Posted on

Study confirms safety and effectiveness of COVID-19 vaccination in people with cancer

Source: Cell Press
Date: 6/10/2021
Link to original
Image of article

Since the early days of the COVID-19 pandemic, there were questions about how people in active cancer treatment would fare if they became infected with SARS-CoV-2. The worries were due, in large part, to the effects that cancer and its treatments can have on the immune system. Now that COVID-19 vaccines are widely available, concerns have shifted to the safety and effectiveness of vaccination in this potentially vulnerable population. A study published June 5 in the journal Cancer Cell aims to allay those fears.

In a review of 200 patients with a wide spectrum of cancer diagnoses, researchers at Montefiore Health System and Albert Einstein College of Medicine in the Bronx, NY, found that after full vaccination, 94% of patients overall demonstrated seroconversion, which was determined by the presence of antibodies to the SARS-CoV-2 spike protein. Response rates were very high among patients with solid tumors and were lower in people with certain blood cancers, but even the majority of those patients mounted an immune response.

“Studies from early in the pandemic found that cancer patients who get COVID-19 have higher rates of morbidity and mortality compared to the general population,” says senior co-author Amit Verma, director of the Division of Hemato-Oncology at Montefiore and professor of medicine and of developmental and molecular biology at Einstein, and associate director, translational science, Albert Einstein Cancer Center. “We really need efforts to protect these vulnerable patients from infection. This study should help people feel reassured that these vaccines work very well, even in those receiving chemotherapy or immunotherapy.”

“This study confirms that there is no need for patients to wait for vaccination until they finish their chemotherapy or immunotherapy,” says senior co-author Balazs Halmos (@DrSteveMartin), director of the Multidisciplinary Thoracic Oncology Program at Montefiore, professor of medicine at Albert Einstein College of Medicine, and a member of the Albert Einstein Cancer Center (AECC). “The side effects from vaccination seen in these populations were not substantially worse than in other groups. Not a single patient had to go to the emergency room or be admitted to the hospital because of side effects from the vaccines.”

This study was the largest of its kind to look at seroconversion rates in cancer patients who have been fully vaccinated. Previous studies have looked at much smaller populations or have analyzed antibody levels after only the first dose of two-dose vaccines.

In serum tests to look for IgG levels after vaccination, the researchers found that among patients with solid tumors, 98% showed seroconversion. Among patients with hematologic cancers, the rate of seroconversion was 85%.

Patients receiving some treatments fared worse than others. Those receiving therapies for blood cancers that work by killing B cells (such as rituximab or CAR T therapies) had seroconversion rates of 70%. For those who had recently had bone marrow or stem cell transplants, the rate was 74%. But those rates were still much higher than expected, the researchers say.

“Although those receiving treatments that affect B cells didn’t do as well, patients with blood cancers that affect the myeloid cells rather than the lymphoid cells had a pretty good response with regard to seropositivity,” says first author Astha Thakkar (@asthakkar15) a Montefiore hematologic oncology fellow. “This includes people with acute myeloid leukemia and myelodysplastic syndrome.”

The researchers say that one reason their data are so significant is that they include patients who had a broad range of cancers and who were undergoing a number of different treatments. “The patients themselves were also diverse and were representative of the patients we treat in the Bronx,” Halmos says. “About one-third were Black and 40% were Hispanic.”

“Vaccination among these populations have been lower, even though these groups were hardest hit by the pandemic,” Verma concludes. “It’s important to stress how well these patient populations did with the vaccines.”

Posted on

Researchers adapt cell phone camera for SARS-CoV-2 detection

Source: Cell Press
Date: 12/10/2020
Link to original
Image of article

Researchers have developed an assay that can detect the presence of SARS-CoV-2 in a nasal swab using a device attached to an ordinary smartphone, they report December 4 in the journal Cell. Although more research is needed before such a test can be rolled out, the results are promising and ultimately may be applicable to screening more broadly for other viruses.

“Our study shows that we can do the detection part of this assay very quickly, making the measurement with mass-produced consumer electronics,” says Daniel Fletcher, a bioengineer at the University of California in Berkeley and co-senior author on the paper. “We don’t need fancy laboratory equipment.”

