Pathophysiology of SARS-CoV-2 Infection of Nasal Respiratory and Olfactory Epithelia and Its Clinical Impact

Abstract

Purpose of review: While the predominant cause for morbidity and mortality with SARS-CoV-2 infection is the lower respiratory tract manifestations of the disease, the effects of SARS-CoV-2 infection on the sinonasal tract have also come to the forefront especially with the increased recognition of olfactory symptom. This review presents a comprehensive summary of the mechanisms of action of the SARS-CoV-2 virus, sinonasal pathophysiology of COVID-19, and the correlation with the clinical and epidemiological impact on olfactory dysfunction.

Recent findings: ACE2 and TMPRSS2 receptors are key players in the mechanism of infection of SARS-CoV-2. They are present within both the nasal respiratory as well as olfactory epithelia. There are however differences in susceptibility between different groups of individuals, as well as between the different SARS-CoV-2 variants. The sinonasal cavity is an important route for SARS-CoV-2 infection. While the mechanism of infection of SARS-CoV-2 in nasal respiratory and olfactory epithelia is similar, there exist small but significant differences in the susceptibility of these epithelia and consequently clinical manifestations of the disease. Understanding the differences and nuances in sinonasal pathophysiology in COVID-19 would allow the clinician to predict and counsel patients suffering from COVID-19. Future research into molecular pathways and cytokine responses at different stages of infection and different variants of SARS-CoV-2 would evaluate the individual clinical phenotype, prognosis, and possibly response to vaccines and therapeutics.

Keywords: COVID-19; Mechanism of action; Nasal epithelium; Olfactory; Pathophysiology; Smell.

Fig. 1

Prevalence of olfactory dysfunction (OD) amongst patients infected by SARS-CoV-2 variants and recovery. *Data obtained from papers analysing OD recovery during period where the Alpha variant was predominant strain