Coronavirus Research Tracking - 22 October
Vaccines - comparisons, dosing intervals, prior infections, mix 'n match, transmission risks, safety & effectiveness for pregnant women and adolescents
This week, multiple papers comparing the effectiveness of different vaccines, the effects of increasing the dosing interval, and the immune effects of a prior infection. Plus, vaccine effects on viral loads and transmission risks, and the safety and effectiveness of vaccines for pregnant women and adolescents.
Non-vaccine papers on viral evolution during long infections, looking for genetic resistance to infection, and how memes may help with coping.
The tracker is shared with the COVID-19 Vaccine Media Hub.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Comparative effectiveness
For health and social care workers in England the Pfizer/BioNTech and AstraZeneca/Oxford vaccines provided the same levels of protection. This was seen for infections and hospitalisations. Effectiveness was assessed out to 20 weeks after the second dose. Comparative effectiveness against more severe Covid could not be assessed because of the small number of cases.
The study was undertaken when the Alpha variant was dominant. The authors note that results may not be the same for more at risk groups, such as elderly people. The paper has not yet been peer reviewed.
Another comparative study found that the Moderna vaccine produced stronger immune responses than the Pfizer/BioNTech. The Johnson & Johnson/Janssen generated substantially lower antibody, neutralisation, and T cell responses than either mRNA vaccine.
These results were mirrored in assessments of the effectiveness against infections, hospitalisations and death. However, the analysis of effectiveness was based on a meta-analysis that did not account for age or other confounding effects. The paper has not yet been peer reviewed.
A Puerto Rican study found that the two mRNA vaccines were more effective than the Johnson & Johnson/Janssen vaccine against infections, hospitalisations and Covid-related deaths. Protection waned over four months, and did not appear to be related to the spread of the Delta variant.
The paper estimated overall effectiveness (capturing infections, hospitalisations, and deaths). Peak protection for the Moderna, Pfizer, and Johnson & Johnson vaccines were 90%, 87%, and 58%, respectively. After four months the estimated levels of effectiveness were 71%, 56%, and 27%. The paper has not yet been peer reviewed.
Another study has shown that while antibody levels decline in the months after vaccination, some T cell levels remain stable. However, the dynamics can differ between vaccines. For the two mRNA vaccines, antibody decline was observed over eight months. Levels generated by the Johnson & Johnson vaccine were lower, but more stable over time (however, only 8 people in the study had the J & J vaccine). Antibody levels and neutralising activity tended to be higher in those who received the Moderna vaccine.
CD4+ T cell levels on the other hand remained relatively stable for all the vaccines over 8 months, with levels being similar for all three vaccines. The paper was published in the New England Journal of Medicine.
Lower effectiveness for CoronaVac and Sinopharm vaccines
A news item in Nature discusses evidence of rapid waning on immunity in the CoronaVac and Sinopharm vaccines. Both are inactivated viruses and evidence indicates that they are less effective that mRNA and sub-unit vaccines. CoronaVac and Sinopharm make up nearly half the vaccine doses given globally. Trials of booster shots and mix and match vaccinations for CoronaVac and Sinopharm are underway.
Effect of a longer interval between doses
A UK study reports that a longer interval between Pfizer/BioNTech doses increases neutralising antibody levels. Compared to a 3-to-4 week gap between the first and second dose, a 6-to-14 week gap resulted in a 2-to-4-fold increase in neutralising antibody levels.
While a longer interval did not result in an overall increase in T cell levels, specific CD4+ T cell types were elevated. Immune responses were assessed four weeks after the second dose.
The study found that there was considerable variation between individuals for both antibody and T cell levels regardless of the dosing interval. The paper was published in Cell.
Effects of prior infection
People who had a SARS-CoV-2 infection before vaccination were better able to neutralise variants of concern than uninfected vaccinated people. This is associated with infections creating a B cell germline that produces potent broadly neutralising antibodies.
This study only involved five previously infected and five uninfected vaccinated people, but analysed thousands of individual B cells, providing a very detailed analysis of immune responses. Vaccinations were with the Pfizer/BioNTech vaccine.
The authors suggest that a third vaccine dose may stimulate the generation of similarly potent antibody germlines, though this has yet to be proven. The paper was published in Nature.
A Swedish study found that healthcare workers with a prior mild infection had more robust immune responses than uninfected vaccinated workers. The study tested participants for three to seven months. Six weeks after vaccination (with Pfizer/BioNTech) those with a prior infection had antibody levels about twice as high as uninfected participants. At 29 weeks post-vaccination the difference was greater. Antibody levels declined substantially (3-to-7-fold) between weeks 6 and 29.
Similar results were seen for the AstraZeneca/Oxford vaccine, although antibody levels were about 4.5-fold lower than found in Pfizer/BioNTech participants. Those receiving the AstraZeneca were only followed for 3 months because the interval between its two doses was 10-to-12 weeks.
