Should we be more concerned about a lethal variant than a more contagious one of COVID-16?

May
26, 2021

7 min read

This story originally appeared on The Conversation

By Salvador Iborra Martín , Complutense University of Madrid

A virus generates hundreds of new viral particles. Mutations may appear in them as a consequence of the “errors” of the replication process. A virus that carries a new mutation becomes a new variant.

Mutations happen randomly. Most have no effect. They can even be harmful to the virus itself, disappearing as they have arrived. Occasionally, a mutation improves the infectivity of the virus, giving it a selective advantage. This new variant can be more pathogenic and even lethal.

Why we thought the British variant was more lethal

Variant B.1.1.7 was detected in September 2020 in the UK. After its rapid expansion in the south-east of England, it began to be seen as worrying at the end of the year.

Variant B.1.1.7 mutations appeared to enhance the ability of the virus protein S to bind to the host cell. Therefore, it was associated with a higher viral load .

Faced with this event, the health authorities were prudent. Although there was a correlation between its rapid spread and the increase in covid-19 cases, the new variant could not be the cause of this increase.

Furthermore, there was no evidence that this variant caused more serious disease. However, following a precautionary principle, more restrictive social distancing measures were applied in the country.

As the days passed and after examining the studies on the new variant, the United Kingdom’s New and Emerging Respiratory Virus Threat Advisory Group ( NERVTAG ) concluded in January that there was a “realistic possibility” that infection with this variant “Is associated with an increased risk of death .”

In addition, in March 2021, three articles were published that suggested an increase of around 60% in the risk of mortality with the new variant.

Variant B.1.1.7 is more contagious but not more lethal

Now, a new study published in The Lancet Infectious Diseases questions this increase, despite confirming that the viral load in patients with the B.1.1.7 variant is higher.

The study, conducted on people with COVID-19 admitted to University College London Hospital and North Middlesex University Hospital, sequenced virus samples from 341 patients. There they found that slightly more than half of the cases were positive for variant B.1.1.7.

The researchers compared the severity of symptoms between the two groups and found that patients infected with this new variant were not at increased risk of becoming seriously ill or dying.

This study is important for four reasons:

1. It was conducted between November and December, prior to the UK’s extensive vaccination program.

2. People who already had symptoms severe enough to require hospitalization were studied, not the general population.

3. Patients B.1.1.7 were younger and had fewer comorbidities than those not B.1.1.7. This may indicate that transmission increased in this population or that the probability of hospital admission associated with the variant increased.

4. People with the B.1.1.7 strain required oxygen more frequently, but the study authors consider that this requirement does not necessarily mean that the variant is more pathogenic or more lethal.

Ultimately, this study shows that a hospitalized person has the same probability of dying if they have the B.1.1.7 strain as if they have any other strain. More studies are likely to be needed to definitively conclude that the variant is not more lethal.

However, it must be taken into account that in any clinical study there are confounding factors. For example, the use of healthcare resources, demographic changes, social and behavioral trends, etc. All of these are difficult to consider without very detailed and robust patient data.

More lethal or more contagious, what should we be afraid of?

A virus cannot survive without a host. As a general rule, viruses evolve and increase their transmissibility, but not their pathogenic capacity. Many times, its high pathogenicity is transitory and reflects that the virus is not adapted to its host.

This is the case of some epidemic outbreaks caused by the jump of a virus from one species to another, such as MERS, with a mortality close to 35%. However, there are always exceptions and there is evidence that many pathogens do not evolve reducing their pathogenicity, but on the contrary.

An important factor to consider is the time period between infection and the onset of symptoms. In the case of the coronavirus, it can be considerably long (up to 14 days). An increase in the replicative capacity, even being parallel to an increase in pathogenicity, would greatly facilitate its transmission before killing its host. Therefore, we cannot completely rule out the appearance of new, more lethal SARS-CoV-2 variants.

What does the virus need to become more deadly?

In order not to disappear, a variant of any virus must constantly replicate and adapt to its host while competing with other variants. The problem is that while viruses “run” very fast, hosts tend to run slowly. For example, in humans the average period between two generations is around 20 to 30 years.

However, evolution has endowed us with a complex immune system capable of evolving and adapting to viruses. There is evidence that the increased fatality or severity of covid-19 is due to an inadequate response of the immune system, not a direct cytopathic effect of the coronavirus, which is more likely to occur in older people.

The good news is that, for these people, the vaccines work very effectively, even against the British variant.

However, we cannot rule out that “escape” variants appear in SARS-CoV-2. Said variants could accumulate mutations that, for example, prevent their recognition by the antibodies that the vaccines based on the original variant induce.

In short, we must be attentive to both aspects of the new variants, that is, their lethality and their transmission capacity. But, especially to those already mentioned of “escape”, since they are the ones that are probably the most pathogenic, multiplying in a more uncontrolled way before the immune system perceives what is happening.

Fortunately, vaccines also generate cellular immunity. Our T cells can recognize not only antigens on the surface of the virus, which tend to accumulate mutations more frequently, but also proteins with essential functions for the pathogen that do not “admit” mutations as frequently. In addition, we can always adapt vaccines to these escape variants.

^{This article is republished from The Conversation under a Creative Commons license. Read the original article .}