{"doi":"10.1093/clinchem/hvab020","title":"Laboratory Action Plan for Emerging SARS-CoV-2 Variants","abstract":"In December 2020, a clinically significant SARS-CoV-2 variant with an increased transmission rate was identified in the United Kingdom (1–3). Currently referred to as SARS-CoV-2 VOC-202012/01 (Variant of Concern, year 2020, month 12, variant; VOC-202012/01) or the B.1.1.7 variant, it has been identified in multiple countries throughout the world and continues to spread unabatedly (1, 4). VOC-202012/01 appears to be detectable by commonly used nucleic acid-based tests with emergency use authorization (EUA) from the United States Food and Drug Administration (FDA), and hopefully will not present a diagnostic challenge for clinical laboratories. As the COVID-19 pandemic continues, we anticipate additional clinically significant SARS-CoV-2 variants will emerge and we propose several preparatory actions for clinical laboratories. VOC-202012/01 was identified in a genomic sequencing investigation of a rapid increase in COVID-19 cases in South East England. VOC-202012/01 was detected in approximately 50% of the increased cases. A retrospective investigation identified the earliest case from September 20, and by December 13 there were 1108 cases identified (1, 2, 5). Despite increased potential transmissibility, there is currently no evidence indicating increased severity of disease or decreased efficacy of vaccines of this variant (4). Reassuringly, antibody responses to vaccine epitopes indicate the genetic changes of the new variant are outside of major antibody binding sites (6). An evaluation of the Pfizer/BioNTech vaccine suggests efficacy against VOC-202012/01 (7). VOC-202012/01 has 17 genetic changes affecting amino acid sequence (missense, deletions, early stop codon) (2) (Table 1); 8 of these genetic changes occur in the S (spike) gene domain. The overall number of genetic changes is considered large compared to other SARS-CoV-2 variants. Globally, most SARS-CoV-2 variants have only a few genetic changes and are estimated to accumulate at a rate of 1–2 per month (2, 8). Current speculation is that the high number of genetic changes in VOC-202012/01 may be due to a rapid selection pressure event such as a prolonged infection in a patient with reduced immunocompetence (1, 9, 10) or that the variant developed within an infected animal and was transmitted back to humans (1, 11). However, in general, coronavirus genomes are relatively genetically stable, particularly when compared to RNA viruses such as influenza A virus. This is because coronaviruses encode a proof-reading mechanism to reduce mutations, whereas influenza A virus and many other RNA viruses have low fidelity, error-prone polymerases (12, 13). Thus, additional knowledge about host pressures that led to the emergence of VOC-202012/01 will be informative from the standpoint of viral evolution. Nucleotide variation in SARS-CoV-2 VOC 202012/01 (2). UCSC Genome Browser on SARS-CoV-2 Jan. 2020/NC_045512.2 Assembly (wuhCor1); , stop codon. Nucleotide variation in SARS-CoV-2 VOC 202012/01 (2). UCSC Genome Browser on SARS-CoV-2 Jan. 2020/NC_045512.2 Assembly (wuhCor1); , stop codon. VOC-202012/01 genetic changes are present in multiple genes, including those commonly targeted by SARS-CoV-2 diagnostic tests: ORF1ab, S-gene, N-gene. As of January 8, 2021, there are 2 nucleic acid-based tests known to be impacted by VOC-202012/01 [TaqPath COVID-19 Combo Kit (TaqPath), Linea COVID-19 Assay Kit (Linea)]; a third test [MesaBiotech Accula (Accula)], may be affected by SARS-CoV-2 variants with a genetic change not present in VOC-202012/01 (14). The TaqPath and Linea assays are impacted by S-gene genetic changes in VOC-202012/01; however, the overall sensitivity of these 2 assays is not known to be affected (14). The TaqPath assay is a multiplex real-time reverse transcription PCR test that targets the ORF1ab, S and N genes; only the S-gene target is affected due to deletion of genome nucleotides 21765_21770del (His69_Val70del). The Linea assay includes 2 targets within the S-gene; ","journal":"Clinical Chemistry","year":2021,"id":204114,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9437,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":383982,"name":"Jeffrey A. SoRelle","orcid":"0000-0003-2588-6277","position":1,"is_corresponding":false},{"id":241087,"name":"John W. Schoggins","orcid":"0000-0002-7944-6800","position":2,"is_corresponding":false},{"id":785891,"name":"Jason Y. Park","orcid":"0000-0001-6797-4000","position":3,"is_corresponding":false},{"id":785890,"name":"Laura Filkins","orcid":"0000-0002-0406-4947","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-18T23:51:22.166488Z","pmid":"33515256","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}