LumiraDx Technical Bulletin: SARS-CoV-2 Variants

Viruses constantly change through mutation, and new variants of a virus are expected to occur over time. Sometimes new variants emerge and disappear. Other times, new variants emerge and persist. Many variants of the virus that cause COVID-19 have been detected globally during this pandemic. A variant may contain one or multiple mutations and these mutations can occur in locations such as the nucleocapsid protein or the spike protein region of the virus.

The LumiraDx SARS-CoV-2 tests and variants

The LumiraDx SARS-CoV-2 Ag, LumiraDx SARS-CoV-2 Ag Ultra, LumiraDx SARS-CoV-2 & Flu A/B and LumiraDx SARS-CoV-2 & RSV tests use antibodies (not nucleic acid based-primers like PCR) to capture SARS-CoV-2 nucleocapsid antigen (not the spike protein). Antibodies typically recognize 9-10 amino acid target sequences (equivalent to 27-30 nucleotide sequences). Thus, single nucleic acid point mutations are not likely to affect the performance of the LumiraDx tests. Furthermore, mutations outside of the nucleocapsid viral coding region (e.g. Spike protein) are highly unlikely to have an effect on the performance of the test.

Testing status of SARS-CoV-2 variants with the LumiraDx tests

LumiraDx is actively monitoring for new mutations in the SARS-CoV-2 viral genome as they arise. The reactivity of the LumiraDx tests is assessed against all mutations prevalent in the population at a level of greater than 1.0%, according to the GISAID database. The LumiraDx SARS-CoV-2 Ag assay is used in the LumiraDx SARS-CoV-2 Ag test, LumiraDx SARS-CoV-2 & Flu A/B test, LumiraDx SARS-CoV-2 Ag Ultra test and LumiraDx SARS-CoV-2 & RSV test. Table 1 is a summary of the performance of this assay with Variants of Concern as designated by the WHO. Evaluation has been carried out using in silico analysis, direct testing using recombinant nucleocapsid protein containing the specific mutations, live viral culture testing and testing of positive live clinical samples.

• Alpha Variant², Beta Variant³ and Gamma Variant³ - Detection was demonstrated in patient samples by UK Department of Health and Social Care, COVID-19 Technologies Validation Group.
• Beta Variant – Detection was demonstrated in patient samples by the South African National Health Laboratory Service.

*No longer VOC according to WHO. From 15 March 2023, the WHO will consider Omicron sublineages independently for classification as VOCs.

† The mutations possessed by BA.1, BA.2, BA.3, BA.4, BA.5, XE and lineages estimated to be >5% prevalent in the UK (England)¹⁷ and US¹⁴ (as of 23rd October 2024) are shown in Table 2.

* All mutations were tested separately. All mutations except P151S are also present in the XE nucleocapsid protein.

† Present mutations determined through mutation frequencies occurring at ≥70% mined from GISAID database for Jan2025.

• Delta Variant – Detection was demonstrated in patient samples as discussed by the UK Department of Health and Social Care, COVID-19 Technologies Validation Group.
• Omicron Variant – Testing with patient live samples was completed by LumiraDx. In addition, a prospective clinical study was carried out by Medical Research Network Diagnostics. Both studies showed that Omicron is detected by the LumiraDx SARS-CoV-2 Ag test with comparable sensitivity to the Delta variant.

In addition, the LumiraDx SARS-CoV-2 Ag test has been evaluated as part of the Foundation for Innovative New Diagnostics (FIND) process (https://www.finddx.org). For the COVID-19 response, FIND has commissioned independent evaluations of in vitro diagnostics following an Expression of Interest (EOI) process available on FIND's website by which all test submissions were scored according to their regulatory status and time to market, the manufacturing and distribution capacity of the supplier and the supplier-reported clinical and analytical performance.

As part of this evaluation, the Analytical sensitivity, i.e., Limit of detection (LoD), was performed at the Liverpool School of Tropical Medicine, U.K in which standardized serial dilutions of cultured viral isolate were prepared. Viral dilution was applied directly to the LumiraDx SARS-CoV-2 Ag test strip. Dilutions were tested in triplicate and the LoD was defined as the last dilution where all repeats were interpreted as positive. The data (Table 3) demonstrate that the LumiraDx SARS-CoV-2 Ag test can detect the U.K Wild Type (B.1), Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529 and B.1.1.529 sub lineage BA.2) variants.

Conclusion

All testing to date has demonstrated that the LumiraDx SARS-CoV-2 Ag test can detect all the SARS-CoV-2 variants of concern with comparable sensitivity.

As the WHO ended the public health emergency of international concern status of COVID-19 in May 2023¹⁵ and the disease is beginning to transition from a pandemic to epidemic state, the focus of LumiraDx variant monitoring is moving from wet testing to in silico surveillance of circulating and newly arising variants.

Definitions

Ag

Antigen

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

VOC

Variant of concern

WHO

World Health Organisation

PCR

Polymerase Chain Reaction

LoD

Limit of Detection

FIND

Foundation for Innovative New Diagnostics

pg

Picogram

pfu

Plaque Forming Unit

References

1. GISAID Regeneron Database - mutation details (https://gisaid.org/hcov19-variants/) (Accessed 20 November 2024).
2. UK Department of Health and Social Care (UK DHSC), COVID-19 Technologies Validation Group (TVG) report on LumiraDx SARS-CoV-2 Antigen test Report (January 2021)
3. UK DHSC COVID-19 TVG: Personal Communication by email (March 2021) Data on File
4. South African National Health Laboratory Service: Laboratory Evaluation Report (April 2021) Data on File
5. UK DHSC COVID-19 TVG: Personal Communication (Data on File May 2021)
6. World Health Organisation (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/) Accessed October 2023
7. FIND Report on the LumiraDx SARS-CoV-2 Ag test https://www.finddx.org/wp-content/uploads/2021/10/Lumira_Ag-Public-Report_v2_20211008.pdf
8. Data on File (Jan 2022)
9. Data on File (Feb 2022)
10. World Health Organisation (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/) Accessed October 2023
11. Data on File (Feb 2022)
12. Data on File (May 2022)
13. UKHSA Technical Briefing 55 (https://www.gov.uk/government/publications/investigation-of-sars-cov-2-variants-technical-briefings)
14. CDC (https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html#anchor_1632154493691) (Accessed October 2023)
15. Statement on the fifteenth meeting of the IHR (2005) Emergency Committee on the COVID-19 pandemic (https://www.who.int/news/item/05-05-2023-statement-on-the-fifteenth-meeting-of-the-international-health-regulations-%282005%29-emergency-committee-regarding-the-coronavirus-disease-%28covid-19%29-pandemic) (Accessed 11Mar2025)

Not all products are available in all countries and regions. Please check with your local LumiraDx sales representative or distributor for availability in specific markets.

The LumiraDx SARS-CoV-2 Ag Ultra, LumiraDx SARS-CoV-2 & Flu A/B and LumiraDx SARS-CoV-2 & RSV tests are not available in the US.