COVID Delta Variant Spread Driven by Combination of Immune Escape and Increased Infectivity

Findings suggest that infection control measures against variants should be continued in the post-vaccination era.

The Delta variant of SARS-CoV-2, which has become the dominant variant in countries like India and the UK, likely has spread due to its ability to evade neutralizing antibodies and increased infectivity, an international team of researchers says.

“By combining laboratory experiments and epidemiology of vaccine breakthrough infections, we have shown that the Delta variant can multiply and spread better than other commonly observed variants.” — Ravi Gupta

The findings were reported in Nature on September 6, 2021.

As SARS-CoV-2 replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or contagious, others help it evade the immune response, potentially making vaccines less effective, while others have little effect. One such variant, called the B.1.617.2 Delta variant, was first observed in India in late 2020. Since then it has spread around the world – in the UK it is responsible for almost all new cases of coronavirus infection.

Professor Ravi Gupta of the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, one of the study’s senior authors, said: “By combining laboratory experiments and epidemiology of vaccine breakthrough infections, we have shown that the Delta variant is better at replicating and spreading than other common variants.There is also some evidence that neutralizing antibodies produced as a result of previous infection or vaccination are less effective at stopping this variant.

“These factors likely contributed to the devastating epidemic wave in India in the first quarter of 2021, where as many as half of the cases were individuals previously infected with an earlier variant.”

To investigate how well the Delta variant was able to evade the immune response, the team extracted serum from blood samples collected as part of the NIHR BioResource’s COVID-19 cohort. The samples came from individuals previously infected with the coronavirus or vaccinated with the Oxford/AstraZeneca or Pfizer vaccine. Serum contains antibodies raised in response to infection or vaccination. The team found that the Delta variant virus was 5.7 times less sensitive to the sera of previously infected individuals, and as much as eight times less sensitive to vaccine sera, compared to the Alpha variant – in other words, it takes eight times longer. . as many antibodies from a vaccinated person to block the virus.

Consistent with this, an analysis of more than 100 infected healthcare workers at three Delhi hospitals, nearly all of whom had been vaccinated against SARS-CoV-2, found that the Delta variant was more widely transmitted between vaccinated personnel 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 spliced, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery so that the virus can multiply and spread.

Using 3D airway organoids – “mini-organs” grown from airway cells that mimic the behavior – the team investigated what happens when the virus reaches the airways. Working under safe conditions, the team used both a live virus and a “pseudotyped virus” — a synthetic form of the virus that mimicked key mutations in the Delta variant — to infect the organoids. They found that the Delta variant was more efficient at breaking into the cells compared to other variants because it bore a greater number of split ends on its surface. Once inside the cells, the variant was also better able to replicate. Both factors give the virus a selection advantage over other variants, which helps explain why it has become so dominant.

dr. Partha Rakshit of the National Center for Disease Control, Delhi, India, joint senior author, said: “The Delta variant has spread widely and has become the dominant variant worldwide as it spreads faster and infects individuals better than most others. variants we’ve seen. It’s also better to evade existing immunity — either through previous exposure to the virus or through vaccination — although the risk of moderate to severe disease is reduced in such cases.”

Professor Anurag Agrawal of the CSIR Institute of Genomics and Integrative Biology, Delhi, India, joint senior author, added: “Infection of vaccinated health professionals with the Delta variant is a major problem. While they can only experience mild COVID themselves, they are at risk of infecting individuals who have a sub-optimal immune response to vaccination because of underlying health conditions — and these patients could then be at risk for serious illness. We urgently need to think about ways to enhance vaccine response to variants among health professionals. It also suggests that infection control measures should be continued into the post-vaccination era.”

Reference: “SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion” by Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Isabella ATM Ferreira, Rawlings Datir, Dami A. Collier, Anna Albecka , Sujeet Singh, Rajesh Pandey, Jonathan Brown, Jie Zhou, Niluka Goonawardane, Swapnil Mishra, Charles Whittaker, Thomas Mellan, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, Venkatraman Srinivasan Radhakrishnan, Adam Abdullahi De Partuto, , Tom Peacock, Dr Chand Wattal, Neeraj Goel, Ambrish Satwik, Raju Vaishya, Meenakshi Agarwal, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The Genotype to Phenotype Japan (G2P-Japan) Consortium, The CITIID- NIHR BioResource COVID -19 collaboration, Antranik Mavousian, Joo Hyeon Lee, Jessica Bassi, Chiara Silacci-Fegni, Christian Saliba, Dora Pinto, Takashi Irie, Isao Yoshida, William L. Hamilton, Kei Sato, Samir Bhatt, Flaxman, Leo C. James, Davide Corti, Luca Piccoli, Wendy S. Barclay, Par tha Rakshit, Anurag Agrawal and Ravindra K. Gupta, September 6, 2021, Nature.
DOI: 10.1038/s41586-021-03944-y

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.