Hyperglycemia, hydroxychloroquine, and the COVID-19 pandemic
Brufsky,
Hyperglycemia, hydroxychloroquine, and the COVID-19 pandemic,
, A., J. Medical Virology, doi:10.1002/jmv.25887 (Theory)
Theory on the effectiveness of HCQ. HCQ has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of proteins involved in the humoral immune response, possibly including the macrophage FcR gamma IgG receptor and other immunomodulatory proteins, potentially through inhibition of UDP-N-acetylglucosamine 2-epimerase. In combination with potential other immunomodulatory effects, this could possibly blunt the progression of COVID-19 pneumonia all to way up to ARDS.
Brufsky et al., 15 Apr 2020, peer-reviewed, 1 author.
Abstract: Received: 10 April 2020
|
Accepted: 13 April 2020
DOI: 10.1002/jmv.25887
REVIEW
Hyperglycemia, hydroxychloroquine, and the COVID‐19
pandemic
Adam Brufsky MD, PhD
UPMC Hillman Cancer Center, Magee
Women's Hospital, University of Pittsburgh
School of Medicine, Pittsburgh, Pennsylvania
Abstract
Coronavirus disease‐2019 (COVID‐19) infection and its severity can be explained by
Correspondence
Adam Brufsky, MD, PhD, UPMC Hillman
Cancer Center, Magee Women's Hospital,
University of Pittsburgh School of Medicine,
Suite 4628, 300 Halket Street, Pittsburgh, PA
15213.
Email: brufskyam@upmc.edu
the concentration of glycosylated severe acute respiratory syndrome‐coronavirus 2
(SARS‐CoV‐2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin‐converting enzyme receptor 2 (ACE2) in the lung epithelium, and
the degree and control of the pulmonary immune response to the SARS‐CoV‐2 spike
protein at approximately day 8 to 10 after symptom onset, which may be related to
both. Binding of ACE2 by SARS‐CoV‐2 in COVID‐19 also suggests that prolonged
uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be
important in the pathogenesis of the disease. It is tempting to consider that the same
mechanism acts in COVID‐19 as in SARS, where an overactive macrophage M1
inflammatory response, as neutralizing antibodies to the SARS‐CoV‐2 spike protein
form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine,
which may interfere with this overly brisk macrophage inflammatory response and
perhaps influence the course of the disease, in particular, those that blunt but do not
completely abrogate the M1 to M2 balance in macrophage polarization, as well as
viral load, which in SARS appears to be temporally related to the onset of ARDS.
KEYWORDS
antibody‐mediated cell‐mediated cytotoxicity, antiviral agents, SARS coronavirus
1 | ROLE OF THE ACE 2 R ECEPTOR I N
COV I D‐ 19 INFECTION
to help us with this understanding. Rapid publication of peer‐
reviewed data has defined the possible risk factors for COVID‐19, its
clinical course, and its possible epidemiology. In this unusual time of a
We are all struggling to understand the human catastrophe of the
public health emergency, numerous non‐peer‐reviewed manuscripts
coronavirus disease‐2019 (COVID‐19) epidemic. As of April 12,
have been uploaded to preprint servers, and their unreviewed data
2020, there were 557043 cases of documented COVID‐19 infection
and conclusions must be evaluated in this spirit.
in the United States, and 21952 deaths.1 Our economy except for
Nevertheless, data both published and in preprint form point to a
limited sectors has come to a complete halt as we practice physical
tantalizing hypothesis: that COVID‐19 infection and its severity can be
distancing to try to mitigate the effects of the pandemic.
explained by the concentration of glycosylated severe acute respiratory
In the 10 weeks since COVID‐19 began to accelerate, there has
syndrome‐coronavirus 2 (SARS‐CoV‐2) viral particles in the lung epithe-
been a flurry of information from corners expected and unexpected
lium, the concentration of glycosylated angiotensin‐converting enzyme
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