Coronavirus Research Tracking - 7 May
Vaccine effectiveness, variants & mutations, antibody responses, oral anti-viral drug
This Research Tracker focuses on new studies of the effectiveness and efficacy of vaccines (largely Pfizer/BioNTech’s), including immune-compromised patients. There are also papers on the distribution and effects of variants, the dynamics and variability of antibody responses, a reason why you may lose your sense of smell with Covid-19, population and wastewater testing, and a new oral drug in animal trials.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
NZ Vaccine Dashboard
Newsroom has developed a dashboard of NZ’s vaccine rollout.
How to make an mRNA vaccine
The New York Times published a detailed article explaining how the Pfizer/BioNTech vaccine is made.
Comparing vaccine efficacy
The efficacy of nine vaccines against different variants is summarised in tables from the Institute for Health Metrics and Evaluation. It uses published results to estimate the efficacy in preventing infections and efficacy in preventing serious disease. Vaccine performance against B.1.1.7, B.1.351 and P.1 variants are also indicated, where data is available.
Exceptional results from Israel’s vaccination programme
Full vaccination with the Pfizer/BioNTech vaccine provided very high levels of protection from both symptomatic and asymptomatic infections, and from severe Covid-19. That’s the conclusion of an analysis of the effect that vaccination of over 70% of Israel’s population has had.
The research, published in The Lancet, found that when assessed at least one week after the second dose the vaccine was 97·0% effective against symptomatic infections, 91.5% against asymptomatic infections, over 97% effective against hospitalisation & severe Covid-19, and nearly 97% effective in preventing death due to Covid-19. The vaccine was highly effective for all age groups (16 years and older).
Two doses of Pfizer/BioNTech vaccine are better than one
A Qatari study found that the Pfizer/BioNTech vaccine was 89.5% effective against infection with the B.1.1.7 variant and 75% effective against B.1.351 two weeks or more after the second dose. A single dose was much less effective at preventing infection.
With two doses the vaccine showed 100% effectiveness in preventing severe Covid-19 for both the B.1.1.7 and B.1.351 variants. In Qatar half of current infections involve the B.1.351 variant. The study was published in the New England Journal of Medicine.
A similar result was found in another Israeli study, at least for B.1.1.7. It compared the frequency of the variants in infections of vaccinated individuals with matched infections of unvaccinated people. B.1.1.7 infections were disproportionately high among people between two weeks after the first vaccine shot and one week after the second, while B.1.351 was over-represented in vaccinated people infected a week or more after the second dose.
Nonetheless, the authors note that both variants appear to be controlled by mass vaccination and non-pharmaceutical interventions. The B.1.351 variant is relatively uncommon in Israel. The paper has not yet been peer reviewed.
Asymptomatic infections also reduced by Pfizer/BioNTech vaccine
Both symptomatic and asymptomatic infections appear to be reduced by the Pfizer/BioNTech vaccine. That’s according to a study, published in JAMA, of regularly monitored healthcare workers at a US Hospital where 3,000 vaccinated staff were compared with 2,000 unvaccinated staff. Symptomatic infections among vaccinated participants were 94% lower than for unvaccinated staff, while asymptomatic infections were 72% lower.
Vaccinations may halve household transmission from subsequent infection
A UK study has found the likelihood of household transmission is 40-50% lower where the infected person was vaccinated (with the Pfizer/BioNTech or AstraZeneca/Oxford vaccine) at least 21 days before being infected. Most of the people studied had received just one vaccine dose. The paper is not yet peer reviewed.
Johnson & Johnson/Janssen vaccine is also effective in reducing infection risk
The Johnson & Johnson/Janssen vaccine, Ad26.COV2.S, had an effectiveness of 76.7% in preventing infection two weeks after vaccination. The study compared infections in 2,100 vaccinated with 21,000 unvaccinated people. The effectiveness of the single dose vaccine in reducing cases of severe Covid-19 in communities is not yet able to be assessed. The study has not yet been peer reviewed.
Novovax vaccine clinical trial indicates 50% efficacy against B.1.351 variant
The Novovax vaccine showed relatively good effectiveness against the B.1.351 variant in a South African Phase 2 clinical trial. Vaccine efficacy was 60.1% for participants without HIV, with lower efficacy for those with HIV. Over 90% of a sample of the infections were from the B.1.351 variant, and efficacy of the vaccine against it was calculated to be 51%. An earlier trial in the UK found efficacy against the B.1.1.7 variant was 86%. The research was published in the New England Journal of Medicine.
Vaccine effectiveness in people with compromised immune systems
The effectiveness of Covid-19 vaccines for people with suppressed immune systems is discussed in Science. It summarises several studies that found that many patients being treated for cancers or had received organ transplants did not produce antibodies after one or two doses of Covid-19 vaccines. The types of medications they were receiving, and in some cases the timing, influenced the antibody response.
