SARS-CoV-2-mediated Disease Impacts Sensory Perception Long After Infection is Cleared

Tuesday - May 16 2023, 09:18 UTC - 1 year ago

A new study found that SARS-CoV-2-mediated disease can cause lasting damage to the nerve pathways associated with sensory perception even after the active infection has been cleared. The study identified gene expression changes associated with neurodegeneration and pain-related pathways, highlighting the need for targeted therapeutics to address somatosensory symptoms and develop new treatments for COVID-19 Long COVID.

New research findings may contribute to the understanding of pathophysiology and help validate novel therapies for the prevention and treatment of COVID-19.

COVID-19, the disease resulting from SARS-CoV-2 infection, is associated with highly variable clinical outcomes that range from asymptomatic disease to death. For those with milder infections, COVID-19 can produce respiratory infection symptoms (cough, congestion, fever) and sensory phenotypes such as headache and loss of sense of smell. In more severe cases, SARS-CoV-2 infection can affect nearly every organ and result in strokes from vascular occlusion, cardiovascular damage and acute renal failure. A substantial number of actively infected patients suffering from both mild and severe infections experience sensory-related symptoms, such as headache, visceral pain, Guillain-Barre syndrome, nerve pain and inflammation. In most patients these symptoms subside after the infection ends, but, for other patients, they can persist.

In a new study, researchers from Boston University Chobanian & Avedisian School of Medicine, Icahn School of Medicine at Mount Sinai (Icahn Mount Sinai) and New York University (NYU) have found that thousands of genes were affected by SARS-CoV-2- mediated disease even after the viral infection had been cleared. These genes were associated with neurodegeneration and pain-related pathways, suggesting lasting damage to dorsal root ganglia (spinal nerves that carry sensory messages from various receptors) that may underlie symptoms of Post-COVID Conditions also known as Long COVID.

"Several studies have found that a high proportion of Long COVID patients suffer from abnormal perception of touch, pressure, temperature, pain or tingling throughout the body. Our work suggests that SARS-CoV-2 might induce lasting pain in a rather unique way, emphasizing the need for therapeutics that target molecular pathways specific to this virus," explains corresponding author Venetia Zachariou, PhD, Edward Avedisian Professor and chair of pharmacology, physiology & biophysics at BU Chobanian & Avedisian School of Medicine. This work was performed in collaboration with Benjamin tenOever, PhD, professor of microbiology and medicine at NYU, formerly at Icahn Mount Sinai.

Using an experimental model infected with SARS-CoV-2, the researchers studied the effects of infection on sensitivity to touch, both during active infection and well after the infection had cleared. They then compared the effects of SARS-CoV-2 to those triggered by influenza A virus infection. In the experimental model, they observed a slow but progressive increase in sensory sensitivity over time – one that differed substantially from viral control, influenza A virus, which caused quick hypersensitivity during active infection but returned to normal by the time infection was over.

According to the researchers, this model cosegregated with distinct gene expression profiles in dorsal root ganglia, with thousands of genes changing in a syndrome-associated direction toward neurodegeneration and pain-related pathways, changes that persisted even after the active infection had cleared.

The findings of this study give further insight into how the differences in clinical symptoms caused by SARS-CoV-2 infection may be related to the underlying pathophysiology of the disease, and how they may differ from those caused by other viruses. It also adds to the growing research supporting the use of targeted therapeutics designed to alleviate pain and other post-COVID symptoms. This research could help elucidate the underlying mechanisms of COVID-19-mediated sensory changes and assist in the development of novel treatments for COVID-19 Long COVID.