Coronavirus Research Tracking - 20 August

Declining vaccine effectiveness, infections in children, new therapies

This week’s papers include several studies looking at changes in vaccine effectiveness against infection and/or hospitalisation over time, or against different variants. Models indicate the risks posed by uneven global vaccination. In other research, studies of infections in children, the ongoing development of novel therapies, and why the Delta variant may be more transmissible.

The tracker is being shared with the COVID-19 Vaccine Media Hub, so vaccine and non-vaccine-related papers are separated.

The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

Vaccine-related papers

Vaccine effectiveness against infection from Delta variant lower than for Alpha

In studies of vaccine effectiveness it is important to distinguish what is being assessed - protection against infection, symptoms, or more serious disease.

A UK study reports that the Pfizer/BioNTech and AstraZeneca/Oxford vaccines provide good protection against infection from the Delta variant. However, compared with the Alpha variant, both vaccines provided lower levels of effectiveness against reducing viral loads and symptomatic infections when infected by the Delta variant. Those with a previous infection and then vaccinated had higher levels of protection from Delta than previously uninfected vaccinated people.

Viral loads in fully vaccinated people infected with the Delta variant were similar to those found in unvaccinated people with the Delta variant. Whether the vaccine reduces transmission risk in these cases is not yet known. [But see the Nature news article on viral load studies in the Non-vaccine section below]

While effectiveness of the Pfizer/BioNTech vaccine after two doses was initially higher (85%) than that for the AstraZeneca/Oxford vaccine (68%), the former’s effectiveness declined more quickly (75% vs 61% for AstraZeneca after three months). By 4 to 5 months after full vaccination it is estimated that the effectiveness of both vaccines will be similar. The results are based on information from 359,000 people. The paper has not yet been peer reviewed

Declines, and stability, in vaccine effectiveness against infection over time in the US

Three papers in the Morbidity and Mortality Weekly Report investigate declines in vaccine effectiveness over time in the US.

A study of Covid-19 hospitalisations in New York found that between May and July overall, age-adjusted vaccine effectiveness against hospitalisation was generally stable, lying between  from 92% to 95%. This was during a time when the Delta variant was rapidly increasing. In contrast, overall age-adjusted vaccine effectiveness against infection declined from 92% to 80%.

The second study, involving nursing home residents, also showed a decline in vaccine effectiveness against infection. Effectiveness in residents (who received the mRNA vaccines) declined from about 75% in March-May to 53% in June-July. Whether the decline is due to waning immunity, or due to the emergence of the Delta variant could not be determined.

Other health data on the nursing home residents was not available, so there may be confounding factors (such as prior infections, and comorbidities) that influence results. 

The third study followed 1,000 fully vaccinated adults (with either mRNA vaccine) and, like the first study, found little decline in effectiveness against hospitalisation. Vaccine effectiveness was 86% 2–12 weeks after vaccination, and 84% at 13–24 weeks. Effectiveness was lower for those who were immunocompromised. Variant-specific effectiveness was not assessed.

Increasing numbers of breakthrough infections in Israel

A news article in Science describes the increasing number of infections in vaccinated people in Israel. Over half of those with serious Covid-19 have been vaccinated, and are mostly over 60 years old. The article concludes by suggesting that booster shots are not the solution to breakthrough infections, continued use of social distancing and mask wearing (alongside vaccination) are.

Mixed vaccine doses may better stimulate neutralising antibodies

A small trial found that neutralising antibody levels were higher for a combination of AstraZeneca/Oxford and Pfizer/BioNTech doses than for two AstraZeneca shots. The mixed vaccine group also showed stronger neutralising activity against the Beta, Gamma, and Delta variants. However, only 11 and 12 people were in the standard and mixed vaccine groups, respectively. The paper was published in The Lancet.

Different antibody and T cell responses to Beta variant seen after one dose of mRNA vaccines

Antibody responses generated by natural infections or a single mRNA vaccine dose are poor against the Beta variant. Vaccine-induced T cell responses are, though, not reduced against the Beta variant.

Much stronger antibody binding and neutralisation activity was observed in tests of sera from people who had received two doses of the Pfizer/BioNTech vaccine, supporting recommendations for two doses. This was a lab-based study that did not assess antibody effectiveness in infected people. The paper was published in Nature Communications.

Models show uneven global vaccination risks emergence of more variants

A modelling study indicates that sustained viral transmission in areas with limited access to vaccines can result in a greater risk of variants evolving resistance to the vaccine(s). This will have global consequences, so the authors stress the importance of equitable access to vaccines. The paper was published in Science.

