The SARS-CoV-2 virus, which causes COVID-19, has had a major impact on human health around the world: it has infected large numbers of people; it has caused serious forms of disease and long-term health consequences; it has led to deaths and excess mortality, particularly among the elderly and vulnerable populations; it has affected the usual health services; it has disrupted travel, commerce, education, and many other social activities; and, in general, it has had negative repercussions on the physical and mental health of populations. Since the beginning of this pandemic, WHO has received several reports of unusual public health problems that could be due to variants of SARS-CoV-2. The Organization regularly evaluates whether the transmission capacity and the clinical picture and the severity of the symptoms caused by any of these variants are different, or if they affect the measures used to combat it, such as means of diagnosis, treatments and vaccines. The previously reported D614G variant and recent reports of virus variants in Denmark, the United Kingdom of Great Britain and Northern Ireland, and South Africa have raised interest and concern about the effects of these virus transformations.
In late January or early February 2020, a variant of SARS-CoV-2 appeared with a D614G substitution in the gene that codes for its protein S. Over the course of several months, it ended up replacing the initial virus detected in China and, in June By 2020, it became the preponderant variant around the world. Studies in human respiratory cells and animal models have shown that the D614G substitution virus is more infectious and transmissible than the parent virus, although it causes less severe symptoms and does not reduce the effectiveness of the means of laboratory diagnosis, treatments, vaccines or existing public health preventive measures.
In August and September 2020, a variant of SARS-CoV-2 was identified in North Jutland (Denmark) that was o transmitted between farm mink and, later, to the human being. This variant, called "cluster 5" by the Danish authorities, has an unprecedented combination of mutations. Preliminary studies conducted in that country have expressed concern about the possibility that the neutralization of the virus is impaired in humans, which would limit the scope and duration of immunological protection after natural infection or vaccination. Neutralization of this variant in humans is being investigated. Following extensive investigation and surveillance activities to date, the Danish authorities have recorded only 12 human cases of the 'cluster 5' variant dating back to September 2020, and the spread of this variant appears limited.
On 14 December 2020, UK authorities notified WHO of a variant, which they designated as SARS-CoV-2 VOC 202012/01 (Investigational Variant, Year 2020, Month 12, Variant 01 »), with 23 nucleotide substitutions and not phylogenetically related to SARS-CoV-2 that was circulating in the country at the time it was detected. Neither the source nor the way in which it initially arose is not clearly known. SARS-CoV-2 VOC 202012/01 was first detected in south-east England, but within weeks it was gradually displacing other lineages of the virus in that area and in London. On December 26, 2020, this variant was found after systematic sampling and genomic analysis carried out throughout the country. According to the first results of epidemiological, modeling, phylogenetic and clinical studies, the transmissibility of SARS-CoV-2 VOC 202012/01 is higher than that of the parent virus, but this variant is not more virulent (according to the length of hospitalization and the case fatality rate at 28 days) and the reinfection rate is not higher than that of other variants of SARS-CoV-2 circulating in the UK.1 On the other hand, the deletion in positions 69/70, another mutation present in the VOC 202012/01 variant, has been shown to affect the sensitivity of some diagnostic PCR tests that target the protein S gene. No However, the majority of PCRs used in the world use multiple targets and, therefore, no significant effects are expected on the ability to diagnose infection. Based on laboratory evaluations, the performance of lateral flow immunoassays for detecting SARS-CoV-2 antigens is not significantly affected. As of December 30, a further 31 countries, territories or areas in five of the six WHO regions had reported the VOC 202012/01 variant.
On December 18, South African authorities announced that they had detected a new variant of SARS-CoV-2 that is spreading rapidly in three provinces of the country. South Africa has named this variant 501Y.V2 because the virus carries the N501Y mutation. Although the VOC 202012/01 variant also exhibits this same mutation, phylogenetic analyzes indicate that the South African variant is not the same as the British variant. During the week of November 16, systematic sequencing carried out by the South African health authorities revealed that this new variant has largely replaced the other SARS-CoV-2 viruses circulating in the Eastern Cape, Western Cape and Western Cape provinces. KwaZulu-Natal. Although genomic data show that the 501Y.V2 variant has rapidly displaced the other lineages that circulate in that country and preliminary studies suggest that it is associated with a higher viral load - which suggests that it has a greater capacity to transmit -, These and other factors that may affect this capacity continue to be studied. In addition, at the moment it has not been clearly demonstrated that this new variant causes more serious symptoms or more adverse results, and further research is required to determine its effects on transmission, the clinical severity of the infection, laboratory diagnosis, the treatments, vaccines and preventive public health measures that are applied. As of December 30, four other countries had reported the South African 501Y.V2 variant.