Fletcher and other co-senior author Melanie Ott, a virologist at Gladstone Institutes and the University of California, San Francisco, began collaborating with Nobel laureate Jennifer Doudna, also a co-author on the study, about two years ago on a rapid, at-home test for HIV. They were looking to address the need for frequent testing that has arisen because of current drug trials that require close monitoring of patients’ viral loads. When COVID-19 hit the scene in January, they quickly pivoted their research to develop a test that would detect the presence of a different virus — SARS-CoV-2.

The test makes use of CRISPR-Cas technology. Specifically, RNA in the sample can be detected with the Cas13 enzyme, eliminating the need for reverse transcription of the RNA into DNA and then amplification by PCR technology used in current standard tests. When Cas13 binds to the RNA from the virus, it cleaves any surrounding RNA sequences; the researchers added an RNA-based probe to the reaction that gets cleaved and produces fluorescence that can be detected with the camera. The assay provides results within 30 minutes of detection time.

In the current study, which was primarily designed to be a test of the amplification-free CRISPR-Cas technology and the detector, the nasal swabs were spiked with SARS-CoV-2 RNA. The investigators are currently working on a solution that would induce a single-step reaction in which the RNA is released from the virus without the need for purification. Because it doesn’t require amplification, the assay is able to quantify the amount of virus in the sample.

“It’s super exciting to have this quantitative aspect in the assay,” Ott says. “PCR is the gold standard, but you have to go through so many steps. There are huge opportunities here for pathogens and for biology in general to make RNA quantification more precise.”

The fluorescence detector consists of a laser to produce illumination and excite the fluorescence and an added lens to help collect light. The phone is placed on top of it. “One takeaway is that the phone camera is ten times better than the plate reader in the lab,” Ott says. “This is directly translatable to it being a better diagnosis reader.” Previous research in Fletcher’s lab has led to phone-based devices that visually detect parasites in blood and other samples, and the current assay demonstrates how phone cameras can also be useful for molecular detection.

Ultimately, Fletcher and Ott would like to have this type of test be part of a broader system that could be used at home to screen not only for SARS-CoV-2 but other viruses — like those that cause colds and flu. But more immediately, the researchers hope to develop a testing device using this technology that could be rolled out to pharmacies and drop-in clinics. They would like to get the cost of testing cartridges down to about $10. The final device would probably not actually use a phone but have a phone camera built into it.

Ott notes that what they’ve learned developing this SARS-CoV-2 test can also be applied to their work with HIV tests. “We will need to change the extraction methods because we’ll be dealing with blood instead of nasal swabs, but it’s really helpful that we’ve developed the fluorescent detection part,” she says. “This is the start of an era when we can give the individual more authority and autonomy” in terms of being able to test themselves.

Posted on

Case study details leukemia patient who shed infectious SARS-CoV-2 for at least 70 days

Source: Cell Press
Date: 11/5/2020
Link to original
Image of article

The majority of people infected with SARS-CoV-2 appear to actively shed infectious virus for about 8 days, but there is a wide range of variability from person to person. Understanding how long people can remain actively infected is important, because it provides new details about a disease and a virus that are still not well understood and informs public health decisions. Researchers report November 4 in the journal Cell an unusual case of one woman with leukemia and a low antibody count who was infected with the coronavirus for at least 105 days, and infectious for at least 70, while remaining asymptomatic the entire time.

“At the time we started this study, we really didn’t know much about the duration of virus shedding,” says senior author Vincent Munster, a virologist at the National Institute of Allergy and Infectious Diseases. “As this virus continues to spread, more people with a range of immunosuppressing disorders will become infected, and it’s important to understand how SARS-CoV-2 behaves in these populations.”

Munster, an expert in emerging infectious diseases, began publishing research on SARS-CoV-2 in January. He was contacted in April by infectious disease specialist Francis Riedo, a study co-author, about a patient in Kirkland, Washington, who had been infected very early in the COVID-19 pandemic. Riedo’s patient had had numerous positive PCR tests for the virus over a period of weeks, and he wanted to know if she was still shedding virus.

The patient, a 71-year-old woman, was immunocompromised due to chronic lymphocytic leukemia and acquired hypogammaglobulinemia. She never showed any symptoms of COVID-19. She was found to be infected with the virus when she was screened after being admitted to the hospital for severe anemia and her doctors recognized that she had been a resident of a rehabilitation facility experiencing a large outbreak.

