic medical centers and large nonprofit systems are also interested in leveraging their VC arms to commercialize internally developed intellectual property.

For example, Cleveland Clinic has spun out almost 80 companies since it was founded just over 20 years ago, Saklecha said. Its fund focuses on medical devices, digital health and life sciences, building off the research and applications developed in the Clinic's research institute and by its physicians.

"How do we innovate on better virtual health programs — not just incrementally better, but really transforming the care?," Saklecha said. "The second thing is, how do we look at patients as consumers of health? How do we create a strategy around interacting with consumers before they become patients?."

Cleveland Clinic Ventures is supported by Cleveland Clinic's treasury funds. Historically, CCV has invested in the low-single-million-dollar range per year into companies. In the last few years, that pace has ramped up to almost $25 million a year into a more targeted pool of startups.

"The venture capital group is really focused on those inventions that have a significant opportunity to impact patients but really based on finding identified white spaces where there's no competition and where there's large market opportunities financially," Saklecha said.

Some early deal data from this year provides a hint into what hospital venture activity could look like as COVID-19 becomes endemic.

Nonprofit VC arms participated in four funding rounds this January totalling almost $238 million, according to CB Insights data of major hospital VCs.By comparison, major nonprofit VCs in January 2021 participated in five funding rounds totaling a little over $183 million; eight funding rounds totaling almost $185 million in January 2020; and four funding rounds totaling almost $49 million in 2019.

Though deal count in the month has fallen since 2020 and 2021 back to 2019's levels, total size of the funding rounds eclipsed any of the recent periods by far, suggesting an early start to the year. It also implies deal size isn't tied to the prevalence of COVID-19 cases, as hospitals continue to bet big on tech-enabled care.

Additionally, it suggests same types of startups — focused on patient relationships and experience, hospital at home and clinical area of mental health — will continue to nab the lion's share of hospital funding this year.

This January, Kaiser Permanente Ventures was particularly active, participating in funding rounds totaling $235 million, followed by Mayo Clinic Ventures, which invested in one $100 million Series D round for Medically Home.

Deal size hiked in January compared to the same month in past years, though the number of deals returned to 2019's level

Hospital VC investment rounds, January 2022

Questions about the level of hospital venture activity as COVID-19 becomes more normalized are less tied directly to the pandemic as they are to what's happening in the public markets today, experts say.

Currently, the markets are seeing a sharp decrease in valuations of digital health companies, many of which went public during the last two years of COVID-19.

Lowering valuations may imply a shift in investor sentiment that is likely to translate into the private markets as well, and could curb venture activity. Additionally, some investors might redirect their attention from the private markets and back to public ones, attracted by companies with long-term growth potential that may currently be undervalued, making shares more affordable.

"As you think about coming out the other side of the pandemic, it's really less about the pandemic and more about what you're seeing happening in the public markets today, and trying to understand how that's impacting and changing valuations going forward," Warrens said.Warrens added he doesn't expect UnityPoint's investment pace to change coming out of the pandemic, though the VC does intend to focus more on enterprise-type solutions that impact multiple facets of the organizations instead of point solutions for future deals.

"You'll see that continue," Warrens said. "That truly is much more a reflection of the organizational strategy coming out of the pandemic paired through our lens of what our venture opportunities are."

Hospital venture activity coming out of the pandemic also depends on ongoing investment performance, HFMA's Gundling said.

"It all depends on if they're meeting their goals," Gundling said. "They're going to monitor and see which ones are working. Are they differentiating themselves in the marketplace?... I think they're very optimistic but they're careful as well."

Risky bets and operational speedbumps

Hospitals' venture activity faces some speedbumps, like worries about investment downside and physician uptake. And for nonprofit systems, their high levels of venture activity has sparked worries about a potential clash between profit-seeking and altruistic motives.

Nonprofits' activity raising eyebrows

Nonprofit hospitals typically are more active in venture activity than their for-profit peers, and the gap in venture activity between the two may widen as nonprofits sit on increasing levels of cash.

Large for-profits, with the exception of HCA Healthcare, don't have direct VC arms, while many major nonprofits do. That complicates drawing direct comparisons between nonprofit and for-profit investing activity. Still, nonprofits seem in general to invest more money over a greater amount of deals, though the VC firm representing Tenet, CHS and LifePoint (along with a slew of smaller nonprofits) — the Heritage Group — did have the fourth-highest levels of investments in 2021, trailing Kaiser Permanente, Ascension and Intermountain in terms of deal size.

Venture is at its core a risky activity, as investments can remain illiquid for a lengthy amount of time.

According to Correlation Ventures data, 65% of VC investment rounds fail to return their capital, while only 4% return more than 10 times the capital invested. It’s also a long-term bet: VC funds generally invest actively for three to four years before being locked in for about seven to 10, though it can take significantly longer to fully liquidate returns.

