Is Long COVID a State of Systemic Pericyte Disarray?

Abstract

The most challenging aspect of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) or Long COVID remains for the discordance between the viral damage from acute infection in the recent past and susceptibility of Long COVID without clear evidence of post infectious inflammation or autoimmune reactions. In this communication we propose that disarray of pericytes plays a central role in emerge of Long COVID. We assume pericytes are agents with "Triple-A" qualities, i.e., analyze-adapt and advance, necessary for sustainability of host homeostasis. Based on this view, we further suggest Long COVID may provide a model system to integrate system theory and complex adaptive systems to explore a new class of maladies those are currently not well defined and with no remedies.

Keywords: Long COVID; Triple-A; complex dynamical systems; emergent systems intelligence; entropy; pericyte.

Figure 1

We envision Long COVID involves microvascular dysfunction due in part to suboptimal recovery of pericytes from viral mediated damage. There are likely to be several root-causes: one, from escalated vascular damage during acute COVID-19 on top of existing microvascular changes particularly in the presence of age associated limitations of regeneration (red line). Another speculation is genetic predisposition to breakdown of pericyte networks upon external insult (blue line) that may include mutations affecting pericyte structure and functions. Males (M) over females (F), the older population, or in the presence of co-morbid factors are more likely to be in the former group. The latter group is more likely to contain females, the younger, the previously healthy, or with postural orthostatic tachycardia syndrome (POTS).

Figure 2

The casual loop proposition of hypothesis presented. Blue line for negative feedback and green line for positive feedback. Root-causes of altered pericyte networks may vary under the influence of different sets of genetic or epigenetic factors, and along the arrow of time.