Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains.

BACKGROUND: Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients. METHODS: Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups. RESULTS: The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls. CONCLUSIONS: Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.

De novo collapsing glomerulopathy in a pediatric kidney transplant recipient with COVID-19 infection.

The negative impact of COVID-19 on adults with underlying chronic kidney disease, including kidney transplant recipients, has been well documented. Children have a less severe presentation and better prognosis compared to adults. However, little is known regarding the spectrum of COVID-19 infection in children and adolescents with underlying autoimmune disorders necessitating solid organ transplant and long-term immunosuppressive therapy. Case Report. An adolescent male developed end-stage kidney disease secondary to microscopic polyangiitis requiring a living-donor kidney transplant. Six years later, he developed antibody-mediated rejection of his kidney transplant. During his rejection treatment course, he contracted SARS-CoV-2 and developed new-onset nephrotic syndrome with severe acute kidney injury. Kidney transplant biopsy revealed de novo collapsing focal segmental glomerulosclerosis on a background of chronic active antibody mediated rejection. Immunostaining for SARS-CoV-2 on the biopsy specimen demonstrated positive staining of the proximal tubular epithelium consistent with intra-renal viral infection. Pulse corticosteroids, intravenous immunoglobulin, and temporary reduction of anti-metabolite therapy resulted in successful recovery with return of graft function back to pre-infection baseline. This case highlights the clinical conundrum of treating kidney transplant recipients with active rejection in the midst of the COVID-19 pandemic. Pediatric kidney transplant recipients can develop severe COVID-19-related kidney complications. Judicious immunosuppression modulation is necessary to balance infection and rejection risk.