Public health response
The authorities of the affected countries are conducting epidemiological and virological investigations to more accurately assess the transmission capacity, severity, risk of reinfection, and antibody response to new variants. Since the N501Y mutation present in the VOC 202012/01 and 501Y.V2 variants is in the receptor binding domain, authorities are studying the neutralizing activity of the sera of patients cured or vaccinated against these variants to determine if the vaccine performance is affected. These investigations are still ongoing.
Genomic data for the VOC 202012/01 and 501Y.V2 variants have been submitted by national authorities, which have been published on the Global Initiative for Avian Influenza Data Exchange (GISAID) platform, and continued worldwide. conducting genomic surveillance of the virus.
The following activities have been launched:
- The national authorities that have notified variants of the virus are intensifying the collection of samples to determine the degree of their circulation.
- Scientific teams in the countries are studying the effect of mutations on reinfection potential, vaccination, diagnostic tests, severity of infection and transmission capacity.
- Researchers and government authorities collaborate with WHO and members of the WHO Working Group on the Evolution of SARS-CoV-2 to evaluate epidemiological, modeling, phylogenetic and laboratory data as they become available.
- WHO is working with countries to determine how current surveillance systems can be strengthened or adapted to assess potential virus variations through systematic and ongoing clinical and epidemiological surveillance, capacity building in genetic sequencing ( when possible) and access to international services to send samples for sequencing and phylogenetic analysis.
- Risk communication and community mobilization activities have been increased to explain the consequences for public health of the variants of SARS-CoV-2 and to underline the importance of maintaining measures that prevent its transmission, such as the use of masks, hand hygiene and proper coughing practices, maintaining physical distance, sufficient ventilation of enclosed spaces, and avoiding crowded places.
As part of the global network of WHO laboratories studying SARS-CoV-2, which tracks mutations detected since the beginning of the pandemic, the WHO Working Group on the evolution of the SARS-CoV-2020 virus composed of experts in sequencing, bioinformatics, and in vivo and in vitro laboratory tests. This group is in charge of: 2) reinforcing the mechanisms to detect mutations that may be important and, if necessary, establish an order of priority between them; 1) rapidly detect important mutations and investigate their possible effects on the characteristics of the virus (for example, its virulence and transmission) and the effectiveness of current and future measures to combat it (such as diagnostics, vaccines and treatments); 2) evaluate possible mitigation strategies to reduce the negative effects of mutations; and 3) study the impact of specific mutations, which entails studying the variants in the laboratory, in vivo and in vitro. The sharing of entire genome sequences is making it easier for partners to conduct detailed analysis. The Task Force collaborates with scientists around the world with a wide range of expertise in virology in general, and coronavirus specifically, to better understand study results and help further research.
Risk assessment by WHO
All viruses, including SARS-CoV-2, evolve over time, most of the time without giving them direct benefits such as increased infectivity or transmissibility and sometimes by limiting their spread (see questions and answers about COVID-19 and other related health topics). Since the mutational potential of viruses increases with the frequency of human and animal infections, reducing the transmission of SARS-CoV-2 by methods of proven efficacy to fight disease and prevent the introduction of viruses into animal populations are key aspects of the global strategy to reduce the occurrence of mutations that may have negative consequences for public health.
Preliminary data indicate that the growth rate and effective breeding numbers are high in areas of the UK where the new variant VOC-202012/01 circulates. In South Africa, genomic data have shown that the 501Y.V2 variant has rapidly displaced other circulating lineages, and preliminary studies suggest that this variant is associated with a higher viral load, suggesting that its transmissibility may be higher; however, these and other factors that affect transmissibility are still being investigated. Epidemiological studies are being carried out to understand the reason for the increasing number of cases in these communities and the possibility that these variants are more transmissible, as well as the degree of application of control measures. According to the initial evaluations, the 202012/01 and 501Y.V2 variants do not alter the clinical picture or the severity of the disease, but they increase the incidence of cases and, therefore, hospitalizations and deaths could also do so. It may be necessary to intensify public health measures to contain the transmission of these variants.
Further research is needed to determine the effects of certain mutations on the properties of the virus and on the efficacy of diagnostics, treatments and vaccines, although these studies, which have already been launched, are complex and time consuming and collaboration between different groups of researchers.
WHO recommendations
National and local authorities should continue to strengthen current activities to combat COVID-19, such as the epidemiological surveillance continuous and strategic realization of screening tests; outbreak investigation and contact tracing, and where necessary the adaptation of social and public health measures to reduce the transmission of SARS-CoV-2.
