New postmortem findings from two patients with severe COVID-19 suggest the virus may enter the central nervous system (CNS) through the olfactory complex. Dr. Patrizia Morbini of the University of Pavia, in Italy, and her colleagues report ultrastructural and immunohistochemical evidence for viral invasion in the olfactory tracts of two patients who died of severe COVID-19 in a letter to JAMA Otolaryngology - Head and Neck Surgery. COVID-19 patients often have neurological problems, but the mechanism responsible remains unclear, Dr. Morbini and her team note in their report. They describe findings in two patients who tested positive by nasal swab for SARS-CoV-2 and were autopsied using minimally invasive techniques. Patient 1 had anosmia and died from pneumonia in the intensive-care unit. Transmission electron microscopy showed viral cytoplasmic inclusion bodies and interstitial viral particles in the patient's olfactory bulb, and the patient also had CD163-positive/CD68-negative microglial cell infiltration. Olfactory dysfunction was not well defined in Patient 2, who died due to cardiopulmonary transthyretin amyloidosis. This patient had viral particles 80 to 100 nanometers in size on respiratory cell membranes in the olfactory mucosa, and rare CD163-positive microglial cells with CD3-positive/CD8-positive perivascular lymphocytes. The second patient also had more inflammation of the nasal and olfactory mucosa, but no ultrastructural evidence of viral infection in the olfactory bulb. "Although confirmatory observations on extensive patient series are needed, 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," Dr. Morbini and her team write. "This report supports the clinical hypothesis that the new onset of olfactory dysfunction should either prompt immediate testing for SARS-CoV-2 infection whenever possible or might be considered an additional clinical criterion for self-isolation," they conclude. "This is a great piece of evidence that the olfactory tract could potentially serve as a route for invasion of the central nervous system for the novel coronavirus," Dr. Ahmad R. Sedaghat, an associate professor and director of the Division of Rhinology, Allergy and Anterior Skull Base Surgery at the University of Cincinnati College of Medicine, told Reuters Health by phone. "This is direct evidence, physicians seeing with electron microscopes that these virions can get into the olfactory tract, travel through those axons and go into the central nervous system," added Dr. Sedaghat, who did not participate in the new research. It's now generally accepted that more than half of patients with COVID-19 develop anosmia, he noted. Dr. Sedaghat and his colleagues recently reported an association between smell-loss severity and symptoms of depressed mood and anxiety in COVID-19 patients. No other symptoms, including shortness of breath, were associated with increased depression or anxiety. COVID-19 patients struggling with depression and anxiety should be sure to ask for help, Dr. Sedaghat said, noting that knowing mood and anxiety problems could be a consequence of the infection, rather than a personal failing, could help reduce the persistent stigma surrounding mental-health issues. "We can treat a lot of these conditions, it's just that we have to know," Dr. Sedaghat said. "What we don't want to happen is for these patients to go months, who knows, even years without being treated for any kind of lasting psychological distress from the disease." Dr. Morbini was not available for an interview by press time. —Anne Harding Source
