“Now we are at the foot of a new pandemic wave in Moldova. Probably, we can predict that there will be a wave that may be dominated by one of the variants of concern, and perhaps it will be Beta, Gamma or Delta. But it could also be a wave caused by a variant of big consequences. We must be prepared for a new confrontation.”
---

There has been a lot of talk about new variants of COVID-19 for a year now. I decided to write this article explaining what the new strains are and what risks they pose for Moldova.

New strains of COVID-19 are classified into three groups: variants of interest; variants of concern; variants of big consequences;

Variant of interest

A variant with changes in the S-protein that binds to the receptors of the human body, endowed with a reduced ability to neutralize antibodies produced after a previous infection or vaccination, a decrease in the effectiveness of treatment, a potential diagnostic effect or a predicted increase in transmissibility or severity of the disease.

Possible attributes of a variant of interest:

• Modified S-protein, which is estimated to affect transmission, diagnosis, therapeutic picture, or immune output.

• Evidence that this is the cause of an increase in the number of cases or individual groups of outbreaks.

• Limited prevalence or presentation in one or more countries.

A variant of interest may require one or more relevant public health actions, including improving sequencing surveillance, equipping laboratories, and expanding epidemiological investigations to assess how easily the virus spreads to others, what the severity of the disease is, the therapeutic efficacy of drugs, and whether vaccines that are currently allowed provide protection against it.

To properly understand and clearly interpret the information below, it is important to know what neutralization is.

Neutralization in our context is the ability of antibodies to neutralize the virus entering the human body.

Antibodies can be obtained naturally, after illness or vaccination, or artificially - after the transfusion of plasma of patients or infusion of monoclonal antibodies.

Reducing the neutralization of antibodies derived from convalescent serums and post-vaccination means that natural antibodies have a reduced ability to neutralize this variant and, possibly, it will pass the immune shield.

A decrease in neutralization – a proven property of a decrease in neutralization, a potential decrease in neutralization – is equivalent to the expected reduction in antibody neutralization in the future. The same goes for the action of monoclonal antibodies. Measurements and evaluations were carried out in vitro, i.e., in test tubes.

The following are current variants of interest in Eastern Europe that are tracked and described.

Epsilon variant

This variant was identified for the first time in the United States – (California) in 2020.

Features:

• ~ 20% increase in transmission.

• Moderate decrease in susceptibility to treatment with combinations of monoclonal antibodies.

• Alternative treatments with monoclonal antibodies are available.

• Reduction of neutralization of antibodies derived from the serum of convalescents and whether after vaccination.

Eta variant

First identification: UK/Nigeria - December 2020.

Features:

• Potential reduction of the effects of treatment with monoclonal antibodies.

• Potential reduction in the neutralization of antibodies derived from the serum of convalescents and whether after vaccination.

Iota variant

First Identification: USA (New York) - November 2020

Features:

• Decreased sensitivity to the treatment with combinations of monoclonal antibodies.

• Alternative treatments with monoclonal antibodies are available.

• Reduction of neutralization of antibodies derived from the serum of convalescents and whether after vaccination.

Kappa variant

First identification: India - December 2020.

Features:

• Potential reduction of the effects of treatment with monoclonal antibodies.

• Potential reduction in neutralization of antibodies derived from post-vaccination serums.

Zeta variant

First identification: Brazil - April 2020.

Features:

• Potential reduction of the effects of treatment with monoclonal antibodies.

• Reduction of neutralization of antibodies derived from the serum of convalescents and whether after vaccination.

Variant of concern

This is a variant for which there is evidence of increased transmissibility, more severe illness (e.g., hospitalization or increased mortality), a significant reduction in neutralization by antibodies generated during a previous infection or vaccination, a decrease in the effectiveness of treatment or vaccines, or failures in diagnostic detection.

The possible attributes of a variant of concern are similar to those of variants of interest.

In addition to the possible attributes of the variant of interest, the variant of concern also has:

• Evidence of effects on diagnosis, treatment, or vaccines.

• Widespread intervention in diagnostic test targets.

• Evidence of significantly low sensitivity to one or more classes of therapy.

• Evidence of a significant decrease in the ability to neutralize antibodies produced during a previous infection or vaccination.

• Evidence of reduced vaccine protection against serious diseases.

• Evidence of increased transmissibility.

• Signs of increased severity of the disease.

Variants of concern may require one or more appropriate public health actions, such as local or regional efforts to combat proliferation, increased testing, or research to determine the effectiveness of vaccines and treatments against the variant. Based on the characteristics of the strain, additional considerations may include the development of new diagnoses or modification of vaccines or treatments.

Current variants of concern in Eastern Europe that are closely monitored by national institutions are described below.

Alpha variant

Originally discovered in the United Kingdom in September 2020.

Features:

• ~ 50% increase in transmission.

• Potential increase in severity based on hospitalization data and mortality rates.

• Does not affect the susceptibility to treatment with monoclonal antibodies.

• Minimal effect on the neutralization of antibodies derived from the serum of convalescents or after vaccination.

Beta variant

This variant was originally discovered in South Africa in December 2020.

Features:

• ~ 50% increase in transmission.

• Significantly reduced sensitivity to treatment with combined monoclonal antibodies.

• Reduction of neutralization of antibodies derived from the serum of convalescents or after vaccination.

Gamma variant

This variant was first discovered in Brazil in January 2021.

Features:

• Significantly reduced sensitivity to treatment with combined monoclonal antibodies.

• Reduction of neutralization of antibodies derived from the serum of convalescents or after vaccination.

Delta variant

This variant was originally discovered in India in December 2020.

Features:

• Increased transmissibility.

• Potentially reduced sensitivity to some treatments with monoclonal antibodies.

• Potential reduction in the neutralization of antibodies derived from the serum of convalescents or after vaccination.

Presumably, these variants of concern are spreading more easily and faster than other strains, which could lead to more COVID-19 cases. An increase in the number of cases will lead to more pressure on medical resources, lead to an increase in the number of hospitalizations and, possibly, an increase in the number of deaths.

To date, research shows that currently approved vaccines work against current circulating options. Scientists will continue to explore these and other variants.

Big Consequences Variant

The big consequences variant has clear evidence that medical countermeasures (MCM) have significantly reduced their effectiveness compared to previous circulating strains.

Possible features of a variant with big consequences, in addition to the possible attributes of the variant of concern, also include:

• Effects on medical countermeasures (MKM).

• Demonstrated failure to diagnose.

• Data showing a significant decrease in vaccine effectiveness, a disproportionately high number of cases among vaccinated or very low vaccine protection against serious diseases.

• Significantly reduced sensitivity to several drugs from approved for emergency use or other approved methods of treatment.

• More severe clinical manifestations of the disease and an increase in the number of hospitalizations.

The variant of big consequences would require a change in prevention or transmission control strategies and recommendations for updating treatments and vaccines.

Currently, there are no variants of SARS-CoV-2 that can match the variants of big consequences.

Currently, for Moldova, the Alpha variant is confirmed as the dominant strain. The Delta variant has been confirmed as the dominant strain in EU countries. Voices are heard that speak with concern about Beta variant and its ability to bypass antibodies, including those developed after the vaccine.

Now we are at the foot of a new pandemic wave in Moldova. Of course, we can predict that there will be a wave that may be dominated by a variant of concern, and perhaps it will be Beta, Gamma, or Delta. But it could also be a wave caused by a variant of big consequences. We must be prepared for another confrontation.