Hospitalizations associated with rotavirus linked to subsequent autoimmune disease in childhood | Image Credit: © fizkes - © fizkes- stock.adobe.com.

Rotavirus-associated hospitalization is substantially linked to subsequent autoimmune disease at the time of patients’ childhoods, according to recent findings.¹

The findings were the results of a new study which was conducted to expand upon the existing limited data which has been shown to link rotavirus infections to autoimmune diseases including type 1 diabetes, pancreatitis, celiac disease, and neuropathy.^2-5

To address the limitations in existing data, the study was conducted and the research was authored by Man Yong Han, MD, from the CHA Bundang Medical Center’s Department of Pediatrics at CHA University School of Medicine in South Korea.

“We performed a systematic literature search and analyzed a nationwide population-based database of nearly 2 million individuals to investigate the association between rotavirus-associated hospitalization and subsequent autoimmune disease, while accounting for confounding factors,” Han and colleagues wrote.

Background and Findings

The investigators used a population-matched cohort design for their research, using data from both children and adolescents under the age of 18 and located in South Korea. The team’s data was sourced from national registers which covered the time from January 1, 2002, to December 31, 2017.

A systematic literature search was done by the research team using PubMed, focusing on Medical Subject Heading (MeSH) terms including "rotavirus infection," "rotavirus," and "autoimmune disease." Their search identified relevant studies completed after 1999, meeting some specific inclusion criteria:

• Investigated the incidence of autoimmune disease-related hospitalizations or outpatient visits following rotavirus infection.
• Collected fecal samples from patients with autoimmune diseases to test for the presence of rotavirus.
• Explored the distribution of specific types of rotavirus associated with autoimmunity, either in vivo or in vitro.

The study’s cohort was made up of 86,157 participants in the exposure arm who had been hospitalized as a result of rotavirus infection, and an equal number of patients were chosen in the unexposed arm to be matched with those who were exposed.

The investigators’ data analysis was done in the period of May 1, 2020, to October 20, 2022, and the exposure of interest was determined to be hospitalization for rotavirus infection. The primary outcome assessed by the research team was reported occurrence of childhood autoimmune diseases, identified through diagnoses reported in the National Health Insurance Database.

The team calculated hazard ratios (HRs) along with 95% confidence intervals (CIs) through the use of a Cox model to account for multiple confounding elements.

In total, the investigators looked at 1,914,461 of those born in South Korea in the period between 2002 - 2005, and included 86,517 participants in both the exposed and unexposed arms of the study after 1:1 incidence density sampling. Of these individuals, 57.0% were shown to be male and the median age at diagnosis for rotavirus-associated hospitalization was found to be 1.5 years.

The research team reported that those in the exposed arm had a hazard ratio (HR) of 1.24 (95% confidence interval [CI]: 1.19 - 1.28) for autoimmune disease compared to the unexposed arm of the study. They also noted that follow-up time for study participants was found to be 12.1 years.

When the investigators used more stringent definitions for exposure and outcomes in a multivariable stratified analysis, they found that the association between rotavirus-associated hospitalization and later autoimmune diseases remained substantial, with an HR of 1.22 (95% CI: 1.16 - 1.28).

Additionally, the research team noted that their sensitivity analysis further demonstrated that those whose hospitalizations were rotavirus-associated were shown to be at increased risk of multiple autoimmune syndromes (2 or more: HR, 1.51 [95% CI: 1.31 - 1.73]; 3 or more: HR, 1.79 [95% CI: 1.18 - 2.72]).

The team added that the risks of autoimmune disease showed a dose-dependent relationship with the amount of hospitalizations which had been rotavirus-associated, with a single hospitalization event having an HR of 1.20 [95% CI: 1.16 - 1.24] and multiple events having an HR of 1.60 [95% CI: 1.49 - 1.72]).

“In this nationwide cohort study, rotavirus-associated hospitalization was associated with an increased risk for childhood autoimmune disease overall and multiple specific autoimmune diseases,” they wrote. “Clinicians should be aware of the increased predisposition for autoimmune disease in individuals who experienced rotavirus-associated hospitalization. Further studies are needed to understand the underlying mechanisms.”

References:

1. Ha EK, Kim JH, Cha HR, et al. Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease. JAMA Netw Open. 2023;6(7):e2324532. doi:10.1001/jamanetworkopen.2023.24532.
2. Kemppainen KM, Lynch KF, Liu E, et al; TEDDY Study Group. Factors that increase risk of celiac disease autoimmunity after a gastrointestinal infection in early life. Clin Gastroenterol Hepatol. 2017;15(5):694-702.e5. doi:10.1016/j.cgh.2016.10.033.
3. Graham KL, Sanders N, Tan Y, Allison J, Kay TW, Coulson BS. Rotavirus infection accelerates type 1 diabetes in mice with established insulitis. J Virol. 2008;82(13):6139-6149. doi:10.1128/JVI.00597-08.
4. Giordano S, Serra G, Dones P, et al. Acute pancreatitis in children and rotavirus infection: description of a case and minireview. New Microbiol. 2013;36(1):97-101.
5. Cho JY, Yeom JS, Kim YS, et al. Neurodevelopmental outcomes of neonatal rotavirus-associated leukoencephalopathy. Neuropediatrics. 2022;53(4):291-294. doi:10.1055/s-0042-1742722.

This article was initially published by our sister publication, HCP Live®.