Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency.
Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency.
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DOI：
10.1093/infdis/jiac085
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发表时间：
2022-11-11
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--
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免疫受损的人可能会慢性感染诺沃克病毒，但目前还没有有效的抗病毒疗法。对一名长期感染诺如病毒的免疫功能低下的患者，先后评估了硝唑尼特、利巴韦林、干扰素α-2a和经鼻十二指肠注射免疫球蛋白的治疗效果。作为支持，这些成分也被应用于在体外肠道培养中测量诺沃克病毒的抑制。在每次治疗期间，检测粪便和血浆样本中的病毒RNA水平，并对病毒基因组进行测序。没有一种抗病毒药物能降低粪便或血浆中的病毒RNA水平。然而，在利巴韦林治疗期间，病毒基因组突变的积累增加。在体外，我们观察了干扰素α-2a对病毒复制的影响，并用免疫球蛋白和诺如病毒感染后的抗血清在体外有效地中和了一株基因相关株。同意的是，在注射免疫球蛋白后，患者的感染症状消失了。肠道肠样培养为评估抗病毒药物和免疫球蛋白的中和潜力提供了一个相关的系统。我们成功地用免疫球蛋白治疗了一名慢性感染患者，尽管其他人报道了不同的结果。这一案例研究为诺沃克病毒的治疗提供了深入、多方面的探索，可作为诺沃克病毒治疗的进一步研究的指导。一名慢性诺如病毒感染的免疫低下患者被成功地用鼻十二指肠注射免疫球蛋白治疗，而硝唑西尼、利巴韦林和干扰素α-2a无效。体外肠样培养证实免疫球蛋白中和了G2.4型诺沃克病毒。
Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available. 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. 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. 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. An immunocompromised patient with a chronic norovirus infection was successfully treated with nasoduodenally administered immunoglobulins while nitazoxanide, ribavirin, and interferon alpha-2a had no effect. In vitro enteroid cultures confirmed GII.4 norovirus neutralization by immunoglobulins.
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