Munster’s lab at NIAID’s Rocky Mountain Laboratories in Hamilton, Montana, began studying samples that were regularly collected from the patient’s upper respiratory tract. They found that infectious virus continued to be present for at least 70 days after the first positive test, and the woman didn’t fully clear the virus until after day 105. “This was something that we expected might happen, but it had never been reported before,” Munster says.

The investigators believe the patient remained infectious for so long because her compromised immune system never allowed her to mount a response. Blood tests showed that her body was never able to make antibodies. At one point she was treated with convalescent plasma, but Munster doesn’t think the treatment had an effect because of its low concentration of antibodies. Despite her inability to mount an antibody response, she never went on to develop COVID-19.

The team performed deep sequencing on all the virus samples obtained from the patient to see how the virus might have changed over the course of the patient’s infection. Samples collected at various times displayed different dominant gene variants. However, the investigators don’t think that these mutations played a role in how long the virus persisted, because they saw no evidence of natural selection. Selection would have been implicated if one of the variants had appeared to provide the virus with a survival benefit and had become the dominant variant, but none of them did. They also tested whether or not the mutations affected the ability or speed of the virus to replicate and found no differences.

Munster says that as far as he knows, this is the longest case of anyone being actively infect-ed with SARS-CoV-2 while remaining asymptomatic. “We’ve seen similar cases with influenza and with Middle East respiratory syndrome, which is also caused by a coronavirus,” he notes. “We expect to see more reports like ours coming out in the future.”

Posted on

Operation Outbreak simulation teaches students how pandemics spread

Source: Cell Press
Date: 9/3/2020
Link to original
Image of article

In 2015, a team of specialists in modeling disease outbreaks got together with educators to create Operation Outbreak, an educational platform and simulation intended to teach high school and college students the fundamentals of responses to pandemics. The program, which is open source and freely available, was designed to simulate outbreaks with different variables (such as R0 and mode of transmission) and to generate data in the context of real human behavior. It includes a Bluetooth-based app that carries out contact tracing by recording transmission events between phones. The details are highlighted in a Commentary published August 31 in the journal Cell.

Operation Outbreak came about after Todd Brown, then a middle school teacher in Florida, contacted Pardis Sabeti (@PardisSabeti), a computational biologist at the Broad Institute of Harvard and MIT, after reading a profile of her in a magazine. He and his students were studying the ongoing Ebola outbreak in West Africa, and he was developing a simulation of how the virus spread using stickers.

As they continued to work together, Sabeti and her team, including Andrés Colubri (@codeanticode), at the time a computational scientist in her lab, began studying mumps outbreaks across Boston college campuses. The idea to create an educational app that “spread” viruses through Bluetooth was soon born. And as recently as December 2019, they were running simulations modeling the outbreak of a virus with a very similar modus operandi to SARS-CoV-2.

“We decided to use a SARS-like virus since it had been high on many pandemic researchers’ lists as a concern,” says Colubri, who is now at the University of Massachusetts Medical School. “To make the simulation more challenging, we included an element of asymptomatic spread. This was a natural concern that would elevate a pandemic’s potential even further.”

This summer, as the COVID-19 pandemic continued to spread, Operation Outbreak was rolled out to 2,000 students in Chicago who were participating as “social distancing ambassadors” as part of the One Summer Chicago program. Participants used the app to track and trace behaviors and learn how “infections” spread in different parts of the city.

“The platform and curriculum are very flexible from an academic and also an experiential learning standpoint,” Brown says. “We tried to gamify the education, so that players’ behaviors and decisions affect not only them, but the entire group they’re playing with.”

The simulation includes elements that have become a familiar part of our daily lives, like limitations in testing abilities and shortages of personal protective equipment (PPE). The program also offers the ability to simulate additional elements that could arise in the current pandemic or in future ones, such as other circulating viruses that can complicate diagnosis.

“We are in one of the most unique situations in the history of the world, by virtue of being able to engage students,” says Brown, who is now community outreach director at Sarasota Military Academy. “Kids are more primed to learn when something directly affects them and their families. This is a chance for future generations to become aware of how infections spread and to recognize warning signs.”

