Covid-19: Waning vaccine efficiency, high pre-symptomatic transmission behind Delta variant’s rapid spread

Reduced vaccine efficiency and high infectiousness during the pre-symptomatic phase are leading to rapid transmission of the coronavirus’ Delta variant, several studies have found.

Recent epidemiological research has found the Delta (B.1.617.2) variant to be 40 per cent more contagious than the Alpha variant, which was first identified in 2020 in the UK. Multiple studies have also shown waning vaccine efficiency against the variant, and also leave vaccinated individuals vulnerable to breakthrough infections.

World Health Organization chief Tedros Adhanom Ghebreyesus had earlier said the Delta variant was the most transmissible mutation identified. He added that it was fast becoming the most dominant strain in several countries.

According to an internal US Centers for Disease Control and Prevention (CDC) presentation, the variant of the virus is more transmissible than those that cause SARS, MERS, Ebola, the seasonal flu, common cold, and smallpox. It has been found to be as contagious as chickenpox.

Why the Delta variant is more infectious
According to a recent study, the mutation of a key amino acid could be the reason behind the delta variant’s ferocity.

A University of Texas Medical Branch team, led by virologist Pei-Yong Shi, pinpointed a key mutation that altered one amino acid in the spike protein of the SARS-CoV-2. The change — called P681R — transforms into an arginine a proline residue, according to the study, which was published in Nature. The study found that the change took place in the furin cleavage site of the spike protein.

Host proteins must cut the SARS-CoV-2 spike protein twice to penetrate the cells. The furin cleavage site is important as the host enzymes, including furin, make the first cut. The newly formed viral particles emerge from an infected cell and can more efficiently infect host cells.

The Alpha variant carries a mutation at the same location. However, it includes change in a different amino acid. The study found that the Delta mutation that altered the furin cleavage has a profound effect.

The researchers said the spike protein in Delta-variant particles is cut much more efficiently as compared to other variants, such as the Alpha. The P681R mutation is mainly responsible for the efficient clipping of the spike protein.

The P681R mutation is key to the Delta variant’s high infectivity.

The findings of the study were similar to research by University of Tokyo Virologist Kei Sato. Sato’s team found spike proteins bearing P681R are able to fuse with plasma membranes of uninfected cells thrice as fast than when there is no mutation.

Are other key mutations responsible?
According to scientists, the Delta variant has several key mutations. They added that the P681R change, despite being significant, is unlikely to be the sole reason behind the rapid transmission.

Ugandan researchers said the P681R change was found in a variant that was widespread in the country early this year, but it was not as infectious as the Delta. The Kappa variant identified in India also has the same mutation, but it was found that the spike protein is cleaved less often and the fusion with cell membranes is less efficient.

Previous studies have shown that L452R and D6146 — other key Delta variant mutations — allow it to attach to receptor cells more firmly and more easily escape immunity.

The multiple mutations of the Delta variant in the spile protein’s S1 subunit improves its capability to bind to the ACE2 receptors and evade the immune system.

Cornell University Virologist Gary Whittaker told Nature that the virus was succeeding on speed and volume and had become much more efficient. He added that it was going through people and cells a lot quicker.

Why it is difficult to stop the Delta variant
A study in China’s Guangzhou found that high infectiousness even in pre-symptomatic phases was a reason behind the delta’s rapid spread. This means people are likely to spread the virus even before suspicion of themselves being infected arises.

A recent study led by University of Hong Kong Epidemiologist Benjamin Cowling found that symptoms were manifesting 5.8 days after Delta infections — 1.8 days after first testing positive for viral RNA. This leaves a dangerous window for transmission.

The study found that 74 per cent of delta infections occurred during the pre-symptomatic period. The Delta’s R-naught, representing the number of individuals a single infected person can transmit the disease to on an average, is 6.4. The Wuhan strain’s R-naught of the Wuhan strain, according to earlier studies done earlier, was between 2 and 4.

Waning vaccine effectiveness
Several studies have discovered that vaccine effectiveness is lower against the Delta variant, thus leaving even vaccinated individuals vulnerable.

A Public Health England study had found that the Oxford-AstraZeneca vaccine’s effectiveness drops to 64 per cent against the Delta. A study in The Lancet had also found that those vaccinated with Pfizer’s vaccine are likely to have five times lower antibody levels against the Delta variant.

Recent Israel Health Ministry data have shown that two doses of Pfizer’s vaccine offer 64 per cent protection against Covid-19. This is at a time when more than 90 per cent of the country’s cases were caused by the Delta variant.

Another recent study by the University of Oxford and the Office for National Statistics has found that the Pfizer vaccine’s effectiveness fell to 90 per cent a month after the second dose, 85 per cent the month after, and 78 per cent after three months. The equivalent protection for the AstraZeneca vaccine was found to be 67 per cent, 65 per cent, and 61 per cent. This waning vaccine effectiveness has emerged as another cause for concern.

The study also revealed that peak viral load even in vaccinated individuals was similar to that of unvaccinated people. Similar results have been found in studies conducted in Singapore and the US.

This means even fully-vaccinated people are at risk of spreading the Delta variant, making it even more difficult to break the chain.

A US CDC report this month said 469 Covid-19 cases were reported in Massachusetts following a large gathering in Provincetown, a beach town. Of these, nearly 75 per cent people were vaccinated.

 Analyses have shown that vaccinated individuals showed his Ct values, similar to unvaccinated people. This indicated a high viral load.

Genome sequencing of 133 samples revealed that 90 per cent of the cases were caused by the Delta variant. The CDC then updated its guidelines on July 27, recommending even vaccinated people to wear masks in areas of substantial and high Covid-19 transmission.