Two qualities a first-class science journalist and a first-class physician must have are patience and a skeptical nature. If a new disease appears somewhere, the journalist and the physician need the skepticism to reject easy explanations of the source. As it has been said of war, first impressions are often wrong. The public may lose interest in the disease if it disappears, but the professionals, knowing the disease may reappear, must be patient in uncovering its origins, even if it takes years.
This happened in spring 2022 when nearly 350 otherwise healthy children in the U.S. suddenly contracted an unusually severe form of hepatitis. At least another 1,000 worldwide came down with the disease. According to the World Health Organization, 22 children died, and another 46 required liver transplants.
The usual precipitating causes of hepatitis, generally a benign illness in children, were quickly eliminated. The source became a medical mystery, and coming in the wake of the omicron wave of COVID-19, some observers concluded that either COVID-19 or the vaccine had caused hepatitis.
Simply from a temporal standpoint, a causal association seemed logical, even though the Centers for Disease Control and Prevention and public health authorities in Israel and Great Britain were skeptical, especially of a link to vaccines. At the time, no cause was conclusively established, and most of the cases subsided as quickly as they had appeared.
The mysterious cases of severe pediatric hepatitis fell off the public radar, so it was left for physicians in the U.S. and United Kingdom to pursue the matter. A year later, researchers have published three studies in the journal Nature that may provide the answer. The most important finding was that there appears to be no link between the acute liver disease in children and COVID-19 infection vaccines.
All three studies found that only a small minority of patients had COVID-19 infections. (In two of the studies, none of the affected children had COVID-19.) Regarding a possible vaccine cause, most children had not been vaccinated, and in fact, the outbreak in the U.K. occurred before most children were eligible for the vaccine. With so few children receiving the vaccine, it was essentially ruled out as a cause for the acute liver disease.
So what had happened? The studies demonstrated that the likely cause of hepatitis in children was an interaction of two typically benign non-COVID-19-related viruses. (For the record, the two viruses are adenovirus and AAV2.) Most of the affected children had a specific genetic susceptibility associated with autoimmune conditions. This suggests that in some way the two viruses acted synergistically and caused the body to react against the liver.
While COVID-19 did not cause pediatric hepatitis, it may have been indirectly involved as a result of public health efforts to contain the virus. The U.K. researchers postulated that the measures to reduce the spread of COVID-19 may have led to less public exposure to viruses in general and resulted in reduced immunity. As lockdowns loosened and schools reopened, the two responsible viruses began circulating among children. Many children became infected for the first time and subsequently infected others. Some of those who were genetically susceptible developed hepatitis.
There are several offshoots to the pediatric hepatitis story. Before COVID-19, we had a limited knowledge of how many cases of pediatric hepatitis there were on a national basis. Once cases began appearing in children, the U.S. and other countries started surveilling the condition, so we developed a better understanding of how many cases of hepatitis typically occur in children. When an abnormally high number appears, it gave us an early warning of a potential outbreak.
Moreover, severe acute hepatitis is traditionally uncommon in children, and in nearly half the cases, the cause is unknown. Now that we are aware of the interaction of these two viruses causing hepatitis, it opens up new avenues for diagnosis and treatment.
The American journalist H.L. Mencken once said, “Every complex problem has a solution which is simple, direct, plausible — and wrong.” It was tempting to believe that COVID-19 was responsible for the 2022 worldwide wave of severe pediatric hepatitis; it turned out not to be true.
That’s why good science journalists and physicians should be skeptical and patient. Because in science, things are not always as they seem at first.
