To follow the unpredictable evolution of the ongoing COVID-19 pandemic, the overall sequencing and surveillance capacity of SARS-CoV-2 must be strengthened, as well as multidisciplinary studies of infectivity, virulence and immune leakage.
The World Health Organization (WHO) set up a group to monitor the evolution of coronavirus 2 (SARS-CoV-2) from severe acute respiratory syndrome, as well as to monitor the characteristics of emerging variants and its impact on medical and non-medical remedies in June 2020. In November 2021, this group moved to the WHO Technical Advisory Group on Virus Development (TAG-VE), which is responsible for monitoring the overall risk of of SARS-CoV-2.
An article in the journal Nature Medicine examines the unpredictable evolution of the ongoing COVID-19 pandemic.
Study: An early warning system for emerging variants of SARS-CoV-2. Image Credit: NIAID
Monitoring of SARS-CoV-2 variants
TAG-VE was responsible for coordinating the exchange of information from research and global surveillance studies that would help monitor any early warning signals. He also assessed the need for public health action against emerging variants. The TAG-VE used a Delphi consensus method to determine which variants should be considered as variants of interest (VOI) and which as variants of concern (VOC). In addition, a naming scheme was adopted that followed WHO guidelines and assigned Greek letters to both VOI and VOC.
TAGS-VE first analyzed viral genome sequences and associated metadata to identify emerging variants. All available sequences are compared to the index virus that first appeared in late December 2019, as all current VOIs and VOCs originated from ancestral variants. The gene mutations that encode the viral spike protein are of high priority, as the spike protein comprises the receptor binding domain that helps the virus bind to host cells and also indicates viral transmissibility. However, other gene mutations have also been found to be crucial.
Mutations affect phenotypic characteristics such as immune leakage, transmissibility, susceptibility to treatment, detectability, and disease severity. This list of mutations is regularly updated and is important because similar mutations arise independently in different SARS-CoV-2 lines. These mutations are indicative of both the adaptation of the virus to the human host and the selection pressure caused by the population’s immunity. However, certain mutations affect the fitness of the virus rather than being a threat to public health. The TAG-VE assesses several indicators of a new emerging variant, such as the speed with which it arises, the geographical area and the population where it spreads, the reinfection rates, the severity of the disease and the progress of the vaccine to determine whether the variant will pose a serious threat. .
Sample acquisition
Studies have shown that the speed at which new variants spread can exceed the ability to assess their threats. While genomic indicators to increase the transmissibility and immune escape of VOCs are easy to assess, real-time data comparison is quite difficult. Improving physical characterization can be done by working with those viruses that have similar mutations. In this regard, the WHO has established a BioHub facility to facilitate the safe, reliable and transparent exchange of new biological material between WHO Member States.
Sequence data analysis
Key challenges include the representativeness, availability, and quality of genetic data. It is clear that viral diversification will require sustained, if not increased, investment by governments in reference laboratories to meet the public health demands of high-quality sequences and viral characterization of SARS-CoV-2, which can then be used to to future infectious virus threats. diseases.
Raw reading analysis to verify sequence quality is vital to detect recombination between SARS-CoV-2 genomes. Verified detection of the emerged Omicron VOC has increased mainly because the availability of genomic surveillance has increased along with natural factors. Detection of recombinant shapes is easier for Omicron due to many mutations that define the lineage. In addition, the chances of coinfection and recombination increase with reinfection with immune escape variants.
Assessment of infectivity and virulence
Infectivity and virulence can be assessed by identifying certain crucial sites and amino acid substitutions that serve as determinants of infectivity. Animal models may be useful in assessing virulence, as they may identify specific characteristics and do not take into account the impact of background immunity.
Determining the severity of the disease in the clinical setting can be challenging, but the interaction of electronic health records, the impartial and systematic collection of epidemiological and clinical data, biological sampling, and virulence characterization are of significant importance. in the assessment of the variant threat.
Until November 2021, the emergence of Delta and Alpha VOCs was associated with increased transmissibility and a modest flight of immunity. However, immune leakage was found to be the driving force behind the shift of Omicron VOC over Delta. Increased population immunity was their selective advantage along with increased transmissibility. The lower virulence of Omicron has been largely attributed to chance. In addition, hybrid immunity in individuals with innovative infections suggests that the continuing evolution of SARS-CoV-2 may be tolerable by population immunity. However, since the transmission and virulence of SARS-CoV-2 are not coupled, the next variant cannot be assumed to have the same virulence, or a lower or higher virulence than Omicron.
Early warning against emerging variants
According to previous retrospective analyzes, some of the key mutations involved in the definition of variants could have been detected earlier using early warning bioinformatics tools that use globally shared data. In addition, machine learning algorithms are being developed to determine the influence of key mutations. However, epidemiological data and in vivo and / or in vitro experiments are still needed to fully evaluate the variants.
It is difficult to predict the future of the pandemic due to factors such as the fact that, unlike other respiratory viruses, variants of SARS-CoV-2 do not emerge from the recently dominant circulating virus, chronic viral infections can lead to intrahostic evolution. Animals can function as secondary reservoirs with the potential for reverse zoonoses and a large percentage of the world’s population is not vaccinated.
In view of the uncertainty about the trajectory of SARS-CoV-2 and its continuous evolution, continuous monitoring is needed. The TAG-VE will continue to predict the evolution of future variants and their threat levels. The pandemic is not over yet. It is time to improve global sequencing capabilities and build a global agreement under the leadership of the WHO R&D plan to prevent epidemics and assess the threat that future variants of SARS-CoV-2 may pose.