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Rotavirus-associated hospitalization was significantly associated with subsequent autoimmune disease during childhood, according to a large population-based cohort study from South Korea.

Over a mean follow-up of 12 years, children who were hospitalized for rotavirus had a significantly greater risk for autoimmune disease compared with those who weren't (HR 1.24, 95% CI 1.19-1.28), reported Man Yong Han, MD, of CHA Bundang Medical Center at the CHA University School of Medicine in Seongnam, and colleagues.

In a multivariable stratified analysis using more stringent definitions for exposure and outcomes, rotavirus-associated hospitalization was also linked with an increased risk of subsequent autoimmune disease (HR 1.22, 95% CI 1.16-1.28), they noted in .

Furthermore, in a sensitivity analysis, they found that the association between rotavirus hospitalization and autoimmune disease was stronger for those with two or more autoimmune syndromes (HR 1.51, 95% CI 1.31-1.73) and those with three or more autoimmune syndromes (HR 1.79, 95% CI 1.18-2.72).

"[T]he greater incidence of autoimmune disease in our exposed group (73.1 vs 58.0 per 10,000 person-years, respectively) suggests the importance of awareness for children who experience rotavirus infections at an early age," Han and team wrote. "Overall, our finding suggests that rotavirus-associated hospitalization is associated with increased risk for developing autoimmune diseases that affect different organs and for developing multiple autoimmune syndromes."

"Further studies are needed to understand the underlying mechanisms," they concluded.

Rotavirus is a . While some people recover with no problems from a rotavirus infection, previous studies have shown that rotavirus can trigger autoimmune diseases, including inflammatory bowel disease, celiac disease, type 1 diabetes, pancreatitis, and neuropathy.

Two vaccines for infants against rotavirus are available in the U.S., which have reduced the prevalence of rotavirus disease.

Associations between rotavirus hospitalization and later autoimmune disease were notable for the following types of diseases:

• Inflammatory arthritis: HR 1.36 (95% CI 1.25-1.48)
• Connective tissue disorders: HR 1.29 (95% CI 1.08-1.55)
• Nervous system diseases: HR 1.29 (95% CI 1.04-1.60)
• Endocrine diseases: HR 1.28 (95% CI 1.17-1.40)
• Vasculitis: HR 1.20 (95% CI 1.12-1.29)

"The differences [in associations] may be attributed to mechanistic interactions between autoimmune diseases and rotavirus infection and variances in pathogenicity," Han and colleagues wrote.

The sensitivity analysis also showed a greater risk when excluding cases diagnosed 2 or 5 years after study entry, when exposure was defined as rotavirus enteritis as the main diagnosis at hospitalization, and when the outcome was defined by diagnosis of an autoimmune disease and the use of medication. There was an increased risk of autoimmune disease depending on the duration of hospitalization (5 days or less: HR 1.17, 95% CI 1.12-1.22; more than 5 days: HR 1.31, 95% CI 1.26-1.37; P=0.04 for interaction) and number of hospitalization events (single event: HR 1.20, 95% CI 1.16-1.24; multiple events: HR 1.60, 95% CI 1.49-1.72; P<0.001 for interaction).

Calendar year of birth, calendar season of birth date, and perinatal status had no significant associations with the HR for autoimmune disease. However, the HR was lower in boys than girls (HR 1.20 vs HR 1.29; P=0.05 for interaction).

For this study, Han and team used data from the National Health Insurance Database on nearly 2 million children born in South Korea from 2002 to 2005. They matched 86,517 children who had been hospitalized for rotavirus with an equal number of children who had not been hospitalized; 57% were boys.

In the rotavirus cohort, the median age at exposure -- the first hospitalization with diagnosed rotavirus -- was 1.5 years.

During the follow-up period, the authors identified diagnosed autoimmune diseases in 8.8% of the kids in the exposed group and in 7.0% of the unexposed group. This corresponded to an absolute difference of 15.1 per 10,000 person-years.

Because this study was observational, Han and colleagues noted that they could not make causal inferences about the relationship between rotavirus-associated hospitalization and autoimmune disease.

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