Coronavirus Research Tracking - 18 June

Vaccine effectiveness, cross protection from other vaccines and colds, REGEN-COV therapy success

This week lots of papers on how effective some of the vaccines are. Vaccines for other diseases may also provide some cross protection, as may a cold. A monoclonal antibody therapy proves effective for certain individuals. Plus, papers on vaccination strategies, immune responses, aerial transmission, and the wildlife species in the Wuhan markets.

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

Variants of concern name reminder

Alpha = B.1.1.7 (first detected in the UK)

Beta = B.1.351 (first detected in South Africa)

Gamma = P.1 (first detected in Brazil & Japan)

Delta = B.1.617.2 (first detected in India)

Delta variant is more transmissible

The Delta variant spread more rapidly within households than the Alpha variant, an English study has shown. A 64% increase in the odds of household transmission was found for the Delta variant, compared to the Alpha. The study didn’t have information on household sizes, which may affect the results. The paper has not yet been peer reviewed.

Vaccine effectiveness against the Delta variant

The Pfizer/BioNTech and AstraZeneca/Oxford vaccines were as effective at preventing hospitalisations for the Delta variant as for the Alpha variant, according to analyses from Public Health England. Both one and two doses the vaccines provided very good protection against severe Covid-19. This is based on an analysis of over 14,000 cases involving the Delta variant. The paper, which is very brief, has not yet been peer reviewed.

In Scotland the Delta variant has rapidly become the most common variant. It is most frequently found in younger people, and the risk of hospitalisation is about twice that as for the Alpha variant. The Pfizer/BioNTech and AstraZeneca/Oxford vaccines reduced the risks of infection and hospitalisation from the Delta variant, but not as much as for the Alpha variant. 

Good protection became evident when assessed at least 4 weeks after the first vaccine dose. The study found that the AstraZeneca vaccine may be less effective at preventing infections from the variant Delta than the Pfizer vaccine, though the nature of the study did not allow for an accurate assessment of efficacy. The paper was published in The Lancet

Pfizer/BioNTech vaccine shows effective neutralisation against several new variants

Sera from 20 people vaccinated with the Pfizer/BioNTech vaccine was able to neutralise several newly emerged variants. While neutralisation was lower for some of the variants, the observed levels were judged to still be effective. Variants tested were Delta, B.1.617.1 & B.1.618 (both first identified in India), and B.1.525 (first identified in Nigeria). The experiments used pseudoviruses containing only the spike protein from the SARS-CoV-2 viruses. The paper was published in Nature.

Johnson & Johnson/Janssen vaccine promising against Beta & Gamma variants

The Johnson & Johnson/Janssen vaccine shows reduced neutralising antibody activity against the Beta and Gamma variants, but still produces robust binding antibody and T cell responses against them. The paper was published in Nature.

Novavax vaccine seems to work well against variants

The Novavax vaccine shows very high efficacy and protection against SARS-CoV-2, including some variants of concern. The results, from a Phase 3 clinical trial involving nearly 30,000 participants, were released as a press statement from the company. A paper on the results is being prepared. Novavax has also produced a fact sheet on the clinical trial. 

CoronaVac vaccine has mixed results in the Amazon

The CoronaVac vaccine was shown to have mixed effectiveness in a case-controlled study of healthcare workers in Manaus, Brazil. Receiving one dose of the vaccine halved the odds of having a symptomatic infection. However, the effectiveness was lower (37%) after two doses, and it isn’t clear why. The high levels of infection in Manaus before vaccination may make assessing vaccination effectiveness there difficult. The paper has not yet been peer reviewed.

Vaccination outcomes in the UK

A random survey of over 380,000 UK residents was used to show that the Pfizer/BioNTech and AstraZeneca/Oxford vaccines have reduced infections and the severity of Covid-19 cases. Receiving both vaccine doses provided greater protection against symptomatic infections and had more effect on reducing viral loads than a single shot. The study did not find a significant difference in effectiveness between the Pfizer and AstraZeneca vaccines. The paper has not yet been peer reviewed

Slides of some of the results of vaccination in the UK have been released by their Cabinet Office. This is based on information published by Public Health UK, and included in last week’s Tracker. 

Vaccination outcomes in Israel

Comparing virus variants in vaccinated and unvaccinated Israelis identified how well the Pfizer/BioNTech vaccine provided protection against the Alpha and Beta variants, and when. The Beta variant was found to be overrepresented in infected vaccinated adults 7–14 days after the second dose, compared to matched unvaccinated controls. The Alpha variant was overrepresented in partially vaccinated individuals between 14 days after the first dose and 6 days after the second dose.

