What if some antibodies our immune system produces against SARS-CoV-2 don't protect us but instead enable a more severe second infection? Researchers from Italy's Treviso Public Health Department propose this concerning mechanism in a peer-reviewed BMJ Global Health commentary.
Published on June 11, 2020, the commentary examines “biphasic” COVID-19 infections, where patients experience mild symptoms initially, followed by a severe form about 10 days later—far more intense and dangerous.
The team attributes this to potential reinfection with SARS-CoV-2 or another coronavirus, driven by an immune dysfunction involving "facilitating" antibodies. Rather than shielding the body, these antibodies heighten vulnerability. If confirmed, this could have profound implications for vaccine development.
This hypothesis draws from key observations: Italy faced one of the world's worst first waves despite countries like Japan and Germany having older populations—typically higher risk—yet far less impact. Notably, Italy's first three COVID-19 cases were imported, suggesting the virus circulated domestically weeks earlier.
Severe cases may stem from repeated infection cycles within communities, especially among vulnerable groups like the elderly and healthcare workers.
A first infection prompts normal antibody production, where antibodies bind the virus and recruit immune cells for destruction. But in a second exposure, these antibodies may facilitate viral entry instead, a phenomenon called antibody-dependent enhancement (ADE).
This could explain global biphasic patterns and cytokine storms—an overzealous immune response causing violent inflammation and many COVID-19 deaths.
While compelling, the theory requires rigorous testing. Vaccines mimic initial infection to generate protective antibodies; if these turn facilitative upon re-exposure, they could backfire.
CNRS research director Morgane Bomsel, interviewed by Sciences et Avenir on July 21, 2020, notes that Moderna's vaccine induces neutralizing antibodies, but facilitating ones remain untested. Oxford's and Wuhan's candidates show good tolerance and immune responses, yet ADE risks are unchecked.
