A detection system for emerging variants of SARS-CoV-2

To keep up with the unpredictable evolution of the ongoing COVID-19 pandemic, the global capacity for sequencing and surveillance of SARS-CoV-2 must be strengthened, as well as multidisciplinary studies of infectivity, virulence and immune evasion. .

The World Health Organization (WHO) has set up a group to track the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as to monitor the characteristics of emerging variants and their impact on medical and non-medical remedies in June 2020. In November 2021, this group transitioned to the WHO Technical Advisory Group on Virus Evolution (TAG-VE), tasked with monitoring the global risk of SARS-CoV variants -2.

An article published in the journal natural 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

SARS-CoV-2 Variant Tracking

TAG-VE was responsible for coordinating the exchange of information from research studies and global surveillance that would help monitor any early warning signs. Additionally, it assessed whether public health action was needed against emerging variants. The TAG-VE used a Delphi consensus method to determine which variants should be considered variants of interest (VOI) and which variants of concern (VOC). Additionally, a naming system was adopted that followed WHO guidelines and assigned Greek letters to VOIs and VOCs.

TAGS-VE first analyzed viral genome sequences and associated metadata to identify emerging variants. All available sequences are compared to the index virus which first appeared at the end of December 2019 since all current VOIs and VOCs were from the ancestral variants. Gene mutations encoding the viral spike protein are of high priority since the spike protein includes the receptor binding domain that aids in virus attachment to host cells and indicates viral transmissibility. However, other genetic mutations have also proven to be crucial.

Mutations impact phenotypic characteristics such as immune escape, transmissibility, susceptibility to treatments, detectability and disease severity. This list of mutations is regularly updated and is important because similar mutations occur independently in different lineages of SARS-CoV-2. These mutations are indicative of both the adaptation of the virus to the human host and the selection pressure induced by population immunity. However, some mutations impact the fitness of the virus rather than being a threat to public health. TAG-VE assesses several indicators about a new emerging variant, such as how quickly it emerges, the geographic area and population it is spreading through, reinfection rates, disease severity, and vaccine breakthroughs 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 capacity of their threat assessment. Although genomic indicators of increased transmissibility as well as immune escape from VOCs are easy to assess, comparing real-time data is quite difficult. Improved physical characterization can be achieved by working with viruses that have similar mutations. In this regard, WHO has established a BioHub facility to facilitate the safe, reliable and transparent exchange of new biological material among WHO Member States.

Sequence data analysis

The main challenges include the representativeness, availability and quality of genetic data. It is evident that viral diversification will require sustained and even increased investment by governments in reference laboratories to meet public health demands for high quality sequences and viral characterization of SARS-CoV-2, which can then be used for future threats of infectious origin. diseases.

Analysis of raw reads to verify sequence quality is essential for detecting recombination between SARS-CoV-2 genomes. Verified detection of the emerged Omicron VOC has increased primarily since the availability of genomic monitoring has increased along with natural factors. Detection of recombinant forms is easier for Omicron due to numerous lineage defining mutations. Additionally, the risks of co-infection and recombination increase upon re-infection with immune evasion 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 can be useful in assessing virulence because they can identify specific characteristics and do not take into account the impact of background immunity.

Determining disease severity in the clinical setting can be challenging, but the interoperability of electronic health records, unbiased and systematic collection of epidemiological and clinical data, biological sampling, and characterization of virulence are important. significant importance in the assessment of the threat variant.

Until November 2021, the emergence of Delta and Alpha COVs was associated with increased transmissibility and modest immunity. However, immune evasion was found to be the driving force behind Omicron VOC’s displacement on Delta. Increased population immunity was its selective advantage with increased transmissibility. Omicron’s lesser virulence has been largely attributed to chance. Moreover, hybrid immunity in people with breakthrough infections suggests that the continued evolution of SARS-CoV-2 may be tolerable by population immunity. Nevertheless, since the transmission and virulence of SARS-CoV-2 are not coupled, it cannot be assumed that the next variant will have the same virulence, or lower or higher virulence than Omicron.

Early warning against emerging variants

According to previous retrospective analyses, some of the key mutations implicated in defining the variants could have been detected earlier using bioinformatics early warning tools that use globally shared data. Additionally, 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 assess the variants.

Predicting the future of the pandemic is difficult due to factors such as the fact that, unlike other respiratory viruses, SARS-CoV-2 variants do not emerge from the recently dominant circulating virus, chronic viral infections can be carriers of intra-host evolution, animals can function as secondary reservoirs with the potential for reverse zoonoses, and a large percentage of the world’s population is unvaccinated.

Given the uncertainty regarding the trajectory of SARS-CoV-2 and its continued evolution, continued monitoring is needed. 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 strengthen global sequencing capabilities and build global agreement under the guidance of the WHO R&D Plan to prevent outbreaks and assess the threat that future SARS-CoV-2 variants may pose.