Relatively few Beta variant infections were seen, so this result may not hold where it is more prevalent. However, in Israel mass vaccination has dramatically reduced infections. The study also indicated that serum-based neutralization studies may provide a good proxy for protection from SARS-CoV-2 infection  The paper was published in Nature Medicine.

Effectiveness of the Pfizer/BioNTech vaccine in Canada

A single dose of the Pfizer/BioNTech vaccine reduced by about two-thirds the risk of infection in eldelrly people in Canada. Good protection against the Alpha and Gamma variants of concern was observed, although slightly less than for other strains. The paper has not yet been peer reviewed

Vaccination decreases infections in unvaccinated household members

Israel’s rapid mass vaccination programme continues to provide evidence of the value of vaccination. A study of 177 communities found that as more adults were vaccinated the proportion of infections in unvaccinated children under 16 also declined. While this is only a correlation, it is suggestive that vaccinations reduce community infection risks. The study was published in Nature Medicine.

Similar declines in infections of unvaccinated adult household members was seen in the homes of vaccinated healthcare workers in Finland, according to a study that is not yet peer reviewed

Mix-and-match vaccine trials

A news item in Science discusses the results of three trials that used combinations of two vaccines (AstraZeneca/Oxford and Pfizer/BioNTech). These all resulted in strong antibody responses, and no safety concerns. Two of the studies, although small, indicate that a mixed vaccination may lead to a stronger immune response. The article notes that none of the studies were designed to test actual protection from infection. Further research on mix-and-match vaccinations is underway.

Some other vaccines may help provide protection from Covid-19

Research has found that having diphtheria and tetanus vaccinations in the last 10 years correlates with less severe Covid-19. This association, based on analyses of UK Biobank records, was not seen for some other vaccinations. 

The authors suggest that the antibodies generated from the diphtheria and tetanus shots may cross-react with SARS-CoV-2. There is some experimental evidence to support this, but the authors emphasise their results only find a correlation not a causation. The paper has not yet been peer reviewed.

Flu vaccine doesn’t affect Novavax vaccine efficacy

Providing the Novavax vaccine alongside a flu vaccine does not appear to affect safety or efficacy of the Covid-19 vaccine. As part of a Phase 3 trial about 200 people (median age 39) were given a flu vaccine as well, and compared with a similar number who only received the Covid-19 vaccine. While subjective local pain and tenderness were higher for those receiving both vaccines, no safety issues were found.

Although antibody responses to the Novavax vaccine were lower in those receiving the flu shot, vaccine effectiveness in preventing infection did not appear to be affected. The small study size and younger age of participants mean that further research into co-vaccination is required. The paper has not yet been peer reviewed.

A cold may also provide some protection

SARS-CoV-2 infection may be inhibited if a person has caught the cold a few days before. Cell culture experiments with a cold-causing Rhinovirus show that it activates interferon-stimulated genes. This led to inhibition of SARS-CoV-2 if cells were infected with it three days later. Blocking the expression of these genes allowed SARS-CoV-2 replication to proceed. Therapies that promote interferon-stimulated gene expression may also be a future prophylactic. The paper was published in the Journal of Experimental Medicine.

Prospects of long term immunity

A News & Views article in Nature discusses the evidence for long term immunity following infection with SARS-CoV-2. This depends on the development of memory cells in blood and plasma that can generate antibody producing cells. Recently in Nature two papers (here and here) reported finding these memory cells 12 months after initial infections. Vaccinations are also expected to result in the development of such memory cells.

T cell responses affect antibody memory cells

An interesting, if detailed, paper illustrates important interactions between the antibody and T cell immune responses. While memory B cells produce antibody producing cells, they require virus-specific T cells to do so. This study showed that different types of CD4+ T cells affect spike protein-specific memory B cells in people who had relatively mild disease compared with those who had severe Covid-19. T cells in those with mild symptoms produced interleukin-21, leading to a robust B cell memory and production of antibodies with stronger spike protein binding capabilities.

In contrast, interleukin-21 was not produced in more serious cases, and while higher levels of antibodies were produced, this resulted in exhaustion of the memory B cells. The antibodies that they produced were also not as effective at binding as those seen in milder Covid-19 cases.

The results may help inform development of more effective vaccines that provide long-term protection. The paper was published in Cell Reports.

