In a recent study published on the medRxiv * prepress server, researchers at KU Leuven investigated whether there was an association between adenovirus co-circulation intensity (AdV) 40/41 and severe acute respiratory syndrome coronavirus 2 ( SARS-CoV). -2) with the number of cases of hepatitis of unknown origin emerging in Belgium.
To this end, they measured the circulation of AdV 40/41 and SARS-CoV-2 in the general population of Leuven, Belgium. The team then monitored the city’s wastewater systems and indoor air quality in kindergartens. In addition, they examined the medical records of 12,672 children who visited a hospital between January 2019 and April 2022.
Study: Environmental circulation of adenovirus 40/41 and SARS-CoV-2 in the context of the onset of acute hepatitis of unknown origin. Image credit: Corona Borealis Studio / Shutterstock
Fund
There were several probable cases of severe acute hepatitis of unknown etiology in children under 16 years of age in Belgium. In fact, there were many more such cases in the European region of the World Health Organization (WHO), with three out of four cases in children under five. Consequently, 181 of the 650 probable cases tested for AdV had 110 (60.8%) positive cases. Also, 23 of 188 cases were positive for SARS-CoV-2.
About the study
In the present study, the researchers hypothesized that Adv and SARS-CoV-2 were pathophysiological contributors to the etiology of severe acute hepatitis of unknown origin, especially in children under 16 years of age.
The team collected weekly wastewater samples from a wastewater treatment plant in Belgium that covers eight municipalities inhabited by 11,500 people. They used a time-proportional automated sampling to collect 50 ml of wastewater every 10 minutes between December 2020 and May 2022.
Evolution of the circulation of AdV 40/41 and SARS-CoV-2 in the general population between December 2020 and May 2022. The signal intensity is captured by the Ct value of the directed PCR tests performed in wastewater.
They also collected aerosol samples from two different environments according to the age group of the children. For children from zero to three years old, they collected air samples from the area near the nursery toilets, and from three to six years old, from the dining area of the nursery. Samples were collected for two hours, one to three times a week, between November 2021 and April 2022.
The researchers extracted viral ribonucleic acid (RNA) from wastewater and aerosol samples, which were then subjected to quantitative reverse transcriptase-polymerase (RT-qPCR) chain reaction tests to detect the presence of SARS-CoV. -2 and AdV 41. They used Sanger. sequencing for AdV subtyping in all positive wastewater samples. The team was actively investigating cases of hepatitis of unknown origin over four time periods covering the periods before and after coronavirus disease 2019 (COVID-19). In addition, they examined the medical records of 63 children (all under the age of 16) who had elevated liver enzymes during all time periods.
A: Evolution of the circulation of Adv 40/41 and SARS-CoV-2 in nurseries between November 2021 and May 2022. The signal intensity is captured by the Ct / Cq value of the targeted PCR tests performed on samples of air. B: The ratio of positive samples to the total number of samples tested is shown in the figure below.
The team used the proportion test function to test for changes in the number of elevated cases of liver enzymes and the positivity of pathogens between study periods. In addition, they used the Kruskal-Wallis test to test for differences between groups of continuous variables and a Dunn test for pairwise comparisons between groups. Finally, they used the Benjamin-Hochberg method for multiple test corrections with a false detection rate (FDR) adjustment cut below 0.05.
Study results
Between September 2021 and April 2022, the authors observed elevated circulation levels of AdV 40/41 and SARS-CoV-2 in the general population. In addition, they identified four probable and five possible cases of non-serious viral hepatitis of unknown origin in children under 16 years of age. The nine children developed hepatitis after October 2021, but recovered without the need for a liver transplant. Although adenovirus infection was not associated with any case, the authors identified a case directly associated with SARS-CoV-2 infection. The child developed COVID-19 four days before the onset of hepatitis. In particular, they did not identify any cases of hepatitis of unknown origin in the four time periods before and after COVID-19.
Sanger sequencing was possible for 57% of the wastewater samples. The authors noted that ADV was detected in 65% of these samples, but only after the increase in 40/41 AdV cases after July 2021. The authors analyzed 158 air samples. , of which 128 were from kindergartens and 30 from kindergartens. They first detected AdV 40/41 in these samples on December 10, 2021. Subsequently, they constantly found AdV 40/41 and SARS-CoV-2 throughout the study period, concomitantly with cases of hepatitis. in Belgium.
Conclusions
Overall, the study observations did not rule out or conclusively confirm the contribution of AdV and SARS-CoV-2 to the increase in acute cases of hepatitis in children. Therefore, even in cases where they possibly contributed, only a few cases progressed to severe hepatitis. In addition, the high rates of community-based transmission of both AdV and SARS-CoV-2 and the lowest hospital admission rates for cases of viral hepatitis of unknown origin in children between September 2021 and April 2022 give support for the study’s findings. More importantly, the study highlighted the need for holistic disease surveillance in large populations to estimate secondary diseases, including hepatitis resulting from a massive circulation of infectious viruses, such as AdV and SARS-CoV-2.
* Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.
Magazine reference:
- Environmental circulation of adenovirus 40/41 and SARS-CoV-2 in the context of the onset of acute hepatitis of unknown origin, Elke Wollants, The Keyaerts, Lize Cuypers, Mandy Bloemen, Marijn Thijssen, Sien Ombelet, Joren Raymenants, Kurt Beuselinck, Lies Laenen, Lore Budts, Bram Pussig, Katrien Lagrou, Marc Van Ranst, Emmanuel Andre, medRxiv preprint 2022, DOI: https://doi.org/10.1101/2022.06.08.22276091,