key: cord-0740565-bm69dsj4 authors: Suso, Andrea S.; Mon, Carmen; Alonso, Irene Oñate; Romo, Karen Galindo; Juarez, Rosa Camacho; Ramirez, Carolina Lentisco; Sanchez, María Sanchez; Valdivia, Verónica Mercado; Librero, Milagros Ortiz; Pala, Aniana Oliet; Marcos, Olimpia Ortega; Herrero Berron, Juan C.; Pascual, Alejandro title: IgA Vasculitis with Nephritis (Henoch-Schönlein purpura) in a COVID-19 patient date: 2020-08-20 journal: Kidney Int Rep DOI: 10.1016/j.ekir.2020.08.016 sha: 5ccc0ba359256eb866b4af08d27571defe69a6aa doc_id: 740565 cord_uid: bm69dsj4 nan In December 2019, a series of pneumonia cases of unknown etiology, which were epidemiologically linked to a seafood market, was reported in Wuhan, Hubei province, China. The disease has rapidly spread around the world, becoming a global pandemic. A coronavirus, which was named 2019 novel coronavirus (2019-nCov), was isolated from respiratory tract samples 1 and later identified as SARS-CoV-2. The name of the disease was officially changed to Coronavirus Disease 2019 (COVID-19). Pulmonary involvement with alveolar damage and acute respiratory failure has been the most remarkable clinical condition of COVID-19 patients. However, there is increasing evidence that this virus also affects other organs, being the kidney injury relatively common in this infection and associated with increased mortality rate 2 . In a large prospective cohort of 701 COVID-19 patients in China, 44% had proteinuria and 27% had hematuria on admission. During hospitalization, 5.1% of them developed acute kidney injury 2 . We report a patient who developed systemic symptoms and renal involvement after being hospitalized due to a COVID-19 infection. A mesangial proliferation and IgA deposits in the glomeruli were seen at the kidney biopsy. We report a 78-year-old man with a medical history of moderate alcohol consumption, essential hypertension treated with losartan, dyslipidemia, moderate aortic valve stenosis, and bladder cancer treated with transurethral resection(currently in remission). His baseline serum creatinine, measured two months before presentation, was 0.78 mg/dl. Proteinuria and microhematuria were negative in previous urinalysis. He was hospitalized on April 4 th , 2020 for bilateral pneumonia due to COVID-19, based on a positive reverse transcriptase-polymerase chain reaction test for SARS-CoV-2 in a nasopharyngeal swab. He was treated with hydroxychloroquine, lopinavir/ritonavir, J o u r n a l P r e -p r o o f dexamethasone, ceftriaxone, azithromycin, and tocilizumab due to respiratory failure and significant inflammatory parameters elevation, including IL-6. He was discharged on April 17th, and three weeks later he returned to the Emergency Department with wrist arthritis and lower limb purpura ( Figure 1 ). Cutaneous vasculitis was diagnosed during a skin biopsy and, consequently, a short-term regimen of prednisone 40 mg/day was prescribed. In addition, proteinuria and hematuria with dysmorphic red blood cells were detected in a urinalysis. The patient was promptly referred to our Nephrology Department. A physical examination showed a blood pressure of 160/90 mmHg. His heart sounds were normal with a systolic aortic murmur. He also had lower extremity pitting edema. The rest of the examination did not reveal anything unusual. On admission his serum creatinine was 1.35 mg/dl, he had hypoalbuminemia, massive proteinuria (10 g/day), and hematuria with 60% of dysmorphic red blood cells. In addition, serologic testing for hepatitis C and HIV were negative, with positive hepatitis B surface antibody. Serum complement testing for C3 and C4 were normal. Anti-nuclear antibodies, anti-DNA antibodies, anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane (GBM) antibodies, and cryoglobulin were all negative. Serum and urine protein electrophoresis and immunofixation were negative for monoclonal protein. Immunoglobulin's value was normal, except for a mild hypogammaglobulinemia. A nasal swab for SARS-CoV-2 was repeated on this admission resulting negative, with positive anti-SARS-CoV-2 by chemiluminescent immunoassay. Laboratory results are detailed in Table 1 . A kidney biopsy was performed to assess the patient's renal disease. A total of 7 glomeruli were identified, one of which was sclerotic. Four glomeruli demonstrated segmental mesangial expansion with hypercellularity, one them showed a synechia with Bowman´s capsule. Epithelial crescents were seen in two glomeruli, one of which obliterated the glomerular capillary lumens. No tubular or interstitial abnormalities were observed. He persisted with gross proteinuria (6 g/day) and hematuria. The cutaneous purpura markedly improved. The patient continues with oral prednisone upon discharge. We hereby report a patient who developed cutaneous vasculitis, arthritis, and nephritic syndrome with hypertension, massive proteinuria (10 g/day) and mild acute kidney