ABSTRACT
Background: COVID-19 has been identified as a disease causing respiratory failure but is now known to affect the kidneys among other organs. Several studies among COVID-19 patients have shown a significant association between acute kidney injury (AKI) and mortality. There is limited data examining if the effect of AKI on mortality is different across variants. The main objective of this study is to examine the association between AKI and in-hospital mortality among COVID-19 pneumonia (PNA) patients during the original strain and the delta variant. Method(s): Data was obtained from a retrospective analysis of patients hospitalized with COVID-19 PNA from March 2020 until March 2021. The database had two cohorts: the original strain and the delta variant. The presence of AKI was confirmed by an examination of medical records for 612 patients using the AKIN criteria (creatinine >=0.3 mg/dL above baseline). Chronic kidney disease was defined by estimated Glomerular Filtration Rate (eGFR) calculated using the CKD-EPI 2021 equation. Logistic regression was used to estimate relative risk (RR) for mortality using factors in Table 1. Result(s): AKI was present in 414 patients (67.6%). Of the 612 patients reviewed, there were 443 survivors and 169 non-survivors at discharge. Among the non-survivors, there were a higher proportion of AKI (84%) and males (64%) and a lower proportion of African Americans (30%). The non-survivors were younger (67 years) and had a lower eGFR (37 mL/min). Logistic regression results are shown in Table 1. Conclusion(s): Analyses showed that among patients hospitalized with COVID-19 PNA, the RR of in-hospital mortality was 3.28 times higher for those with AKI compared to those without AKI. We found no significant difference for in-hospital mortality between the two cohorts when adjusted for presence of AKI. Other findings showed that males may have a greater risk of mortality as compared to females and those of African American race may have a potential survival advantage. (Table Presented).
ABSTRACT
Background: Prior studies demonstrated glomerular tuft staining for annexin A3 (Anxa3), a marker of parietal epithelial cells (PECs), and cathepsin C (Ctsc), a master regulatory protease, distinguishing primary collapsing glomerulopathy (CG) from other glomerular diseases. We hypothesized these staining patterns would differentiate COVID-19 associated CG (COVID-19+/CG+) from COVID-19(+) without CG (COVID-19+/CG-). Method(s): Biopsy sections used were from patients with COVID-19 infections and a pathologist-based tissue diagnoses including CG (COVID-19+/CG+;n=4) or lacking CG diagnosis (COVID-19+/CG-;n=6) were stained for Anxa3 and Ctsc using published protocols. HIVAN-associated CG (n=4) biopsies were used as a secondary CG control. Historical controls data for non-CG biospies (PMID:32561683). Glomerular staining was tabulated as for PEC staining, phenotypic characteristics of normal and activated (enlarged nuclei, hypertrophic/enlarged cuboidal shape cells, vacuolization) PECs, and for glomerular tuft to Bowman's capsule adhesions or cellular PEC bridges. Globally scarred glomerulii were omitted from analysis. Serial section staining was used to demonstrate Anxa3 and Ctsc co-localization. Differences in the mean (i) number of glomeruli staining OR (ii) glomerular tuft area stained for Anxa3 and Ctsc per biopsy were compared by one-tailed t-test assuming an increase in staining in CG over non-glomerular disease. A p-value <0.05 was used for statistical significance. Result(s): All COVID-19+/CG+ and HIVAN patients with CG demonstrated extensive Anxa3 and Ctsc glomerular tuft staining. The frequency of glomerular tuft Anxa3 and Ctsc staining and percent glomerular area was significantly (p<0.05) increased in biopsies with COVID-19+/CG+, compared to COVID-19+/CG- (log2FC 2.8-2.9). No statistical difference in frequency or area stained for Anxa3 and Ctsc was observed between COVID-19+/CG+ and HIVAN-associated CG. Conclusion(s): Anxa3 and Ctsc glomerular tuft expression is increased significantly in COVID-19 and HIVAN patients with CG, mirroring our findings in primary CG. These data support the hypotheses that (a) migration of activated PECs into the glomerular tuft is a prevalent event in both primary CG and virus-associated secondary CG, and (b) glomerular Anxa3 or Ctsc may be theragnostic biomarkers of CG.