Coronavirus Research Tracking - 9 July

Vaccines and viral origins

This week it’s mostly about vaccine effectiveness and vaccination strategies. There are also four papers looking for, or at, the origin of SARS-CoV-2.

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

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

Vaccine-related papers

Your reaction to a vaccine isn’t a good indicator of how effective it is likely to be

Lack of a reaction to the Pfizer/BioNTech vaccine shots does not mean that a poor immune response is generated. In this study of 206 healthcare workers antibody levels were measured one month after vaccination. There was no relationship between antibody levels and adverse reactions. Increasing age and weight, and being female, correlated with the reporting of adverse reactions. Systemic symptoms were more frequent after the second vaccination. Older people had lower levels of vaccine-induced antibodies. The paper has not yet been peer reviewed.

BBV152 vaccine demonstrates good efficacy and safety

The BBV152 vaccine, based on a whole but inactivated virus, had nearly 77% efficacy overall in an Indian clinical trial. The double-blind trial involved 24,000 participants, with effects being assessed two weeks after the second dose. Efficacy against the protection from infection from the Delta variant was calculated to be 65%, efficacy against symptomatic infection was 78%, and efficacy against severe disease was 93%. Neutralisation activity of vaccine-induced antibodies was 2-to-3 fold lower against the Beta and Delta variants, compared to the Alpha variant. Side effects to the vaccine were not serious. The paper has not yet been peer reviewed.

Johnson & Johnson/Janssen vaccine shows good neutralisation of Delta variant

The Johnson & Johnson/Janssen single dose vaccine elicits comparatively robust neutralising activity against the Delta variant. Neutralising activity of sera from eight vaccinated people was 3-to-4 fold lower against the Beta and Gamma variants, compared with an earlier Wuhan strain. Earlier evidence from South Africa (published in the New England Journal of Medicine), where the Beta variant is very common, indicated that this vaccine reduces Covid-19 related hospitalisations and deaths. The paper has not yet been peer reviewed.

Prior infection followed by vaccination may provide better protection against the Delta variant

Having a prior infection and then one or two doses of the Covishield vaccine (the Indian made version of AstraZeneca/Oxford vaccine) may provide greater protection from the Delta variant than just two vaccine doses. The study involved 116 vaccinated participants and measured neutralising antibody levels against the Delta variant and an earlier B.1 variant. Becoming infected after vaccination also resulted in stronger neutralisation activity against the Delta variant. The paper has not yet been peer reviewed.

Full vaccination provides greater protection

A study of healthcare workers in Delhi found that fully vaccinated staff had lower risks of reinfection than unvaccinated or partially vaccinated staff. The healthcare workers were vaccinated with the AstraZeneca/Oxford vaccine. Unvaccinated workers had a 1.57 times higher risk of infection, compared to partially vaccinated, and 2.49 times than fully vaccinated staff.

Severe Covid-19 cases were not seen in either the partially or fully vaccinated infected staff.  Higher antibody responses were found in fully vaccinated staff compared to partially vaccinated staff. The paper has not yet been peer reviewed.

Single doses may still provide good protection …

Single doses of the Pfizer/BioNTech, Moderna, and AstraZeneca/Oxford vaccines may all provide relatively good protection against the Alpha, Beta, Gamma, and Delta variants. This is based on a study of tens of thousands of infections in Canada. Partial vaccinations showed stronger protection against severe Covid-19 and death than against milder symptomatic infections, with the Moderna vaccine showing higher levels of protection. Full vaccination enhanced protection against the Delta variant for the Pfizer/BioNTech vaccine.

A study limitation is that infection with the Delta variant was based on detecting two mutations, rather than whole genomes, so variant identification was not always certain. The paper has not yet been peer reviewed.

… or they may not

In another study, sera from people who had one dose of the Pfizer/BioNTech or AstraZeneca/Oxford vaccine “barely inhibited” the Delta variant (and the Beta variant). The Canadian study noted above is based on actual infections, while this study looks just at antibody neutralisation.

Thirteen percent of those vaccinated with the Pfizer/BioNTech vaccine were able to neutralise the Delta variant after one dose. Two vaccine doses did demonstrate better neutralising activity against Delta, although three to five fold lower than for the Alpha variant. Sera from 59 vaccinated people were tested. The paper was published in Nature.

UK data shows real world effectiveness of vaccines

Lab-based neutralisation tests don’t necessarily provide an accurate prediction of real world effectiveness. Public Health England’s Week 27 Covid-19 Vaccine Surveillance Report summarises the real world effectiveness of the Pfizer/BioNTech and AstraZeneca/Oxford vaccines in the UK. Most of the analyses relate to the Alpha variant, with both vaccines providing over 70% effectiveness against hospitalisation and death after a single dose. The levels of effectiveness in preventing infection or transmission are currently less certain.

