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- Title
Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency.
- Authors
van Kampen, Jeroen J A; Dalm, Virgil A S H; Fraaij, Pieter L A; Oude Munnink, Bas B; Schapendonk, Claudia M E; Izquierdo-Lara, Ray W; Villabruna, Nele; Ettayebi, Khalil; Estes, Mary K; Koopmans, Marion P G; de Graaf, Miranda
- Abstract
<bold>Background: </bold>Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available.<bold>Methods: </bold>Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced.<bold>Results: </bold>None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation of virus genome mutations. In vitro, an effect of interferon alpha-2a on virus replication was observed and a genetically related strain was neutralized effectively in vitro using immunoglobulins and post-norovirus-infection antiserum. In agreement, after administration of immunoglobulins, the patient cleared the infection.<bold>Conclusions: </bold>Intestinal enteroid cultures provide a relevant system to evaluate antivirals and the neutralizing potential of immunoglobulins. We successfully treated a chronically infected patient with immunoglobulins, despite varying results reported by others. This case study provides in-depth, multifaceted exploration of norovirus treatment that can be used as a guidance for further research towards norovirus treatments.
- Subjects
COMMON variable immunodeficiency; NOROVIRUS diseases; VIRAL genomes; IMMUNOGLOBULINS; IMMUNE serums
- Publication
Journal of Infectious Diseases, 2022, Vol 226, Issue 10, p1781
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiac085