Neurological Tip of the Iceberg

Written by: Zohair Ahmed
Edited by: Esther Melamed

Since the start of the COVID-19 pandemic one year ago, COVID-19 research has become arguably one of the hottest topics in the history of research. One of the key emerging research areas at this time is the effect of the coronavirus, SARS-CoV-2, on individuals with “Post-Acute Sequelae of SARS-CoV-2 Infection” (PASC). PASC can present with varied symptoms but appears to affect different body organs.

Emerging evidence on neurologic manifestations of PASC points to a spectrum of neurologic dysfunction in patients, ranging from mild headaches, anosmia, and dysgeusia (loss of sense of smell and taste), to more severe complications. About one-third of COVID-19 survivors may develop a new onset neurological or psychiatric disorders, such as debilitating fatigue, dysautonomia, anxiety, depression, substance abuse disorder, dementia, encephalitis, insomnia, intracranial hemorrhage, ischemic stroke, seizures, myelitis, muscle disease, Guillain-Barré syndrome, or parkinsonism (Rachel Nania, AARP [4]). Persistent neurological and psychiatric symptoms may be more common in patients who had been hospitalized for COVID-19 but also appear to be present in patients who had mild COVID and had not required hospitalization. These symptoms may last as long as 6 months post initial acute COVID-19 illness (Taquet, et al., The Lancet [8]). 

There are several explanations of why the coronavirus is leading to neurological complications. First, the angiotensin-converting enzyme receptor (ACE2R), through which the virus enters human cells, has a widespread distribution in the body, including different regions of the brain as well as different brain cells (eg neurons and glia)! This means that coronavirus could easily infect brain cells and potentially stay dormant thereafter the acute COVID-19 infection (Zangbar, et al., NCBI [7]). There are potentially several ways that the coronavirus can get inside the brain, such as through the bloodstream (once the blood-brain barrier is “opened” due to inflammation in the body), through the lymphatic vessels, or via a Trojan horse mechanism (by hitchhiking into the brain inside immune cells, such as macrophages) (Zangbar, et al., NCBI [7]). Another possible mechanism of how the virus may be damaging the brain is through a rise in autoimmunity in infected individuals. Several groups, including our lab, are currently studying how and why autoimmunity may be emerging in COVID-19 patients. Researchers at Yale and UCSF have linked neurological symptoms to autoantibodies in the brain by examining spiral fluid from patients. The study found “16 autoantibodies that target cytokines, chemokines, growth factors, complement factors, and cell surface proteins” (Iwasaki, et al., NCBI [3]). 

At this time, there continues to be a wide gap in our understanding about the pathophysiology of neurological and psychiatric complications observed in PASC, and it will be very important going forward to conduct research to better understand why patients have persistent neurological and psychiatric symptoms and what treatments could benefit patients with PASC.