In that Alert, we included the prediction by the Centers for Disease Control (CDC) that the B.1.1.7 variant (significantly more infectious or transmissible than the original strain of the virus and dubbed the “UK” variant) would become dominant in the US during March; that did indeed occur, and may have accounted for many of the surging COVID-19 cases in the late winter and early spring. Thankfully, the vaccines authorized for use by the FDA have shown little or no reduction in efficacy against B.1.1.7 compared to the original strain, in terms of both infection and severe disease, and so the recent mass vaccination campaign has been highly successful in greatly dampening the spread of COVID-19.

A New Variant From India

Meanwhile, three substrains of a new variant B.1.617 (designated B.1.617.1, B.1.617.2, and B.1.617.3) have appeared in India, initially in the state of Maharashtra (which includes Mumbai); all exhibit multiple mutations, with the common elements being those identified as L452R and D614G. (See our February Alert for an explanation of such terms.) Of these, B.1.617.2, first detected last December and with at least nine mutations, became the most commonly reported variant in India by mid-April. By May 19, according to the global GISAID database, it had been detected in 43 countries across six continents, and on June 16 an official from the World Health Organization (WHO) reported that it was now in over 80 countries. Probably as a result of recently increased international travel it is now associated with multiple outbreaks in urban areas across the United Kingdom, primarily among the unvaccinated. In Moscow, the Mayor has warned that the city’s new daily infections could exceed 9,000 (a record) by June 18, with the spread of the Delta variant as the probable culprit.

Some of the mutations in B.1.617.2, including L452R and also T478K (not found in the .1 and .3 subvariants), appear to be associated with increased transmission, while others may have an adverse impact on immune responses. The latest estimate is that B.1.617.2 is 60% more transmissible than the “UK” variant B.1.1.7, which itself is about 50% more transmissible than the original strain of the virus, so the net result is that this Indian variant is roughly two and a half times more infectious than the original strain. Speaking on “Face the Nation” on June 12, former FDA commissioner Dr. Scott Gottlieb said that while the Indian variant currently accounts for only about 10% of US infections it is doubling every two weeks, is likely to become the dominant source of new US infections, and could lead to new outbreaks in the fall.

WHO Goes Greek

As we noted in our February Alert, there is more than one “scientific” naming system for coronavirus variants – in fact, there are three in use – in addition to the unofficial method of identifying a variant by the country in which it is first reported (but not necessarily where it originated), which can lead to possible stigma for that country and its inhabitants. Thus, the so-called “UK variant” is widely known as B.1.1.7 (Pango lineage), but is also identified as 20I/501Y.V1 (Nextstrain clade) and GRY or GR/501Y.V1 (GISAID clade). These conflicting names can hinder accurate communication between scientists, health officials, and the media, for example, and minor typos can create confusion. As a result, the WHO, in an attempt to rationalize the naming of variants to assist the majority of people who are not researchers in the field, has just announced yet another, much simpler, naming scheme for “variants of interest and concern” based on the Greek alphabet, which it describes in the journal Nature Microbiology (Konings et al., 2021.)[1] As a result, the UK variant B.1.1.7 becomes Alpha, the South African variant B.1.351 becomes Beta, the Brazilian variant P.1 becomes Gamma, and the Indian variant B.1.617.2 becomes Delta.

CDC Classifies Delta as “Variant of Concern”

On June 14, CDC officially classified Delta as a “Variant of Concern,” joining a list that already includes Alpha, Beta, and Gamma, plus two strains of Epsilon (from California). With this new CDC classification of Delta come to the following variant-specific attributes:

• Increased transmissibility
• Potential reduction in neutralization by some EUA monoclonal antibody treatments
• Potential reduction in neutralization by post-vaccination sera

along with the following potential general attributes for all Variants of Concern:

• Evidence of impact on diagnostics, treatments, or vaccines
  • Widespread interference with diagnostic test targets
  • Evidence of substantially decreased susceptibility to one or more class of therapies
  • Evidence of significant decreased neutralization by antibodies generated during previous infection or vaccination
  • Evidence of reduced vaccine-induced protection from severe disease
• Evidence of increased disease severity

To illustrate the second bullet, for example, the US Department of Health and Human Services has paused distribution of a combination monoclonal antibody treatment for COVID-19 to nine states over the past month (the most recent being Rhode Island on June 15), citing reduced effectiveness against both delta and gamma variants.

Delta’s Effect on Hospitalization and Vaccine Efficacy

A study from Public Health Scotland and the University of Edinburgh, just published online as a letter to The Lancet on June 14, reported that hospital admission was approximately doubled in patients with the Delta variant when compared to the Alpha variant; the study was based on almost 20,000 confirmed infections between April 1 and June 6. (Sheikh et al., 2021.)

