Cited 5 times since 2022 (3.3 per year) source: EuropePMC The Journal of infectious diseases, Volume 226, Issue 10, 1 1 2022, Pages 1781-1789 Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency. van Kampen JJA, Dalm VASH, Fraaij PLA, Oude Munnink BB, Schapendonk CME, Izquierdo-Lara RW, Villabruna N, Ettayebi K, Estes MK, Koopmans MPG, de Graaf M
Background
Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available.
Methods
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.
Results
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.
Conclusions
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.
