Avinash Shekhar Jaiswal - Department of Otorhinolaryngology and Head & Neck Surgery, All India Institute of Medical Sciences, New Delhi, India.
Aanchal Kakkar - Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Kavneet Kaur - Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Alok Thakar - Department of Otorhinolaryngology and Head & Neck Surgery, All India Institute of Medical Sciences, New Delhi, India.
Kapil Sikka - Department of Otorhinolaryngology and Head & Neck Surgery, All India Institute of Medical Sciences, New Delhi, India.
Hitesh Verma - Department of Otorhinolaryngology and Head & Neck Surgery, All India Institute of Medical Sciences, New Delhi, India.

Introduction: 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 ACE۲ and TMPRSS۲ in the nasal and paranasal sinus tissues among patients with COVID-۱۹-associated Mucormycosis (CAM), COVID-۱۹-negative mucormycosis (CNM), and healthy individuals. Materials and Methods: 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 ACE۲ and TMPRSS۲ receptors. The level was compared among the three groups. Results: The study encompassed ۴۴ patients with CAN, ۲۰ with CNM, and ten healthy individuals. ACE۲ positivity was seen only in the apical cilia, with no significant difference among the groups (p=۰.۶). In contrast, TMPRSS۲ positivity was seen in the cytoplasm and nucleus of epithelium and submucosal glands in addition to apical cilia. TMPRSS۲ was increasingly expressed in patients with CAM compared to CNM (p=۰.۰۰۹) and the healthy group (p=۰.۰۰۲). Conclusion: The expression of TMPRSS۲ receptors is elevated in patients with COVID-۱۹-associated mucormycosis with no significant change in the expression of ACE۲ receptors. This finding could account for the heightened susceptibility to infection by SARS-CoV-۲ and the subsequent immune dysregulation, providing a fertile ground for Mucorales co-infection.

COVID-۱۹, SARS-CoV-۲, Mucormycosis, Angiotensin-Converting Enzyme ۲, Transmembrane serine protease ۲