A study from Public Health England (PHE), published in pre-print form in medRxiv on May 24, investigated whether the Delta variant reduced the efficacy of the Pfizer or AstraZeneca vaccines (Lopez Bernal et al., 2021). For this, the authors used data from all symptomatic sequenced cases of COVID-19 in England from October 26, 2020 to May 16, 2021, that included 11,621 cases of the Alpha variant and 1054 cases of Delta. They reported that efficacy of both vaccines was notably lower after a single dose for Delta variant cases compared to cases of the previously dominant Alpha (“UK”) strain: 33.5% compared to 51.1%, with similar results for both vaccines. However, they reported only modest reductions in efficacy after the second dose: from 93.4% to 87.9% for the Pfizer mRNA vaccine and from 66.1% to 59.8% for the AstraZeneca adenovirus-based vaccine. (Similar efficacy results against the Delta strain were just reported by Dr. Gottlieb for two doses of Moderna’s mRNA vaccine (about 88%) and the single dose of Johnson & Johnson’s adenovirus-based vaccine (about 60%).)

Further, in a June 14 press release, PHE announced that both the Pfizer and the AstraZeneca vaccines had been shown to be highly effective against hospitalization from the Delta variant after the second dose.[2] PHE had analyzed 14,000 cases of the Delta variant in England and subsequent hospitalizations over a period of eight weeks through June 4 and found the efficacies of the two vaccines against hospitalization to be 96% and 92%, respectively.[3]

The Spread of Delta

PHE’s most recent Technical Briefing (no.16) on variants, published on June 18, reports that 91% of COVID-19 cases in the UK are now due to the Delta variant, the number of confirmed Delta cases has exceeded 60,000, and cases in England are doubling between every 3.5 and 16 days (depending on the region), with the highest growth rates seen in the younger age groups. As a result, on June 14, the UK Government announced a delay in the long-awaited easing of lockdown restrictions in England by 4 weeks, to July 19, during which time the existing vaccination campaign (already one of the most successful in the world) is to be further accelerated in order to provide as many second doses as possible to combat the Delta variant. (According to the government’s official coronavirus dashboard on June 17, 80.1% of the adult population had received at least one dose and 58.2% had received both doses. In the prior 7 days, however, the total number of confirmed COVID-19 cases had increased by 33.7%, the number of hospitalizations by 43%, and the number of deaths by 41.8%.)

In the US, a study published on June 21 as a preprint in medRxiv by scientists from Helix, a company that has analyzed almost 250,000 COVID-19 tests since the beginning of 2021, reported that both Delta and Gamma variants are now rapidly replacing Alpha (Bolze et al., 2021). As of the week June 9-15, Gamma accounted for at least 16% of new cases and Delta 14%, but the growth rate of Delta was about 3 times that of Gamma, and Delta was on track to become the dominant variant. Although there was considerable variation in the Delta-to-Gamma ratio from state to state, it was clear to the authors that the more transmissible Delta was growing more rapidly in counties with lower vaccination rates.

Conclusion

So where does this leave the United States? The good news is, of course, that across the nation new cases, hospitalizations, deaths, and positivity rates have reached their lowest levels since the beginning of the pandemic. Further, the recent scientific reports discussed above indicate that vaccine efficacy rates are only marginally reduced by the Delta variant in fully vaccinated (but not partially vaccinated) individuals, and the available vaccines remain highly effective against hospitalization.

The bad news is that vaccination rates in the US have been far from uniform, and there remain large areas of the country, and many pockets (especially rural counties) within otherwise well-vaccinated states, where vaccination rates are depressingly low, leaving large numbers of individuals completely unprotected against the increased transmissibility and lethality of the Delta variant. The rate at which it is spreading in the UK provides a clear warning to the rest of the world that we cannot afford to be complacent now, and that we should make full use of the latest weapons at our disposal – including some amazingly effective vaccines provided free of charge – to minimize the opportunities for the coronavirus to spread and mutate further within infected individuals into variants that are even more challenging to combat, such as the “Delta-Plus” just reported in the Times of India.

[1] See also commentary in Nature, 10 June 2021; Vol. 594: p. 149. [d41586-021-01508-8.pdf (nature.com)]

[2] Both vaccines have been widely distributed in the UK, while AstraZeneca is the predominant vaccine in India, manufactured locally by the Serum Institute.

[3] The study itself was published simultaneously as a preprint (Stowe et al., 2021).