Microglia and Female Bias of Long COVID Neurological Symptoms

Since the emergence of SARS-CoV-2 and the start of the COVID-19 pandemic, there has been a call to investigate sex differences – particularly focusing on girls, women, and sexual and gender minorities – in the manifestation and treatment of this disease. Postdoctoral fellow Dr. Haley Vecchiarelli (pictured; Tremblay Lab) will help answer this call thanks to her Fellowship-level 2024 Graduate and Fellowship Research Award in Women’s Health from the Women’s Health Research Institute (WHRI) at BC Women’s Health Foundation. This work is the continuation of an ongoing collaboration between Drs. Marie-Ève Tremblay and Leigh Anne Swayne at the UVic Division of Medical Sciences and Dr. Darwyn Kobasa at the National Microbiology Laboratory.

Dr. Vecchiarelli received the award for her project investigating long COVID, a group of health problems that persist or develop after SARS-CoV-2 infection. Long COVID affects approximately 10 – 20 per cent of people who contract COVID in Canada, and female patients are more likely to showcase neurological symptoms.

Dr. Vecchiarelli is trying to understand the mechanisms underlying these neurological symptoms. Her research is focused on microglia, the brain’s resident immune cells, as changes to microglia following a SARS-CoV-2 infection could potentially contribute to the female bias in long COVID neurological symptoms. Specifically, she is interested in dark microglia, a specific state of microglia that show unique cellular stress markers and that have reputed roles in pathologically altering how neurons (brain cells) communicate with each other.

Dark microglia were discovered by Dr. Vecchiarelli’s mentor, Dr. Tremblay, and are uniquely able to be studied using electron microscopy. For her work, Dr. Vecchiarelli will use the Tremblay lab’s CFI-funded Zeiss Crossbeam 350 focused ion-beam scanning electron microscope, which is unique in Canada and ideal for understanding the relationship between (dark) microglia and neurons. She will use the electron microscope to study if dark microglia are linked to the alterations between neurons that have been observed following SARS-CoV-2 infection. If they are linked, Dr. Vecchiarelli says future researchers may be able to alleviate long-COVID symptoms by targeting dark microglia.

Dr. Vecchiarelli has long been interested in researching and explaining how infections can alter the nervous system, cognition, and behaviour. Throughout the COVID-19 pandemic, she read many first-hand accounts of those affected by long COVID and she understood the importance of investigating post-acute infection syndrome as more and more people developed the associated health problems. She hopes that this work will contribute to therapeutic discoveries not only for long COVID, but for other post-acute infection syndromes and associated conditions as well. These highly stigmatized conditions include myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Dr. Vecchiarelli strongly believes in reducing stigma in neurological and mental health research and in equity, diversity, and inclusion practices, so researching these understudied conditions aligns with her values.

The WHRI launched this research award in 2020 with the goal of creating a funding opportunity specific to the trainee community in BC. Dr. Vecchiarelli’s fellowship is one of four WHRI graduate and postdoctoral-level awards granted in 2024. The awards are supported through funding provided by the BC Women’s Health Foundation.