Renal Injury and Inflammatory Response in New Onset IgA Nephropathy After Infection With SARS-CoV-2 or COVID-19 Vaccination

Background: After infection with SARS-Cov-2 or vaccination against COVID-19, some patients develop kidney diseases, including minimal change nephrotic syndrome and IgA Nephropathy (IgAN). Here we characterized renal injury and inflammatory response in biopsies from patients with new onset IgAN diagnosed promptly after COVID-19 disease or vaccination. Method(s): Eleven kidney biopsies from patients who developed IgAN after SARSCov-2 infection and 6 from patients with new onset IgAN after vaccination against COVID-19 were diagnosed at Dep. of Nephropathology, FAU Erlangen-Nuremberg. Biopsies from patients with IgAN who had no prior COVID-19 disease (n=10) and zero-time biopsies from transplants (ZB;n=6) served as controls. Serum creatinine was assessed and kidney injury by analysis of podocyte loss, detection of Pax-8 positive parietal epithelial cells on the glomerular tuft and IF/TA. Macrophages and granulocytes were detected by triple staining of CD68, CD163 and myeloperoxidase. Result(s): Significant podocyte loss, as assessed by nephrin staining, was observed in all three IgAN groups compared to ZB, as well as Pax8-positve parietal epithelial cells on glomerular tuft. The serum creatinine, as a marker of kidney function, was on average 1.8-3.5-fold higher in the IgAN groups compared to ZB, but did not reach significance level due to small sample numbers. IF/TA was below 20% in most investigated biopsies. No significant differences in renal function or injury were observed between different IgAN groups. While CD68+CD163+MPO+, CD68+CD163-MPO+ and CD68+CD163+MPO-(M2c-like macrophages) inflammatory cells were significantly increased in both COVID-19 IgAN groups, significant increase of CD68-CD163+MPO-cells compared to ZB control was restricted to IgAN w/o COVID-19 group (11.7+/-8.1 vs 0.8+/-0.9 cells / mm2). CD68+CD163-MPO-M1-like macrophages and CD68-CD163-MPO+ neutrophils tended to be higher in all IgAN groups but failed to reach the level of significance. Conclusion(s): Changes in kidney function and renal damage was comparable in all three investigated IgAN groups independent on experience of COVID-19 or vaccination. Renal macrophage and neutrophil invasion tended to by higher in COVID-19 IgAN groups. However, no significant differences in inflammatory were observed in direct comparisons of IgAN groups.

[COVID-19 effects on the kidney]. / COVID-19-Auswirkungen auf die Niere.

Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV­2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV­2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.

COVID-19 effects on the kidney.

Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV­2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV­2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.

Allograft infiltration and meningoencephalitis by sars-cov-2 in a pancreas-kidney transplant recipient

Introduction: COVID-19 primarily affects epithelia of the upper and lower respiratory tract. Thus, impairment of kidney function has been primarily attributed to secondary effects like cytokine release or fluid balance disturbances so far. Methods: We provide evidence that SARS-CoV-2 can directly infiltrate a kidney allograft. Results: A 69-year old male pancreas-kidney transplant recipient presented to our hospital with COVID-19 pneumonia and impaired pancreas and kidney allograft function. Kidney biopsy was performed showing tubular damage and an interstitial mononuclear cell infiltrate. RT-PCR from the biopsy specimen was positive for SARS-CoV-2, while being negative in a peripheral blood sample. Subsequently, he suffered from two convulsive seizures. Magnetic resonance tomography suggested meningoencephalitis, which was confirmed by SARS-CoV-2 RNA transcripts in the cerebrospinal fluid. Conclusion: The present case demonstrates that SARS-CoV-2 can infiltrate diverse organs. The patient suffered from COVID-19 pneumonia, meningoencephalitis and nephritis. SARS-CoV-2 binds to its target cells through angiotensin-converting enzyme 2, which is expressed in a broad variety of tissues including the lung, brain and kidney. SARS-CoV-2 thereby shares features with other human coronaviruses including SARS-CoV that were identified as pathogens beyond the respiratory tract as well. The present case should provide awareness that extrapulmonary symptoms in COVID-19 may be attributable to viral infiltration of diverse organs.

Monitoring of general immune status and sars-cov-2 reactive t-cell and humoral immunity facilitates the clinical decision in a severe sars-cov-2-associated pneumonia, meningoencephalitis and gastroenteritis in a pancreas-kidney transplant patient

Introduction: The optimal management in transplant recipients with COVID-19 remains uncertain. The main concern is the ability of immunosuppressed patients to generate sufficient immunity for antiviral protection. Methods: Here, we report on immune monitoring facilitating a successful outcome of severe SARS-CoV-2-associated pneumonia, meningoencephalitis, gastroenteritis and acute kidney and pancreas graft failure in a pancreaskidney transplant recipient. Results: Despite the verylownumbersof circulating B-,NK,andT-cells identified in follow up, a strong SARS-CoV-2 reactive T-cell response was observed. Importantly, we detected T cells reactive to Spike,Membrane and Nucleocapsid proteins of SARS-CoV-2 with majority of T-cells showing polyfunctional proinflammatory Th1 phenotype with advanced differentiation stage at all analyzed time points. Antibodies against Spike protein were also detected with increasing titers in follow up. A correlation between cellular and humoral immunity was observed underscoring the specificity of demonstrated data. Conclusion: We conclude that analyzing the kinetics of non-specific and SARS-CoV-2-reactive cellular and humoral immunity can facilitate the clinical decision on immunosuppression adjustment and allow successful outcome as demonstrated in the current clinical case. While the antiviral protection of the detected SARS-CoV-2-reactive T-cells requires further evaluation, our data prove an ability mounting a strong SARS-CoV-2-reactive T-cell response with functional capacity in immunosuppressed patients.

[COVID-19 and kidney involvement]. / COVID-19 und Nierenbefall: Pathologie.

Apart from the pulmonary disease, acute kidney injury is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could also be detected in renal tissue. Patients with chronic kidney disease and on dialysis as well as kidney transplantation patients represent a particularly vulnerable population. The increasing number of patients infected with SARS-CoV­2 has aroused increased interest in the exact pathophysiology and morphology of kidney damage as well as the direct detection of the virus in the kidneys, which in contrast to the lungs is overall more difficult to perform. Meanwhile, data from several large autopsy and kidney biopsy studies are now available. While the detection of SARS-CoV­2 RNA in tissue leads to consistently reproducible results, the use of electron microscopy for visualization of the virus is critically discussed due to various artefacts. The exact and direct effects of SARS-CoV­2 on the kidneys are not yet known in detail and are currently the focus of intensive research.