Studies Explain the Molecular Basis of Long COVID Symptoms-ScienceDaily

In most people, the virus SARS-CoV-2 is successfully cleared by the immune system, but some suffer from long-term complications of unknown cause.

The study, led by researchers at the NYU Grossman School of Medicine, examined tissue samples of hamsters and humans and found the most severe biological changes in the nasal olfactory system after the initial viral infection. I knew it would happen. , The special cells that line it, and the adjacent brain region that receives the input of the sense of smell, the olfactory bulb. A recent study in the same laboratory showed how SARS-COV-2 infection interferes with the sense of smell by altering the activity of certain olfactory proteins (receptors), but a new study shows persistent olfactory tissue. Emotions and cognition reveal how a positive immune response affects the governing center of the brain.

Published online on June 7th Scientific translation medicineThe study’s authors state that this study is the first to show that hamsters previously infected with SARS-CoV-2 have a unique inflammatory response to the sensory tissues. Unlike many of the COVID-19 studies published so far, this study compared the hamster’s SARS-CoV- with influenza A, the virus that caused the 2009 “swine flu” pandemic. I benchmarked the reaction to 2. The two viruses responded similarly in the lungs, but only SARS-CoV-2 elicited a chronic immune response in the sensory system, which was also apparent one month after viral clearance.

This chronic inflammatory condition seen in SARS-CoV-2 responds to the invasion of immune cells such as microglia and macrophages and cleans up the debris left behind the inner layer of dead and dying sensory cells. They not only recycle their materials, but also cause additional production of cytokines, pro-inflammatory signaling proteins. This biology recovered from the initial COVID-19 infection, but was also evident in the sensory tissues taken from autopsy of patients who died from other causes.

“Given the systematic scope of its discovery, this study describes an animal model that is so close to human biology that the molecular mechanisms behind many long COVID-19 symptoms help design future therapies. However, it suggests that it comes from this persistent inflammation. ” Senior Research Author Benjaminten Oever, PhD, Professor of Medicine and Microbiology at NYU Langone Health.

Systemic effect

SARS-CoV-2 and influenza A virus infect both hamsters and humans naturally. Researchers say it lasts about 7-10 in both hosts. In the current study, the authors examined genetic and histological changes at 3, 14, and 31 days after infection, both acute and persistent responses to these infections. In previous studies, the golden hamster model better copied the human biological response to SARS-COV-2 than, for example, mice that needed to change either the virus or the mouse to develop the infection. I know I will.

The researchers found that SARS-COV-2 can provoke a stronger immune response than the same amount of influenza A because the virus has a habit of copying itself. Hamster lungs and kidneys 31 days after initial infection.

The findings also confirmed that the long-term immune response seen with long COVIDs occurs in tissues where the SARS-COV-2 virus is no longer present. One of the team’s theories is that the damage from the initial infection leaves behind dead cell debris and viral RNA fragments, which prolongs inflammation. They also provide bacterial access to cells that are not normally exposed (eg, bulbous brain cells), with extensive damage to the inner layers of the sensory cells that cause the loss of odor seen in SARS-CoV-2. I think there is a possibility. ), Then triggers an immune response.

Whatever the cause, the chronic immune response in the olfactory tissue of SARS-CoV-2 infected hamsters was accompanied by behavioral changes of the study authors followed by established tests. For example, hamsters in the SARS-CoV-2 group were quicker to stop swimming attempts, a measure of depression, and to respond to foreign bodies (marbles) in their cages, anxiety-related behaviors. Depression and anxiety have long been common attributes of COVID, and these behavioral abnormalities have been found to correlate with unique changes to brain cell biology, the researchers say.

The authors examined the lungs beyond the brain, one month after virus removal, and after each acute lung infection. They found that in the aftermath of SARS-COV-2, airway reconstruction was significantly slower than in influenza A. This is the result of COVID-19 causing more extensive damage. Examination of tissue slides under a microscope also showed more extensive lung scarring in SARS-COV-2 infected lungs. This can partially explain the shortness of breath seen in some long COVID patients. The study also found that the inflammatory response to SARS-COV-2 resulted in longer-lasting kidney damage than the damage caused by influenza A virus infection.

In addition to tenOever, the research authors of the Department of Microbiology at NYU Langone Health were the first authors Justin Frere, Kohei Oishi, Ilona Golynker, Maryline Panis, Shu Horiuchi, and Rasmus Møller. Other authors include Daisy Hoagland, currently enrolled at Harvard University, Randall Serafini of the Department of Neuroscience, Kelly Price, Jeffrey Zimmering, Ann Lewis, and Venezia Zachario. Similar to Jonathan Overdevest in Neurosurgery. The research authors at Columbia University were Martimer B. Zuckerman Mind, Marianna Zazhytska, Albana Kodra, and Stavros Lomvardas of the Brain and Behavior Institute. The same is true for Peter Canoll in the Department of Pathology and Cell Biology. The research authors of Weill Cornell Medicine were Alain Borczuk in the Department of Pathology and Experimental Medicine and Vasuretha Chandar, Yaron Bram, and Robert Schwartz in the Department of Physiology, Biophysics, and Systems Biology.

This work was funded by the Zegar Family Foundation’s generous support for the tenOever Lab and the National Institutes of Health grants NS111251, NSO86444, and NSO86444S1.