One of the dozens of atypical symptoms that have appeared in COVID-19 patients is a condition that is informally referred to as “COVID brain” or “brain fog.” It is characterized by confusion, headaches, and short-term memory loss. In severe cases, it can lead to psychosis and even seizures. It usually appears weeks after someone first became ill with COVID-19.
In the February 8, 2021, issue of the magazine Cancer cell, a multidisciplinary team from Memorial Sloan Kettering reports an underlying cause for brain COVID: the presence of inflammatory molecules in the fluid around the brain and spine (known as the cerebrospinal fluid). The findings suggest that anti-inflammatory drugs, such as steroids, may be helpful in treating the condition, but more research is needed.
We were first discussed with our colleagues in emergency care medicine who had seen severe delirium in many hospitalized patients with COVID-19. That meeting turned out to be an amazing collaboration between neurology, critical care, microbiology, and neuroradiology to learn what was going on and to see how we could better help our patients. “
Jessica Wilcox, Principal Fellow in Neuro-Oncology, MSK and one of the first authors of the new study
Recognizing a familiar symptom
Encephalopathy is the medical term for COVID brain. Members of the MSK Department of Neurology felt able to study it, Dr. Wilcox says, because they are used to treating the condition in other systemic inflammatory syndromes. It is a side effect in patients receiving a type of immunotherapy called chimeric receptor receptor (CAR) T cell, a treatment for blood cancer. When CAR T cell therapy is given, it causes immune cells to release molecules called cytokines, which help the body to kill the cancer. But cytokines can jump into the area around the brain and cause inflammation.
When the MSK team first began studying the COVID brain, however, they did not know that cytokines were to blame. They initially suspected that the virus itself was affecting the brain. The study in the paper Cancer Cell focused on 18 patients who were hospitalized at MSK with COVID-19 and who were experiencing severe neurologic disorders. Patients underwent full neurology work, including brain scans such as MRI and CT and an electroencephalogram (EEG) scan, to try to find the cause of their delirium. When nothing was found in the scans that explained their condition, the researchers thought the answer may be lying in the cerebrospinal fluid.
The MSK microbiology team designed a test to detect the COVID-19 virus in the stream. Thirteen of the 18 patients had spinal taps to detect the virus, but it was not detected. At that point, the rest of the liquid was taken to the laboratory of MSK physicist Adrienne Boire for further study.
Using science to ask clinical questions
The study of the stream was led by Jan Remsik, a researcher in Dr. Boire’s laboratory in the Human Oncology and Pathogenesis Program and the first other author in the paper. “We found that their cerebrospinal patients had persistent inflammation and high levels of cytokines, which explained their symptoms,” Dr. Remsik says. He says there have been some smaller case studies with only a few patients reporting similar results, but this study is the largest to date to look at this effect.
“The nervous system used to be thought to be an immune-beneficial organ, meaning it had no relationship with the immune system,” says Dr Boire. “But the more we look, the more we find connections between the two.” One focus of Dr. Boire ‘s laboratory is to study how immune cells can override. the blood-brain barrier and entry into this space, an area of research that is also important for learning how cancer cells can spread from other parts of the body to the brain.
“One thing that was really special about Jan’s approach was that he was able to make a very wide molecular screen to find out what was going on,” adds Dr Boire. “He took the tools we use in cancer biology and transferred them to COVID-19. “
The inflammatory symptoms detected in the COVID-19 patients were similar, but not identical, to those seen in people who received CAR T cell therapy. And as with CAR T cell therapy , the neurologic effects are sometimes delayed. The initial inflammatory response with CAR T cell treatment is very similar to the reaction known as cytokine storm that is often reported in people with COVID-19, Dr. Wilcox explains. With both COVID-19 and CAR T cell therapy, the neurologic effects come days or weeks later. In CAR T cell patients, neurologic symptoms are treated with steroids, but doctors still do not know the role of anti-inflammatory medications for people with neurologic symptoms of COVID-19. “A lot of them are already on steroids, and it’s possible they could benefit,” Dr. Wilcox says.
“This type of research is about the collaboration across MSK departments and the interdisciplinary work we can do,” concludes Dr. Boire. “We have seen people become ill, and we were able to use our ideas to ask big clinical questions and then bring those questions into the lab to answer them. “
Dr. Boire is a patent innovator related to altering the permeability of the blood-brain barrier and is an unpaid member of EVREN Technologies ’scientific advisory board.
Source:
Sloan Kettering Cancer Memory Center