High Prevalence of Prolonged Norovirus Shedding and Illness among Hospitalized Patients: A Model for In Vivo Molecular Evolution

Abstract

During a 2-year survey in an academic hospital, 8 (8.4%) of all norovirus (NoV)-positive patients showed prolonged norovirus illness and shedding (duration, 21-182 days). All patients had underlying illnesses, resulting in some level of immunodeficiency in 5. Four patients were admitted to the hospital with gastroenteritis, 2 acquired norovirus while hospitalized, and 2 were outpatients. Genotypes GII.4 and GIIb-GII.3 were found. Reinfection occurred in 3 patients. Full capsid sequences were determined from strains detected in sequentially collected stool specimens to study evolution. The greatest number of amino acid mutations in a given patient was 11; they were detected in NoV isolates recovered over a 119-day period and were mapped to positions at or near putative antigenic sites. In the patient with most severe immune dysfunction, only 5 amino acids mutated over 182 days, suggesting immune-driven selection. The severe impact on patients and hospitals and the potential role of prolonged shedders as a reservoir for viral antigenic variants lead us to stress the importance of confinement of outbreaks of NoV infection that occur in hospitals.

Chimpanzees as an animal model for human norovirus infection and vaccine development

“…Changes in the norovirus genome over time have been previously described in samples collected from immunocompromised patients infected with the virus, but not during the entire course of an infection (42). Most of the nonsynonymous amino acid changes observed 12-34 dpi were located in surface-exposed regions of the outermost viral capsid region, P2.…”

Norovirus vaccines: Correlates of protection, challenges and limitations

“…59,60 More than 90% of individuals are seropositive to NoV by the time they reach adulthood; however, the role of pre-existing immunity is still not fully understood when related to protection or reducing the risk of acquiring new NoV infections. 15 The fact that asymptomatic infection occurs at an early age as reported by outbreak and human challenge studies 48,[61][62][63] provides critical insight to the potential reservoir of transmission at an early age and its clear implication on the need for an effective vaccine.…”

“…64,65 Long-term shedding was described among children less than 6 months, 63 in elderly, 64 hospitalized and immunosuppressed patients. 62 Predictive modeling of viral shedding classifies shedding into regular shedding with a mean of 14-16 d and long shedding with a mean ranging between 105 and 136 d 66 Recent studies suggest the lack of a significant difference of virus shedding between asymptomatic and symptomatic NoV infections despite the individual variation in virus peak levels detected in stool. 67,68 This study reported different viral shedding activities as compared to previous reports 7,69 whereby infected adults shed virus during a range of 15-56 d. The authors argued that the variable results in NoV shedding might be due to the use of different PCR techniques to detect the virus.…”

Noroviruses: Recent Updates

“…Chronic shedding of NoVs occurring over two weeks after clearance of symptoms may have an important role in outbreaks in variable settings [26].…”