SARS-CoV-2 Variant – United Kingdom

On 14 December 2020, the United Kingdom (UK) authorities informed the WHO that a new viral genomic sequence had been identified with a new variant of SARS-CoV-2. This variant is called SARS-CoV-2 VUI 202012/01 (Researched variant, year 2020, month 12, variant 01). Initial analysis shows that the variant can be more easily spread among humans. Investigations are underway to determine if this variant is associated with any changes in symptom severity, antibody response, or vaccine efficacy.

A total of 1108 cases of SARS-CoV-2 VUI 202012/01 infected have been detected in the UK since 13 December 2020. The variant was taken as part of an epidemiological and virological investigation launched earlier in December 2020 following an unexpected increase in COVID-19 cases in South East England . It was characterized by more than a threefold increase in the 14-day case notification rate from epidemiological week 41 to week 50 (October 5 to December 13, 2020). On average, between 5 – 10% of all SARS-CoV-2 viruses are routinely sequenced in the UK and 4% routinely in the South East of England since the onset of the pandemic. From 5 October to 13 December, more than 50% of the isolates were identified as a variant strain in south-east England. A retrospective analysis followed the first identified variant in Kent in south-east England on 20 September 2020, followed by a rapid increase in the same variant identified later in November. Most cases of COVID-19 from which this variant was identified occurred in persons under 60 years of age.

The variant was defined by the presence of a series of 14 mutations resulting in amino acid changes and three deletions. Some of these mutations can affect the transmission of the virus to humans:

• One of the identified mutations (N501Y) alters the amino acid within six key residues in the receptor binding domain (RBD). According to the Global Avian Influenza Data Exchange Initiative (GISAID), the same same mutation of the receptor-binding domain (N501Y) has been independently reported in several countries, including South Africa (n = 45) and Australia (n = 37). Sequence analysis revealed that the N501Y virus mutation reported in the UK and South Africa originated separately.
• Another mutation of biological significance, P681H, was found in RBD.
• Finally, deletion at position 69/70 was found to affect the performance of some diagnostic PCR assays using the S gene target. Most PCR tests in the world use multiple targets, and therefore the impact of the variant on diagnosis is not expected to be significant.

A new variant of VUI-202012/01 has been identified in several countries, including Australia, Denmark, Italy, Iceland and the Netherlands.

Preliminary UK reports are that this variant is more transmissible than previous circulating viruses, with an estimated increase in portability between 40% and 70% (adding 0.4 to the basic reproductive number of R0, bringing it to a range of 1.5 to 1.7). Laboratory studies are underway to determine whether these virus variants have different biological properties or alter vaccine efficacy. There are currently insufficient data to determine whether this variant is associated with any change in clinical disease severity, antibody response, or vaccine efficacy.

Public health response

Authorities in the UK are conducting epidemiological and virological investigations to further assess the transmission, severity of the infection, the risk of re-infection and the antibody response to this new variant. Since one of the mutations (N501Y) is in the domain of receptor binding, the authorities are urgently investigating the serum neutralization activity of recovered and vaccinated patients according to this variant to determine if it has an impact on vaccine performance.

The UK authorities have transferred the genomic data of this variant to GISAID, and genomic surveillance of the virus is continuing across the country to monitor the situation.

On 19 December 2020, UK authorities announced that the affected areas would be subject to Level 4 restrictions, including reduced social gatherings, stricter restrictions on movement, demands to work from home whenever possible and the closure of irrelevant businesses.

WHO risk assessment

All viruses, including SARS-CoV-2, change over time, but most of these mutations or changes do not directly benefit the virus or may even be detrimental to its spread. Further laboratory testing is needed to better understand the impact of a specific mutation on viral properties and the efficacy of diagnostics, therapy, and vaccines. These researches are complex and require the time and cooperation of different research groups.

Sequencing the full genome allows for detailed analysis of the partner. The WHO SARS-CoV-2 Virus Evolution Working Group is working with colleagues from the UK to better understand the available results and support further research.

Further epidemiological and laboratory studies are rapidly needed to understand the implications of these viruses in terms of available clinical presentation of SARS-CoV-2, diagnosis, treatment, and vaccine development.

WHO advice

Preliminary UK findings signal the wider issue of SARS-CoV-2 virus mutations, and the WHO stresses the importance of rapidly sharing epidemiological, virological and whole genome data with other countries and research teams, including through open source platforms such as GISAID and others.

The WHO advises that further epidemiological and virological studies be conducted to understand the specific mutations described by the UK and other countries in order to further investigate any changes in virus function in terms of infectivity and pathogenicity. The WHO advises all countries to increase routine SARS-CoV-2 virus sequencing, where possible, and the international exchange of sequence data, especially to report if the same mutations of concern are identified.

The WHO would like to draw attention to concerns about the reported loss of performance of PCR tests targeting the spike (S) gene virus. Laboratories using commercial PCR kits for which the target viral genes are not clearly identified in the manufacturer’s instructions are advised to contact the manufacturer for additional information. Laboratories using internal PCR tests targeting the S gene virus should also be aware of this potential problem. To limit the impact on detection capacities in countries, an approach using different tests in parallel or multiplex tests targeting different viral genes is also recommended to allow the detection of potential variants.

All countries should assess the level of local transmission and implement appropriate preventive and control activities, including adjusting public health and social measures to WHO guidelines.

It is important to remind communities and health professionals of the basic principles of how to reduce the overall risk of transmitting acute respiratory infections:

• Avoiding close contact with people suffering from acute respiratory infections;
• Frequent hand washing, especially after direct contact with sick people or their surroundings;
• People with symptoms of an acute respiratory infection should behave in a manner of coughing (keep their distance, cover their cough and sneeze with disposable tissues or clothes and wash their hands);
• Improve standard infection prevention and control practices in healthcare facilities in hospitals, especially in emergency departments; and
• Wearing masks as needed and ensuring good ventilation.

The WHO recommends health measures as outlined above for all travelers, including to and from the UK. In case of symptoms indicating acute respiratory illness during or after the trip, travelers are advised to seek medical attention and share their travel history with their doctor. Health authorities should work with the travel, transport and tourism sectors to provide passengers with information on reducing the overall risk of acute respiratory infections through health clinics, travel agencies, carriers and entry points.

In line with the advice given by the COVID-19 Emergency Committee at its most recent meeting, the WHO recommends that States Parties regularly review measures applicable to international travel in accordance with Article 43 of the IHR (2005) and continue to provide information and WHO explanation of measures that significantly impede international traffic. Countries should also ensure that measures affecting international traffic are risk-based, evidence-based, coherent, proportionate and time-bound.

The WHO recently issued interim guidelines – “Considerations for applying a risk-based approach to international travel in the context of COVID-19“, provide countries with a risk-based approach to the decision-making process to calibrate travel mitigation measures in the context of international travel, with a view to reducing exports, imports and the further transfer of travel-related SARS-CoV-2, while avoiding unnecessary disruption to international traffic.

The WHO recommends that countries approach a risk-based approach. National authorities are encouraged to publish their risk assessment methodology and list of countries of departure to which restrictions apply; and they need to be updated regularly. In all circumstances, emergency travel (eg emergency services; public health technical support providers; critical personnel in the transport and security sector, such as seafarers; repatriation and transport of goods for basic necessities such as food, medicine and fuel) identified by States should always be given priority and make it easier.

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