Urine Cytokines as biomarkers in COVID‐19 Patients

Komnenov, Dragana; Dhar, Nivedita; Lamb, Laura; Wills, Melissa; Khaliq, Fareea; Timar, Ryan; Chancellor, Michael; Bartolone, Sarah; Ward, Elijah; Rossi, Noreen; Bitar, Ali; Dhar, Sorabh; Cohn, Johnathan

INTRODUCTION: COVID‐19 pandemic has been one of the main global health concerns in 2020, and many aspects of the disease remain enigmatic. While some patients infected with the disease‐causing virus SARS‐CoV2 have no or mild symptoms, others experience severe symptoms requiring hospitalization. Of these more severe patients, some remain stable while others experience cytokine storm syndrome or an exaggerated immune response that has been correlated with disease severity and progression of acute respiratory deterioration. It is currently unknown why some patients with COVID‐19 demonstrate this response and others do not. In light of the apparent prominent role of the inflammatory mediators (i.e. cytokines) in COVID‐19 pathogenesis, the ability to identify screening tools not only for the SARS‐CoV2 virus but also for cytokines is important. The present investigation was designed to identify the urinary cytokine signature in COVID‐19 patients. METHODS: The study enrolled 17 COVID‐19 patients and 10 control subjects (SARS‐CoV‐2 negative) 18 years or older with glomerular filtration rate of > 60mL/min. Urine samples were collected and cytokines quantitated using the Luminex multiplex assay. The cytokines analyzed were growth‐regulated oncogene (GRO), interleukin‐8 (IL‐8), and interleukin‐6 (IL‐6). RESULTS: The levels of GRO and IL‐6 were significantly elevated in urine samples obtained from COVID‐19 patients compared to controls (mean 16.8 pg/ml vs. 9.2 pg/ml ± 2.39, p < 0.0171 and mean 16.8 pg/ml vs 9.2 pg/ml ± 2.42, p < 0.0157, respectively). Conversely, IL‐8 level was similar between COVID‐19 patients and controls (15.6 pg/ml vs 11.3 pg/ml ± 1.3, p<0.1833). CONCLUSION: The present investigation found that the levels of urinary cytokines GRO and IL‐6 were significantly elevated in COVID‐19 patients compared to controls and may serve as urinary biomarkers of disease progression. Furthermore, IL‐8 although elevated in COVID‐19 patients, did not reach statistical significance in our population sample. The findings of this proof of concept study underscore that the urinary cytokines may serve as prognostic and diagnostic accessible biomarkers in COVID‐19.