Fig. 5: Viral-hijacked host cellular factors and consequences.

Clinical outcomes of COVID-19 depend on the ability of SARS-CoV-2 pathogen to hijack host metabolic machinery as well as cellular factors of an infected individual for invasion and internalization, followed by intra-cellular replication to assemble and release multiple viral copies for ultimate propagation/transmission. Each of the viral hijacked host cellular factor is also a quintessential functional component of human metabolism. Viral host receptor ACE2, is a critical regulator of blood pressure, controller of blood volume involved in systemic vascular resistance, and in CV homeostasis²⁹². Viral host receptor NRP1, is vital for several physiological pathways including nervous and vascular development, VEGF-dependent angiogenesis (i.e., new blood vessel formation), immunity and tumorigenesis^321,322. Viral membrane fusion priming enzyme furin, is known for intracellular proteolytic processing of precursor polypeptides, which is an essential step in the maturation of many proteins such as plasma proteins, hormones, neuropeptides, and growth factors³³¹. Viral membrane fusion priming enzyme TMPRSS2 plays a key role in digestion, salt-water balance, iron metabolism, tissue remodeling, blood coagulation, auditory nerve development, and fertility³⁶⁶. Viral endocytosis-mediator CTSL is involved in functional development of immune system, skeletal physiology including bone collagen degradation/resorption and thyroid hormone release^384,385. Consequential to the viral hijack, these essential host cellular factors could malfunction and lead to a plethora of organ/system impairments with detrimental consequences to the human body. If not corrected or reset, this HMRD condition may persist in a PASC patient for weeks or months even after viral clearance and recovery from COVID-19.