Namandje Bumpus, PhD: What you need to know about coronavirus variants Reports on variants of the coronavirus that causes COVID-19 have swept the news over the past few months, but what exactly is a virus variant? Namandjé Bumpus, PhD, director of the Department of Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine, breaks down what is changing in the variants and what we can do to stop them. “Variants of viruses are expected. Every virus changes and evolves,” says Bumpus. “However, the ones that are really of interest are the ones that are changing the parts of the virus that are targeted by the vaccines.” Researchers may have unclouded the mistery of COVID-19 ‘brain fog’ People who survive a severe case of COVID-19 have reported a variety of lingering aftereffects, but perhaps none as unusual as what has been popularly called “brain fog.” Clinically known as dysexecutive syndrome, the condition is a COVID-19-kindled delirium, initially experienced by patients — mostly older — while sick as a state of confusion and impaired awareness. It then often stays on after recovery to torment as persistent cognitive sluggishness. Unfortunately, the origin of brain fog has remained unclear. Now, pathologists at Johns Hopkins Medicine in Baltimore and Brigham and Women’s Hospital in Boston have found evidence that large bone marrow cells known as megakaryocytes may be responsible for the brain fog. They suggest that megakaryocytes migrate to the brain in a journey precipitated by the destructive activity of SARS-CoV-2, the virus that causes COVID-19. There, the researchers believe, the out-of-place cells may reduce or completely block the flow of nourishing blood through individual capillaries in the cerebral cortex — the area of the brain where most information processing occurs. Such capillary occlusions, they say, could lead to neurological impairment. The team’s findings are reported in a research letter published Feb. 12 in JAMA Neurology. Megakaryocytes are the cells responsible for production of platelets —blood components that are necessary for clotting and wound repair. Interestingly, the researchers say, a scientific literature search they conducted indicates this may be the first time that megakaryocytes have been found in blood vessels in the human brain. The researchers evaluated brain tissue from autopsies of 15 patients who died of COVID-19. In five of the samples, they discovered large cell nuclei resembling those of megakaryocytes in the cortical capillaries. Immunohistochemical testing confirmed that the nuclei were those of megakaryocyte immigrants from bone marrow. No megakaryocyte nuclei were found in post-mortem brain tissues from decedents who were negative for the COVID-19 coronavirus and served as the study’s control group. What isn’t clear is how the COVID-19-associated megakaryocytes are signaled to leave the bone marrow or how they can navigate the fine network of lung blood vessels on their way to the brain, says David Nauen, MD, PhD, study lead author and assistant professor of pathology at the Johns Hopkins University School of Medicine. “We suspect that SARS-CoV-2 damages lung tissue, leading to the release of chemical signals that induce the megakaryocytes to travel there from the bone marrow,” says Nauen. “When that happens, these large cells somehow find a way to pass through the lung capillaries and get to the brain.” “We don’t yet know if the megakaryocytes we found in the brain are just the result of blood flow carrying them there or if a specific change occurs in the brain vessels that trap them,” he adds. Nauen says the researchers plan next to characterize what happens in the brain tissue and cortical capillaries during severe cases of COVID-19 to better understand how megakaryocytes are signaled and recruited. “Because standard brain autopsy sections represent only a minute portion of the cerebral cortex, the actual numbers of these cells in the brain as a result of COVID-19 could be considerable — as could their potentially negative neurological impacts on those who survive,” says Nauen. Teen survives life-threatening battle with inflammatory disease associated with COVID-19 A few days before her 18th birthday in November, Tyona Montgomery’s throat started to hurt. Eventually, testing showed she had COVID-19. Later, she lost her sense of smell. She quarantined at home, and her symptoms went away. A few weeks later, her head, eyes and body ached, and she became disoriented, so she went to a local hospital and was admitted. While there, she had a fever, her heart was beating abnormally fast, her breathing was labored, she began vomiting, and her eyes and lips became red. Soon, Tyona’s major organs appeared to be shutting down, and she was quickly transferred to Johns Hopkins Children’s Center. Upon arrival, Tyona’s heart function — her ability to pump blood — was severely diminished, and doctors, nurses and clinical team members rushed to save her. It was at Johns Hopkins that Tyona’s mother, Kristia Reynolds, was told that her daughter had multisystem inflammatory syndrome in children, (MIS-C), a condition that results in widespread inflammation of various organs including the heart, lungs, kidneys, blood, brain, skin, eyes and gastrointestinal tract. The exact cause of MIS-C is not known, but it is understood to be an inflammatory response following exposure to COVID-19, whether after a personal illness or contact with someone with COVID-19. MIS-C is not an active COVID-19 infection but is the exaggerated inflammatory illness that develops weeks after the COVID-19 exposure. According to the Centers for Disease Control and Prevention, more than 2,000 children and adolescents in the U.S. have been diagnosed with MIS-C associated with COVID-19 since May 2020 in the United States. Doctors are trying to determine why some children and adolescents develop the condition and others do not. The clinical team at Johns Hopkins was able to stabilize Tyona in the pediatric intensive care unit. She received