Delta (B.1.617.2)

Background

  • This variant has been named as the Delta variant by the WHO.
  • The Delta variant was first detected in India in December 2020 and became the most commonly reported variant in the country from mid-April 2021.
  • The variant could be more than twice as transmissible as the original strain of SARS-CoV-2.
  • The variant was first detectable in infected people four days after exposure, compared with an average of six days among infected people with the original virus, suggesting enhanced replication of this variant.
  • Individuals infected with this variant also had viral loads up to 1,260 times higher than those in people infected with the original virus.
  • The Delta variant is now contributing to a surge of cases around the world. It now makes up more than 80% of new cases in the United States
  • As of July 2021, the variant had been detected in more than 130 countries.
  • In the UK, there has been a rapid increase in cases with this variant associated with travel to India and community transmission. The Delta variant already makes up more than 90% of all infections.
  • Growth rates show that the Delta variant is growing faster than the Alpha variant.
  • A modeling study predicts that there is a “realistic possibility” that B.1.617.2 is 60% more transmissible than the Alpha variant (B.1.1.7).
  • Variant is defined by 19R, (G142D), 156del, 157del, R158G, L452R, T478K, D614G, P681R, D950N mutations in the spike protein.
  • Several of these mutations may impact on immune responses directed towards the key antigenic regions of receptor binding protein (452 and 478) and deletion of part of the N terminal domain (156 and 157).
  • P681R mutation changes an amino acid at a spot directly beside the furin cleavage site, a key step enabling the virus to invade human cells, thus enhancing viral infectivity.

Reference:

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant
Medrxiv, July 23, 2021

Rapid displacement of SARS-CoV-2 variant B.1.1.7 by B.1.617.2 and P.1 in the United States
Medrxiv, June 21, 2021

Sub Delta Variant (AY.4.2)

  • The variant currently accounts for 8% of sequenced coronavirus cases in the UK.
  • The variant could be 10 percent more transmissible than the most common Delta variant in the UK.
  • It carries two characteristic mutations in the spike, Y145H and A222V.

The Delta Plus Variant (AY.1)

  • The Delta plus variant was first found in India in April, 2021
  • The variant has also been found in nine other countries: USA, UK, Portugal, Switzerland, Japan, Poland, Nepal, Russia and China. 
  • The variant contains an additional mutation called K417N on the spike protein. It has been suggested that this change slightly reduces binding affinity to ACE2. 
  • Currently, it is uncertain whether this additional mutation is causing enhanced severity, transmissibility, and immune evasion of this Delta Plus variant compared to the Delta variant.

Disease Severity

  • A recent study showed that the hamsters infected with B.1.617.1 demonstrated increased body weight loss, higher viral load in lungs and pronounced lung lesions as compared to B.1 variant. Further studies will be required to confirm its disease severity.
  • It is not clear whether this variant enhances the disease severity.

Therapeutic Efficacy

  • B.1.617 S protein-mediated entry was efficiently inhibited by Etesevimab (LY-CoV016), Imdevimab (REGN10987) and by a cocktail of Casirivimab (REGN10933) and Imdevimab.
  • B.1.617 was resistant against Bamlanivimab (LY-CoV555).

Diagnostic Efficacy

  • The current molecular tests detect most of the variants and thus are able to diagnose COVID-19 infection by such variants. Yet, the fine identification of the type of variants is still based on sequence analysis although multiplex PCR test are being evaluated.
  • Indeed, the current variants of concern show distinctive mutations in the spike protein. Due to such mutations, most diagnostic tests for COVID-19 have been designed by targeting not only the spike protein but also other conserved proteins. For example, molecular tests designed to detect multiple SARS-CoV-2 genes (i.e., multiplex reverse transcription polymerase chain reaction targeting ORF1ab, N, and E genes) are less susceptible to the effects of genetic variation than tests designed to detect a single gene. The FDA is also monitoring the potential effects of genetic variation in molecular tests that have received Emergency Use Authorization and provides information about the tests.
  • Overall, the precise characterization of the variants still relies on genomic sequencing analysis. For instance, CDC is currently increasing sequence surveillance to more than 6000 samples per week to efficiently monitor the variants of concerns and other emerging variants. COVID-19 caused by variants in the U.S. can be found here.

Vaccine Efficacy

  • Use of  a live virus assay showed that the B.1.617.1 variant is 6.8-fold more resistant to neutralization by sera from COVID-19 convalescent and Moderna and Pfizer vaccinated individuals. 
  • Despite this, a majority of the sera from convalescent individuals and all sera from vaccinated individuals were still able to neutralize the B.1.617.1 variant. 
  • Protective immunity by the mRNA vaccines tested here are likely retained against the B.1.617.1 variant. This needs to be further evaluated by evaluating clinical data from vaccinated individuals.
  • In the U.K. trial, efficacy of 2-dose Pfizer vaccine against this variant was 87.9% (93.4% against B.1.1.7); 2-dose AstraZeneca showed 59.8% efficacy against this variant and 66.1% against B.1.1.7.

Publications