A Bigger Picture Other researchers are looking at larger brain structures. Kyle Pattinson , senior clinical research fellow at University of Oxford, heads an MRI project that focuses on the brainstem. “Other coronaviruses have been shown to
about underlying etiology.” A consortium of researchers from 30 countries are participating in a study to trace a possible path from Covid-19 to neurodegenerative diseases, particularly dementia. “It’s a ‘study of studies,’” says Heather Snyder , vice president, Medical “Groups around the world will collect blood, MRI images, clinical data, depending on their resources. Some studies will involve hospitalized individuals only; other studies, patients in the community.” The resulting trove of data will be pooled, shared, and subjected to meta-analysis “to identify associations and connections, and answer some of the big questions about the long-term impact of Covid-19 on the brain and nervous system,” she says. Sudra Seshadri , founding director of and Scientific Relations, of the Alzheimer’s Association, which is funding the initial effort. notes that inflammation is prominent among the effects of SARS-CoV-2. “We know that immune problems have a role in Alzheimer’ disease, too. And direct effects of the virus, such as increasing clotting tendency, might lead to small strokes, which tend to worsen dementia.” Earlier researchers have suggested a link between diverse viral infections and Alzheimer’s disease, she points out. The plan is to follow participants for 18 months or longer, tracking variables including cognitive functioning. All ages will be involved, “but we are focusing on older people [including] some who have MCI (mild cognitive impairment) and early Alzheimer’s,” says Seshadri. This particular area of research is poised to accelerate. The National Institute on Aging recently called for grant proposals to fund projects exploring the impact of Covid-19 on neurodegenerative disorders and the aging process. A year-plus into the pandemic, the story is far from over. the Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases at University of Texas, San Antonio, and coauthor of a paper that outlined the rationale for the project, Although vaccination stands to stem the tide, Covid-19 won’t be gone overnight, and variants of the SARS-CoV-2 virus, according to many experts, are likely to be around for a long time. And even if just ten percent of those infected develop persistent symptoms, with 130 million cases worldwide and counting, that’s a lot of need for whatever neuroscience can deliver. “If we know whether they are due to neuroinvasion, autoimmune, vascular, or other mechanisms, it will change how we manage symptoms and the disease long-term,” says Song. “We often forget why we do this research. Ultimately, it’s to help patients.” l
be neurotropic to the brainstem,” he says. “If the virus enters via the nasal mucosa, it will have a direct route through the olfactory bulb down to the ventrolateral medulla, which regulates heart and lung function.” Brainstem structures also govern perception of internal sensations, and their dysfunction might account for “’happy hypoxia’, a condition where acutely ill Covid-19 patients don’t sense they’re having respiratory compromise,” he says. Conversely, brainstem involvement “may make breathlessness feel worse than it should be if only the lungs were affected.” Pattinson himself struggled with post-Covid fatigue as well as breathlessness—the two most common phenomena—for six months. “Probably all the symptoms in Long Covid will be from a multitude of factors, and the brainstem will be one of these factors,” he says. His study will look at higher centers as well; he is working with Hampshire to correlate structural changes with cognitive decline, and with fellow Oxford researchers to explore neurotransmitter systems, inflammatory markers, and neuronal integrity. “We’re hoping to get an idea just what neural effects occur,” Pattinson says. His group has a particular interest in following people who are having prolonged symptoms but were not hospitalized when acutely ill. The Oxford brain study is one of an increasing number that are tracking the course of Covid-19 over time. How long does Long Covid last? When will the “brain fog” lift? What can help? Researchers, clinicians—and above all patients—are eager for answers. The National Institutes of Health is allocating more than $1 billion to research investigating Long Covid in all its multi-organ complexity—causes, manifestations, natural history, and treatments. Frontera has finished a six-month follow-up evaluation of anxiety, fatigue, and other neurological symptoms in her NYU group of hospitalized Covid-19 patients and plans another at one year. “We’re looking at trajectories of recovery,” says Frontera, who is also on the steering committee of the Covid-19 Neuro Databank/Biobank, funded by the NINDS and maintained by NYU. This project will collect information on neurological symptoms and the course of the disease from health care providers, hospitals, and researchers across the country, along with biological materials such as blood and CSF. “We may see regional variations in viral genotype and get information on different strategies used with different patients,” she says. “Hopefully we’ll answer some questions
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