Viral Coinfections in Kawasaki Disease: A Meta-analysis

Abstract

CONTEXT Viral infections are suspected triggers in Kawasaki disease (KD); however, a specific viral trigger has not been identified. OBJECTIVES In children with KD, to identify (1) overall prevalence of viral infections; (2) prevalence of specific viruses; and (3) whether viral positivity was associated with coronary artery aneurysms (CAAs) or refractoriness to intravenous immunoglobin (IVIG). DATA SOURCES We searched Embase, Medline, and Cochrane databases and gray literature. STUDY SELECTION Eligible studies were conducted between 1999 and 2019, and included children diagnosed with KD who underwent viral testing. DATA EXTRACTION Two investigators independently reviewed full-text articles to confirm eligibility, extract data, appraise for bias, and assess evidence quality for outcomes using the Grading of Recommendations Assessment Development and Evaluation criteria. We defined viral positivity as number of children with a positive viral test divided by total tested. Secondary outcomes were CAA (z score ≥2.5) and IVIG refractoriness (fever ≥36 hours after IVIG). RESULTS Of 3189 unique articles identified, 54 full-text articles were reviewed, and 18 observational studies were included. Viral positivity weighted mean prevalence was 30% (95% confidence interval [CI], 14–51) and varied from 5% to 66%, with significant between-study heterogeneity. Individual virus positivity was highest for rhinovirus (19%), adenovirus (10%), and coronavirus (7%). Odds of CAA (odds ratio, 1.08; 95% CI, 0.75–1.56) or IVIG refractoriness (odds ratio, 0.88; 95% CI, 0.58–1.35) did not differ on the basis of viral status. LIMITATIONS Low or very low evidence quality. CONCLUSIONS Viral infection was common with KD but without a predominant virus. Viral positivity was not associated with CAAs or IVIG refractoriness.