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 at a time there is no preventive vaccine nor specific drug available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It would be an absolute tragedy if currently used diagnostic reagents are undermined in any manner. Based on the genotyping of 7818 SARS-CoV-2 genome samples collected up to May 1, 2020, we reveal that essentially all of the current COVID-19 diagnostic targets have had mutations. We further show that SARS-CoV-2 has the most devastating mutations on the targets of various nucleocapsid (N) gene primers and probes, which have been unfortunately used by countries around the world to diagnose COVID-19. Our findings explain what has seriously gone wrong with a specific diagnostic reagent made in China. To understand whether SARS-CoV-2 genes have mutated unevenly, we have computed the mutation ratio and mutation $h$-index of all SARS-CoV genes, indicating that the N gene is the most non-conservative gene in the SARS-CoV-2 genome. Our findings enable researchers to target the most conservative SARS-CoV-2 genes and proteins for the design and development of COVID-19 diagnostic reagents, preventive vaccines, and therapeutic medicines.