The impact of novel variants of SARS-CoV-2 on diagnostic testing

The impact of novel variants of SARS-CoV-2 on diagnostic testing

What do we know about the impact of SARS-CoV-2 variants of concern on diagnostic tests, vaccines, and public health measures? How can genomic surveillance support in identifying and managing the impact of these variants?

Read our new report developed with the PHG Foundation.

Three SARS-CoV-2 variants of potential concern have recently been identified, characterized by several novel genetic mutations.1,2 Although mutations in viral genetic sequences have the potential to alter the performance of diagnostic tests, based on analysis of the specific mutations carried by the two novel variants, it is expected that the majority of tests currently used in primary detection of SARS-CoV-2 will be unaffected. However, laboratories should be aware of potential effects on certain diagnostic tests. The image below the table shows the SARS-CoV-2 genome, mutations reported across the three variants, and the specific genetic region targeted by several molecular and antigen-detection assays.

Variant designation B.1.1.7
(VOC-202012/01, 501y.v1 )
B.1.351
501Y.V2
P.1 (501Y.V3) and P.2 

Location first identified

United Kingdom1 South Africa2 Brazil3

Mutations

23 mutations, of which 17 are of concern (13 non-synonymous, 4 deletions)1

Mutations in ORF1ab, ORF8 and N also reported1

21 mutations, including 9 amino acid changes in the S gene (3 at key sites in the receptor binding domain)2

Mutations in ORF1ab, ORF3a, N and E genes also reported2

10 mutations in the
S gene (3 at key sites in the receptor binding domain)3Mutations in ORF1ab, ORF8 and N genes also reported3

Impact on performance of molecular diagnostics

Minimal impact

69–70 deletion causes S gene dropout1

Minimal impact

No data on impact of mutations on assay performance but may impact assays that target S gene sequences

Minimal impact

No data on impact of mutations on assay performance but may impact assays that target S gene sequences

PCR assays targeting the S gene are not widely used for primary detection, and many assays target multiple genes.4 Laboratories using S-gene based assays should monitor for dropout and consider implementing assays specific for other genomic targets (e.g., E or RdRP genes) if not already included as part of existing panel

Impact on performance of antigen-based tests (including rapid lateral flow devices)

Most antigen-based tests target the C-terminus of the viral nucleocapsid protein, encoded by the N gene

Minimal impact

The N gene mutations in this variant are located at the N-terminal. An assessment by Public Health England found that five SARS-CoV-2 rapid antigen tests evaluated were all able to successfully detect the variant5*

Minimal impact anticipated

To date, no evaluation studies have been carried out to confirm that test performance is not affected but no major performance deficits are anticipated

Minimal impact anticipated

To date, no evaluation studies have been carried out to confirm that test performance is not affected, but no major performance deficits are anticipated.

Impact on performance of serological antibody tests

No data No data No data
There is potential for the performance of assays detecting antibodies to viral spike protein or nucleocapsid to be affected, but to date no evaluations have been performed

*Tests evaluated were Abbott Panbio, Fortress, Innova, Roche/SD Biosensor nasal swab, and Surescreen.
The information in this table will be updated as data become available. Last updated 9 February 2021.

Notably, the B.1.1.7 and  B.1.351 variants have been associated with higher viral loads compared with existing variants in preliminary analyses,6,7 resulting in lower cycle threshold (Ct) values for PCR testing. Detection rates with antigen tests may increase due to increased concentration of antigen in samples.

Both the B.1.1.7 and B.1.351 variants have been associated with higher transmission rates compared with existing variants, suggesting that they carry a selective advantage.2,8 There is no evidence yet of a change in transmissibility with the P.1. variant, however, the presence of shared mutations with the B.1.1.7 and B.1.351 variants indicates that increased transmissibility is plausible.9 The impact of the novel mutations carried by the three variants on pathogenicity or resistance to antibodies or vaccines is yet to be determined.9

The rapid emergence of these three novel variants clearly demonstrates the need for continued, robust and widespread SARS-CoV-2 surveillance, to ensure that other novel mutations are identified as early as possible.

Click on image to enlarge

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  1. Public Health England. Investigation of novel SARS-COV-2 variant: Technical briefing 1. https://www.gov.uk/government/publications/investigation-of-novel-sars-cov-2-variant-variant-of-concern-20201201. Accessed 4 January 2021
  2. Tegally H et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv 2020. doi: 10.1101/2020.12.21.20248640
  3. Faria NR et al. Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings. https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586. Accessed 9 February 2021
  4. World Health Organization (WHO). Molecular assays to diagnose COVID-19: Summary table of available protocols. https://www.who.int/publications/m/item/molecular-assays-to-diagnose-covid-19-summary-table-of-available-protocols. Accessed 4 January 2021
  5. Public Health England. SARS-CoV-2 lateral flow antigen tests: evaluation of VUI-202012/01. https://www.gov.uk/government/publications/sars-cov-2-lateral-flow-antigen-tests-evaluation-of-vui-20201201/sars-cov-2-lateral-flow-antigen-tests-evaluation-of-vui-20201201. Accessed 5 January 2021
  6. New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG). NERVTAG meeting on SARS-CoV-2 variant under investigation VUI-202012/01. https://khub.net/documents/135939561/338928724/SARS-CoV-2+variant+under+investigation%2C+meeting+minutes.pdf/962e866b-161f-2fd5-1030-32b6ab467896?t=1608491166921. Accessed 4 January 2021
  7. Karim SA. Presentation on the 18 December 2020 describing the new SARS-CoV-2 variant (501Y.V2) in South Africa.https://www.krisp.org.za/ngs-sa/ngs-sa_updates_covid-19_analysis_narratives_reports/token/19. Accessed 6 January 2021
  8. Davies NG et al. Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England. medRxiv 2020. doi: 10.1101/2020.12.24.20248822 European Centre for Disease Prevention and Control (ECDC). Risk related to the spread of new SARS-CoV-2 variants of concern in the EU/EEA – first update. https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-risk-related-to-spread-of-new-SARS-CoV-2-variants-EU-EEA-first-update.pdf

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