Environmental circulation of adenovirus 40/41 and SARS-CoV-2 in the context of the emergence of acute hepatitis of unknown origin

Abstract

The recent surge of hepatitis of unknown origin in children is hypothesized to be caused by adenovirus 41 and/or SARS-CoV-2 infections. A relatively high proportion of patients testing positive for these viruses concomitantly with the development of acute hepatitis supports this hypothesis. To formally incriminate these viral infections as causative agents of hepatitis, both a plausible physiopathological pathway and supporting epidemiological dynamics in the community need demonstration. In this study, we measured the level of circulation of adenovirus 40/41 and SARS-CoV-2 in the general population of the city of Leuven in Belgium using wastewater monitoring between December 2020 and May 2022 and indoor air sampling in day care centers between November 2021 and May 2022. We also retrospectively analyzed medical records of 12.672 children attending a tertiary hospital draining the same region between January 2019 and April 2022. Our results demonstrate a recent but modest increase in hepatitis of unknown origin concomitant with a surge of circulating adenovirus 41 and SARS-CoV-2 in the general population, including in children under 5.

Characterization of a Hepatitis Outbreak in Children, 2021 to 2022

“…We identified a total of 22 studies that included 1643 cases. We have summarized the available studies for 22 distinct populations in the eTable in the Supplement, including country, age, case definition, testing for adenovirus and/or SARS-CoV-2, treatments, and outcomes . The Table summarizes the hypotheses raised by these case series.…”

“…Most studies used the WHO case definition . Countries included the UK, Israel, the US, India, Sweden, Belgium, the Netherlands, Italy, and several multicountry collaboratives …”

“…For those with information regarding outcomes, 84 of 261 (32.2%) were admitted to the intensive care unit or the hemodialysis unit, and 18 of 208 (8.7%) received a transplant. Other series, including preprints 20,26,31,32 and technical reports, 11,14,18,22,23 are summarized in the eTable in the Supplement.…”

“…A peer-reviewed publication of cases submitted to the European Surveillance System summarized 427 cases reported by 20 countries. 30 20,26,31,32 and technical reports, 11,14,18,22,23 are summarized in the eTable in the Supplement.…”

“…Most studies used the WHO case definition. 2 Countries included the UK, 1,10,11,29,31,32 Israel, 12,22,23 the US, [14][15][16][17]19,24,33 India, 20 Sweden, 25 Belgium, 26 the Netherlands, 27 Italy, 28 and several multicountry collaboratives. 13,18,21,30 Among peer-reviewed series, 9 children from Alabama are described who presented with hepatitis of unknown etiology and positive test findings for adenovirus on whole blood testing between October 2021 and February 2022.…”