Mood, anxiety and olfactory dysfunction in COVID-19: evidence of central nervous system involvement?

INTRODUCTION: The objective of this study was to determine the burden of depressed mood and anxiety in COVID-19, and associated disease characteristics. MATERIALS AND METHODS: This is a prospective, cross-sectional study of 114 COVID-19 positive patients diagnosed using RT-PCR-based testing over a 6-week period. The 2-item Patient Health Questionnaire (PHQ-2) and the 2-item Generalized Anxiety Disorder questionnaire (GAD-2) were used to measure depressed mood and anxiety level, respectively, at enrollment and for participants' baseline, pre-COVID-19 state. Severity of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath (SOB) during COVID-19 were assessed. RESULTS: PHQ-2 and GAD-2 significantly (p<0.001) increased from baseline to enrollment. PHQ-2 was associated with smell loss (adjusted incidence rate ratio [aIRR]=1.40, 95%CI: 1.10-1.78, p=0.006), age (aIRR=1.02, 95%CI: 1.01-1.04, p=0.006), and baseline PHQ-2 score (aIRR=1.39, 95%CI: 1.09-1.76, p=0.007). GAD-2 score was associated with smell loss (aIRR=1.29, 95%CI: 1.02-1.62, p=0.035), age (aIRR=1.02, 95%CI: 1.01-1.04, p=0.025) and baseline GAD-2 score (aIRR=1.55, 95%CI: 1.24-1.93, p<0.001). Loss of taste also exhibited similar associations with PHQ-2 and GAD-2. PHQ-2 and GAD-2 scores were not associated with severities of any other symptoms during the COVID-19 course. CONCLUSIONS: Despite the occurrence of symptoms-such as SOB-associated with severe manifestations of COVID-19, only the severities of smell and taste loss were associated with depressed mood and anxiety. These results may raise the novel possibility of emotional disturbance as a CNS manifestation of COVID-19 given trans-olfactory tract penetration of the central nervous system (CNS) by coronaviruses.