injury, after a pneumonia COVID-19. In addition, diffuse mesangial proliferation with IgA mesangial staining was confirmed in a kidney biopsy, as well as crescent deposits in 28% of the glomeruli. To our knowledge, this is the first reported case of IgA vasculitis related to COVID-19. The first glomerular disease described in the setting of COVID-19 was collapsing glomerulopathy. All these patients were reported to have severe acute kidney injury and massive proteinuria 3,4,5,6 . Among renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China, one case showed IgA staining in the mesangial area as well as capillary wall, J o u r n a l P r e -p r o o f associated with mesangial and subendothelial deposits by electron microscopy 7 . The medical history and clinical manifestations of that case were not described. IgA vasculitis (Henoch-Schönlein purpura) is a small-vessel vasculitis mediated by immune-complexes deposits containing IgA. It is usually preceded by respiratory tract infections and its association with multiple microorganisms is known, including different viruses 8 . The main clinical manifestations are nonthrombocytopenic purpura, arthritis/arthralgia, and abdominal pain 8,9,S1,S2 . Renal involvement occurs in 40-50% of patients 9,S2 , being more severe among the adult population S1 . A recent meta-analysis of patients with IgA vasculitis showed that older age at onset, lower glomerular filtration rate, nephrotic or nephritic syndrome, and kidney biopsy with crescentic nephritis (ISKDC grades III-V) were significant risk factors associated with poor outcomes S3 . It has been proposed that increased level of circulating form of IgA1 with aberrant glycosylation (Gd-IgA1) plays a role in the pathogenic mechanism of IgA nephritis. This variant of IgA1 would be able to antigenically recognize structures of some microorganisms and form circulating complexes. Through specific receptors they would be deposited in the mesangium, inducing the activation of the mesangial cells, which would finally lead to renal damage. It has also been hypothesized that mucosal infections lead to upregulation of IL-6, which could lead to development of Gd-IgA1 by altering the glycosylation machinery 9 , thereby perpetuating kidney damage. In our patient´s case, he previously had a significant elevation of inflammatory biomarkers due to the bilateral COVID-19 pneumonia, with PCR value of 129 mg/L (reference range 0-So far, the pathogenic mechanism of kidney damage associated with COVID-19 is not completely understood. The renal involvement is considered to be multifactorial. The possible underlying mechanisms are direct kidney infection through ACE-2 receptors expressed in tubular cells 7,S4,S5 and podocytes 4,7,S5 as well as an indirect mechanism through the cytokine release syndrome characteristic of patients with COVID-19. Cytokine storm appears to be responsible for endothelial S6 and glomerular 3,5,6 damage, as described in collapsing glomerulopathy cases reported so far. Although future research will be needed to determine the role of SARS-CoV-2 in the pathogenesis of IgA Vasculitis, its frequent association with respiratory viruses and the recent COVID-19 pneumonia in our patient suggest that this case might be the first IgA Vasculitis related to COVID-19 (Table 2) . We report a patient who developed an IgA Vasculitis with nephritis after he had been hospitalized for a COVID-19. This case highlights that SARS-CoV-2 could be the trigger for IgA nephritis, which calls for a need to determine a specific management for such cases. However, we cannot rule out that the IgA Vasculitis is unrelated to the virus in this patient, and was disclosed in the setting of COVID-19. All the authors declared no competing interests. Supplementary material can be found on the KI Reports' web site (PDF). J o u r n a l P r e -p r o o f Clinical features of patients infected with 2019 novel coronavirus in Wuhan Kidney disease is associated with in-hospital death of patients with COVID-19 Collapsing Glomerulopathy in a Patient With Coronavirus Disease 2019 (COVID-19) Collapsing glomerulopathy in a COVID-19 patient Acute Kidney Injury Due to Collapsing Glomerulopathy Following COVID-19 Infection Tubuloreticular inclusions in COVID-19-related collapsing glomerulopathy Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Association of the infectious triggers with childhood Henoch-Schönlein purpura in Anhui province New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura) SARS-CoV-2 could be a trigger for IgA Vasculitis Mucosal infections lead to upregulation of IL-6 that results in the circulating form of IgA with aberrant glycosylation SARS-CoV-2 was not detected by electron microscopy in our patient, suggesting that glomerular damage could appear in the setting of cytokine storm, rather than a direct viral infection SARS-Cov-2, severe acute respiratory syndrome-novel Coronavirus 2; IL-6