The VERX: a transient flare-up of Long COVID symptoms

Abstract

People with Long COVID frequently experience strong transient flare-ups triggered by various foods, supplements, and medicines. We propose that the increased symptoms, pressure, aches, and pains felt during a flare-up reflect transiently stronger antiviral immune responses at sites of low-level persistent viral infection. We call this phenomenon a “Verx'' to distinguish it from a bacterial-triggered Jarisch-Herxheimer reaction or “Herx”. Our hypothesis is based on emerging evidence for SARS-CoV-2 viral persistence in many different cell types, tissues, and organs in long-haulers. Activation of innate immunity and increased local presentation of viral antigens may stimulate patient antiviral immune responses, resulting in sudden worsening or reoccurrence of a great variety of common symptoms. Furthermore, we describe how the degradative and recycling pathway of autophagy within cells may be key to making SARS-CoV-2 infected cells suddenly “visible” to patrolling natural killer cells and cytotoxic T cells. Over 30 compounds known to induce autophagy, a dozen foods and some probiotics that activate innate immunity are anecdotally associated with Verx reactions. We outline how periodic induction of autophagy and the resulting stimulation of innate immunity might plausibly support viral containment and clearance. The 'Verx Hypothesis' presents a conceptual framework for future translational research. Thorough evaluation in preclinical models and prospective clinical trials is required before clinical utility can be established.