“I hope we can convey that we don’t have to wait for the next pandemic to learn how to respond to them,” Sabeti says. “Ultimately, we can exquisitely model every aspect of viruses and how they spread, even in the ways that we react through vaccines, protective gear, and diagnostics.”

The team has put together a scalable curriculum, including a textbook and series of educational videos, that can be integrated at schools around the country. The materials, which have been funded by philanthropy, are open source and are available for free.

This work is supported by the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute. Additional funding grants include L’Oreal USA Women in Science Changing the Face of STEM, Toshiba America Foundation, Florida Association of International Baccalaureate World Schools, and Voya Financial.

Posted on

COVID-19 patients who experience cytokine storms may make few memory B cells

Source: Cell Press
Date: 8/19/2020
Link to original
Image of article

Newswise — The release of massive amounts of proteins called cytokines can lead to some of the most severe symptoms of COVID-19. When large numbers of immune cells release cytokines, this increases inflammation and creates a feedback loop in which more immune cells are activated and this is sometimes called a cytokine storm. An August 19 study in the journal Cell now suggests that high levels of some cytokines may also prevent people who are infected from developing long-term immunity as affected patients were observed to make very few of the type of B cells needed to develop a durable immune response.

“We’ve seen a lot of studies suggesting that immunity to COVID-19 is not durable because the antibodies decline over time,” says co-senior author Shiv Pillai, a professor at Harvard Medical School and member of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard. “This study provides a mechanism that explains this lower-quality immune response.”

The investigators focused on germinal centers–the areas within the lymph nodes and spleens where B cells, the immune cells that produce antibodies, differentiate. Differentiation and changes in antibody genes are required to build immunity to an infectious agent.

“When we looked at the lymph nodes and spleens of patients who died from COVID-19, including some who died very soon after getting the disease, we saw that these germinal center structures had not formed,” says co-senior author Robert Padera, a pathology professor at Harvard. “We decided to determine why that’s the case.”

Because the disease was so new, animal models for studying COVID-19 infection were not yet available at the time they began their study. The researchers instead gained insights from previous studies involving mouse models of other infections that induce cytokine storm syndrome–a malaria model and one of bacterial infection in which germinal centers were lost.

In people with severe COVID-19, one of most abundant cytokines released is called TNF. In the infected mice, TNF appeared to block the formation of germinal centers. In previous cytokine storm models, when the mice were given antibodies to block TNF or had their TNF gene deleted, the germinal centers were able to form. When the researchers studied the lymph nodes of patients who had died of the disease, they found high levels of TNF in these organs. This led them to conclude that TNF may be preventing the germinal centers from forming in people with COVID-19 as well.

“Studies have suggested this lack of germinal centers happens with SARS infections,” Pillai says. “We even think this phenomenon occurs in some patients with Ebola, so it was not surprising to us.”

The researchers also studied blood and lymphoid tissue from people with active infections who were in different stages of COVID-19. They found that although germinal centers were not formed, B cells were still activated and appeared in the blood, which would allow the patients to produce some neutralizing antibodies. “There is an immune response,” Padera says. “It’s just not coming from a germinal center.”

“Without the germinal centers, there is no long-term memory to the antigens,” Pillai adds. He notes that studies of other coronaviruses that cause colds have suggested that someone can get infected with the same coronavirus three or four times in the same year.

The authors say despite their findings, they still believe a successful COVID-19 vaccine can be developed as it should not cause high levels of cytokines to be released.

Posted on

‘Bright spot’ during COVID-19: Increased power from solar panels thanks to cleaner air

Source: Cell Press
Date: 6/22/2020
Link to original
Image of article

During the COVID-19 pandemic, one unexpected outcome in cities around the world has been a reduction in air pollution, as people stay home to avoid contracting the coronavirus. Based on data collected in Delhi, India, researchers report that this cleaner air has led to more sunlight reaching solar panels, resulting in the production of more clean energy. The work appears June 19 in the journal Joule.

“Delhi is one of the most polluted cities on the planet,” says first author Ian Marius Peters of Helmholtz-Institut Erlangen-Nürnberg for Renewable Energies in Germany. “Moreover, India enacted a drastic and sudden lockdown at the start of the pandemic. That means that reductions in air pollution happened very suddenly, making them easier to detect.”

