Preprint / Version 1

The Pathogenetic Dilemma of Post-COVID-19 Mucormycosis in India

Authors

  • Sankha Chakrabarti Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.
  • Upinder Kaur Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.
  • Sushil Aggarwal Department of Otorhinolaryngology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.
  • Ahalya Kanakan Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.
  • Adesh Saini Department of Biotechnology, Maharishi Markandeshwar (deemed to be) University, Mullana, Haryana, India.
  • Bimal Agrawal Department of Medicine, Maharishi Markandeshwar (deemed to be) University, Mullana, Haryana, India.
  • Kunlin Jin Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA.
  • Sasanka Chakrabarti Department of Biochemistry and Central Research Cell, Maharishi Markandeshwar (deemed to be) University, Mullana, Haryana, India

Keywords:

GRP78, Rhizopus, rhino-orbito-cerebral, spleen tyrosine kinase

Abstract

There has been a surge of mucormycosis cases in India in the wake of the second wave of COVID-19 with more than 40000 cases reported. Mucormycosis in patients of COVID-19 in India is at variance to other countries where Aspergillus, Pneumocystis, and Candida have been reported to be the major secondary fungal pathogens. We discuss the probable causes of the mucormycosis epidemic in India. Whereas dysglycaemia and inappropriate steroid use have been widely suggested as tentative reasons, we explore other biological, iatrogenic, and environmental factors. The likelihood of a two-hit pathogenesis remains strong. We propose that COVID-19 itself provides the predisposition to invasive mucormycosis (first hit), through upregulation of GRP78 and downregulation of spleen tyrosine kinase involved in anti-fungal defense, as also through inhibition of CD8+ T-cell mediated immunity. The other iatrogenic and environmental factors may provide the second hit which may have resulted in the surge. Keywords: GRP78, Rhizopus, rhino-orbito-cerebral, spleen tyrosine kinase