Mutations on COVID-19 diagnostic targets

Abstract

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.

Computational Investigation of Increased Virulence and Pathogenesis of SARS-CoV-2 Lineage B.1.1.7

“…22 The UK variant was also found to have impact on diagnosis of SARS-CoV-2 as the deletion mutations in 69-70 can cause negative result from S-gene in RT-PCR assay. [23][24][25][26] Mutations in the RBD of spike protein or other surface structures can alter the antigenic property of new SARS-CoV-2 variant that could lead to reduction in neutralization activity of antibodies and thereby resulting in higher risk of reinfection or decreased effectiveness of vaccines. 27 Therefore, there is an urgent need to study the mutation pattern of SARS-CoV-2 and mechanism of virulence or pathogenesis of new variant B.1.1.7 to develop effective therapeutics.…”

Quantitative and Ultrasensitive In-situ Immunoassay Technology for SARS-CoV-2 Detection in Saliva

“…Another concern is that primers for different genes can be affected by variations in the genomic sequences of the virus due to their rapid mutations, which can generate false-negative results. 8 …”

What are SARS-CoV-2 genomes from the WHO Africa region member states telling us?

“… 1 A recent analysis has shown that the majority of current PCR diagnostic targets have undergone mutations with the nucleocapsid (N) gene primers and probes having undergone the most mutations. 2 …”

“…1 A recent analysis has shown that the majority of current PCR diagnostic targets have undergone mutations with the nucleocapsid (N) gene primers and probes having undergone the most mutations. 2 In Africa, analysing virus genome sequences revealed transmission patterns within individual countries. For example, analyses of sequences in Kenya during the early phase of the epidemic identified both imported and local community transmission, demonstrating transmission from Nairobi to the coastal regions.…”