Peters and his colleagues had previously done research in different cities, including Delhi, looking at how haze and air pollution impact how much sunlight reaches the ground and the effect of air pollution on the output of solar panels. The photovoltaic (PV) system installation in Delhi used for the earlier work was still in place, and data on the amount of solar radiation reaching the PV installation (called the level of insolation) was available for the time before and during the shutdown.

Insolation is measured with a pyranometer, an instrument that determines the solar radiation flux density from the hemisphere within a given range of wavelengths. Using data from some of their previous studies, the researchers calculated the changes in insolation.

They found that in late March, the amount of sunlight reaching the solar panels in Delhi increased about 8%, compared with data from the same dates from 2017 to 2019. The insolation at noon increased from about 880 W/sqm to about 950 W/sqm. Information on air quality and particulate matter suggested that reduced pollution levels were a major cause for the rise.

“The increase that we saw is equivalent to the difference between what a PV installation in Houston would produce compared with one in Toronto,” Peters says. “I expected to see some difference, but I was surprised by how clearly the effect was visible.”

The researchers say the new data from Delhi, combined with their earlier findings, provide a solid foundation to further study the impact of air pollution on solar resources. They expect to also find increased output of power from solar panels in other areas where air was cleaner due to lockdown measures.

“The pandemic has been a dramatic event in so many ways, and the world will emerge different than how it was before,” Peters says. “We’ve gotten a glimpse of what a world with better air looks like and see that there may be an opportunity to ‘flatten the climate curve.’ I believe solar panels can play an important role, and that going forward having more PV installations could help drive a positive feedback loop that will result in clearer and cleaner skies.”

Posted on

Team shares blueprint for adapting academic research center to SARS-CoV-2 testing lab

Source: Cell Press
Date: 5/12/2020
Link to original
Image of article

During the COVID-19 pandemic, as demand for SARS-CoV2 diagnostic testing has far outweighed the supply, academic research scientists have begun converting their labs to testing facilities. In a paper published May 10 in Med, a team of investigators from Boston University School of Medicine and Boston Medical Center (BMC) outline how they adapted their lab to test patient samples for SARS-CoV2, and they provide a blueprint for other labs that want to do the same thing.

“As with other basic biology labs across the country, we were forced to shutter operations due to the pandemic,” says senior author George Murphy, an Associate Professor of Medicine in the Division of Hematology and Oncology. “We saw that our friends and colleagues at Boston Medical Center were going into battle on the front lines of this pandemic, but that they were having to wait seven to 10 days for results from state and commercial laboratory facilities. This was unacceptable to us, and we decided we needed to take action.”

Murphy is normally co-director of the Boston University and Boston Medical Center (BMC) Center for Regenerative Medicine (CReM) and focuses on stem cell research. As stem cell and molecular biologists, he and the members of the lab had extensive experience developing and running the type of quantitative, real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assay that was needed to detect the presence of viral RNA in patient samples.

The bigger challenge was adapting their lab to the strict policies required to run a Clinical Laboratory Improvement Amendments (CLIA)-certified, College of American Pathologists (CAP)-accredited diagnostic lab. The team requested and received emergency permission from the FDA to repurpose the lab, and they began operating in less than a week. As of April 20, 2020, they had already tested more than 3,000 samples, with a sample turnaround time that’s under 24 hours. Nearly 45% of those tests were positive, a large number due in part to the high-risk population served by BMC, the largest safety net hospital in New England.

“For about a month or so, we were the only game in town,” Murphy notes. “Results from samples that were sent out to large commercial labs were taking up to a week, but even a wait-time of 24 hours delays the ability to make decisions about whether or not someone needs to be isolated and whether precious PPE [personal protective equipment] should be used.”

The team developed a test that could be done with technologies and reagents that are likely to remain available. The test was also designed with the ability to use different reagents at each step of the process. “Our ‘home-brew’ assay is extremely flexible, allowing us to slot in various reagents at multiple points and eliminating potential supply-chain issues,” Murphy says.

He doesn’t expect the need for testing to decline any time soon. “Although we have gotten through the early stages of this pandemic, which involved the testing of critically ill and symptomatic patients during a time of acute need, everyone is going to soon need to transition into asymptomatic and surveillance testing. It may be extremely difficult for large commercial labs to contend with the enormous number of samples this will entail,” Murphy says. “We decided to share what we did so that other institutions can implement their own in-house testing.”

