Mutations on COVID-19 diagnostic targets

Effective, sensitive, and reliable diagnostic reagents are of paramount importance for combating the ongoing coronavirus disease 2019 (COVID-19) pandemic when there is neither a preventive vaccine nor a specific drug available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It will cause a large number of false-positive and false-negative tests if currently used diagnostic reagents are undermined. Based on genotyping of 31,421 SARS-CoV-2 genome samples collected up to July 23, 2020, we reveal that essentially all of the current COVID-19 diagnostic targets have undergone mutations. We further show that SARS-CoV-2 has the most mutations on the targets of various nucleocapsid (N) gene primers and probes, which have been widely used around the world to diagnose COVID-19. To understand whether SARS-CoV-2 genes have mutated unevenly, we have computed the mutation rate and mutation h-index of all SARS-CoV-2 genes, indicating that the N gene is one of the most non-conservative genes in the SARS-CoV-2 genome. We show that due to human immune response induced APOBEC mRNA (C > T) editing, diagnostic targets should also be selected to avoid cytidines. Our findings might enable optimally selecting the conservative SARS-CoV-2 genes and proteins for the design and development of COVID-19 diagnostic reagents, prophylactic vaccines, and therapeutic medicines. Availability: Interactive real-time online Mutation Tracker.