Abstract
Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March—June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if <18 years, or opted out of research. The primary composite outcome was intubation or death within 180 days. Secondary outcomes included mortality alone, intensive care unit admission, use of vasopressors, and CPR. Enrolled patients had mean age 64 years (SD±17), were 53% males, and 48% non-whites. Mean renalase levels was 14,108·4 ng/ml (SD±8,137 ng/ml). Compared to patients with high renalase, those with low renalase (< 8,922 ng/ml) were more likely to present with hypoxia, increased ICU admission (54% vs. 33%, p < 0.001), and cardiopulmonary resuscitation (10% vs. 4%, p = 0·023). In Cox proportional hazard model, every 1000 ng/ml increase in renalase decreased the risk of death or intubation by 5% (HR 0·95; 95% CI 0·91–0·98) and increased survival alone by 6% (HR 0·95; CI 0·90–0·98), after adjusting for socio-demographics, initial disease severity, comorbidities and inflammation. Patients with high renalase-low IL-6 levels had the best survival compared to other groups (p = 0·04). Renalase was independently associated with reduced intubation and mortality in hospitalized COVID-19 patients. Future studies should assess the pathophysiological relevance of renalase in COVID-19 disease.
Highlights
As of December 2021, approximately 277 million global cases of COVID-19 had caused ~5.3 million deaths [1]
Study patients were similar in age and sex distribution but had higher comorbidities, and slightly longer hospital length of stay compared to the population of hospitalized patients admitted with COVID-19 between March-June 2020 (S1 Table in S1 File)
Patients with low renalase were similar in age, sex, race, ethnicity compared to patients with high renalase
Summary
As of December 2021, approximately 277 million global cases of COVID-19 had caused ~5.3 million deaths [1]. 81% of those infected have mild disease, 14% develop severe disease and 5% become critically ill with organ failure [3]. COVID-19 primarily manifests as a respiratory illness, there is substantial evidence of endothelial injury, thrombosis and dysfunction in vital organs including heart, kidney and brain. Severe COVID-19 is characterized by apoptosis of pericytes in the microvasculature [9], causing immune-thrombotic dysregulation, and development of inflammatory thrombi that lead to endothelial dysfunction and ARDS [10]. Recent evidence questions the role of “COVID-19 cytokine storm”, since the inflammatory dysregulation in COVID-19 is neither as coordinated nor as intense as in other ARDS conditions [11, 12] the quest to develop therapeutics that target cell death, endothelial dysfunction and immunomodulation in COVID-19 has high clinical relevance [13, 14]
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