The role of serum undercarboxylated osteocalcin in COVID-19 infection

Gerard Karsenty, Paul A. Marks Professor of Genetics and Development and Professor of Medicine, Department of Genetics and Development

Bone-derived OCN has a complex relationship with many organ systems, and its many endocrine functions have led to the suggestion that it may be a “master regulator.” OCN in mice has been shown to regulate the sympathetic stress response, influence muscle activation, regulate memory/alertness/behavior, and play a role in insulin secretion and glucose metabolism. COVID-19 infection commonly involves many organs including the lungs, kidneys, heart, GI tract, and the central and peripheral nervous systems. We propose to study the role of OCN in COVID-19 through serum measurements of OCN in COVID-19-infected patients of ICU-level severity, and how it relates to other markers of the acute phase reaction and of inflammation

Firstly, OCN blocks parasympathetic nerve transmission – this allows the sympathetic nervous system to respond to acute danger (Berger, 2019). Circulating OCN levels surge in mice and humans exposed to fearful stimulus, while the steroid hormone cortisol takes hours to peak. In COVID-19 infection, severely ill patients commonly exhibit serum troponemia without evidence of myocardial infarction. This suggests a demand ischemia – which could be regulated by the sympathetic nervous system. We surmise that OCN may rise significantly in COVID-19 as well, in response to the acute stress of severe infection requiring ICU stay. Further, OCN and IL-6 are locked into a feed-forward loop regulating muscle function (Booth, 2016). IL-6 has been shown to be remarkably elevated in COVID-19 infection, and to portend a worse prognosis. Because of its prognostic utility, IL-6 is now routinely collected in severe COVID-19 patients. We propose that OCN could be driven by the stark increases in IL-6 in COVID-19 ICU patients, and play a role in skeletal muscle myopathy in the appendicular and possibly respiratory muscles.

1. To determine the role of circulating undercarboxylated and bioactive osteocalcin (OCN) in severely ill, intensive-care unit (ICU) COVID-19 patients. the acute phase reaction and sympathetic activation of SARS-CoV-2 infection.
a. To understand the change in OCN levels over the course of a COVID-19 hospitalization involving ICU care, and determine whether its trajectory can be a useful prognostic marker.
b. To compare OCN levels in patients with COVID-19 infections of varying severity, to establish whether there is an association with OCN and infection categorization.
c. To compare OCN levels with levels of other acute phase reactants in COVID-19 infection, to establish whether OCN is associated with other acute phase reactants routinely measured in hospitalized patients, such as ferritin, platelets, fibrinogen, and albumin.

2. To understand whether OCN and IL-6 are associated in patients especially with myopathic complaints or laboratory findings.