There was no difference in IgG antibody levels between those who had Pfizer doses 6-to-8 weeks apart and those with a 3-to-4 week interval (regardless of prior infection or not). However, neutralising antibody levels were slightly higher in those with a longer interval between doses. Participants were mostly women. The paper has not yet been peer reviewed.
Mix & Match effectiveness
A Swedish study reports that combining an AstraZeneca/Oxford dose with an mRNA dose improves effectiveness against infection. Effectiveness of two AstraZeneca doses was 50%, but 67% when the second dose was Pfizer, and 79% if it was the Moderna vaccine. Effectiveness of two doses of Pfizer was 78%, and 87% for two Moderna shots.
Participants were followed for an average of 76 days. Times between doses was not stated, though the paper notes that this did not influence levels of effectiveness. The paper was published in The Lancet Regional Health Europe.
Vaccine effect on transmission risks
A Dutch study found that vaccination reduces transmission to others in the same household. Vaccinated people in the household were also less likely to become infected than unvaccinated people. When the index case was fully vaccinated effectiveness against transmission to unvaccinated household contacts was 63% for the Delta variant, compared with 73% for the Alpha variant. The reasons for the difference between the two variants was not investigated. The paper has not yet been peer reviewed.
Similarly, a UK study found that vaccination (with either Pfizer/BioNTech or AstraZeneca/Oxford) reduces transmission. This applied to both the Alpha and Delta variants, but transmission risk was higher for Delta.
In this study lower transmission risk in vaccinated people was not solely due to lower viral loads. The authors suggest that vaccines may help clear viable infectious virus more quickly, and so decrease the risk. They agree with other authors that cycle threshold values probably don’t provide a good indication of infection risk.
About 12 weeks after full vaccination transmission risk for Delta was similar in vaccinated and unvaccinated cases, indicating a waning of effectiveness. The paper has not yet been peer reviewed.
Another study reports that viral loads and levels of infectious virus can be similar in fully vaccinated and unvaccinated people. Vaccinated individuals had received one of the mRNA vaccines. The Delta variant was predominant during the study. The paper has not yet been peer reviewed.
A study of over 800 people reports similar results. It also didn’t find significant differences between viral loads in vaccinated people who had symptomatic or asymptomatic infections.
These results contradict other studies that reported lower viral loads in vaccinated people, but agree with others that did not find differences. Viral loads, as measured by PCR cycle counts, varied widely in both vaccinated and unvaccinated people. A major limitation of this study is that viral loads were not measured at the same time point in the infection cycle (see also the 8 October Tracker). The paper has not yet been peer reviewed.
Pfizer/BioNTech safe and effective for pregnant women
The Pfizer/BioNTech vaccine appears to be as safe and effective for pregnant women as for other adults. This study compared over 10,000 vaccinated pregnant women with a matched set of unvaccinated pregnant women in Israel. Effectiveness against infections was 96% in the two months after full vaccination. The study was undertaken when the Alpha variant was dominant. The paper was published in Nature Medicine.
Pfizer/BioNTech safe and effective for 12-18 year olds
The Pfizer/BioNTech vaccine was highly effective (93%) at preventing Covid-related hospitalisations among 12 to 18 year olds. This was a case-controlled observational study involving 464 adolescents. None of the hospitalised vaccinated cases required critical life support, but some of the unvaccinated cases did. The Delta variant was the most common circulating strain during the period of the study. The paper was published in the Morbidity and Mortality Weekly Report.
Non-vaccine-related papers
Viral evolution during long infections
Studying viral evolution in people with long-lived infections can help understand the development of variants. A former cancer patient developed a year-long Covid-19 infection that resulted in two unusual viral deletions. One was at the end of the spike protein gene, and a similar deletion occurs in the Lambda variant. The other was a large deletion of two coding sequences elsewhere in the genome.
The earlier cancer treatment had depleted the patients B cells, and treatment with convalescent plasma during the initial infection may have provided selective pressure on the viral mutations. The patient eventually recovered following additional treatment. The paper has not yet been peer reviewed.
The paper and the broader issue of viral evolution in immunocompromised patients is discussed in a news article in Science.
Searching for genetic bases for infection resistance
A paper in Nature Immunology describes a new international initiative - the COVID Human Genetic Effort - to identify genetic factors that may contribute to resistance to infection. It discusses some of the proposed genetic associations with resistance, along with the often weak evidence, and the difficulties in identifying a genetic basis for resistance. The initiative is currently recruiting participants.
Memes may help reduce pandemic anxiety
Some types of memes may help in coping with pandemic anxiety, a study concludes. The authors suggest that this may be due to certain memes providing useful perspectives, comfort, and validation of the audience’s own experience. This can increase positive emotions, indirectly helping with coping.
Memes with Covid-related captions were found to be more effective for coping than other captions. Human images also appeared to be more efficacious than memes with animal images. The paper was published in Psychology of Popular Media.