Abstract
SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a
disease that reached pandemic proportions among the human population
within months. The reasons for the spectrum of differences in the
severity of the disease across the population, and in particular why the
disease affects more severely the aging population and those with
specific preconditions are unclear. We developed machine learning models
to mine 240,000 scientific articles openly accessible in the CORD-19
database, and constructed knowledge graphs to synthesize the extracted
information and navigate the collective knowledge in an attempt to
search for a potential common underlying reason for disease severity.
The machine-driven framework we developed repeatedly pointed to elevated
blood glucose as a key facilitator in the progression of COVID-19.
Indeed, when we systematically retraced the steps of the SARS-CoV-2
infection, we found evidence linking elevated glucose to each major step
of the life-cycle of the virus, progression of the disease, and
presentation of symptoms. Specifically, elevations of glucose provide
ideal conditions for the virus to evade and weaken the first level of
the immune defense system in the lungs, gain access to deep alveolar
cells, bind to the ACE2 receptor and enter the pulmonary cells,
accelerate replication of the virus within cells increasing cell death
and inducing an pulmonary inflammatory response, which overwhelms an
already weakened innate immune system to trigger an avalanche of
systemic infections, inflammation and cell damage, a cytokine storm and
thrombotic events. We tested the feasibility of the hypothesis by
manually reviewing the literature referenced by the machine-generated
synthesis, reconstructing atomistically the virus at the surface of the
pulmonary airways, and performing quantitative computational modeling of
the effects of glucose levels on the infection process. We conclude
that elevation in glucose levels can facilitate the progression of the
disease through multiple mechanisms and can explain much of the
differences in disease severity seen across the population. The study
provides diagnostic considerations, new areas of research and potential
treatments, and cautions on treatment strategies and critical care
conditions that induce elevations in blood glucose levels.
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