The team is also looking at expanding to other kinds of assays, including saliva-based tests.

Murphy credits his colleagues and coauthors, including laboratorian Chris Andry, pathologist Nancy Miller and bioinformaticist Taylor Matte, for putting together this testing program so quickly. “We think it’s important for the public to see something positive in these very challenging times,” he concludes. “This project was a wonderful example of collaboration and teamwork in which scientists, clinicians, diagnostic laboratory technicians, and administrators came together to solve a seemingly insurmountable problem.”

Posted on

STUDYING PANDEMIC’S EFFECT ON MENTAL HEALTH IN YOUNG ADULTS

Source: Brigham and Women's Hospital
Date: 1/7/2021
Link to original
Image of article

The COVID-19 pandemic has been challenging for almost everyone, and different populations have been hit in different ways. For people aged 18–30 years, it has had an outsized effect on mental health, especially in terms of depression, anxiety and post-traumatic stress disorder (PTSD).

“Even before the pandemic, young adults had high rates of mental health problems,” said Cindy H. Liu, PhD, a psychologist in the Department of Pediatric Newborn Medicine and the Department of Psychiatry at Brigham and Women’s Hospital and a Tynan Faculty Research Fellow within the Connors Center for Women’s Health and Gender Biology. “The pandemic hasn’t necessarily caused these problems, but it has exacerbated them.”

She explained that young adults have higher rates of certain mental health conditions because so many are going through a period of extreme change in their lives. “They may be moving away from home for the first time, or graduating or finding their first job,” she said. “They may also be looking for a life partner or thinking about starting families. It’s a time of many transitions.”

Collecting Mental Health Data on Young Adults

Dr. Liu and her colleague Hyeouk Chris Hahm, PhD, of Boston University, have published several articles on mental health in the young-adult population since the onset of the pandemic. One study looked at factors associated with depression, anxiety and PTSD in young adults; one looked at the effects on sleep; and another focused on college students.

“When the pandemic began, college students were one of the first populations who were confronted with disruption,” she noted. “Unlike other groups in the U.S., many of them had to physically move as campuses closed.”

In a viewpoint article published in the Journal of American College Health, Dr. Liu and her coauthors highlighted two urgent priorities for addressing current college mental health needs: the development of strategies for ensuring access to mental health services and intentional outreach to college students with special circumstances. “Such widescale disruptions can do the most damage to those who already face challenges in obtaining resources, even for institutions that actively promote equitable access,” she said.

Two of her other studies employed data collected from a population of 898 young adults who volunteered to be assessed online between April 13, 2020, and May 19, 2020. “We really wanted to document what was transpiring after the United States designated COVID-19 as a pandemic,” she said.

A study published in Psychiatry Research found high levels of depression (43.3%), anxiety (45.4%) and PTSD symptoms (31.8%) in young adults. Participants also reported high levels of loneliness and COVID-19-specific worry along with low tolerance for distress. Another study, also published in Psychiatry Research, looked at the effects of the pandemic specifically on sleep disturbances. “There’s a strong association between mental health and sleep, and it affects quality of life,” she said.

Expanding Mental Health Research Beyond the Pandemic

Since the initial data were collected, the United States has continued to undergo upheaval, in particular in areas surrounding racial discrimination and social justice. Dr. Liu and her colleagues are studying the volunteers from their earlier work to measure further the impact of these circumstances on mental health.

“We know that young adults are quite involved and participating in a lot of the conversations and the advocacy around social justice,” she said. “We didn’t want to discount that.”

Dr. Liu added that because the population of young adults in the United States is more diverse, they are also more likely to be personally affected by racial discrimination. Some of her future work will focus on this issue.

Posted on

BRIGHAM’S ENDOCRINOLOGY CHIEF REFLECTS ON RECENT SUCCESSES

Source: Brigham and Women's Hospital
Date: 2/3/2021
Link to original
Image of article

Brigham and Women’s Hospital’s Division of Endocrinology, Diabetes and Hypertension cares for patients with a wide range of hormonal and other related disorders, including diabetes, hypertension and thyroid disease. Division Chief Ursula B. Kaiser, MD, recently discussed some of her group’s accomplishments and how the COVID-19 pandemic has affected physicians and other health care providers in the division.

