Nephrotic syndrome following COVID-19 vaccination: a systematic review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection has caused significant morbidity and mortality. Vaccines produced against this virus have proven highly effective. However, adverse events following vaccination have also been reported. One of them is nephrotic syndrome, that can be associated with different pathologic pictures. This review aims to provide a wider understanding of incidence, etiopathogenesis, and management of nephrotic syndrome following vaccination against SARS-CoV-2. METHODS AND RESULTS: A literature search was undertaken using appropriate keywords in various databases like PubMed, Google Scholar, Europe PMC, and Science Direct. Twenty-one articles were included following qualitative assessment. Data of 74 patients from these articles were included. DISCUSSION: The pathogenesis of nephrotic syndrome following COVID vaccination has been widely attributed to the activation of angiotensin-converting enzyme-2 receptors, leading to podocyte effacement. Relapses have also been reported in patients with prior history of nephrotic syndrome following COVID-19 vaccination. A renal biopsy is necessary to identify the histopathological picture. Management of COVID-19 vaccine-induced nephrotic syndrome was mainly reported as successfully attainable with corticosteroids and supportive management. CONCLUSION: Further investigations will help in establishing an early diagnosis and salvaging kidney function.

Infection of neonatal mice with the murine norovirus strain WU23 is a robust model to study norovirus pathogenesis.

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe, with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. The development of the murine norovirus (MNV) model nearly two decades ago has facilitated progress in understanding host-norovirus interactions and norovirus strain variability. However, MNV strains tested thus far either do not cause intestinal disease or were isolated from extraintestinal tissue, raising concerns about translatability of research findings to human norovirus disease. Consequently, the field lacks a strong model of norovirus gastroenteritis. Here we provide a comprehensive characterization of a new small animal model system for the norovirus field that overcomes prior weaknesses. Specifically, we demonstrate that the WU23 MNV strain isolated from a mouse naturally presenting with diarrhea causes a transient reduction in weight gain and acute self-resolving diarrhea in neonatal mice of several inbred mouse lines. Moreover, our findings reveal that norovirus-induced diarrhea is associated with infection of subepithelial cells in the small intestine and systemic spread. Finally, type I interferons (IFNs) are critical to protect hosts from norovirus-induced intestinal disease whereas type III IFNs exacerbate diarrhea. This latter finding is consistent with other emerging data implicating type III IFNs in the exacerbation of some viral diseases. This new model system should enable a detailed investigation of norovirus disease mechanisms.

Environmentally-triggered contraction of the norovirus virion determines diarrheagenic potential.

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course mirroring human norovirus disease. Using this robust pathogenesis model system, we demonstrate that virulence is regulated by the responsiveness of the viral capsid to environmental cues that trigger contraction of the VP1 protruding (P) domain onto the particle shell, thus enhancing receptor binding and infectivity. The capacity of a given MNV strain to undergo this contraction positively correlates with infection of cells expressing low abundance of the virus receptor CD300lf, supporting a model whereby virion contraction triggers infection of CD300lflo cell types that are responsible for diarrhea induction. These findings directly link environmentally-influenced biophysical features with norovirus disease severity.