BY Prof. Suranjith Seneviratne All viruses including the severe acute respiratory syndrome corona virus two (SARS-CoV-2) Virus changes over time. Most of the changes that occur are of little clinical significance, but from time to time, a variant comes up, that makes scientists around the world sit up and take particular note of. The new SARS-CoV-2 variant, currently called B.1.1.529 possibly fits this profile. This SARS-CoV-2 variant is highly mutated and has an unusual set of mutations. Some of the mutations are different to that seen in other important SARS-CoV-2 variants that have been in circulation during the past several months. The World Health Organization is likely to assign a Greek letter designation to this new variant shortly. This B.1.1.529 variant has 50 gene mutations in total, with 32 of them found on the spike protein gene. A total of 10 of these changes occur within the receptor binding domain (RBD). In comparison, the currently globally widespread Delta SARS-CoV-2 variant, has two changes in the RBD region. The spike protein is used by the Virus to bind to angiotensin- converting enzyme (ACE) receptors on cells, and at present, is also the target of most Covid- 19 vaccines. So far, it has been suggested that the large number of mutations in the variant, accumulated in a single burst. It may have evolved during a chronic infection in an immunocompromised individual, possibly an untreated human immunodeficiency virus (HIV) patient. We know that the number of mutations present per se is not what determines the true clinical significance of a viral variant, but that it is the actual change that occurs and the combination in which they occur. Some mutations may make it easier for the virus to spread (that is result in increased transmissibility), whereas others may make it more difficult for antibodies (that are formed following a SARS-CoV-2 infection or Covid-19 vaccination) to bind to the virus. A combination of adverse properties may be more relevant to the clinical effect. For instance, the Delta variant had both transmissibility and moderate immune escape effects and took over as the dominant global variant very quickly. On the other hand, the Beta variant had important immune escape properties but the transmissibility was less. The B.1.1.529 variant is very different to the Virus that was originally identified in Wuhan, China in early 2020. The new variant has some mutations seen in other variants that are known to be associated with both higher transmissibility and immune escape. Where is the B.1.1.529 variant found? The new variant was first detected in Botswana on 11 November 2021. So far, around 100 confirmed cases have been recorded in the Gauteng Province in South Africa (an area that encompasses both Pretoria and Johannesburg), and may account for around 90% of the new cases in this location. It is likely to have spread to other Provinces in South Africa. So far, the variant has been seen spreading mostly among young people, particularly in schools. Overall in South Africa, approximately 41% and 35% of adults have received one and two vaccine doses, respectively. However, we need to note that in the Continent of Africa, the average double vaccination rate is much lower at less than 7%. There have been four cases in Botswana and one in Hong Kong, but it is likely that the new variant has spread more widely. The Hong Kong case was of a 36-year-old man who was polymerase chain reaction (PCR) negative before flying from Hong Kong to South Africa on 22 October 2021. He stayed in South Africa till 11 November and tested negative on his return to Hong Kong. However, on 13 November 2021, he tested positive whilst in quarantine. Laboratory studies are ongoing to delineate the exact properties of the new variant. It would take a few weeks for us to understand what potential impact this variant has on the currently used vaccines. Presently, we do not know if it spreads faster than Delta or causes more severe illness. The variant harbours a spike mutation that allows it to be detected by genotyping tests that deliver results much more rapidly than genome sequencing. Studies are been done to assess the extent to which it may be able to evade immune protection post-illness or vaccination. The current variant needs to be assessed rapidly and monitored carefully. Concern would increase if the number of cases starts increasing in several parts of the world. Precautionary steps may be needed before we have all the answers and this may contribute for some of the travel advisories that have been instituted in the United Kingdom (UK). Yesterday (25), the UK announced that it would temporarily suspend all flights from South Africa, Botswana, Eswatini, Namibia, Lesotho, and Zimbabwe as a precaution. Israel has also imposed a travel ban for those six countries, as well as Mozambique. In the face of the regular appearance of new variants, people should get appropriately vaccinated, practice hand hygiene, wear masks, maintain social distancing, and gather in well ventilated spaces, in order to limit its spread. (The writer is a Professor and Consultant in Clinical Immunology and Allergy at the Institute of Immunity and Transplantation and Health Services Laboratories, London, UK)