tetano
Editor, Senior Moderator
J Mol Diagn
. 2022 May 4;S1525-1578(22)00108-8.
doi: 10.1016/j.jmoldx.2022.04.003. Online ahead of print.
RT-PCR/MALDI-TOF diagnostic target performance reflects circulating SARS-CoV-2 variant diversity in New York City
Matthew M Hernandez[SUP] 1 [/SUP], Radhika Banu[SUP] 2 [/SUP], Ana S Gonzalez-Reiche[SUP] 3 [/SUP], Brandon Gray[SUP] 2 [/SUP], Paras Shrestha[SUP] 2 [/SUP], Liyong Cao[SUP] 2 [/SUP], Feng Chen[SUP] 2 [/SUP], Huanzhi Shi[SUP] 2 [/SUP], Ayman Hanna[SUP] 2 [/SUP], Juan David Ramírez[SUP] 4 [/SUP], Adriana van de Guchte[SUP] 3 [/SUP], Robert Sebra[SUP] 5 [/SUP], Melissa R Gitman[SUP] 2 [/SUP], Michael D Nowak[SUP] 2 [/SUP], Carlos Cordon-Cardo[SUP] 2 [/SUP], Ted E Schutzbank[SUP] 6 [/SUP], Viviana Simon[SUP] 7 [/SUP], Harm van Bakel[SUP] 8 [/SUP], Emilia Mia Sordillo[SUP] 2 [/SUP], Alberto E Paniz-Mondolfi[SUP] 9 [/SUP], Mount Sinai PSP Study Group
Affiliations
Abstract
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate, multiple variants of concern (VOC) have emerged. New variants pose challenges for diagnostic platforms since sequence diversity can alter primer/probe binding sites (PBS), causing false-negative results. The Agena MassARRAY SARS-CoV-2 Panel utilizes reverse-transcription polymerase chain reaction and mass-spectrometry to detect five multiplex targets across N and ORF1ab genes. Herein, we utilize a dataset of 256 SARS-CoV-2-positive specimens collected between April 11, 2021-August 28, 2021 to evaluate target performance with paired sequencing data. During this timeframe, two targets in the N gene (N2, N3) were subject to the greatest sequence diversity. In specimens with N3 dropout, 69% harbored the Alpha-specific A28095U polymorphism that introduces a 3'-mismatch to the N3 forward PBS and increases risk of target dropout relative to specimens with 28095A (relative risk (RR): 20.02; p<0.0001; 95% Confidence Interval (CI): 11.36-35.72). Furthermore, among specimens with N2 dropout, 90% harbored the Delta-specific G28916U polymorphism that creates a 3'-mismatch to the N2 probe PBS and increases target dropout risk (RR: 11.92; p<0.0001; 95% CI: 8.17-14.06). These findings highlight the robust capability of Agena MassARRAY SARS-CoV-2 Panel target results to reveal circulating virus diversity and underscore the power of multi-target design to capture VOC.
Keywords: Delta; MALDI-TOF; RT-PCR; SARS-CoV-2; diagnostic; dropout; variants.
. 2022 May 4;S1525-1578(22)00108-8.
doi: 10.1016/j.jmoldx.2022.04.003. Online ahead of print.
RT-PCR/MALDI-TOF diagnostic target performance reflects circulating SARS-CoV-2 variant diversity in New York City
Matthew M Hernandez[SUP] 1 [/SUP], Radhika Banu[SUP] 2 [/SUP], Ana S Gonzalez-Reiche[SUP] 3 [/SUP], Brandon Gray[SUP] 2 [/SUP], Paras Shrestha[SUP] 2 [/SUP], Liyong Cao[SUP] 2 [/SUP], Feng Chen[SUP] 2 [/SUP], Huanzhi Shi[SUP] 2 [/SUP], Ayman Hanna[SUP] 2 [/SUP], Juan David Ramírez[SUP] 4 [/SUP], Adriana van de Guchte[SUP] 3 [/SUP], Robert Sebra[SUP] 5 [/SUP], Melissa R Gitman[SUP] 2 [/SUP], Michael D Nowak[SUP] 2 [/SUP], Carlos Cordon-Cardo[SUP] 2 [/SUP], Ted E Schutzbank[SUP] 6 [/SUP], Viviana Simon[SUP] 7 [/SUP], Harm van Bakel[SUP] 8 [/SUP], Emilia Mia Sordillo[SUP] 2 [/SUP], Alberto E Paniz-Mondolfi[SUP] 9 [/SUP], Mount Sinai PSP Study Group
Affiliations
- PMID: 35525388
- DOI: 10.1016/j.jmoldx.2022.04.003
Abstract
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate, multiple variants of concern (VOC) have emerged. New variants pose challenges for diagnostic platforms since sequence diversity can alter primer/probe binding sites (PBS), causing false-negative results. The Agena MassARRAY SARS-CoV-2 Panel utilizes reverse-transcription polymerase chain reaction and mass-spectrometry to detect five multiplex targets across N and ORF1ab genes. Herein, we utilize a dataset of 256 SARS-CoV-2-positive specimens collected between April 11, 2021-August 28, 2021 to evaluate target performance with paired sequencing data. During this timeframe, two targets in the N gene (N2, N3) were subject to the greatest sequence diversity. In specimens with N3 dropout, 69% harbored the Alpha-specific A28095U polymorphism that introduces a 3'-mismatch to the N3 forward PBS and increases risk of target dropout relative to specimens with 28095A (relative risk (RR): 20.02; p<0.0001; 95% Confidence Interval (CI): 11.36-35.72). Furthermore, among specimens with N2 dropout, 90% harbored the Delta-specific G28916U polymorphism that creates a 3'-mismatch to the N2 probe PBS and increases target dropout risk (RR: 11.92; p<0.0001; 95% CI: 8.17-14.06). These findings highlight the robust capability of Agena MassARRAY SARS-CoV-2 Panel target results to reveal circulating virus diversity and underscore the power of multi-target design to capture VOC.
Keywords: Delta; MALDI-TOF; RT-PCR; SARS-CoV-2; diagnostic; dropout; variants.