Paper suggests cause for COVID-19’s aftereffects in children

Siddappa Byrareddy, PhD, associate professor and vice chair of research, pharmacology and experimental neuroscience, was interested in what is happening with children during the COVID-19 pandemic.

Based on reports, we are starting to see that, by the numbers, children tend to contract less severe cases of COVID-19.

But kids, even those with mild or asymptomatic cases, can later develop what is called multisystem inflammatory syndrome in children (MIS-C). The Centers for Disease Control and Prevention’s (CDC) Health Alert Network issued a global alert in May about MIS-C, citing a possible link between the condition and infection by SARS-CoV-2.

MIS-C can result in “a severe inflammatory state, including fever, diarrhea, shock,” rash, and even multi-organ failure, requiring ICU care.

Dr. Byrareddy and his collaborator, Hussin Rothan, PhD, of Georgia State University, had an idea of what might be happening. There is not yet enough data to know for sure, but they published a paper in Pediatric Allergy and Immunology, “postulating based upon what we know,” Dr. Byrareddy said.

Those who have had COVID-19, even without knowing it, have antibodies. But, these come in two types — neutralizing and non-neutralizing antibodies. The spike protein of SARS-CoV-2 induces the human system to produce both types.

Then there is the phenomenon of antibody-development enhancement (ADE). ADE means in addition to the usual way, the virus may get into our bodies by binding with non-neutralizing antibodies. Rather than fighting the virus, these antibodies, as the name says, enhance it.

A similar ADE phenomenon was seen earlier in Dengue and Zika virus infections.

The scientists wrote: “Neutralizing antibodies afford a protective effect against virus entry into the host cells. On the other hand, the antibodies generated against the non-neutralizing epitopes could enhance virus entry leading to severe disease outcomes.”

And even low levels of non-neutralizing antibodies can “enhance virus entry and worsen the disease outcome.”

They concluded: “We reasoned that there may be a potential role of the ADE that could trigger the MIS-C syndromes whereby the non-neutralizing pathogen-specific antibodies can promote pathology.”

As with many cases of the disease, “A growing body of evidence suggests the host’s innate immune response to SARS-CoV-2 infection triggers the inflammation cascade that causes severe tissue damage.”

Additionally, this ADE phenomenon “should be considered in vaccine development against SARS-CoV-2.”

Previous studies on other conditions have shown this is a safety concern in addition to a factor in the effectiveness of a potential vaccine.