COVID-19: THE PLAGUE THAT STRIKES BEHIND THE EAR

Abstract

Nontypeable Haemophilus Influenzae (NTHI) is a major cause of invasive disease worldwide.  Viral infections in patients colonized with NTHI may be at risk for serious complications as specific viruses, like SAR-CoV-2, on top of a bacterial infection significantly enhances the risk for excessive inflammation and upregulation of ICAM-1.  ICAM-1 is elevated in COVID-19 patients with mild disease and dramatically elevated in severe cases.  C-C chemokine receptor CCR5 is also upregulated in COVID-19 patients.  Incidentally, ICAM-1 and CCR5 upregulation are both implicated in the pathogenesis and progression of HIV.  Like the HIV, SARS-CoV-2 gains cellular entry through CD4 T-cells.  A NTHI / SARS-CoV-2 co-infection causes LFA-1 binding to ICAM-1.  LFA-1 activation on target CD4 T-cells enhances SARS-CoV-2 infectivity and transmission by promoting virus binding and cell to cell spread via the CCR5 coreceptor.  These mechanisms allow SARS-CoV-2 cellular access to multiple cellular systems inducing a cytokine storm in some patients.  LFA-1also increases the cell susceptibility to bacterial toxin LtxA that preferentially targets active LFA-1.  Leukotoxin (LtxA; Leukothera), is a protein toxin secreted by the oral bacterium Aggregatibacter actinomycetemcomitans, which specifically kills white blood cells.  Interestingly, Aggregatibacter actinomycetemcomitans and NTHI are two species under genus Pasteurellaceae.  Throughout history, plagues have been associated with divine punishments from God caused by bacterias.  Prophet Muhammadﷺ told us over 1400 years ago that when fornication becomes widespread new diseases like COVID-19 would increase. A holistic approach including Spiritual, Physical, Emotional, and Mental interventions must be employed to treat COVID-19 as well as to prevent the next pandemic.