#799 M1-M2 macrophages in postmortem biopsies from patients with acute kidney injury with COVID-19 compared to pulmonary bacterial sepsis
Authors: Hurtado Angela Maria Cordoba , Ortiz Rafael Valdez , Abraham Virgilia Soto , Madero Magdalena , Merino-Lopez Maribel , Navarro Lucia Monserrat Perez 
Published: May 2024

Abstract

Background and Aims
AKI associated with COVID19 is highly prevalent; there is controversy if it is similar to AKI in sepsis of bacterial origin. Macrophage differentiation M1-M2 is a predictor of outcomes. Macrophage expression in kidney tissue is not known in patients with severe COVID19 compared to sepsis of bacterial origin. We compare the tissue expression of macrophage differentiation markers M1-M2, through the expression of CD163, CD68, INOS in postmortem biopsies from patients with C19-LRA and S-AKI.

Method
Observational, comparative, analytical study.

Results
49 subjects were analyzed, 39(COVID-19) and 10(pulmonary sepsis of bacterial origin). No significant baseline differences. The degree of AKI had no difference between groups, but in COVID-19 there were severe grades 2-3, compared to bacterial sepsis p = 0.89. Histopathologically there were no differences with the degree of LTA and IFTA. NTI was more frequent in bacterial sepsis vs COVID-19 100%/12.8% (p &lt; 0.001). When comparing macrophage expression we found that the expression of M1(INOS) was not different, the expression of M2(CD163) was higher in patients with bacterial Sepsis with 100% corresponding to severe grade vs 28.2% in patients with COVID19 p&gt;0.001. The classification between degrees of AKI were statistically positive for patients with COVID19 and CD163 with r2: 0.26 and CD68 with r2: 0.36 with p 0.01 and 0.02 respectively. The classification with NTI was positive in COVID19 and bacterial sepsis with an r2: 0.34 for CD163, r2: 0.11 for CD68 p &lt; 0.001. Regarding IFTA in COVID-19 and bacterial sepsis, r2: 0.12 for CD163, r2: 0.11 for CD68 (p 0.01 and 0.03 respectively). Steroid use was negatively correlated on the COVID19 with bacterial sobreinfectión + the bacterial sepsis group with the marker CD163 with r2: 0.23 p = 0.005. The association between moderate and severe positivity for CD68+ and NTI had an OR of 15.5 (CI 3.21-64.6) p = 0.001.

Conclusion
The 2 groups had a similar severity, AKI in COVID19 was more severe compared to bacterial Sepsis, histologically there were no differences in AKI, but there was a marked difference in the presence of NTI, this being more frequent in the bacterial sepsis group. Findings different from those reported in other bibliographies where the degree of acute kidney injury was higher in COVID19. When comparing the dominant macrophage phenotype, iNOS(M1) had no difference between the groups, on the contrary CD163(M2) was different, with severe staining in all cases with bacterial sepsis, similar to what was seen with NTI and lower degrees of clinical severity of LRA. When evaluating the correlations we found a moderate correlation between the presence of NTI and CD163(M2), mild for NTI and CD68(M0). Finding suggestive of the macrophage role especially low M2 in the context of NTI, it is important to note that those with CD163 had lower degrees of acute kidney injury, more reported as KDIGO1, which is reproducible taking into account other studies in which the CD163(M2) was associated with higher degrees of repair, while their depletion was associated with greater severity of kidney injury. With respect to the treatment established, there was a slight correlation between the use of steroids in the population with bacterial superinfection with CD163(M2), in a recent study it was shown that the use of steroids could induce the repopulation of CD163.