Still, investors are attracted by the promise of oversized returns: VC generally delivers returns higher than other investment options, like the stock market or real estate. Hospitals — especially nonprofits — have cash reserves available and their funds say they're generally unconcerned about exit timeline or return.

"We don't invest with a mindset to say that we need to exit from the investment in five years or seven years. I think our goal is really to get the technology to patients," Cleveland Clinic's Saklecha said.

And "it's not too different from the way that personal financial planners tell you — you have your safe investments, and then you get into the stock market and then you kind of build up and have a little bit for innovation," Gundling said. "It's not pie-in-the-sky, but it is riskier."

Part of that risk is that startups can fail for myriad reasons. For example, hospitals can subset platforms due to apprehensions about their commercial prospects, or discover the business case for using startups' products isn't a strong as expected. In addition, they may face poor clinician uptake, or become concerned for their budget if a large chunk of cash is tied up in illiquid investments.

North Carolina nonprofit Cone Health disclosed in 2020 it was shutting down a smartphone-based product called Wellsmith, aimed at helping people manage their diabetes, because they didn’t expect it to be profitable in a cluttered digital health market, KHN reported in August. That's despite Wellsmith's promising initial results.

"There's companies where the initial strategy of forming the company and the target market and the opportunity, that didn't end up materializing or the plan changed as the company matured. There's a lot of reasons that companies may not go in that direction or may fail," Saklecha said.

Saklecha gave the example of Renovo Neural, a Cleveland Clinic spinoff founded over a decade ago to fill a gap in the research market for a targeted contract research organization focused on finding novel drug therapy solutions for multiple sclerosis and other neurological diseases.

Renovo was formed to become that CRO, but the market was never a big one, Saklecha said.

"It didn't make sense to continue supporting the company because it would continue to lose money, and ultimately those services could be provided by other vendors in different ways," Saklecha said. Cleveland Clinic ended up selling Renovo's assets to a third party.

It's a vignette of when hospitals acting as venture capitalists goes sour, and illustrates the risks of long-term investing.

But for every Renovo, there's a Centerline Biomedical, a Cleveland Clinic startup that created a surgical navigation tool to maps out the endovascular system, reducing radiation exposure for patients and physicians, Saklecha added.

Centerline's tool is now cleared by the Food and Drug Administration, and is being commercialized and placed in some of the biggest health systems in the U.S., Saklecha said.

"If we were investing in solutions that were widely being adopted today I don't think that those would be the type of companies that would be providing the financial returns that we're looking to underwrite," Warrens noted. "From that aspect, I think it's about finding a blend of those things that you're ready to embrace in certain parts of your organization, with a look or a thought towards wide scaling in the future."

To be sure, venture capital can reap sizeable dividends for early investors. For example, nonprofits including 15-hospital Spectrum Health, Bon Secours Mercy Health, Memorial Hermann Health System and Rush University System saw a significant return in 2020 with Chicago-based fund 7wireVentures when its portfolio company Livongo got acquired by virtual care giant Teladoc in a deal valued at $18.5 billion.

"Healthcare organizations have always moved the ball forward. This is just another way to fund innovation, maybe take it to the market quicker," Gundling said. "This just kind of accelerates that. Not that it won't be without controversy."

Note on data analysis: The analysis includes data from venture subsidiaries of some of the largest nonprofit and for-profit operators in the U.S. provided by market research firm CB Insights. It includes funding data from Ascension Ventures, Providence Ventures, Kaiser Permanente Ventures, UPMC Enterprises, Mayo Clinic Ventures, Cleveland Clinic Ventures, Intermountain Ventures, UnityPoint Ventures, the Heritage Group, Health Insight Capital (HCA's VC) and Jumpstart Nova, a new fund that's co-backed by several health system investors, including HCA, Atrium Health and Henry Ford Health System.

Other major U.S. systems, including CommonSpirit, AdventHealth, Baylor Scott & White, Bon Secours Mercy, Sanford, Avera and Baptist, all invest directly through hospital entities and have no known venture arm. As such, their investments are not included in this analysis.

Ballad Health's Ballad Ventures appears to exist, per a LinkedIn page, but has no known website, and only one employee. It seems to have just launched in 2019.

It's important to note this is not an exhaustive list, but does put some parameters around hospitals activity as venture capitalists, both alone and as a whole.

There some limitations with the data: The round or dollar amount is the entire round's size, and so almost certainly overestimates the total amount of a specific hospital VC's investment in a startup. The analysis uses round size as a proxy for hospital VC investment volume, meaning it's the largest possible amount the fund may have invested in the round.

Additionally, for deals with undisclosed amounts, Healthcare Dive included the deal in annual deal counts but did not change the aggregate dollar amount for a given time period.

CommonSpirit, AdventHealth, Baylor Scott & White, Bon Secours Mercy, Sanford, Avera and Baptist all invest directly through hospital entities and have no known venture arm. As such, their investments are not included in this analysis.

https://www.healthcaredive.com/news/hospital-venture-capital-COVID-19/619852/