Toward Personalized Medicine: The Effect of Treatment of Chronic Enterovirus Diarrhea in an Immunocompromised Patient and the Correlation With In Vitro Models
Moreni, Giulia Calitz, Carlemi Koen, Gerrit van Eijk, Hetty Johannesson, Nina De Ruijter, Jamy Benschop, Kimberley SM Cremer, Jeroen Pajkrt, Dasja Sridhar, Adithya
Moreni, Giulia
Calitz, Carlemi
Koen, Gerrit
van Eijk, Hetty
Johannesson, Nina
De Ruijter, Jamy
Benschop, Kimberley SM
Cremer, Jeroen
Pajkrt, Dasja
Sridhar, Adithya
Series / Report no.
Open Access
Type
Journal Article
Article
Article
Language
en
Date of publication
2025-04-10
Year of publication
Research Projects
Organizational Units
Journal Issue
Title
Toward Personalized Medicine: The Effect of Treatment of Chronic Enterovirus Diarrhea in an Immunocompromised Patient and the Correlation With In Vitro Models
Translated Title
Published in
Open Forum Infect Dis 2025; 12(5):ofaf212
Abstract
Enteroviruses (EV) usually cause acute, mild, self-limiting disease. Chronic infections with EVs are rare, and typically occur in patients with immunodeficiency, posing a high risk of severe outcomes. We report a rare case of chronic diarrhea caused by coxsackievirus A1 (CVA1) (from EV-C species) infection in a patient with a common variable immunodeficiency, who was on treatment with pooled intravenous immunoglobulin (IVIG) from the Netherlands. To explore treatment options, we assessed the presence of neutralizing antibodies (nAbs) against CVA1 in pooled IVIG from South Africa, where EV-Cs are prevalent, and tested the antiviral efficacy of US Food and Drug Administration-approved drugs like fluoxetine, itraconazole, ribavirin, and remdesivir (RDV) against CVA1 in vitro. Both Dutch and South African IVIG showed low nAb titers against CVA1. The patient, treated with Dutch IVIG, also received a combination of amantadine and fluoxetine, which were discontinued due to side effects. Among the drugs tested, only RDV significantly inhibited CVA1 replication in rhabdomyosarcoma (RD) cells. This in vitro efficacy was not reflected by a favorable clinical response after treatment of the patient with RDV. In concordance with unfavorable antiviral response in the patient, preliminary tests on a co-culture model containing isogenic human intestinal cells and intestinal fibroblasts showed no significant reduction in CVA1 RNA copies after RDV administration. In conclusion, our results showed that repurposing of drugs that have shown in vitro efficacy does not translate well to the patients, and this is also reflected in a more physiologically relevant model of the human intestine.