A Decade of Chronic Norovirus Infection Surveillance at the National Institutes of Health Clinical Research Center: Clinical Characteristics, Molecular Epidemiology, and Replication.

Abstract

Noroviruses are an important viral cause of chronic diarrhea in immunocompromised individuals. We collected norovirus-positive stool samples (n = 448) from immunocompromised patients (n = 88) at the National Institutes of Health (NIH) Clinical Research Center from 2010 to 2022. We assessed norovirus molecular epidemiology and infectivity in human intestinal enteroid (HIE) monolayers and clinical characteristics of the cohort. Noroviruses were genetically diverse: both genogroup I (GI.2, GI.5 and GI.6) and genogroup II (GII.1-GII.4, GII.6, GII.7, GII.12, GII.14, and GII.17) genotypes were detected, with GII.4 variants (Osaka, Apeldoorn, Den Haag, New Orleans, and Sydney) predominant (51/88 [57.9%]). Viruses belonging to the GII.4 Sydney variant group that replicated in HIEs (n = 9) showed a higher fold-increase in RNA genome copies compared to others that replicated. Chronic norovirus infection was documented in thirty-nine patients with shedding levels ranging from 104 to 1011 genome copies/g of stool. The majority (32/39 [82%]) had clinical evidence of an inborn error of immunity (13 identified monogenic diseases), most with combined immunodeficiency (15 of 32) or common variable immunodeficiency (11 of 32). Genetically and biologically diverse noroviruses established chronic infection in NIH patients with both inborn and acquired immunologic defects.