ACROSS - Assessing cross-reactive and pre-existing immunity to SARS-CoV-2 in adolescents

As of 12 July 2020, 12.9 million people worldwide were confirmed to be infected with the novel coronavirus SARS-CoV-2 (COVID-19), resulting in more than 569,000 deaths. Strategies for prevention, treatment, and diagnosis are urgently needed to reduce the disease burden of COVID-19 but are hampered by the lack of knowledge regarding SARS-CoV-2 immunity. Correlates of protective immunity to SARS-CoV-2 may be similar to SARS-CoV-1, involving both humoral and cellular responses. Recently, studies have described pre-existing and cross-reactive T cell responses to SARS-CoV-2 in unexposed adults, likely due to memory responses from previous non-SARS coronavirus infections. Since children and adolescents are less susceptible to COVID-19 and typically have milder disease compared to adults, this disease presentation may be due to higher pre-existing immunity to SARS-CoV-2 from more frequent infections with common cold human coronaviruses. In addition, this study hypothesises that adolescents who have recovered from COVID-19 will have greater immunity to SARS-CoV-2 than recovered adults, since pre-existing responses may be boosted by SARS-CoV-2 infection. First, pre-existing antibody responses to SARS-CoV-2 will be measured in pre-pandemic plasma samples from South African adolescents. Antibody responses to the common cold coronaviruses hCoV-NL63 and hCoV-OC43 will also be measured in these individuals, to estimate the rate of seropositivity in SA adolescents, and whether detection of SARS-CoV-2 cross-reactive antibodies resulted from exposure to these coronaviruses. Since pre-existing immunity is primarily mediated by cellular responses, this study will deeply characterise the function and phenotype of pre-existing CD4+ and CD8+ T cell responses to SARS-CoV-2 in pre-pandemic samples collected from South African adolescents. Finally, antibody and T cell responses to SARS-CoV-2 will be compared between adolescents and adults who have recovered from COVID-19, to investigate whether pre-existing responses in adolescents may be boosted by subsequent SARS-CoV-2 infection, resulting in higher responses than adults. The proposed study will generate important new knowledge on adolescents, who are typically understudied during this pandemic. Findings from this study will also have implications for the design of interventions, especially vaccines and serological tests. In addition, this fellowship will provide the fellow with the opportunity to remain in academia, to lead this project under the guidance of an experienced mentor, and to expand and hone the skills required to become an independent research leader in the field of infectious disease immunology in Africa.