COVID-19-associated nephropathy (COVAN): An emerging entity of severe viral podocyte injury and collapsing glomerulopathy in kidney biopsies

ABSTRACT

Background: COVID19 caused by novel Coronavirus SARS-COV-2 initially presenting primarily as a respiratory illness, is now known to affect several organ systems as part of multiorgan failure including acute kidny injury (AKI), some cases also manifesting nephrotic range proteinuria or syndrome. Methods: 10 renal biopsies from 6 institutions (1 transplant) performed in April-May 2020 were processed for light microscopy, immunostaining (IS) and electron microscopy (EM) for clinco-pathologic analysis. Results: The 10 patients ranged from 25-73 years (Mean 43), malefemale 55, 8 African American, 1 Hispanic, 1 Asian Indian, having pre-existing co-morbidities of hypertension (7), Diabetes mellitus (5), obesity (9), presenting with AKI (10), nephrotic syndrome (9), proteinuria ranging from 1.5-25g/24hrs, lung symptoms or pneumonia (7), fever (5). SARS-COV-2 RT-PCR positive (7), IgG antibody positive (2), both negative (1). All kidney biopsies showed widespread acute tubular injury with focal necrosis, 9 with typical features of segmental/global collapsing glomerulopathy in 10-53% of glomeruli, global glomerulosclerosis (0-35%), focal tubular microcystic changes (8), patchy (7) or diffuse (2) active tubulointerstitial inflammation and scarring (10-40%), focal & diffuse peritubular capillary inflammation, moderate vascular sclerosis anddiabetic kidney disease in 2. No immune deposits were localized by IS. By EM, varied glomerular capillary wall wrinkling and collapse with segmental or global loss of patency (7), total foot process effacement (7), with hyperplastic and vacuolated epithelial cells having protein droplets are noted. The endothelial cells are variably swollen, with tubuloreticular inclusions in 2. Viral particles are identified within cells of glomeruli and tubulointerstitium, scattered or in clustesr in the cytoplasm and endoplasmic reticulum vesicles, confirmed by IS. Conclusions: The constellation of typical glomerular collapsing features with tubulointerstitial findings and localization of virus by EM, suggests a distinct viral associated nephropathy, reminicent of HIV associated nephropathy. A role for viral cytopathic effect, cytokines and underlying APOL1 gene variants could be considered.