All 3 cases were young people. Olfactory dysfunction occurred, on average, 6 days after the onset of the first symptom related to COVID–19 and aggravated rapidly. The qRT-PCR tests showed positive detection to throat swab and nagetive to nasal mucosa swab. Specifically, all patients recovered rapidly from common symptoms of COVID–19. However, the median recovery time of olfactory dysfunction was 20 days reflecting the slow recovery of neurological function. Neither hematology examination nor cranial CT showed any significant abnormality (Fig. 1b), which excluded olfactory/taste disorders caused by innate diseases, drugs, trauma, intracranial occupancy, influenza and para-flu viral infections.
Studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV–2) has the typical characteristics of Coronaviridae and shares approximately 85% homology with severe acute respiratory syndrome coronavirus (SARS- CoV) (Gralinski and Menachery, 2020). Moreover, coronavirus has neuropathic effects. There have been reports of human severe acute respiratory syndrome (SARS) with concomitant peripheral neuropathy in all four limbs or acute olfactory neuropath (Tsai et al, 2005; Hwang, 2006). Cases 2 and 3 were accompanied by nasal obstruction and recovered rapidly. Inflammatory edema of the mucous membrane may be the main mechanism. However, the slow relief on olfactory dysfunction may be related to damage to the olfactory central or peripheral nervous system.
Angiotensin-converting enzyme 2 (ACE2) is thought to be the main host cell receptor of SARS-CoV–2. The expression pattern of ACE2 in different organs indicates the potential high risk for SARS-CoV–2 infection and may be closely related to clinical manifestations (Zou et al, 2020). In particular, a high level of ACE2 expression was identified in numerous cell types, including esophageal upper and stratified epithelial cells, type II alveolar cells of lung, myocardial cells, absorptive enterocytes of the ileum and colon, cholangiocytes, kidney proximal tubule cells and bladder urothelial cells (Zou et al, 2020). For example, high expression of ACE2 in the genitourinary system in patients with COVID–19 causes rare symptoms of orchitis. Thus, the accompanying taste disorders in these two cases may be also related to the expression level of ACE2 in the epithelial cells of the oral mucosa (Xu et al, 2020). The aforementioned examples provided a potential link between SARS-CoV–2 infection and olfactory disorders. However, the underlying mechanism require further study. In addition, all three patients in this report were young people and whether the expression level of ACE2 is related to age is currently unknown.
COVID–19 could be a special neuropathy that can cause permanent damage on human health. Additionally, intensive consultation and further detection are required in these cases according to the ignorance of rare symptoms, such as symptoms of neurological injury. Furthermore, there is no clinical evidence to show an effective clinical intervention, despite the use of corticosteroids or neurotrophic drugs (Harless and Liang, 2016). Based on these three cases, early diagnosis and intervention would be the key to the recovery of olfactory dysfunction, particularly for young people.