Widespread SARS‐CoV‐2 Transmission Despite Limited Reported Cases and Clinical Disease: Exploring the Role of Pre‐Existing Humoral Immunity to SARS‐CoV‐2 in Eastern Sierra Leone

BACKGROUND: Since December 2019, SARS-CoV-2 has infected over 700 million people and caused > 7 million deaths. While much of the global north was severely affected, sub-Saharan Africa was relatively spared. Possible reasons include a younger population, fewer comorbidities, and pre-existing immunity. Here, we expand on previous work through a cohort of 306 subjects, with samples drawn pre-pandemic, intra-pandemic, and post-vaccination. METHODS: We assessed antibody reactivity to seasonal coronaviruses, emerging coronaviruses, and SARS-CoV-2 spike (S), nucleoprotein (N), and receptor binding domain (RBD) proteins in a longitudinal cohort. Antibody neutralization was measured using a pseudovirus neutralization assay. RESULTS: Our data show that 16%-20% of pre-pandemic samples had reactivity to SARS-CoV-2 N protein. Further, we noted relatively high reactivity to SARS-CoV-2 RBD (~31%), and low, but notable, seropositivity to SARS-CoV-2 S protein (3.3%-3.4%). We additionally found a significant jump in seropositivity to all SARS-CoV-2 proteins by March 2022 (intra-pandemic), and high levels of neutralization in the intra-pandemic samples compared to pre-pandemic samples. A boosting effect on SARS-CoV-2 Spike was observed after vaccination. CONCLUSIONS: We report widespread circulation of SARS-CoV-2 in eastern Sierra Leone by March 2022 despite low national reporting. Furthermore, we provide evidence of pre-existing humoral immunity to SARS-CoV-2 as compared to US controls. This may have resulted in less severe disease, less COVID-19 testing and the apparent lack of clinical cases. Finally, we show boosting of SARS-CoV-2 Spike following vaccination. Studies comparing HLA type between symptomatic and asymptomatic cases are being planned. Studies to better characterize cellular immunity from pre-pandemic timepoints should also be prioritized.