Neurological Sequelae of COVID-19

Part III

In Part I of this series focused on the neurological long-term consequences of COVID-19, I reviewed what we know so far about anosmia (loss of smell) and parosmia (abnormal sense of smell). In Part II, I reviewed what we know about cognitive defects following COVID-19, or what many refer to as “brain fog.”

In this Part III, we will wrap up our review of neurological consequences of COVID-19, however, there remains much more that we could cover. This blog post will look at an autopsy study that provides evidence of viral persistence, one of the explanations thought to contribute to the development of Long COVID.

A very recent study sheds additional light on the issue of viral persistence in the brain and other tissues and organs based upon autopsy studies.

“SARS-CoV-2 Infection and Persistence in the Human Body and Brain at Autopsy” was published on December 14, 2022.[1] The investigators conducted complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients. The study included both patients who died with acute infection, as well as others with PASC (Post-Acute Sequelae of SARS-CoV-2 or Long COVID) lasting as long as 7 months. They found that evidence of viral persistence was widely distributed, especially in those who died with severe COVID-19. The evidence for viral persistence in both lung tissue and non-respiratory tissues (heart, lymph nodes, GI tract, adrenal glands and eyes was very strong in that they could culture replicating virus from these tissues. Persistent viral RNA was found in multiple anatomic sites throughout the brain as late as 230 days following onset of illness in one case.

SARS-CoV-2 RNA was detected in 84 distinct anatomic sites and body fluids (including plasma, pleural fluid and vitreous fluid). However, RNA levels were highest in respiratory tissues. More than half of the late cases had persistent RNA in the heart muscle, lymph nodes from the head and neck, the sciatic nerve, the eyes, and from all areas of the central nervous system sampled other than the dura mater.

The investigators observed very little evidence of inflammation or direct viral-induced cell damage outside of the respiratory tract. This is concerning relative to a person’s long-term health because it is possible that the persistent virus causes chronic antigenic stimulation of the immune system, which in turn may cause T-cell exhaustion and immune dysfunction (see later blog posts on immune system sequelae of COVID-19), but also because we don’t know whether the SARS-CoV-2 virus can be reactivated and cause disease if the patient is later treated with immunosuppressive medications or develops an immune-compromising condition.

The persistence of SARS-CoV-2 virus in the body is one of the theories as to why some people may develop Long COVID. Persistence of virus can mean persistence of antigenic stimulation of the immune system. In addition, a concern that must always be considered when people do not kill and eliminate viruses efficiently from their body, is whether they become latent and can be reactivated years later if the person becomes elderly, develops cancer, or requires immunosuppressive medications. In fact, with SARS-CoV-2 infections, we have seen cases in which latent viruses become reactivated, particularly Epstein Barr Virus (EBV) and Human Herpes Virus-6. The former has been associated with persons who develop myalgic encephalitis/chronic fatigue syndrome (ME/CFS) following COVID-19.

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[1] https://doi.org/10.1038/s41586-022-05542-y.