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 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- - This..