The Binary Model of Chronic Diseases Applied to COVID-19

Abstract

A binary model for the classification of chronic diseases has formerly been proposed. The model classifies chronic diseases as “high Treg” or “low Treg” diseases according to the extent of regulatory T cells (Treg) activity (frequency or function) observed. The present paper applies this model to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The model correctly predicts the efficacy or inefficacy of several immune-modulating drugs in the treatment of severe coronavirus disease 2019 (COVID-19) disease. It also correctly predicts the class of pathogens mostly associated with SARS-CoV-2 infection. The clinical implications are the following: (a) any search for new immune-modulating drugs for the treatment of COVID-19 should exclude candidates that do not induce “high Treg” immune reaction or those that do not spare CD8+ T cells; (b) immune-modulating drugs, which are effective against SARS-CoV-2, may not be effective against any variant of the virus that does not induce “low Treg” reaction; (c) any immune-modulating drug, which is effective in treating COVID-19, will also alleviate most coinfections; and (d) severe COVID-19 patients should avoid contact with carriers of “low Treg” pathogens.

Elucidating T Cell and B Cell Responses to SARS-CoV-2 in Humans: Gaining Insights into Protective Immunity and Immunopathology

“…Given that patients with severe COVID-19 are often treated with immune suppressants, ex vivo expanded SARS-CoV-2 specific T cells can be additionally manipulated by CRISPR-Cas9 gene-editing methods to render them resistant to glucocorticoids by inactivating the glucocorticoid receptor gene ( NR3C1 ) [ 42 ]. Evidence of imbalance in the regulatory T cell (Treg)/Th17 cell ratio has also been described in patients that experience respiratory failure in the setting of SARS-CoV-2 infection, hence adoptive immunotherapy approaches that utilize Tregs to mitigate SARS-CoV-2 associated hyper-inflammation are also being explored [ 43 , 44 , 45 , 46 ].…”

“… Potential downstream applications of profiling bulk or virus-specific T cells in the context of SARS-CoV-2 infection and/or after COVID-19 vaccination. Reference(s) [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. …”

Cancer and Autoimmune Diseases: A Tale of Two Immunological Opposites?

“…Earlier work proposed a classification of chronic diseases into pro- and anti-inflammatory diseases based on the extent of regulatory T cells (Treg) activity observed (“high Treg” or “low Treg”) ( 1 ). This classification was found useful (a) in understanding the efficacy of drugs for the treatment of different chronic diseases, (b) in explaining the association of specific chronic diseases with specific pathogens, and (c) in interpreting the effects of different pathogens on cancer and autoimmune diseases ( 1 – 3 ).…”

SARS-CoV-2 Omicron (B.1.1.529) Variant: Corticosteroids Treatment/Respiratory Coinfection

“…In a recent publication, the binary model of chronic diseases was applied to SARS-CoV-2 infection ( 1 ). The efficiency of corticosteroids in the treatment of severe COVID-19 was explained by their ability to promote Treg expansion while sparing SARS-CoV-2 specific CD8 + T cells.…”

“…With the earlier variants of SARS-CoV-2, a severe disease was related to a surge of pro-inflammatory cytokines, the so called “cytokine storm” ( 11 ). This “chronic” high pro-inflammatory state correlated with low Treg levels ( 1 ). The seemingly lower intrinsic severity with Omicron may suggest a lower extent of cytokine storm with this variant.…”