Chronic norovirus infection and common variable immunodeficiency

Abstract

SummaryChronic infection with norovirus is emerging as a significant risk for patients with immunodeficiency -either primary or secondary to therapeutic immunosuppression. Patients with primary immunodeficiency present a range of pathological responses to norovirus infection. Asymptomatic infections occur and differentiating viral carriage or prolonged viral shedding after self-limiting infection from infection causing protracted diarrhoea can be challenging, due to relatively mild pathological changes that may mimic other causes of diarrhoea in such patients (for instance pathogenic bacteria or parasites or graft-versus-host disease). However, a subset of patients with common variable immunodeficiency (CVID) experience a severe norovirus-associated enteropathy leading to intestinal villous atrophy and malabsorption. Symptomatic infection of up to 8 years has been demonstrated with clinical and histological recovery on viral clearance. Although oral immunoglobulins and nitazoxanide have been used to treat noroviral infections associated with immunosuppression, ribavirin is the only agent to date that has been linked to viral clearance in the Noroviral enteropathy associated with CVID.

Viral infection in primary antibody deficiency syndromes

“…Prolonged shedding times of norovirus have been reported by several studies in both symptomatic and apparently asymptomatic individuals with CVID. Shedding times have been reported by others as long as 1200 days with serial positive faecal samples and gastrointestinal biopsies, while we have recently described a patient infected with the US95/96 strain of norovirus (which circulated until 2002) who was still excreting virus in 2017 . Of particular interest in this regard is the potential association of norovirus with “CVID enteropathy.” This term has been used to describe various pathological entities in CVID patients with diarrhoea, including nonspecific colitis or inflammation resembling classical inflammatory bowel disease.…”

“…However, the term is probably best reserved for patients presenting with malabsorption and villous atrophy, often with intraepithelial lymphocytosis, of unknown cause . Despite histological similarities to coeliac disease, patients do not respond to gluten withdrawal . Affecting approximately 5% of patients with CVID, it is particularly associated with T‐cell defects .…”

17. Cytological diagnosis of medullary carcinoma of thyroid

“…This case illustrates the potential for chronic novovirus infection in patients with CVID. 1,2 Recognition of this condition is critical to the institution of appropriate therapy.…”

Humoral immunodeficiencies: conferred risk of infections and benefits of immunoglobulin replacement therapy

“…[21][22][23] Some patients may benefit from antiviral therapy to clear norovirus infection. 22 Patients are also predisposed to GI infections with Campylobacter jejuni, Salmonella species, and cytomegalovirus (CMV). Surprisingly, despite frequent courses of antibiotics, patients with CVID appear to be at no greater risk than the general population of infection due to Clostridium difficile.…”