Insight into Covid Associated Mucormycosis: A Prospective Study

The notable increase in cases of rhino-orbito-cerebral Mucormycosis during the COVID pandemic is alarming. Both share a common route of entry, the nasal mucosa, leading to speculation about whether similar receptors play a role in both diseases. We aim to compare the expression of ACE2 and TMPRSS2 in the nasal and paranasal sinus tissues among patients with COVID-19-associated Mucormycosis (CAM), COVID-19-negative mucormycosis (CNM), and healthy individuals.  This prospective study included patients with CAM, CNM, and healthy individuals who underwent surgical management. Immunohistochemistry was performed in the sino-nasal tissue to detect the presence of ACE2 and TMPRSS2 receptors. The level was compared among the three groups.  The study encompassed 44 patients with CAN, 20 with CNM, and ten healthy individuals. ACE2 positivity was seen only in the apical cilia, with no significant difference among the groups (p=0.6). In contrast, TMPRSS2 positivity was seen in the cytoplasm and nucleus of epithelium and submucosal glands in addition to apical cilia. TMPRSS2 was increasingly expressed in patients with CAM compared to CNM (p=0.009) and the healthy group (p=0.002).  The expression of TMPRSS2 receptors is elevated in patients with COVID-19-associated mucormycosis with no significant change in the expression of ACE2 receptors. This finding could account for the heightened susceptibility to infection by SARS-CoV-2 and the subsequent immune dysregulation, providing a fertile ground for Mucorales co-infection.