Does previous infection with the SARS-CoV-2 virus increase susceptibility to developing new allergies in the pediatric population?

A recent Greek narrative review of epidemiologic and immunological evidence suggests that while data are as yet inconclusive, COVID could be associated with new-onset allergies as a result of increased inflammation and epigenetic “scars” left in the airways by the virus.

“Evidence from large multinational cohorts supports an increased risk of asthma and allergic rhinitis, yet findings remain inconsistent across regions, underlining the need for harmonized global surveillance,” the investigators, led by Filippos Filippatos, wrote in their review. Filippatos is a researcher at the Aghia Sophia Children’s Hospital in Athens, Greece.

The work was published online in Cells.

Filippatos and his colleagues wrote that the SARS-CoV-2 virus can cause epithelial injury, leading to the release of alarmin cytokines such as interleukin (IL)-33, IL-25, and thymic stromal lymphopoietin, causing inflammation. The investigators also pointed to potential long-term immune “imprinting,” such as epigenetic scars that can change gene methylation.

Other potential causes of allergic susceptibility Filippatos and his colleagues noted the potential reprogramming of hematopoietic stem cells that may contribute to a sustained T helper type 2 cell (Th2)-skewed state. Th2 cells mediate the activation of the immune system against allergens and parasites.

“Cytokine memory involving IL-7 and IL-15 contributes to altered T- and B-cell homeostasis, whereas disrupted regulatory T-cell function may reduce tolerance thresholds. Paradoxical trade-offs exist, such as ACE2 downregulation in allergic airways, which may lower viral entry but simultaneously amplify type 2 inflammation,” Filippatos and his coauthors wrote.

Population-level findings vary widely, according to the review. Large cohort studies from Korea and several multinational groups reported higher rates of asthma and allergic rhinitis in children following SARS-CoV-2 infection. Data from US cohorts, meanwhile, showed neutral associations between the virus and novel allergies, or even that the virus might be protective against future allergies.

For Edwin Kim, MD, MS, the inability to control for many variables is an important factor in the possibility of COVID-related new-onset allergy.

“While the concept of epithelial injury leading to activation of alarmin pathways and Th2 skewing could make sense for increasing the risk of allergic sensitization, separating out the effect of COVID infection from the many other immunological and environmental exposures and insults as well as the timing of these exposures experienced by patients makes this correlation difficult,” Kim told Medscape Medical News. Kim is the Division Chief of Pediatric Allergy and Immunology at the University of North Carolina at Chapel Hill.

“Data from different parts of the world have yielded conflicting conclusions on the risk of COVID on development of atopy,” Kim continued. “It will be interesting to follow these patients, in particular those young patients whose early-life exposures were significantly affected by the COVID pandemic, to see the ultimate outcomes of their atopic trajectories.”

Clinical pediatric allergist Nana Mireku, MD, said she was struck by what she called, “the biological plausibility.”

“We now understand the mechanisms by which COVID could lower the threshold for allergic sensitization in some children. The geographic variability in the data reminds us that medicine isn’t one-size-fits-all.” Mireku is a pediatric allergist and immunologist at TexasAllergyMD, in the greater Dallas area.

Mireku said that this study means clinicians should now have a higher index of suspicion “for new respiratory symptoms in the year following COVID, especially in unvaccinated children or those who had severe disease.”

Filippatos, Kim, and Mireku reported having no relevant disclosures.