Intrinsic Kidney Pathology Following COVID-19 Infection in Children and Adolescents: A Systematic Review

Introduction: COVID-19 infections resulting in pathological kidney manifestations have frequently been reported in adults since the onset of the global COVID-19 pandemic in December 2019. Gradually, there have been an increased number of COVID-19-associated intrinsic kidney pathologies in children and adolescents reported as well. The pathophysiological mechanisms between COVID-19 and the onset of kidney pathology are not fully known in children; it remains a challenge to distinguish between intrinsic kidney pathologies that were caused directly by COVID-19 viral invasion, and cases which occurred as a result of multisystem inflammatory syndrome due to the infection. This challenge is made more difficult in children, due to the ethical limitations of performing kidney biopsies to reach a biopsy-proven diagnosis. Although previous systematic reviews have summarized the various pathological kidney manifestations that have occurred in adults following acute COVID-19 infection, such reviews have not yet been published for children and adolescents. We describe the results of a systematic review for intrinsic kidney pathology following COVID-19 infection in children and adolescents. Methods: A systematic literature search of published data up until 31 October was completed through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Research articles reporting new-onset or relapsed intrinsic kidney pathology in children or adolescents (<= 18 years) following acute COVID-19 infection were included for qualitative review. COVID-19 infection status was defined by a positive result from a RT-PCR, or nuclear antibody testing. Only full-text articles published in the English language were selected for review. Results: Twenty-nine cases from fifteen articles were included in the qualitative synthesis of this systematic review. Nephrotic syndrome, as an umbrella condition, appeared as the most frequently observed presentation (20 cases) with disease remission noted in all cases with steroid treatment. Other cases included numerous glomerulonephritides, such as acute necrotizing glomerulonephritis, MPO vasculitis and collapsing glomerulopathy, and thrombotic microangiopathies, such as aHUS. For patients with transplanted kidneys, T-cell-mediated rejection and mild tubular interstitial infiltration were noted following testing positive for COVID-19. There were no mortalities reported in any of the included cases, although two patients remained dialysis dependent at hospital discharge. Conclusion: This systematic review highlights the various intrinsic pathological kidney manifestations in children and adolescents as a result of acute COVID-19 infection. The clinical timeline and presentation of these cases support the mechanistic hypothesis between COVID-19 infection and the onset of intrinsic kidney pathologies within this context. The progressive introduction of vaccination programs for children and adolescents may hopefully reduce the severity of COVID-19-associated illnesses, and pathological kidney manifestations in this population.