Likewise, the WHO recommends that countries, whenever possible, increase the systematic sequencing of this virus to better understand its transmission and control the appearance of variants. Sequence data should be disseminated internationally in publicly accessible databases. For countries with sequencing capacity, WHO recommends sequencing isolated samples from a systematically selected subset of SARS-CoV-2 infection cases, the number of which will depend on local capacity. Genetic sequencing should also be considered when studying unusual patterns of transmission (eg, increased transmission despite existing control measures) or unexpected severity or clinical picture of the disease. If sequencing capacity is limited, countries should increase it by collaborating with public, university and private sequencing laboratories and collaborating laboratories from the network of reference laboratories for COVID-19..
SARS-CoV-2 will continue to mutate and it is important to continue studying the consequences for public health of its new variants, since an increase in transmissibility could make it difficult to fight the virus. The current control measures for COVID-19 recommended by the WHO continue to be effective and must be adapted in the event that the incidence of the disease increases, whether or not this increase is associated with a new variant.
with prevention, particularly precautions On the other hand, it is necessary to continue transmitting to the population advice related to protect yourself and others, such as physical distancing, the use of masks, adequate ventilation of closed spaces, the avoidance of crowds, hand hygiene and the precaution of coughing in the elbow flexure or in a tissue. In addition, the guidelines and anti-infectious control measures between them:
- use appropriate personal protective equipment when caring for people with acute respiratory illnesses;
- wash your hands frequently, especially after direct contact with sick people or their environment;
- cover your nose and mouth with tissues or clothing when sneezing or coughing, and wash your hands;
- improve routine anti-infective control practices in hospitals, especially in emergency services;
- wear a mask if necessary, ensure that there is good ventilation whenever possible and avoid crowded areas.
WHO has recently published interim guidance «Considerations for implementing a risk-based approach to international travel in the context of COVID-19 «, (Aspects that must be taken into account to apply risk-based criteria to international travel in the context of COVID-19), in which the following principles are recommended for people who have to make such movements:
- confirmed, probable and suspected cases, as well as contacts of confirmed or probable cases, should not travel;
- People with signs or symptoms suggestive of COVID-19 should not travel unless they have undergone a diagnostic test for this disease and infection with SARS-CoV-2 has been ruled out;
- people who are not feeling well have to postpone the trip;
- Travel should also be postponed by people at risk of severe symptoms of COVID-19, including those 60 years of age and older and those with diseases that increase their risk (for example, heart disease, cancer and diabetes);
- Depending on local restrictions, persons residing in areas where travel restrictions have been imposed should not make non-essential travel;
- Travelers with symptoms of acute respiratory illness during or after the trip should seek medical attention and report trips made to health professionals.
Health authorities should collaborate with the travel, transport and tourism sectors to provide people who travel, including to and from countries affected by the new variants, the aforementioned information, through health centers to travelers, travel agencies and carriers, and at points of entry; This information should also be provided to communities living in areas contiguous to land borders with affected countries.
These interim guidance also provide countries with risk-based criteria for making decisions regarding risk mitigation measures for international travel, taking into account both the need to avoid the export, import, and transmission of SARS-CoV- 2 and unnecessary obstacles to international transit. Some countries have recently imposed travel restrictions as a precaution against the emergence of new variants. WHO recommends that all countries adopt a risk-based approach to adapt any measure in the context of international travel, including considering local transmission, capacity of health services, available data on the transmissibility of different variants, the social and economic repercussions of the restrictions, and the degree of compliance with social and public health measures. National authorities should make public the methods they use to assess risks and the list of countries or exit areas to which restrictions apply, and regularly update this information.
In accordance with the recommendation of the Emergency Committee on COVID-19 in its most recent meeting, WHO advises States Parties to regularly review measures applied to international travel, in accordance with Article 43 of the International Health Regulations (2005), and to continue to provide information and justifications to WHO for measures that significantly impede international transit. In addition, they must ensure that measures affecting international traffic are risk-based and evidence-based, consistent and proportionate, and applied within defined time frames.
In all circumstances, priority should always be given to travel that is essential (for example, emergency response personnel and those providing technical support to public health services, essential workers in the transport and transportation sectors). security, such as sailors; repatriations and the transport of essential goods such as food, medicine and fuel), as determined by the countries; those trips must be facilitated.
For more information on COVID-19, please consult the following sources:
1 Public Health England. Investigation of novel SARS-CoV-2 variant, Variant of Concern 202012/01 Technical briefing 2- 28 December 2020. PHE: London; 2020