High population burden of Omicron variant (B.1.1.529) is associated with the emergence of severe hepatitis of unknown etiology in children

Abstract

Objectives: To explore a potential country-based ecological link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) infection and an apparent current global outbreak of severe hepatitis of unknown etiology among children.

Methods: We examined country-level statistical associations between reported detection of one or more unexplained severe hepatitis cases in children and the cumulative number of Omicron (B.1.1.529) cases in 38 Organisation for Economic Co-operation and Development (OECD) member countries plus Romania.

Results: At least one focal hepatitis case was detected in 12 of the 39 countries included in our analysis. Numbers of confirmed Omicron cases reported in these 12 countries ranged from 4.4 to 11.9 million. Among the remaining 27 countries, this measure ranged from 0.5 to 5.5 million cases. Countries which reported focal hepatitis cases experienced higher precedent population burdens of Omicron cases relative to those which did not report any such hepatitis cases (p=0.013).

Conclusion: Prior exposure to Omicron variant (B.1.1.529) may be associated with an increased risk for severe hepatitis among children, indicating a critical need to conduct cofactor studies.

Keywords: Adenovirus; Causality; Ecological study; Hepatitis; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Statistical association.

Figure 1

Cumulative number of Omicron cases in relation to the detection of severe acute hepatitis of unknown etiology among children. A total of 38 countries that belong to the Organization for Economic Cooperation and Development plus Romania were included (n=39). Omicron (B.1.1.529) cases were calculated as the cumulative count from 1 December 2021 to 27 April 2022. Box plot measures the quartiles and median. Whiskers extend to 1st quartile - 1.5*(interquartile range) and 3rd quartile + 1.5*(interquartile range), respectively.