How dangerous is the Delta variant (B.1.617.2)?
For a world that has become weary but used to playing defense against SARS-CoV-2, the evolution of the Delta variant is unwelcome and unsurprising. Delta, or B.1.617.2 , was first identified in India in December 2020. In a matter of months, this specific variant has spread to over 98 countries around the world, becoming the dominant variant in over a dozen of these countries, including India, Scotland, the United Kingdom, Israel and the United States. Delta now accounts for more than 83% of reported COVID-19 cases in the US, and with only 48% of the total US population fully vaccinated, conditions are ripe for the continued evolution and spread of SARS-CoV-2. Three fundamental questions continue to drive research with each new variant identified.
1. HOW CONTAGIOUS IS THE DELTA VARIANT?
Data indicate that Delta is 40-60% more transmissible than Alpha and nearly twice as transmissible than the original Wuhan strain of SARS-CoV-2. In addition, significantly more viral particles were found in the airways of patients infected with the Delta variant. A Chinese study reported that viral loads in Delta infections were about 1,000 times higher than in infections caused by other strains. In response to this information, the World Health Organization (WHO) considers Delta to be the “ fastest and most suitable ” variant to date.
2. IS THE DELTA VARIANT MORE DANGEROUS THAN OTHER WORRYING VARIANTS?
According to research carried out in the UK, where Delta accounts for ~90% of current COVID-19 cases, Delta's symptoms tend to be somewhat different from those of other strains, but this does not necessarily mean that the associated symptoms are more serious. Fever, headache, sore throat and runny nose are common, while coughing and loss of smell are not. Other reports link Delta to more serious symptoms , including hearing loss, severe gastrointestinal problems and blood clots that lead to tissue death and gangrene. Research is underway to determine whether Delta infection is associated with increased hospitalization and death. A previous study that assessed the risk of hospital admission in Scotland reported that hospitalization is twice as likely in individuals not vaccinated with Delta than in individuals not vaccinated with Alpha.
The number of cases and hospitalizations are once again on the rise in the United States, especially in states where vaccination rates are low and the Delta variant is increasing. As of July 16, 2021, the Centers for Disease Control and Prevention (CDC) reported an average 7-day increase in new COVID-19 cases of 69.3% and a 35% increase in hospitalizations. Still, it's difficult to determine whether Delta is actually making people sicker than previous forms of the virus or is simply circulating among the most vulnerable populations where case numbers are high, vaccination rates are low and the Increased stress on hospital systems is affecting patient care and disease outcomes.
What is clear is that the majority of hospitalizations and deaths associated with COVID-19 in the US are occurring in unvaccinated people , leading to a startling warning from CDC director Dr. Rochelle Walensky that "this is becoming a pandemic of unvaccinated".
3. WILL VACCINES REMAIN PROTECTIVE AGAINST THE DELTA VARIANT?
Studies show that 2 doses of vaccine are effective in preventing hospitalization and death, but neutralizing levels of vaccinated sera are lower against the Delta variant compared to the original strain. A study published in the New England Journal of Medicine tested the neutralizing activity of sera from individuals who had recovered from natural SARS-CoV-2 infection and sera from individuals who had been fully vaccinated with Moderna or Pfizer B.1.617 virus vaccines .2 infectious. The study data indicated that, on average, the Delta variant was 2.9 times less susceptible to neutralization than the Wuhan strain, but most convalescent serum samples and all vaccination serum samples showed detectable neutralizing activity. . As a result, the researchers concluded that the immunity conferred by mRNA vaccines will likely be maintained against the Delta variant.
These results were supported by research, published in Nature , which evaluated the sensitivity of the infectious Delta virus against monoclonal antibodies, convalescent sera and sera developed after vaccination. The study found that some antibodies targeting the N-terminal domain and the spike protein receptor binding domain (S protein) showed impaired binding and neutralization of the Delta variant. In addition, convalescent sera, collected up to 12 months after symptoms from individuals who recovered from natural SAR-CoV-2 infection, were 4 times less effective in neutralizing Delta than Alpha. Sera from partially vaccinated individuals (who received 1 dose of Pfizer or AstraZeneca vaccine) showed little or no neutralizing activity against Delta. Serum from 95% of those who received 2 doses of either vaccine generated a neutralizing response that was 3 to 5 times less potent against Delta than Alpha.
CULPABLE MUTATIONS OF THE DELTA VARIANT
Receiver binding domain
The receptor binding domain is the portion of the spike protein that binds directly to human ACE2 receptors. Delta has 3 RBD mutations. The first, a lysine to asparagine substitution at position 417, is present in some, but not all, sequences of B.1.617.2. It is also common to the Beta variant and has been associated with protein S conformational changes, which can aid in immune escape. The second mutation, a leucine-arginine substitution at position 452, is common to the first variant of interest Epsilon and is known to increase affinity for ACE2 receptors found on the surface of a variety of human cells, including the lungs. And the third, a threonine to lysine substitution at position 478, is common to the B.1.1.519 lineage, and was predicted to increase electrostatic potential and steric hindrance , which may further increase RBD/ACE2 binding affinity and allow for immune escape.
Furin Cleavage Site
The spike protein consists of a receptor-binding subunit (S1) and a fusion subunit (S2), which must be cleaved from each other to mediate membrane fusion and cause infection. The furin cleavage site is the junction where this cleavage occurs, and Delta contains a proline-to-arginine substitution (also common for Alpha) near this cleavage site at position 681. The mutation is believed to increase infectivity and transmissibility viral; however, research indicates that it must occur in the context of additional spike protein mutations to have consequences.
NTD-Antigenic Supersite
Scientists have identified regions in the N-terminal domain of the S protein that are especially vulnerable to recognition and attack by antibodies, called NTD antigenic supersites. Delta contains a number of mutations that fit into an antigenic supersite, including a threonine to arginine substitution at position 19, a glycine to aspartate substitution at position 142, deletions at positions 156 and 157, and an arginine to glycine substitution at position 158 . Accumulated mutations in antigenic supersites are believed to increase the virus's ability to evade immunological detection.
STOPPING TRANSMISSION IS KEY TO CONTROLLING VARIANTS
Humanity is busy as the virus continues to mutate and develop potential mechanisms to evade the immune defenses its hosts worked so hard and sacrificed to develop. In addition to the variants of interest currently being monitored, the researchers are looking at a number of variants of interest, including Lambda . When specific mutations (such as K417N/T) lock into different virus strains, it is evidence that natural selection may be taking place. According to Dr. Vaughn Cooper , Director and evolutionary biologist elected by the ASM Council on Microbial Sciences, stopping the virus is key. "The more infections, the greater the chance of mutations occurring and, therefore, it is more likely that selection will enrich the best mutations to improve the virus," he explained. Vaccination is the best weapon in the fight to contain transmission.
AUTHOR: ASHLEY HAGEN, MS
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