The Dominance Of Delta - Credit CDC NOWCAST
#16,183
While there are a lot of concerns about what comes after Delta, for now - and for the foreseeable future - the Delta variant is firmly in charge (see CDC chart above). Mu, Beta, Gamma, or Kappa may have some new tricks to show us (e.g. vaccine escape), but they'll have to wait their turn to get a crack at us.
Although we still call it COVID-19, the Delta variant might as well be considered a new pandemic virus, as different as it is from the wild-type of 2020.
Instead of mutating into a milder, less aggressive virus - as was suggested by some last year (see Healthline's Is the New Coronavirus Getting Weaker? What to Know) - COVID instead has upped its game with a procession of increasingly formidable variants.
Although we can see the resulting dominance of the Delta variant by the charts showing it accounting for 98% of all cases in the United States, understanding how it became this viral juggernaut is important, if we are to find ways to successfully deal with it (and variants that may follow).
With growing calls to eliminate many of the NPIs (nonpharmaceutical interventions) used over the past 18 months to combat the virus (e.g. face masks in public, social distancing, school closures, etc.), we need to have some idea of how those actions are likely to impact the pandemic's course.
To this end we have a research article, published last week in Nature, that looks at the newfound abilities of the Delta variant, and warns that while vaccines will certainly help - particularly in reducing the severity of illness - they alone are not going to be enough to contain this variant.
This is a lengthy and fairly technical report. For those who would like to spare themselves that deep dive, I've also included the press release/summary provided by Cambridge University following the abstract.
SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
Petra Mlcochova,Steven Kemp,[…] Ravindra K. Gupta
Nature (2021) Cite this article
Abstract
The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G.Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N- terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7, associated with B.1.617.2 spike in a predominantly cleaved state compared to B.1.1.7.The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralising antibody as compared to WT spike. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance.In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx-1 vaccine effectiveness against B.1.617.2 relative to non- B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
Spread of Delta SARS-CoV-2 variant driven by combination of immune escape and increased infectivity
Findings suggest infection control measures against variants will need to continue in the post-vaccination era.
"By combining lab-based experiments and epidemiology of vaccine breakthrough infections, we’ve shown that the Delta variant is better at replicating and spreading than other commonly-observed variants" - Ravi Gupta
The Delta variant of SARS-CoV-2, which has become the dominant variant in countries including India and the UK, has most likely spread through its ability to evade neutralising antibodies and its increased infectivity, say an international team of researchers.
The findings are reported today in Nature.
As SARS-CoV-2 replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect. One such variant, labelled the B.1.617.2 Delta variant, was first observed in India in late 2020. It has since spread around the globe – in the UK, it is responsible nearly all new cases of coronavirus infection.
Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, one of the study’s senior authors, said: “By combining lab-based experiments and epidemiology of vaccine breakthrough infections, we’ve shown that the Delta variant is better at replicating and spreading than other commonly-observed variants. There’s also evidence that neutralising antibodies produced as a result of previous infection or vaccination are less effective at stopping this variant.
“These factors are likely to have contributed to the devastating epidemic wave in India during the first quarter of 2021, where as many as half of the cases were individuals who had previously been infected with an earlier variant.”
To examine how well the Delta variant was able to evade the immune response, the team extracted serum from blood samples collected as part of the COVID-19 cohort of the NIHR BioResource. The samples came from individuals who had previously been infected with the coronavirus or who had been vaccinated with either the Oxford/AstraZeneca or Pfizer vaccines. Serum contains antibodies raised in response to infection or vaccination.
The team found that the Delta variant virus was 5.7-fold less sensitive to the sera from previously-infected individuals, and as much as eight-fold less sensitive to vaccine sera, compared with the Alpha variant - in other words, it takes eight times as many antibodies from a vaccinated individual to block the virus.
Consistent with this, an analysis of over 100 infected healthcare workers at three Delhi hospitals, nearly all of whom had been vaccinated against SARS-CoV-2, found the Delta variant to be transmitted between vaccinated staff to a greater extent than the alpha variant.
SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.
Using 3D airway organoids – ‘mini-organs’ grown from cells from the airway, which mimic its behaviour – the team studied what happens when the virus reaches the respiratory tract. Working under secure conditions, the team used both a live virus and a ‘pseudotyped virus’ – a synthetic form of the virus that mimicked key mutations on the Delta variant – and used this to infect the organoids. They found that the Delta variant was more efficient at breaking into the cells compared with other variants as it carried a larger number of cleaved spikes on its surface. Once inside the cells, the variant was also better able to replicate. Both of these factors give the virus a selection advantage compared to other variants, helping explain why it has become so dominant.
Dr Partha Rakshit from the National Centre for Disease Control, Delhi, India, joint senior author, said: “The Delta variant has spread widely to become the dominant variants worldwide because it is faster to spread and better at infecting individuals than most other variants we’ve seen. It is also better at getting around existing immunity – either through previous exposure to the virus or to vaccination – though the risk of moderate to severe disease is reduced in such cases.”
Professor Anurag Agrawal from the CSIR Institute of Genomics and Integrative Biology, Delhi, India , joint senior author, added: “Infection of vaccinated healthcare workers with the Delta variant is a significant problem. Although they themselves may only experience mild COVID, they risk infecting individuals who have suboptimal immune responses to vaccination due to underlying health conditions – and these patients could then be at risk of severe disease. We urgently need to consider ways of boosting vaccine responses against variants among healthcare workers. It also suggests infection control measures will need to continue in the post-vaccine era.”
The research was largely supported in India by the Ministry of Health and Family Welfare, the Council of Scientific and Industrial Research, and the Department of Biotechnology; and in the UK by Wellcome, the Medical Research Council and the National Institute of Health Research.
Reference:
Micochova, P & Kemp, S et al. SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough. Nature; 6 Sept 2021; DOI: 10.1038/s41586-021-03944-y
While I understand the desire to declare victory over this virus, and return to a more `normal life', simply saying it won't make it so.
Hopefully, over time - Delta may weaken - or eventually yield to a less dangerous variant.
But until that happens - face masks, vaccines (and boosters), and some degree of social distancing - are probably all going to be needed if we are to minimize the damage this formidable pandemic does.