In addition to her leadership role at the Brigham, Dr. Kaiser serves on the National Institutes of Health (NIH)/National Institute of Child Health and Human Development Board of Scientific Counselors, as deputy editor-in-chief of The Journal of Clinical Endocrinology and Metabolism and as director of the Brigham Research Institute.

Facing the Challenges of COVID-19

Although endocrinology is not the specialty that most people think of first with regard to treating COVID-19, members of the division have helped care for those who were hospitalized.

“Many patients with severe cases of COVID-19 have underlying endocrine and metabolic disorders, and those can be profoundly exacerbated by the disease,” Dr. Kaiser explained. “Many critically ill patients with COVID-19 and underlying diabetes became profoundly hyperglycemic with severe insulin resistance, and we had to come up with completely new treatment protocols for them.”

Division members also helped lead the way in addressing the challenges of the pandemic to the broader endocrinology community. These included Marie E. McDonnell, MD, who co-authored several publications providing guidance for management of patients with diabetes mellitus and COVID-19. Brigham endocrine faculty and fellows also stepped in to help care for patients with COVID-19 when extra providers were needed.

Dr. Kaiser noted that the pandemic has substantially changed care delivery through an expanded use of telemedicine. “I was very proud of how quickly our endocrine faculty adapted,” she said. “Endocrinology is a field that’s well-suited to virtual care.”

She expects virtual care will continue to have an important role going forward because it offers many advantages to patients with chronic health conditions who need to be seen often. In addition to reducing the risk of exposure to the virus that causes COVID-19, telemedicine lessens the need for patients to take time off from work. This can translate to fewer missed or canceled appointments and hence improved, more regular and more frequent care.

Collaborative Programs to Address Obesity

Much progress has been made in supporting patients who struggle with weight management, weight control and obesity, Dr. Kaiser said. Within the Brigham’s Center for Weight Management and Wellness, division members work closely with Brigham bariatric surgeons, gastroenterologists and experts in other areas to provide comprehensive care for these patients.

“The Brigham has recognized that weight control is a major challenge for many people,” Dr. Kaiser said. “This is especially true for disadvantaged patients and underserved minority groups.” Many studies have shown higher rates of obesity in Black and Latinx populations compared with whites, she noted. One reason for this is socioeconomic status, which can impact access to fresh, healthy foods such as fruits and vegetables.

New efforts in weight management and wellness are being instituted not only at the main hospital, but also in critical satellite locations throughout the Boston area. “We’re going where there is the greatest need for these services, due to a higher number of people in these populations struggling with obesity,” Dr. Kaiser said.

A Focus on Interdisciplinary Initiatives

Dr. Kaiser, who recently received the Endocrine Society’s 2021 Sidney H. Ingbar Award for Distinguished Service and has been named president-elect of the society for 2021, highlighted several other interdisciplinary programs that she is excited about. These include new efforts in thyroid care, particularly for people with thyroid nodules and thyroid cancer.

Furthermore, division members are collaborating with colleagues in radiology and oncology to conduct laboratory research and to achieve new advances in diagnosis and clinical care. For example, thyroid specialists at the Brigham have been at the forefront of using gene-expression classifiers for preoperative risk assessment. They also have a multidisciplinary clinic, in which radiologists aid in preoperative diagnosis and surgeons aid in perioperative care and management.

Adrenal disorders is another area where the division continues to play a leading role. “Our Center for Adrenal Disorders brings in patients not only from around the United States, but international patients as well,” Dr. Kaiser said. This partnership among the Brigham, Boston Children’s Hospital and Dana-Farber Cancer Institute (DFCI) is focused on patient care along with basic and translational research.

Accolades for Division Members

Dr. Kaiser noted a number of honors and awards received in the past year by members of the Division of Endocrinology, Diabetes and Hypertension, including:

  • Erik K. Alexander, MD, was appointed as the inaugural Brigham Health vice president of education.
  • Mehmet Furkan Burak, MD, was the recipient of the 2020 Endocrine Society Early Investigator Award.
  • Ole-Peter R. Hamnvik, MBBCH, received the Gail Backus Endocrinology Faculty Clinical Teaching Award and the Ambulatory Lecturing Attending Award.
  • Sylvia Kehlenbrink Oh, MD, was named chair of the International Alliance for Diabetes Action and was the invited Plenary Speaker at the IDF Congress 2019.
  • Meryl Susan LeBoff, MD, was awarded the 2020 American Association of Clinical Endocrinologists: ACE Distinction in Endocrinology Award in recognition of advancing the understanding of endocrinology through research and education.

