Patients with COVID-19 are experiencing an array of neurological effects, ranging from confusion to loss of smell and taste, to life-threatening strokes. And, it’s not unusual to see younger patients in their 30s and 40s suffer potentially life-changing neurological issues due to strokes.
Critical care physician and neurointensivist Robert Stevens, who is associate director of the Johns Hopkins Neurocritical Care Precision Medicine Center of Excellence, has been tracking patient cases at Johns Hopkins in which patients with COVID-19 also develop neurological problems. And, thanks to a new research consortium of more than 20 institutions, including the University of Pittsburgh Medical Center, New York University, Johns Hopkins and health systems in Europe, researchers are studying clinical features, imaging, EEG and tests of blood and spinal fluid. Their goals are to understand the mechanisms by which the coronavirus interacts with the nervous system and to develop strategies to prevent and treat any neurological manifestations.
Stevens recently talked about some of the prevailing scientific theories on this topic.
Q: In what ways does coronavirus affect the brain?
A: Cases around the world show that patients with COVID-19 can have a variety of neurological presentations, including confusion, loss of consciousness, seizures and stroke. Additional manifestations that have been reported are loss of smell and taste, headaches, trouble focusing and changes in behavior. Patients are also having peripheral nerve issues, such as Guillain-Barré syndrome, which can lead to paralysis and respiratory failure. I estimate that at least half of the patients I’m seeing in the COVID units have neurological symptoms.
Q: How do researchers think COVID-19 causes neurological issues?
A: There are several potential mechanisms by which this could happen — either independently or in conjunction with coronavirus impacting other body systems —, but each needs to be studied rigorously before any conclusions can be made.
The first possible mechanism is that the virus may gain entry into the brain, causing a form of encephalitis. Recent cases reported in China and Japan found the virus’ genetic material in cerebrospinal fluid, and a case in Florida found viral particles in endothelial cells and neurons. Viral transmission to the brain may occur via the bloodstream, the so-called “hematogenous” route or, alternatively, by entering peripheral or cranial nerve endings and then traveling in a retrograde, trans-synaptic fashion, toward the central nervous system. The loss of smell in a subset of patients with COVID-19 is an intriguing finding that could suggest a point of entry via the olfactory bulb, which is located right above the nose and communicates smell signals to the brain.
A second possibility is that the immune system goes into overdrive in an attempt to fight SARS-CoV-2, producing a maladaptive inflammatory response that perhaps causes more damage than the virus itself. We have learned about the “cytokine storm” — a cascade of systemic pro-inflammatory signaling — that may induce much of the tissue and organ injury seen in patients with severe COVID-19. These same cytokines can, directly or indirectly, relay inflammatory signals to the brain.
The third postulated mechanism is that physiological changes induced by COVID-19 — ranging from high fevers to hypoxemia to multisystem organ failure — contribute to brain dysfunction, leading to neurological syndromes such as delirium or coma, seen in many patients with severe COVID-19 cases.
The fourth way COVID-19 might affect the brain has to do with the tendency for these patients to have a stroke. The coagulation system is highly abnormal in COVID-19 patients, with thromboembolic events much more likely to occur in these patients than in others. Patients can suffer deep venous thrombosis or pulmonary embolism. It is not a stretch to consider how ischemic stroke could occur in the setting of this hypercoagulable state.
Q: Some patients with COVID-19 in their 30s and 40s are having strokes. Why is that happening?
A: While we haven’t had any of these young stroke patients at Johns Hopkins, I have seen reports of these incidents from colleagues in New York and China.
It may have something to do with the hypercoagulable state of these patients. These patients with COVID-19 also have hyperactivated endothelial systems, which are more biologically active in younger patients. The combination of hyperactive endothelial and coagulation systems puts patients at a high risk for developing blood clots.
But it would be premature to conclude from available data that COVID-19 preferentially causes strokes in younger patients. It is also plausible that there’s an increase in stroke in COVID-19 patients of all ages.
Q: How is Johns Hopkins studying neurological issues associated with COVID-19?
A: We’re investigating selected cases by conducting the appropriate studies and imaging, such as MRIs, electroencephalograms (EEGs), serum biomarkers and samples of spinal fluid. However, it can be challenging to get these studies. For example, we wanted to get an MRI on one of my patients, but she was physiologically very unstable, and it would have been dangerous to transport her to the MRI suite. We also have to be careful about who leaves the COVID unit, as we don’t want to increase nosocomial disease transmission. There’s a tradeoff between the research you’d like to conduct and what is feasible and safe in an environment with complex patients, busy clinical staff and the ever-present risk of contagion.