Coronavirus Research Tracking - 14 May
Variants, vaccines, viral surveillance, and learning before the next one
This week a mixture of different vaccination studies, including early results of a trial that gives both the AstraZeneca and Pfizer vaccines. Plus, research suggesting a universal coronavirus vaccine may be possible. There are also reports on the B.1.617 variant, supercarriers, a possible way to reduce sharing of misinformation, and a controversial paper about virus integration into the human genome. Some lessons too to help be better prepared for another pandemic.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Another Variant of Concern declared
The variant B.1.617.2 from India has been classed as a variant of concern in the UK by Public Health England. Data indicates that it is at least as transmissible as B.1.1.7. Some laboratory tests indicate that it is able to be controlled by immune responses and vaccines, though further research is required. It is uncertain at the moment whether it causes more severe Covid-19. The World Health Organisation has classified B.1.617 as a global “variant of concern” (alongside B.1.1.7, B.1.351, and P.1)
A news article in Nature discusses what is known about the variants spreading in India.
B.1.617 variant may have higher pathogenicity
A B.1.617 variant with L452R, E484Q and P681R mutations in the spike protein shows a modest ability to avoid neutralising antibodies generated by the Pfizer/BioNTech vaccine. While lab tests indicated that the variant was less effective at infecting cells, the P681R mutation enhanced fusion between an infected cell and other cells, which may lead to increased pathogenicity. The study has not yet been peer reviewed.
Global vaccination rates
A paper in Nature Human Behaviour highlights the Our World in Data dataset on vaccination rates by country. It notes the different vaccination approaches taken by different countries. At the time of publication 169 countries had begun Covid-19 vaccinations. The effects of vaccination are not covered. The paper also illustrates the times taken to develop a range of vaccines over the last 150 years.
J&J vaccine effectiveness
The real world effectiveness of the Johnson & Johnson/Janssen vaccine has been estimated to be 76.7% in preventing infection. This is based on comparing infections in 2,000 people two weeks after vaccination with 22,000 unvaccinated people in the US. Most participants (90%) were Caucasian, so the study is not representative of the general population. It is not yet possible to assess the impact the incidence of severe Covid-19 symptoms. The paper has been submitted to The Lancet, but has not yet been peer reviewed.
Concern over published data on the Sputnik V vaccine
Correspondence in The Lancet describes inconsistencies and lack of transparencies about published information from clinical trials of the Sputnik V vaccine. It asks the journal to provide access to the data provided by the authors.
New Moderna booster vaccine in early trials
An updated version of Moderna’s vaccine shows promise in an early stage clinical trial. Strong neutralisation activity was seen after giving a third dose of the original vaccine or one containing the B.1.351 spike protein sequence six months after the standard two dose. The mRNA-1273.351 booster produced stronger neutralisation against the B.1.351 variant than a third dose of the original mRNA-1273. Only small numbers of participants were involved, and future testing will involve a vaccine with a mix of both the 1273 and 1273.351 types. The study has not yet been peer reviewed.
Innate immunity affected by the Pfizer/BioNTech vaccine
The Pfizer/BioNTech vaccine affects innate immunity as well as adaptive immunity (antibodies and T cells) a study has shown. In lab tests the production of several cytokines was affected both by SARS-CoV-2 and by other pathogens following vaccination, and not always in the same way.
Production of interferon-gamma, a cytokine that helps modulate immune responses, was often higher after vaccination and exposure to SARS-CoV-2, with the level of responses differing between viral variants. Production of two pro-inflammatory cytokines decreased after vaccination and exposure to the virus, but increased when exposed to the fungal pathogen Candida albicans.
Further research is necessary to determine if the effects on the innate immune response could interfere with the responses to other pathogens and vaccines. The study involved only 16 participants, all of white/Western European ancestry so further research is necessary. It is unknown whether the other mRNA vaccine has a similar effect. The paper has not yet been peer reviewed.
“Covid arm”
Rashes may develop around the site of Moderna vaccines a week after vaccination, and last for up to three weeks. This has been called “Covid arm”. The symptoms are not serious and don’t prevent receiving the second dose. The cause appears to be a delayed hypersensitive reaction. In earlier clinical trials Covid arm occurred in less than 1% of vaccinees, but the frequency of occurrence in population vaccinations is not known. The study was published in JAMA Dermatology.
No red flags yet in trial that gives two different vaccines
Initial data indicate that having an AstraZeneca/Oxford vaccine followed by the Pfizer/BioNTech vaccine, or vice versa, resulted in greater reactogenicity than receiving two doses of the same vaccine. Symptoms such as fever, chills, fever and headache, were more common with mixed doses, although they did not last long. Participants in the trial were over 50 years old and, based on standard vaccine trials, younger people may show greater reactogenicity to mixed doses. The effectiveness of mixed vaccines won’t be known before June. The study was published in The Lancet.
Potential for a universal coronavirus vaccine
A mouse monoclonal antibody that binds to at least eight lineages of beta coronavirus offers the possibility of a universal coronavirus therapy or vaccine. Structural analysis of where the antibody binds has identified conserved amino acids that may provide a good vaccine target. The paper was published in Nature Structural and Molecular Biology.