Similar responses can be seen for other vaccines, although for organ transplantees the suppression of antibody production appears worse after the first Covid-19 vaccine shot than for the flu vaccine .
Distribution and frequency of variants
The distribution and frequency of a large number (17 at the moment) of variants over time, and by country, is shown at CoVariants. This is based on genome sequences, so the prevalence of particular variants is biased by how well different countries are sequencing viral samples. The prevalence of specific mutations can also be examined.
Tight transmission bottleneck means few viral mutations are passed on
The development and transmission of new variants is uncommon during typical Covid-19 infections. A study found that during acute infections few mutations appear, and that only a small proportion of viral particles are transmitted to new hosts, making it unlikely that uncommon new mutations are spread. The paper has not yet been peer reviewed.
Less concern now about risk of B.1.526 New York variant
Despite some members of the B.1.526 variant group (originally identified in New York city) having the E484K mutation in the spike protein, there is no evidence that B.1.526 causes more severe disease, or is more likely than some other common variants to infect vaccinated people. This is based on a study of infections in New York, and published in the Morbidity and Mortality Weekly Report.
N440K mutation may increase infectiousness
An Indian study of recent variants with the N440K spike protein mutation found that these variants are more infectious. The research used cultured cells and reports that N440K variants produce much higher levels of viruses in cell lines than another prevalent strain, and was more infectious than another variant that was better at reproducing inside cells. The authors predict variants with the N440K mutation will soon dominate in India. The paper has not yet been peer reviewed.
Need to study the impact of mutation combinations, not just single ones
Testing all possible mutations in the spike protein against convalescent plasma found that there is considerable variation in responses between individuals. This suggests that a single viral mutation will not result in widespread immune evasion. The study recognises that it is critical to study combinations of mutations not just single mutations, and the study did not take account of how the protein naturally folds in actual infections. However, the study identifies actual or potential spike protein mutations to keep an eye on. The paper was published in Cell.
Timing of antibody response affects Covid-19 patient outcome
Delayed production of neutralising antibodies is associated with fatal Covid-19. The study of 229 patients found that neutralising antibodies need to be produced within 2 weeks to effectively control the infection. The paper was published in Nature Medicine.
There’s a lot of variability in antibody neutralisation activity between individuals
Mild Covid-19 often results in IgG antibody responses that are stable for at least 10 months after infection. However, the study, involving 963 people, found that there was considerable variability between individuals in the level of neutralisation activity. Twenty-one percent showed no neutralisation activity, while 3% had “elite” activity (where there was very effective neutralisation of SARS-CoV-2 and of SARS-CoV-1). Stronger neutralisation activity was associated with older age and more severe symptoms. The paper was published in Cell Host & Microbe.
Many antibodies target the N-terminal domain of the spoke protein
A study of four convalescent Covid-19 patients found that most of the IgG antibodies target the N-terminal domain (NTD) of the spike protein. This is outside of the receptor binding domain where most of the research has been directed. Some of the recent viral variants have mutations in the NTD, which may reduce the effectiveness of antibody neutralisation. The research was published in Science.
Cause of loss of sense of smell in Covid-19 cases may have been found (at least in hamsters)
Loss of the sense of smell in some cases of Covid-19 is linked to the virus infecting the olfactory neuroepithelium. The persistence of anosmia is associated with ongoing SARS-CoV-2 infection and inflammation in the epithelium of Syrian hamsters. The paper was published in Science Translational Medicine. (Only the abstract is free to view).
A review of population-scale testing
How population-scale testing for Covid-19 is changing is described in an article in Nature Reviews Genetics. It summarises the debates about the benefits and deficiencies of large scale testing and includes a useful diagram describing test sensitivity and specificity.
Wastewater sampling could provide good estimates of virus reproduction rate
Wastewater sampling can be used to estimate the effective reproductive number of SARS-CoV-2. That's according to a Swiss study, which quantified the amount of viral RNA in wastewater sludge from Zurich and San Jose, California to calculate effective reproduction values. These were then compared to reported case numbers in the area. Good correlations were found, although variability could be high. The authors recommend sampling wastewater at least three times a week to produce reliable estimates, and they also note some biases associated with sampling wastewater. The paper has not yet been peer reviewed.
Oral anti-viral drug shows promise in hamster trial
A nucleoside analogue that can be given orally reduced virus replication in Syrian hamsters. Nucleoside analogues are similar to one of the four nucleotides in DNA or RNA, but prevent the DNA or RNA from being copied. The drug, MK-4482, reduced levels of the virus and the amount of cellular damage in lungs of infected Syrian hamsters. Only small numbers of hamsters were used in the experiments. The research was published in Nature Communications.