SARS-CoV-2 particles and associated inflammation were seen in the olfactory nervous system of patients who had severe COVID-19, a report from Italy showed.
Minimally invasive autopsy with nasal endoscopic dissection showed viral particles and CD163-positive microglial cells in the olfactory complex of two COVID patients, reported Patrizia Morbini, MD, PhD, of University of Pavia, and co-authors in JAMA Otolaryngology.
“Our finding is important because it is the first evidence of a direct SARS-CoV-2 infection in cells of the olfactory bulb, in the central nervous system,” Morbini said.
“Recent imaging studies have shown that this area of the nervous system is altered in a subset of COVID patients, while we have directly documented the presence of viral particles and associated severe inflammation,” she told MedPage Today. “So far, one other case report has shown viral particles in the cells of the vessels of the central nervous system, but not specifically localized to the olfactory bulb.”
The finding suggests SARS-CoV-2 “could actually have the capability of infecting the nervous system cells — as was shown for other coronaviruses in experimental settings — and could enter the central nervous system through the nervous fibers of the nervous receptors of the olfactory mucosa, which is particularly interesting in the view of the very common olfactory symptoms of COVID patients,” she added.
In the olfactory bulb of the first patient, who died of COVID-19 pneumonia in the ICU, Morbini and co-authors found intracytoplasmic viral inclusion bodies, interstitial viral particles, and marked CD163-positive/CD68-negative microglial cell infiltration.
In the second COVID-19 patient, who died of cardiopulmonary transthyretin amyloidosis, they found viral particles on the cell membrane of ciliated respiratory cells in the olfactory mucosa. The researchers also saw CD163-positive microglial cells and CD3-positive/CD8-positive perivascular lymphocytes in the olfactory bulb, but no ultrastructural evidence of viral particles.
CD163 is a potential inflammation biomarker. It is induced by proinflammatory cytokine storms in systemic inflammatory disorders such as Ebola virus infection, Morbini and colleagues noted. “A possible role of CD163-positive microglia in virus-mediated inflammation and neuropathogenesis has been previously proposed in patients with HIV and HIV-related encephalitis and various degrees of neurocognitive impairment and might also be a result of SARS-CoV-2–induced hyperinflammation,” they wrote.
“Our findings suggest that passive diffusion and axonal transport through the olfactory complex may be a major route of SARS-CoV-2 entry into the central nervous system, as it was previously shown in animal studies with a human coronavirus strain, human coronavirus OC43,” they added.
The report presents “only one single observation, which is a great limitation in scientific writing, but we believe it adds another piece of information to the complicated picture of COVID manifestations,” Morbini said.
A mechanism for how the virus is causing smell loss in such a high number of COVID-19 patients can’t be made based on this finding, said Eric Holbrook, MD, director of the rhinology division of Massachusetts Eye and Ear in Boston. “This paper alone does not alter clinical care or our understanding of COVID-19 and its role in causing smell loss,” he told MedPage Today.
“There are already many clinical studies demonstrating the high percentage of COVID-19 positive patients that develop loss of smell. This is now well known, and for that reason the symptom of sudden loss of smell and/or taste should be an early warning for possible COVID-19 infection,” Holbrook added. “Recognizing this association among the public as well as health care providers can help limit spread of the virus by initiating early isolation and testing.”
More studies on larger numbers of people are needed to understand how the virus is causing damage to the olfactory system, he observed.
“In the majority of patients, the loss of smell is temporary and returns to normal after 10 to 14 days, but there is a significant proportion of patients who have long-standing loss of smell lasting several months,” he pointed out.
“This difference isn’t clearly related to severity of the overall disease,” Holbrook said. “We need to understand what the differences are between these groups and how the virus interacts with the sense of smell system before we can propose treatment strategies.”
Last Updated August 13, 2020
- Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow
Morbini reported personal fees from MSD and Roche outside the submitted work. No other disclosures were reported.
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