Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic
MD Adam Brufsky
Journal of Medical Virology, doi:10.1002/jmv.25887
Coronavirus disease-2019 (COVID-19) infection and its severity can be explained by 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. antibody-mediated cell-mediated cytotoxicity, antiviral agents, SARS coronavirus
| ROLE OF THE ACE2 RECEPTOR IN COVID-19 INFECTION We are all struggling to understand the human catastrophe of the coronavirus disease-2019 (COVID-19) epidemic. As of April 12, 2020, there were 557043 cases of documented COVID-19 infection in the United States, and 21952 deaths. 1 Our economy except for limited sectors has come to a complete halt as we practice physical distancing to try to mitigate the effects of the pandemic. In the 10 weeks since COVID-19 began to accelerate, there has been a flurry of information from corners expected and unexpected to help us with this understanding. Rapid publication of peerreviewed data has defined the possible risk factors for COVID-19, its clinical course, and its possible epidemiology. In this unusual time of a public health emergency, numerous non-peer-reviewed manuscripts have been uploaded to preprint servers, and their unreviewed data and conclusions must be evaluated in this spirit. Nevertheless, data both published and in preprint form point to a tantalizing hypothesis: that COVID-19 infection and its severity can be explained by 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
CONFLICT OF INTERESTS The authors declare that there are no conflict of interests.
ORCID
Adam Brufsky http://orcid.org/0000-0001-8080-7960
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