Understanding the dangers presented by the SARS-CoV2 Delta variant

Professor Sunit K. Singh from the Institute of Medical Sciences at Banaras Hindu University, discusses the SARS-CoV2 Delta variant.

The Delta variant (B.1.617.2 strain) of SARS-CoV-2, has been reported to be a key culprit in the second wave of the COVID-19 pandemic, and it became the most dominant coronavirus strain globally. This variant is more transmissible than any previously reported SARS-CoV2 variant. Few reports on pre-print servers suggest that the rate of replication of Delta is more than any other variant which leads to a higher viral load in less time. Some groups reported that persons infected with the Delta variant tested positive sooner than other SARS-CoV2 variants infected patients.

Recently, a new mutation, P681R, has been reported in the Delta variant. The P681R mutation has been reported at a site between two subunits of the SARS-CoV2 spike protein. This site is the place for the action of cellular enzyme furin, which cleaves the spike into two parts. One school of thought suggest this mutation helps in the efficient entry of the Delta variant into a host cell.

In addition, another mutation, K417N, has been acquired by the Delta variant of SARS-CoV2 in the spike protein. The Delta variant having K417N has been named as the ‘Delta plus’ or ‘AY.1’ variant or (B.1.617.2.1), a sub-lineage of Delta. The K417N mutation was previously reported in the Beta variant (B.1.351 lineage) in Africa. The Delta plus variant has been reported to have some degree of immune evasive property and reduced effect of therapeutic monoclonal antibodies Casirivimab and Imdevimab.

Vaccine efficacy

Few vaccines had shown reduced efficacy with a single dose against the Delta variant compared to their double doses. The Pfizer-BioNTech vaccine had an efficacy of 33% with a single dose and 88% with both doses against the Delta variant, whereas Covishield had 33% after the first dose but 60% after the second dose against the Delta variant.

The Delta variant is reported to reduce the neutralising ability of antibodies to the virus by 2.5-fold compared to primary isolate among persons vaccinated with Pfizer-BioNTech or Moderna mRNA vaccines. This may be due to the mutations in the receptor-binding domain of the Delta variant. This mutation may result in reduced antibody binding with the receptor-binding domain of the Delta variant.

Few breakthrough infections (infections among persons having both doses of vaccines) have been reported in cases of the Delta variant, but that is not something to worry about because most of the vaccines currently in use do not provide absolute sterilising immunity, but reduce the severity of the COVID-19 disease. We also need the vaccines to access mucosal tissues in the nose and upper respiratory tract against SARS-CoV2.

The increased transmissibility and immune-evasive potential of the Delta variant of SARS-CoV2 is a matter of concern. This suggests that countries with low vaccination rates may see new outbreaks and so must follow COVID safe behaviour such as the use of masks and social distancing etc.

© iStock/Morsa Images
Countries with low vaccination rates may see new outbreaks and so must follow COVID safe behaviour such as the use of masks and social distancing

Immune evasion

Some features in the Delta variant (B.1.617.2) make it more transmissible and immune-evasive. The immune evasion properties might also be linked to the mutations at a specific site; termed as supersite in the N-terminal domain (NTD) of the spike proteins rather than the receptor-binding domain.

As per the published report, the unique mutations in the Delta variant results in the deletion of the amino acids at positions 156 and 157 in the supersite and changes the 158th amino acid from arginine to glycine. These changes eliminate a direct interaction of the neutralising antibody with the specific point or supersite, leading to more immune-evasion phenotype among Delta variants.

A recent pre-print study based on in-vitro experiments, suggests that SARS-CoV-2 infection leads to the cell fusion, forming syncytia, which has been reported in the lungs of people infected with SARS-CoV2.

Interestingly, hamsters infected with SARS-CoV-2 viruses engineered to express the P681R mutation showed more signs of obstructed airways, and lost weight rapidly than those infected with the SARS-CoV-2 without P681R mutation. The Delta variant may affect lungs adversely through larger syncytia formation. The syncytia formation also allows the variant to migrate from one cell to others without coming out of the cells. Such processes help the spread of the virus by hiding itself from the antibody attack.

The generation of SARS-CoV2 variants suggests that the SARS-CoV2 is trying its best to acquire fitness within the host, though I do not believe that this spread will continue forever. As seen in various other viral outbreaks, such an evolution in SARS-CoV2 may be stabilised after acquiring maximum transmission. That would stop the generation of new variants with high transmissibility or infectivity. Overall, one should get vaccinated with the COVID19 vaccines available in the area and follow COVID safe behaviour to contain the spread of SARS-CoV2.

Professor Sunit K. Singh
Professor of Molecular Immunology and Virology
Institute of Medical Sciences
Banaras Hindu University
+91 9621668812

Please note, this article will also appear in the seventh edition of our quarterly publication.

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