New research seems to help explain the biology behind COVID’s long-term symptoms such as brain fog and increased anxiety and depression.
In a study published in Science Translational Medicine, The researchers found that the immune response in the olfactory tissue affects the brain centers that control emotions and cognition.
Justin J. Frere, a doctor / doctoral student at Icahn School of Medicine in Mount Sinai, and colleagues compared the response of SARS-CoV-2 to influenza A in tissue samples. Researchers report that both viruses generate similar reactions in lung tissue; however, only SARS-CoV-2 elicited a chronic immune response in the olfactory system that lasted 1 month after clearance of the virus.
Healio spoke with Frere about why SARS-CoV-2 causes long-term symptoms and how the results of new studies could help inform future research about treatment.
Healio: What is the simplest way to explain to patients the reasons why SARS-CoV-2 causes symptoms such as brain fog, depression and anxiety after the acute phase of the infection is over?
Frere: During its initial infection, SARS-CoV-2 causes a massive immune response that extends to almost every part of the body. This systematic response to the virus – although it makes us feel sick – is what allows us to eventually remove the virus from our bodies. This is a process that occurs in many infections, and in our study we see a similar process that occurs in the body’s response to influenza. In normal infections, once the pathogen is cleared, the immune response is no longer needed and it will quickly fade, returning your body to a normal state that is not sick; however, in SARS-CoV-2, while most of the systemic immune response fades when the virus clears, there is a small area of the brain called the olfactory bulb in which this immune response appears to last for a long time, even after the infection has disappeared. Long-term immune reactions and related inflammation in the brain can cause the nervous system to function abnormally, leading to symptoms such as brain fog, depression and anxiety. Thus, we believe that this sustained immune response in the brain caused by SARS-CoV-2 infection may be a major contributor to the development of some of the cognitive and behavioral symptoms observed in long-term patients with COVID. With this in mind, we still have a lot of work to do to confirm the specifics of what is happening here. SARS-CoV-2 can cause damage to the body in a variety of ways, and this makes it possible – if unlikely – that this persistent inflammation is just one of several processes by which the virus can cause these long-lasting COVID symptoms.
Healio: What are the implications of your findings?
Frere: Our study highlights a unique molecular process caused by SARS-CoV-2 that may underlie some of the cognitive symptoms associated with prolonged COVID. In defining this process, we hope that it serves as a potential goal that can be therapeutically treated in long-term patients with COVID – to hope that it will alleviate or prevent the development of these symptoms. In addition, we show that hamsters may exhibit persistent symptoms and pathological processes in response to SARS-CoV-2 infection, potentially mimicking similar processes that may occur in individuals suffering from prolonged COVID. This makes hamsters a potential model in which we can try new long-term therapies for COVID. We hope that this will facilitate the identification of drugs that can treat this condition.
Healio: How could these new discoveries affect future research on potential therapeutic goals?
Frere: We believe that our study highlights a potential therapeutic goal that we may be able to effectively treat with drugs. In addition, in our study, we showed that the hamster is a potential animal model for long-term COVID, and as such we hope to be able to use this knowledge to try new therapeutic agents against long-term COVID in hamsters. As new long-term therapeutic goals for COVID are identified, we hope that others will be able to test new drugs against these goals in the hamster model to identify more effective treatments for the disease more quickly.
Healio: What are the next steps in your research?
Frere: First, we really hope to further investigate this phenomenon of persistent olfactory inflammation in patients. We also hope to start testing drugs in a hamster model to see if we can successfully alleviate any behavioral changes caused by SARS-CoV-2 infection. We would like to test Paxlovid and corticosteroids to see if any of these drugs can successfully alleviate the persistent inflammation we see, and in turn alleviate the behavioral abnormalities we experience in hamsters.
Healio: Is there anything else you would like to add?
Frere: Comparing our outcomes of SARS-CoV-2-infected hamsters with those of influenza-infected hamsters, we present one of the first studies to compare SARS-CoV-2 infection against other pandemic-related pathogens. In doing so, we were able not only to better understand the severity of SARS-CoV-2 infection, but also to really emphasize the processes uniquely induced by SARS-CoV-2.