This retrospective descriptive study included 81 confirmed cases of COVID-19 with a median age of 58 years. The median age of the severe group was 11.5 years older than that of the non-severe group. The ratio between males and females was about 0.88 (46.9% vs 53.1%). However, males accounted for 66.7% in the severe group, compared with 41.3% in the non-severe group. These results seem to suggest that males and older patients are more likely to develop severe disease, which is consistent with other reports[12]. On admission, fever and respiratory symptoms were the most common clinical manifestations. Compared with the non-severe group, there were more patients with dark urine in the severe group. This might suggest a potential relationship between urinary system dysfunction and disease severity. Among 81 patients, more than half had at least one comorbidity. Patients with cardiovascular and cerebrovascular diseases are more likely to develop severe illness. These above findings are consistent with the previous studies [2, 8, 13]. This study focuses on the OD and GD in COVID-19 patients in Wuhan.
On admission or during hospitalization, patients self-reported OD, GD, and both accounted for 13.6%, 25.9%, and 8.6% of all subjects, respectively. The incidence of OD and GD in the severe cases was not significantly different from the non-severe cases, suggesting OD and GD are not related to the severity of the disease. In addition, 48.0% of patients had persistent OD or GD after the other clinical manifestations of COVID-19 disappeared.
Most of the previous trials focused on the patient's respiratory symptoms, sensory disturbances were largely ignored. There are currently few studies on the incidence of OD and GD in Asia. One study found that 5.6% of COVID-19 patients reported hypogeusia, while 5.1% reported hyposmia[14]. Compared with this study, we found a higher rate of hypogeusia (13.6%) and hyposmia (25.9%). A multicenter European study conducted a quantitative analysis of patients with OD and GD, showing that 66.2%, 13.5%, and 88.8% of patients suffer from anosmia, hyposmia, and gustatory disorders, respectively[15]. These results indicate that compared with Asian patients, olfactory disorders are more common in European patients.
The reasons for the different incidence of OD and OD may be as follows: 1) Quantitative measurement is more sensitive than self-report. Studies have shown that only 35% of patients are aware of their olfactory deficits[16]. 2) The different affinity of the virus to different populations may lead to clinical differences between patients in different regions. A study showed that ACE2 mutations can reduce the correlation between human ACE2 and SARS-CoV S-protein, thereby reducing the chance of infection[17]. ACE2 polymorphisms and the differences in expression levels between Asian and European populations may explain the difference in olfactory dysfunction between Asian and European populations [18]. 3) Different strains of virus may cause different clinical manifestations.
In addition, Pearson correlation coefficient showed that headache or dizziness, dark urine, IgM, and diabetes all showed a positive correlation with OD and GD (all P < 0.05). We noted that chronic rhinitis and certain neurodegenerative diseases may directly lead to taste or smell disorders. In this study, such patients had been excluded. Headache or dizziness are the most common symptoms of the nervous system. It has been reported that the incidence of headache and dizziness in COVID-19 patients were 13.1% and 16.8%, respectively[14]. OD and GD are positively related to dizziness and headache. It has been reported that ACE2 is highly expressed in the nasal goblet and ciliated cells[19]. The virus may infect the olfactory nerve early and cause OD, before other neurological manifestations. OD and GD were also significantly related to dark urine. This may suggest that dark urine, like OD/GD, were signs of early infection and damage to the urinary system. IgM is an early antibody produced by the immune system after infection. The interaction of infectivity, virulence, and immune response may explain the positive correlation between IgM and OD/GD. Consistent with other results, diabetes was significantly correlated with smell dysfunction[20]. The infection might exacerbate potential nerve damage in diabetic patients.
One month after discharge, some patients still suffer from OD and GD. A few patients who did not have OD or GD during hospitalization developed these symptoms after discharge. Considering the damage of the virus to the olfactory or gustatory nerve, this may be one of the possible sequelae of COVID-19 patients. Our analysis found that drug treatment is not related to the recovery of OD and GD in patients with COVID-19, suggesting that the OD and GD are most likely to be the primary symptoms caused by SARS-CoV-2, rather than the side effects of drugs. It is worth noting that SARS-CoV can be detected 60 to 66 h after infection and is most abundant in the olfactory bulb[21]. While the infection routes of SARS-COV-2 and SARS-COV are similar, OD may be an early symptom of COCID-19. Early screening of people with OG and GD, early detection of virus infections, and early isolation of COVID-19 patients can help prevent the spread of COVID-19.
In conclusion, we found that OD and GD are common symptoms of COVID-19. They appear early during the course of disease and may last for at least 1 month. Headache or dizziness, IgM titers, and diabetes are correlated with the occurrence of OD and GD. This retrospective study has some limitations. First, we collected self-reported data, which may lead to information bias. Second, the sample size was small and geographically limited. Third, we only collected data 1 months after discharge. The duration of OD and GD in these patients need to be followed up.