For antibody geeks

A detailed review of antibody and B cell responses to Covid-19, and what is still unknown, was published in Cell Host & Microbe. Longevity and correlates of immune protection are still uncertain, and the paper notes the need for further study of antibody responses in tissues and organs, not just blood.

Dual monoclonal antibody therapy effective for some who don’t mount an immune response

A large randomised trial in the UK has provided the first evidence that an antiviral therapy can reduce mortality in hospitalised Covid-19 patients. At least for those who had not developed their own immune response. It found that the REGEN-COV treatment (a combination of two monoclonal antibodies) was effective in reducing deaths (by 20%, 28 days after treatment) and time to discharge of hospitalised Covid-19 patients who had not developed their own immune response. The study estimated that this would mean six fewer deaths per 100 patients receiving the treatment. 

REGEN-COV was not effective for patients who had produced their own antibodies. The study was part of the UK’s RECOVERY trial which has been very successful in identifying beneficial Covid-19 treatments. The paper has not yet been peer reviewed.

A US study has also found that REGEN-COV reduces the risk of disease progression. In a randomised, double-blind, placebo-controlled trial the treatment, given to 155 infected but asymptomatic patients, reduced the risk of developing symptomatic disease by 31.5%. It also reduced viral loads and the duration of symptoms.

Most of the asymptomatic patients had not yet mounted an immune response, but some data from the study indicated that REGEN-COV may also have beneficial effects in some patients with antibodies, if it is given soon after infection. The paper has not yet been peer reviewed.

Transmission patterns and simulating vaccination strategies in Iceland

An analysis of transmissions in Iceland found that people of working age (16-66 years old) were 47% more infectious than other age groups. The paper does not discuss the reason for this, but it may be (in part at least) due to the working age group having more social contacts. [A strong relationship between age, viral loads, and infectivity was not found in a recent paper published in Science.]

The researchers used this transmission information to see the effect of different simulated vaccination strategies. They found that vaccinating people in ascending order of age or uniformly but randomly (so equal proportions of all ages are vaccinated) could be more effective in controlling this pattern of transmission than vaccinating the oldest people first.

However, the authors note that vaccination has two purposes - reducing transmission and reducing disease severity. So, a uniform random strategy may be the best to address both of these outcomes, although this hasn’t been tested in the real world. The paper has not yet been peer reviewed.

Updated guidance on airborne transmission required

An opinion published in the Canadian Medical Association Journal notes that public health guidance, in Canada at least, needs to be updated to reflect the risk of both short and longer distance airborne transmission. It says that discussions have often been caught up in the debate over the importance of droplets vs aerosols. Better guidance needs to be provided to businesses and schools on appropriate ventilation, and guidelines on personal protective equipment for hospitals and care facilities should also be updated.

Speech droplets of a certain size may be a key transmission risk

Intermediate-sized speech droplets have been implicated as an important avenue for SARS-CoV-2 transmission. These droplets can remain airborne for minutes, can travel relatively far, and can contain high viral loads. The paper was published in the Journal of Internal Medicine.

Finding the origin of the virus may take a long time

The current evidence, or lack of it, for SARS-CoV-2 escaping from a lab is considered by a news article in Nature. It highlights that many of the claims used to support a lab origin or leak are currently conjecture or disputed. It agrees that the possibility of a lab escape needs further investigation, but notes that a quick answer may not be found. There is also no guarantee that the origin will be identified.

Wuhan markets had many protected animal species for sale before the pandemic

Thirty eight wildlife species, including 31 protected species, were being sold in Wuhan wet shops and markets in the two years before the pandemic a survey has shown. About 30% appeared to be wild caught, the remainder being farmed. No bats or pangolins were being sold in the shops. Animal welfare, hygiene and health conditions in the markets were considered to be poor, which could have facilitated zoonotic infections. Whether such markets played a role in the Covid-19 pandemic remains uncertain, as not all the early cases could be shown to have links to such shops.

The study notes that many wildlife species are regarded as “prestige items” in China, fetching high prices, though government efforts are trying to reduce or eliminate this demand. Last year the Hubei provincial government announced that the sale of live wild animals and poultry will be prohibited when markets reopen. The paper was published in Scientific Reports.

Improving transdisciplinary research needed to be better prepared for the next one

An opinion piece published in the New Zealand Medical Journal argues the need for New Zealand to improve transdisciplinary research capabilities and funding. This, the researchers suggest, is critical for improving preparedness for subsequent epidemics and pandemics. 

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