bilevel positive airway pressure (BiPAP) — a treatment using a type of breathing machine — and additional oxygen to support her breathing. Her MIS-C condition required a cocktail of medication, including intravenous medicines to help her heart pump and to reduce the inflammation. This included high doses of steroids and the anti-inflammatory medication anakinra. Eventually she was transitioned off BiPAP and weaned off oxygen. While at Johns Hopkins Children’s Center, Tyona suffered a seizure — her first ever. Her doctors believe MIS-C may have caused it. Soon, however, she was well enough to be weaned off most of her medications, and after nine days at the Children’s Center — on Christmas Eve — Tyona was able to go home. Her heart function has since returned to normal, but doctors at Johns Hopkins Children’s Center are still monitoring her. “Tyona presented with a severe case of MIS-C with significant cardiac dysfunction. The fact that she is alive is an incredible feat,” says Ekemini Ogbu, M.B.B.S., M.Sc., pediatric rheumatologist at Johns Hopkins Children’s Center and assistant professor of pediatrics at the Johns Hopkins University School of Medicine. Ogbu is among the doctors continuing to follow Tyona’s progress. “We are reassured by her significantly improved cardiac function, but Tyona will require continued surveillance as we expand our knowledge of long-term cardiac effects of MIS-C,” says Lasya Gaur, M.D., Tyona’s pediatric cardiologist at Johns Hopkins Children’s Center and an assistant professor of pediatrics at the Johns Hopkins University School of Medicine. “We plan to use all the tools at our disposal, including advanced cardiac testing to monitor her cardiac status closely.” “Right now, she has good and bad days,” her mother says. Tyona, who never had major health issues before her MIS-C diagnosis. She still gets winded easily and has dizziness and little appetite. Since research is still being done on the long-term effects of MIS-C, it’s unclear how long these symptoms could last for Tyona. Tyona, who loves art, fashion, makeup and singer-songwriter Justin Bieber, isn’t allowing MIS-C to interfere with her future aspirations. “I want to have my own business,” she says. Tyona and her mother, who works at The Johns Hopkins Hospital as a rehabilitation technician, are available to speak about their experience. Tyona’s doctors can also talk about Tyona’s case as well as MIS-C. Scientists are building more comprehensive tests for COVID-19 New strains of SARS-CoV-2, the virus that causes COVID-19, may have greater transmissibility or altered virulence, or may exhibit resistance to the current vaccines. Now, scientists are racing to develop better ways to detect emerging SARS-CoV-2 strains among the high number of diagnosed infections. Johns Hopkins assistant professor of pathology Ben Larman, PhD, and his team have been working to improve the analysis of genetic material called RNA that forms the genome of many viruses. Specifically, the Johns Hopkins team is developing a technique to scan biological specimens, including saliva or specimens obtained with nasal swabs, using specialized DNA probes that sift through a complex “forest” of RNA sequences. The probes can detect specific RNA sequences of viruses and other disease-causing pathogens. A report describing the development and application of the test (cRASL-seq), led by Larman and postdoctoral fellow Joel Credle, PhD, appeared online Feb. 3 in the journal Modern Pathology. A key feature of the newly developed test, says Larman, is its ability to analyze and detect the many subtle changes that can occur in the SARS-CoV-2 viral genome — so-called variants, such as those first identified in the United Kingdom and South Africa. Vaccine prioritization dashboard launches for people with disabilities A new Johns Hopkins data tool helps people with disabilities determine when they qualify for the COVID-19 vaccine and compares how states prioritize the disability community in vaccine rollout plans. The website, designed and run by researchers, students and advocates with disabilities for people with disabilities, aims not only to help the disability community be informed and ultimately get vaccinated but also to arm policymakers with data to improve the health care system. The COVID-19 Vaccine Prioritization Dashboard can be accessed here: https://disabilityhealth.jhu.edu/vaccine/. “There’s been a persistent gap in the pandemic response for the disabled community. It started with testing and we’re seeing it being echoed in the vaccine rollout,” says Bonnielin Swenor,director of the Johns Hopkins Disability Health Research Center and associate professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute at the Johns Hopkins University School of Medicine.“Being part of that community, we understand the need to empower stakeholders and policymakers with data.” The idea was sparked by Johns Hopkins University senior Sabrina Epstein, who has the genetic connective tissue disorder Ehlers-Danlos Syndrome (EDS), which places her at increased risk for severe illness from COVID-19. Because EDS is considered a rare disease, it is not listed as a high-risk chronic illness for vaccine prioritization, making it difficult for Epstein to determine when she can get vaccinated. “I was trying to register my grandfather for his vaccine in Texas and I noticed that I already qualified in Texas because of my chronic conditions, but in Maryland, I don’t qualify yet. I’m still waiting,” says Epstein, who is majoring in public health studies. “I realized from my own example that it’s happening to lots of people and there’s so much confusion. We want people to be able to use this tool to identify if they or their family or friends qualify for a vaccine in their state and to advance advocacy efforts.” The university’s Disability Health Research Center created the dashboard in collaboration with theCenter for Dignity in Healthcare for People with Disabilities. The tool will be updated weekly. Source