A number of research grants also were awarded to division faculty, including a Dubai Harvard Foundation for Medical Research Fellowship, an NIH Specialized Center of Research Excellence (SCORE) in Women’s Health grant and an NIH Building Interdisciplinary Research Careers in Women’s Health K12 award.

Posted on

UNCOVERING RISKS FOR SEVERE AKI IN COVID-19 PATIENTS

Source: Brigham and Women's Hospital
Date: 11/12/2020
Link to original
Image of article

Infection with SARS-CoV-2 can affect any organ system in the body, and acute kidney injury (AKI) is common in people with more severe cases of COVID-19. Researchers at Brigham and Women’s Hospital recently led a study that looked at critically ill patients with COVID-19 and identified both patient- and hospital-level risk factors for development of AKI treated with dialysis.

“Our study is different from others that preceded it because we specifically focused on what we thought was the most clinically meaningful form of AKI — kidney injury that’s severe enough to require dialysis,” said Shruti Gupta, MD, MPH, a Brigham nephrologist and first author of the study published in October in the Journal of the American Society of Nephrology.

The investigators used data from 3,099 critically ill patients with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals, primarily in March and April. The analysis was part of Study of the Treatment of Outcomes in Patients with COVID-19 (STOP-COVID), a multicenter initiative that includes geographically diverse hospitals across the United States.

Analysis revealed that slightly more than one in five (637 patients) required dialysis within 14 days of ICU admission, and more than half of those who required dialysis (350 patients) died within 28 days. Of the 216 patients with AKI treated with dialysis who survived to hospital discharge, more than one in three (73 patients) still required dialysis at the time of discharge. In addition, 39 patients were still dependent on dialysis 60 days after their ICU admission, illustrating the long-lasting effects that COVID-19 can have on the kidneys.

Preexisting Conditions Linked to AKI

The researchers identified several preexisting conditions in COVID-19 patients that were linked to a higher risk of developing severe AKI. These included high blood pressure, diabetes, male sex, non-White race and a higher body mass index. COVID-19-specific features linked to severe AKI were higher levels of D-dimer and greater severity of hypoxemia.

“We obviously don’t have control over preexisting conditions,” Dr. Gupta said. “But there are ways we can optimize the treatment of hospitalized patients with COVID-19 so that they are likely to do better with regard to their renal function.”

These measures include careful management of patients on ventilators so that they don’t become hypotensive, according to Dr. Gupta. She added that AKI also can be minimized by avoiding major shifts in fluids that can put strain on the kidneys — for example, through more mindful use of infusions and diuretics.

Diverse Factors Influence AKI Incidence

The study also looked at hospital-level risk factors. The investigators found that the percentage of patients who developed AKI treated with dialysis varied widely, from 7.5 percent at the lowest-risk hospitals to 44.6 percent at the highest. Patients admitted to hospitals with greater regional density of COVID-19, which the investigators used as a surrogate for hospital strain, were less likely to be treated with dialysis.

“There might have been issues related to strain or availability of resources that prevented people from getting treated,” Dr. Gupta said. However, she cautioned that there were several other potential explanations that could account for this finding, including differences in patient populations and severity of illness that may not have been captured.

As nephrologists and other specialists continue to treat COVID-19 patients, they’re learning more about the underlying mechanisms of the disease. Some degree of kidney damage may be caused by tubular injury and possible direct viral invasion. In addition, there are issues likely related to inflammation and cytokine storm.

“We recently found in another study published in JAMA Internal Medicine that early use of the interleukin-6 inhibitor, tocilizumab, is associated with a 30 percent reduction in mortality among critically ill patients with COVID-19,” said David E. Leaf, MD, MMSc, a nephrologist at the Brigham and senior author on both studies. “It would be interesting to see if drugs such as tocilizumab may reduce rates of AKI in patients with COVID-19, perhaps due to lowering of the inflammatory burden.”