Chronic sequelae and severe complications of norovirus infection: A systematic review of literature.

Norovirus causes an estimated 18% of all cases of acute gastroenteritis worldwide and is found to be associated with mortality. To create a first overview of severe complications and chronic sequelae of norovirus infections, a systematic review of literature was performed. Of 3928 individual hits, 176 publications remained for data extraction. Study periods varied between 1974 and 2017, though strongly skewed towards the last decade (n = 122, 70%). Countries of studies were worldwide, though Africa, and Carribean, Central and South America were underrepresented. Strong evidence was found for chronic diarrhea in immunocompromised patients, affecting 9%-100% of investigated cohorts. The duration of chronic diarrhea varied from four weeks up to nine years, leading to either wasting, weight loss or failure to thrive in a third of the reported cases (224). Other complications with significant evidence were necrotizing enterocolitis (NEC) in preterm infants associated with norovirus infection (8 papers), and benign infantile convulsions with gastroenteritis (BICG; 19 papers). Studies on norovirus infection and inflammatory bowel disease (IBD) mostly concluded against this association (5 of 7). The remaining papers mentioned a large variety of possible sequelae or complications. Based on the available literature, chronic norovirus diarrhea is the major sequela of norovirus infection in primary immune deficient, oncologic and transplant patients. Norovirus infection - like other gastrointestinal pathogens - can cause a range of sequelae and complications, and should be considered in the differential diagnosis of these manifestations.