A single dose of either vaccine shows a 14% reduction in effectiveness against symptomatic disease for the Delta variant, compared to the Alpha variant. After two doses the reduction is 10%. Single doses were very effective in preventing hospitalisation due to the Delta variant.

Vaccinated people still at risk if they live with an infected person

A previous study highlighted in the Tracker found that vaccination helps protect unvaccinated people in households. A more recent study in Israel found that vaccine effectiveness may be slightly lower if vaccinated people live with an infected person.

The Pfizer/BioNTech vaccine effectiveness was 80% for a fully vaccinated person compared to an unvaccinated person, and 82% if compared with someone who had recently had their first dose. These figures are lower than the 90% effectiveness calculated in clinical trials. Masks or other protection may, therefore, still be advisable following vaccination. The paper has not yet been peer reviewed.

Strategies to cope with vaccine shortages

Reducing vaccine doses may be a way to overcome current vaccine shortages. For example, providing half doses to a particular number of people may, in some situations, provide more protection than giving full doses to half as many people. This Letter to the Editor notes that some early clinical trials indicated good immune responses to lower doses of some vaccines. However larger trials of low doses have not been undertaken, but would be useful. The paper was published in Nature Medicine.

A lower dose version of Moderna’s vaccine was able to generate antibody and T cell levels similar to those seen after natural infection, and the responses persisted for at least 7 months. The lower dose was 25 micrograms, compared with 100 micrograms in the standard dose. The standard dose generates higher levels of antibodies and T cells. Thirty three people received the low dose vaccine in this trial. The paper has not yet been peer reviewed.

Excluding previously infected people from vaccination programmes has also been suggested, in a paper published in Vaccine, as a strategy if there are vaccine shortages.

Transparency about vaccine risks has longer term benefits

Being transparent about the risks of vaccines may reduce acceptance of vaccines, but it also increases trust in health authorities. Experiments involving over 13,000 American and Danish people found that vague information about a fictitious Covid-19 vaccine did not increase vaccination uptake and resulted in greater endorsement of conspiracy theories.

The consistency of the results between two different countries supports the importance of health authorities in being transparent, even if there are short term risks of vaccine hesitancy. The strongest predictors of vaccine skepticism  were found to be individual differences in political cynicism and conspiratorial thinking. The paper was published in the Proceedings of the National Academy of Sciences.

Non-vaccine papers

The pandemic’s “immunity debt”

The reduction in exposure to other viral and bacterial pathogens, and reduced vaccination programmes during pandemic lockdowns, create risks of outbreaks and epidemics when greater social mixing occurs again. This is particularly likely in young children who have limited immunity, and has been called an “immunity debt.” French researchers predicted in May that respiratory syncytial virus and influenza pandemics may become more common because of reduced exposure to immune system stimulants.

The authors advocate rapid expansion of vaccination programmes as non-pharmaceutical interventions stop, and quick screening and reinforcement of hygiene measures for diseases that lack vaccines. The paper was published in Infectious Diseases Now.

Several bat coronaviruses are potential ancestors

Four out of 24 coronavirus genomes isolated from bats in Yunnan province, China, were found to be very similar to SARS-CoV-2. One, RpYN06, had 94.5% overall sequence identity with SARS-CoV-2, although the spike gene was less similar, as were the spike genes from the other species. RpYN06 is the second closest relative, after RaTG13, so far found for SARS-CoV-2.

The study also found that different bat species can harbour the same coronavirus, supporting a hypothesis of frequent inter-species transmission. The study illustrates the diversity in bat coronaviruses. The paper was published in Cell.

Mutation patterns may support a natural origin

The patterns of mutations in SARS-CoV-2 are similar to those seen in several other bat and pangolin coronaviruses, and so is potentially suggestive of a natural origin. The researchers suggest that if SARS-CoV-2 was developed in a laboratory then the pattern of mutations is expected to be different, although comparison to a lab-developed or cell-cultured coronavirus is not included in the study. The paper has not yet been peer reviewed.

Review of evidence on viral origin

A review has considered available evidence for and against natural and laboratory origins for SARS.CoV-2. It concludes that so far there is no evidence supporting a lab escape, although this can not yet be excluded. The authors find that current evidence favours a natural origin, and note similarities to the origin of SARS. Some of the authors have previously published papers proposing that the virus is most likely a natural spillover from another animal. The paper has not yet been peer reviewed.

The Australian Science Media Centre has an expert reaction to the paper.

A letter in The Lancet urges less rhetoric and more scientific inquiry about the origins of the virus. It notes that published evidence supports a natural origin, but also that further investigations are required.

Other SMC resources