IMPACT OF MONOCYTE CHEMOATTRACTANTS ON IN-HOSPITAL MORTALITY IN RELATION TO KIDNEY FUNCTION IN PATIENTS WITH COVID-19

Abstract Background and Aims Patients with chronic kidney disease (CKD) are at higher risk of severe complications and mortality due to Covid-19 than patients with other known risk factors. The association between CKD and mortality persist in analyses adjusted for covariates known to associate with worse Covid-19 outcomes, suggesting that CKD confers a risk beyond that associated to comorbid conditions. The mechanisms underlying the increased susceptibility to severe Covid-19 in CKD remains unclear but morphologic and functional differences in monocytes have been associated with prolonged hospitalization in other cohorts of patients. The monocyte is capable to contribute to the pathophysiology through different mechanisms. There is however insufficient information on factors that orchestrate different aspects of monocyte function and how these factors relate to outcomes. Increased knowledge into which features of monocyte function that contribute to risks in CKD patients with Covid-19 is important to guide treatment strategies. The aim of the present study was to examine the concentrations of monocyte chemoattractant markers MCP-1 (Monocyte Chemoattractant Protein-1; CCL2) and MIP-1α (Macrophage Inflammatory Protein 1-α; CCL3) in patients with Covid-19 and normal or impaired kidney function and to compare that to CKD patients matched for sex and eGFR, and sex matched healthy subjects. We analyzed the impact of these monocyte chemoattractant markers on in-hospital and 30 days mortality by logistic and multiple regression analyses. We related this to established risk factors for morbidity and mortality in Covid-19 patients, e.g. CRP and IL-6. Method We prospectively included 110 patients with Covid-19 (mean age 59 yr., mean eGFR 75 ml/min/1.73m2) admitted to Danderyd University Hospital, Stockholm, Sweden, during the first pandemic wave in April to May 2020 and 33 sex and eGFR-matched patients (mean age 51 yr., eGFR 52 ml/min/1.73m2) with CKD and 35 sex matched healthy subjects (mean age 47 yr., eGFR 101 ml/min/1.73m2).We used Luminex assays to analyze MCP-1, MIP-1α and IL-6 and routine laboratory tests to determine white blood cell count (WBC) and CRP. Results Patients with Covid-19 had significantly lower concentrations of MIP-1α (p<0.001), and higher IL-6 (p<0.001) and CRP (p<0.001) than patients with CKD and healthy subjects (Kruskal-Wallis), there were no differences in MCP-1 between groups. We found significant negative correlations between MCP-1 (p<0.05), MIP-1α (p<0.05) and IL-6 (p<0.05) with eGFR in patients with Covid-19 (Spearman´s rank correlation). Logistic regression analysis (Odds ratio, OR, 95% Confidence Intervals (CI)) and Cox proportional hazard models (Hazard ratio, HR), both adjusted for age, showed significant associations between in-hospital mortality and WBC, CRP, IL-6, MCP-1 and MIP-1α (Table, Figure). Similar findings were observed also for 30 days mortality. Conclusion We demonstrate that factors related to monocyte recruitment and activation, MCP-1 and MIP-1α, are associated with in-hospital and 30-days mortality in CKD patients with Covid-19. In this patient group general inflammatory markers as IL-6 and CRP are also associated with risk of mortality. These data contribute to an increased understanding of the impact of monocyte activation in Covid-19 and may be of value when treatment strategies are evaluated.