| Almost a year ago, I reported on a frightening outbreak of severe acute hepatitis in young children. By July more than 1,000 cases across 35 countries were reported to the World Health Organization. Two dozen children died and 50 were so sick they needed liver transplants. A group headed by Charles Chiu, director of the clinical microbiology lab at the University of California, San Francisco, and separate teams in the UK identified the microbial culprits in three studies published on March 30 in Nature. The viruses identified aren't especially interesting, but what made this outbreak striking was their timing. Chiu describes it as a "perfect storm." His metagenomic sleuthing was informed by research he began more than a decade earlier. By studying the viruses in the poop of dozens of infants over three years, Chiu found kids were progressively acquiring germs from their moms, diet, and environment, giving them a vastly different composition of gut microbes at age 3 compared with what they started with as newborns. These viruses often don't cause actual disease and they are commonly shared among kids at school, in the playground, and wherever else they mingle. The acquisition of these microbes, usually one after another, plays an important role in training the body's immune defenses. But for a generation of children, that training was hampered by Covid mitigation measures that kept them out of school and away from each other for months on end. Once these restrictions began easing and normal social contact resumed in 2021 and 2022, kids were exposed to many germs simultaneously. This led to epidemics of numerous diseases, including respiratory syncytial virus, influenza, and group A streptococcus. A specific combination of infections was particularly dangerous for some children. The latest research showed that adenovirus — especially human adenovirus-41, a common cause of gastro — and either adeno-associated virus 2 or a herpesvirus worked synergistically to cause liver damage in a subset of children, almost all of whom carried a rare genetic variation that made them susceptible to the liver-inflaming condition. Cases of severe hepatitis have since abated, presumably as kids' acquisition of viruses resumed a more normal pattern. But for the affected children who required a donor liver, the consequences of this phenomenon will last a lifetime. And for scientists like Chiu, they will spur continued research on the pediatric immune system — especially those of kids who got the liver disease. "What impact is that going to have on both the child's risk of infection later in life, or perhaps their risk of infection-related autoimmune diseases?" Chiu said. "It's another example of the potential impact of the Covid pandemic that really needs to be studied in detail." — Jason Gale | 
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