Moderna vaccine stimulates antibody production in saliva and respiratory tract fluids
Previous research has described the production of antibodies in sera following vaccination. A new study, not yet peer reviewed, reports that SARS-CoV-2-specific IgG antibodies are produced in mucosal and upper respiratory tract fluids following vaccination with the Moderna vaccine.
Different antibody profiles from natural infection and vaccination
The antibody profile created by natural infection of SARS-CoV-2 differs from that following vaccination with either the Pfizer/BioNTech or Moderna vaccines. Vaccination induced higher antibody levels and more diverse antibody populations than natural infections, particularly for antibodies targeting the receptor binding domain. Consistent with other studies, people with prior exposure to the virus showed stronger antibody responses after vaccination than those who were not infected.
The immune responses of nine vaccinated people varied, with some showing strong responses after the first dose, while others required both doses to achieve high specific antibody levels. The paper has not yet been peer reviewed.
“Prebunking” misinformation
A paper in Big Data & Society describes how a short web-based game can reduce susceptibility to misinformation about Covid-19. The game, called Go Viral!, improved players’ confidence in their ability to spot misinformation in selected social media posts, and reduced willingness to share misinformation. The study also looked at a passive intervention - showing UNESCO infographics - and found that this could increase awareness of manipulation too, but less effectively than the game.
The study calls these “prebunking” interventions. However, impacts were only studied for a week after playing the game, so the long term effect is unknown. Participants were more often self-described as politically left, and from Europe or North America, so the results may not be generalisable.
The possibility of pre-existing immunity in parts of Africa
Serum samples collected in the Democratic Republic of Congo before 2019 showed higher levels of reactivity to several SARS-CoV-2 proteins than pre-pandemic samples from France. An exception was that both groups showed similar reactivity to the receptor binding site antigen. The authors suggest that this could indicate that people in the DRC (and other parts of sub-Saharan Africa) may have pre-existing immunity due to being previously exposed to a SARS-CoV-2-like virus. This could account (in part at least) for apparently relatively low levels of infection in some African countries. Further research is required to prove this. The paper has not yet been peer reviewed.
Supercarriers
A saliva testing study in Colorado found that just 2% of asymptomatic people tested carried 90% of the virus load. Around half of the people testing positive had very low levels of virus, which may mean that they were not infectious. These results are similar to studies of viral levels in people with Covid-19 symptoms. However, it isn’t known whether only certain individuals carry very high loads, or whether many people have short periods of very high viral levels. Nor is it known whether the supercarriers become superspreaders. The research was published in the Proceedings of the National Academy of Sciences.
COVIDPoops
A website called COVIDPoops19 shows all the sites globally where wastewater monitoring is occurring. The Netherlands has, pardon the pun, sh*tloads, while it’s neighbour Germany has hardly any. New Zealand’s on the map. Locations are often derived from media reports, so many may not be regularly testing wastewater.
Poor global monitoring hampers control
A viral lineage, B.1.620, that is present in several European countries was inferred to have originated in central Africa. This is based on an analysis of travel histories and phylogenies. The paper highlights the importance of improving infectious disease monitoring across the world. It has not yet been peer reviewed.
Can parts of the virus become integrated into the human genome?
A controversial study suggests that parts of the SARS-CoV-2 virus may integrate into the human genome, at least in cultured cells. The research involved expressing high levels of reverse transcriptase (which transcribes RNA into DNA) in the cells. The frequency of such integration events couldn’t be determined. Nor is it certain if such integration occurs in infected people. There is no evidence that the complete virus integrates, or that viral proteins are produced after integration. The paper was published in the Proceedings of the National Academy of Sciences.
An earlier paper, not yet peer reviewed, criticised an earlier draft of the study, suggesting that the results are due to artefacts from the method rather than real integration. The paper and the criticisms are discussed in Science.
An interesting aspect of the published paper is that the original authors collaborated with one of their critics to undertake further tests to address his criticisms. That person became a co-author of the published paper and, according to the Science article, concluded that the original hypothesis of viral integration cannot be excluded in some cases. Further research on this is likely.
Learning how to be better prepared for the next one
An article published in Nature describes how early in the pandemic there was a lot of wasted effort on small, poorly designed trials to evaluate benefits of a range of drugs. It highlights the need for countries to have in place protocols for large-scale national and international clinical-trials that can be rapidly implemented during a new pandemic.
Better pandemic preparedness is also emphasised in the WHO’s Independent panel report. This is also discussed in an associated commentary in Science, which points out that the suggestions in the Independent Panel report are very similar to those made in 2015 in a review of the West African Ebola outbreak, but not implemented.
A letter in Science from leading epidemiologists and infectious disease scientists calls for further investigation into the possibility of the virus escaping from a laboratory. They are concerned the WHO investigation earlier in the year was not as thorough, or as transparent, on this hypothesis as for the natural spillover hypothesis.