New York was the site of one of the first major COVID-19 outbreaks in the United States, and few regions of the state were hit as hard as the Bronx, which had seen more than 49,000 cases and 3924 deaths by August 3, 2020. With our collaborators Dr. Marla Keller in the Department of Medicine and Dr. Erika Orner in the Department of Pathology at Montefiore Medical center, we established a large repository of samples from both pediatric and adult samples hospitalized at the Children’s Hospital at Montefiore and at Montefiore Medical Center - Moses Division. With our collaborators Dr. Steven Almo in the Department of Biochemistry, and Drs. Kevan Herold and Aaron Ring, both at Yale, we are employing this unique resource in our comprehensive efforts to characterize differences in the immune response to SARS-CoV-2 infection in pediatric relative to adult patients.
In our initial study of 65 pediatric and 60 adult patients we identified differences in serum cytokine (pro-inflammatory protein) concentrations, antibody functionalities, and CD4 T cell responses. While other cytokines were found to be higher in adult patients, IL-17A was significantly elevated in the pediatric groups. While normally considered a product of CD4 T cells, a part of the adaptive immune system, we did not detect production of IL-17A by CD4 T cells from recovered COVID-19 patients when we stimulated the cells with SARS-CoV-2 Spike protein, suggesting that IL-17A in pediatric patients was produced by cells of the innate immune system.
The innate arm of the immune system is typically the first to respond to infection, suggesting that children may mount a more effective defense against SARS-CoV-2 infection in the early phases, whereas adults rely on the adaptive response, leading to a disordered and over-exuberant response that contributes to the well-documented immunopathology in severe COVID-19 patients.
We also observed that both pediatric and adult patients produced antibodies capable of neutralizing SARS-CoV-2 and mediating antibody-dependent phagocytosis of SARS-CoV-2 visions. Antibodies from children were found to have lower viral neutralizing activity and be less efficient at inducing phagocytosis than antibodies from adult patients, particularly those from adults with severe COVID-19. The finding that patients with severe disease or who died had higher levels of neutralizing antibodies than children and patients who recovered suggests that convalescent plasma, a source of high levels of neutralizing antibodies, may not be an effective treatment for adult patients who have developed signs of acute respiratory distress syndrome (ARDS).