Another modelling study found that rapid vaccination reduces the risk of resistant variants emerging. However, the risk increases if non-pharmaceutical interventions are stopped before vaccination campaigns end and transmission is not under control. The authors recommend not relaxing other transmission controls before most people have been vaccinated. 

The paper also concludes that uneven global vaccination rates are likely to lead to the emergence of variants of concern. The paper was published in Scientific Reports.

Non-vaccine-related papers

Over 90% of adults in the UK have Covid-19 antibodies

The UK’s Office of National Statistics estimates that in late July over 90% of adults in England, Wales, Scotland & Northern Ireland were likely to have antibodies against Covid-19. This would be due either to infections or vaccination. However, the report notes that antibody presence does not indicate the level of immunity from infection.

Young children more likely to spread virus in households than older children

Children under 3 may be more likely to transmit the virus than older children within households. The Canadian study was based on over 6,000 households where the child was the index case. However, older children were more likely than younger children to be the index case in the households studied, probably because they are more mobile. Higher transmission from the younger children is probably because they are less able to be isolated from others when infected. 

The paper was published in JAMA Pediatrics. An editorial on the research was also published in the same issue.

Children can also have high viral loads

Infected children can have high viral loads, even when asymptomatic.  They were most infectious in the first five days of developing illness. Viral levels were not correlated with disease severity. Children may, therefore, be a reservoir for existing and new viral variants. The study only involved 110 children, and viral samples were collected early in the pandemic. The paper has not yet been peer reviewed.

However, kids can have stronger innate immunity

Children have stronger innate immunity responses in their airways against the virus than adults. This results in more rapid production of type I interferons, which disrupt viral replication. The paper was published in Nature Biotechnology.

Some monoclonal antibodies effective against several variants of concern

Some monoclonal antibodies generated following inoculation with the Pfizer/BioNTech vaccine demonstrate good neutralising antibodies against variants of concern. Five were effective against the Delta variant.

One, 20C8, neutralised the Alpha, Beta and Delta variants in lab tests. When given to hamsters it reduced viral levels and lung damage when animals were infected with the wild type, Beta or Delta variant. This antibody was found in about one fifth of previously infected or vaccinated people examined. The paper was published in Immunity.

Potential drug looks like a potent inhibitor of infection

A drug based on a molecule that binds to the ACE2 receptor shows it is effective in blocking SARS-CoV-2 infection. The drug development process involved in vitro evolution to rapidly increase binding affinity for ACE2. The resulting molecule had 1,000 times greater affinity for ACE2 than the wild type receptor binding domain of the spike protein from the early Wuhan strain. It was able to block the Alpha, Beta and Gamma variants in cell assays (the Delta variant wasn’t tested). 

Importantly the drug did not appear to affect the enzymatic activities of the ACE2 receptor, so normal cellular processes could continue.

When given to hamsters either before or after infection the drug was able to reduce clinical disease. The paper was published in Nature Microbiology.

Delta variant infects cells more quickly

A study of the spike proteins of several variants found that the Delta variant protein is able to infect cells more quickly than other variants. This could explain Delta’s higher transmissibility and viral loads after infection. 

Rather than having a greater affinity for the ACE2 receptor, lab tests indicate that it is more efficient at fusing with cells that have fewer ACE2 receptors than other variants. It also appears to enter cells more quickly. The research is based on the use of pseudoviruses with the variant spike proteins. The paper has not yet been peer reviewed.

A news article in Nature summarises other recent research that demonstrates higher viral loads in people infected with the Delta variant. Different studies are reporting conflicting results as to whether fully vaccinated people have as high viral loads as unvaccinated people for the Delta variant. This is due to different study methods and sample sizes. The role or significance infected vaccinated people play in transmission is still uncertain.

The benefits of using real-time genomic sequencing

The use of real-time genomic sequencing was critical to effective management of community outbreaks in New Zealand. The authors of this paper note that the technique is also useful for regular surveillance of non-pandemic infectious diseases. The paper was published in Emerging Infectious Diseases.

Did a pork shortage in China trigger the pandemic?

An opinion article published in Science suggests that a pork shortage in China in 2019 probably increased demand for wild animal meat, and this may have led to the emergence of SARS-CoV-2. This is speculative and doesn’t provide evidence of causation. The paper also notes that unusually the virus rapidly spread between people early on. This, combined with cases of the virus infecting other animal species, suggests that the virus did not require a period of adaptation to humans but is a more generalist virus. This may result in further infections from bats to other species.

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