key to creating new COVID-19 variants

The COVID-19 pandemic has shown that respiratory viruses can quickly adapt to their environment, which is reflected in the emergence of new variants of SARS-CoV-2. These variants largely arise from mutations that allow the virus to improve its ability to transmit and evade immune defenses. In this context, studies have shown that immunocompromised patients may play a fundamental role in the evolution of these viruses by serving as reservoirs in which mutations are generated.

In the framework of Hemato2024, the National Congress of the Spanish Society of Hematology and Hemotherapy (SEHH) and the Spanish Society of Thrombosis and Hemostasis (SETH), Adolfo García Sastre, Professor in the Department of Microbiology and Director of the Institute for Global Health and Emerging Pathogens at the Icahn School of Medicine at Mount Sinai in New York Cityhosted an educational conference on the relationship of COVID-19 to immunosuppressed hematology patients.

To understand this process of viral evolution, we must go back to the early days of the pandemic, when what we know as the “prototype” SARS-CoV-2 virus was circulating. This initial version of the virus was soon replaced options with improved transmission characteristicssuch as the D614G mutation, which increased its ability to infect and became prevalent worldwide. Since then, successive variants such as Alpha, Beta, Gamma and, most recently, Omicron have marked different phases of the pandemic. Each of these variants has accumulated mutations that improve their survival in an environment where pre-existing immunity in the population is becoming more common.

Selection of mutations that promote reproduction

Selecting specific mutations responds to the virus’s need to survive and spread in a changing environment. For example, García Sastre explained that in the early months of the pandemic, “it was observed that the D614G mutation, which affects the spike protein, gave the virus greater binding ability to the ACE2 receptor in human cells. This mutation significantly increased the transmissibility of the virus and quickly became dominant, present in almost all subsequent variants.

“The spread of these variants occurs when a mutation allows the virus overcome immunity pre-existing condition of the infected person,” the expert said. If a mutant virus manages to infect someone with some immunity, such as a vaccinated person or someone who has already beaten the disease, then the variant can evade the immune response and begin successfully replicating and transmitting, generating more viruses with this ability. . That’s what happened with several variants of concern.

The role of immunosuppressed patients

“Immunocompromised patients represent a special and critical situation in the evolution of the SARS-CoV-2 virus,” explained García Sastre. Due to a weakened immune system, these patients often experience long-term infectionsbecause their defenses cannot destroy the virus as quickly as those of a person with a functional immune system. “This creates an environment in which the virus can multiply stably and generate multiple mutations,” he added.

In these patients, the virus remains active longer, which increases the likelihood of creating options. “While many of these mutations may not have a significant impact, some may give the virus an adaptive advantage, either in terms of immunological evasion or greater transmission capacity,” said the specialist, who also explained that “this phenomenon explains why” some variants arise in immunocompromised people and can then spread to the general population.”

Studies in animal models and cell cultures have shown that certain mutations in the spike protein region, such as those affecting the furin cleavage site, They increase the transmission capacity and infectivity of the virus. The expert explained that in an experiment with hamsters, researchers found that a virus with certain mutations spreads more efficiently and dominates other variants of the virus when both variants are in the same environment. “This supports the idea that in environments where the virus can persist for long periods of time, such as in immunocompromised patients, mutations that increase its spread are naturally selected for,” he said.

Omicron variant: immune evasion and low pathogenicity.

The Omicron variant was unexpected in the evolution of the SARS-CoV-2 virus. Unlike previous variants, Omicron has less cell fusion ability and replicates predominantly in the upper respiratory tract, which partly explains its lower pathogenicity compared to options like Delta. However, Omicron has become dominant in many countries around the world due to its ability to evade the immune response. This ability allows it to infect people who have already been vaccinated or have recovered from previous infections.

This variant accumulates a large number of mutations in the receptor binding region and in the cutting region of the spike protein, allowing it evade antibodies created in comparison with previous versions. “This combination of high immune evasion and low pathogenicity has led to the rapid spread of Omicron, although in many cases it causes less severe symptoms,” García Sastre said. However, new subvariants of Omicron have begun to show a return to greater cell fusion capacity, which may indicate a change in its behavior and clinical impact.

Strategies for controlling new variants

“To minimize the risk of new variants emerging, it is important to implement infection control strategies in immunosuppressed patients, such as those with cancer, those receiving immunosuppressive treatment, or those with debilitating chronic illnesses,” the expert said, as these people have a higher chance of having infection for a long time. generate variants that can spread in communities of people.

In addition, “it is critical to develop vaccines and antiviral treatments that provide broad and durable protection against multiple variants of SARS-CoV-2,” Garcia-Sastre said, assuring that “the new generation of vaccines under investigation are aimed at defense, not defense.” only against severe forms of COVID-19, but also to reduce the transmission of the virus, which is necessary to stop its evolution.” However, advances in antiviral treatments and immunotherapy may help shorten the duration of infections in immunocompromised patients by limiting the ability of the virus to develop within them.

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