We report two cases of olfactory neuropathy diagnosed at autopsy in patients with severe acute respiratory syndrome due to coronavirus 2 (Sars-CoV-2) infection. One patient experienced anosmia. Information about anosmia was not available in the other patient.
Patient 1, a 70-year-old male and patient 2, a 79-year-old male, both tested positive for Sars-CoV-2. Patient 1 was a renal transplant recipient with coronary artery disease and arterial hypertension. He developed progressive respiratory failure due to coronavirus disease-19-associated (Covid-19) pneumonia and required mechanical ventilation. He was treated with hydroxychloroquine (total 1600mg). Patient 2 was previously diagnosed with severe pulmonary hypertension and was admitted with fever, cough, and increasing dyspnea as well as loss of taste and smell. He was also treated with hydroxychloroquine (total 1600mg); however, he declined invasive treatment. Patient 1 died eight days, patient 2 six days after hospitalization.
Post-mortem histological analysis of the olfactory epithelium in both patients showed prominent leukocytic infiltrates in the lamina propria, and focal atrophy of the mucosa (Figures 1a,g,h,i). There was a slight predominance of CD3+ T over CD20+ B lymphocytes. Expectedly, olfactory nerve fibers in the lamina propria were negative for myelin basic protein. However, they showed numerous CD68+ digestion chambers, suggestive of axonal damage (Figures 1b,i). Scattered intraneural CD45+ leukocytes were consistent with an inflammatory neuropathy (Figures 1c,h), the infiltrates comprised both CD4+ and CD8+ T lymphocytes, CD20 was negative (Figure 1d-e). In patient 1, the olfactory tract showed CD45+ infiltrates (Figure 1f), isolated CD45+ leukocytes were seen in patient 2. In both cases, the olfactory striae were unremarkable. Both brains showed perivascular leukocytic infiltrates, predominantly in the basal ganglia; patient 2 harbored intravascular microthrombi.
Anosmia is a common symptom in Covid-19 patients 1. Inflammation of the olfactory system and anosmia have been reported in other viral diseases 2 as was age-related atrophy of the olfactory epithelium 3. The observed neuritis is most likely associated with axonal damage, as olfactory fila lack myelin 4. Sars-CoV-2-induced damage might be mediated by viral entry through its receptor angiotensin converting enzyme 2 and the transmembrane serine protease 2, which are expressed in non-neural cells of the olfactory epithelium 5. It is unclear whether the observed inflammatory neuropathy is a result of direct viral damage or is mediated by damage to supporting non-neural cells. Due to the rapidly evolving pandemic, unravelling the neuroinvasive properties of Sars-CoV-2 will have major implications for Covid-19 patients.