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Coronavirus Research Tracking - 6 August

This article was published on
August 6, 2021

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This week, several papers look at effectiveness of vaccines against Delta variant infections. Other studies test how to nudge behaviours, and there is a review of factors that helped the rapid development and deployment (in richer countries) of vaccines. Non-vaccine research papers include further promising results for the REGEN-COV antibody therapy, T cell effectiveness against variants, increasing neutralisation potency over time, and finding new variants in wastewater. 

This week, several papers look at effectiveness of vaccines against Delta variant infections. Other studies test how to nudge behaviours, and there is a review of factors that helped the rapid development and deployment (in richer countries) of vaccines. Non-vaccine research papers include further promising results for the REGEN-COV antibody therapy, T cell effectiveness against variants, increasing neutralisation potency over time, and finding new variants in wastewater. 

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It is easy to get swamped by all the coronavirus research. New Zealand’s Science Media Centre is keeping track of much of it so you don’t have to. The weekly Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre New Zealand.

Vaccine-related papers

Breakthrough infections involving the Delta variant

A town in Massachusetts that held several large closely packed public gatherings in July resulted in 469 cases of Covid-19. Participants in the events were mostly young males who came from elsewhere. Three quarters of the cases were in fully vaccinated people (who had an mRNA or the Johnson & Johnson/Janssen vaccine). Ninety percent of sequenced viruses were Delta variants. Seventy nine percent of vaccinated cases had symptoms, but only five cases required hospitalisation.

Based on PCR results, viral levels were similar in vaccinated, partially vaccinated and unvaccinated cases, although this requires further study (see the Singaporean paper below). The authors also noted that the circumstances and data from this outbreak prevent making general conclusions about the effectiveness of vaccines against the Delta variant. The report was published in the CDC Morbidity and Mortality Weekly Report.

Another US study also found little difference in viral loads between vaccinated and unvaccinated people. However, viral load was only measured once. Seventy nine of 291 (27%) infections were in fully vaccinated people. Disease severity was not reported. Asymptomatic infections were also not investigated, so the frequency of breakthrough infections was not determined, The paper has not yet been peer reviewed.

A Singaporean study of infections involving the Delta variant found one third of 218 cases were fully vaccinated. However, the incidence of symptomatic and severe Covid-19 was significantly lower among the fully vaccinated group.

While viral loads appeared similar in vaccinated and unvaccinated cases when diagnosed, viral loads fell more quickly in vaccinated patients, and was associated with rapidly rising neutralising antibody levels. The authors concluded that mRNA vaccines provide protection against symptomatic and severe Covid-19 from the Delta variant. The paper has not yet been peer reviewed.

A large UK study estimated vaccine effectiveness against infection in June and July was between 49% and 58% for those aged 18 to 64. The range comes from whether all or only the strongest PCR results are counted. These results are based on random sampling of both asymptomatic and symptomatic cases, and included people vaccinated with either the Pfizer/BioNTech or AstraZeneca/Oxford vaccines.

The study, part of an ongoing trial called REACT-1, sampled about 100,000 people, and involved sending coronavirus tests kits out to people. The Delta variant was dominant during this period, and infection levels were rapidly increasing. The highest rates of infections were seen in unvaccinated 12-24 year olds.

Infections in unvaccinated people were three times higher than those who were vaccinated. Viral loads (based on PCR results) in vaccinated people were also lower than for those who were unvaccinated. This may result in lower levels of infectiousness in vaccinated people, but this wasn’t tested or assessed.

Limitations of the study include reliance on self-reporting of vaccine status, not distinguishing the effectiveness of the two vaccines separately, and large ranges for estimated vaccine effectiveness. The paper has not yet been peer reviewed.

Antibody levels decline after vaccination

Spike protein-specific antibody levels decline in the three to 10 weeks after the second doses of the Pfizer/BioNTech and AstraZeneca/Oxford vaccines. Declines were greater (five-fold) for the AstraZeneca vaccine, compared with the Pfizer vaccine (two-fold), and greater for older people. Antibody levels were higher in people who had been previously infected before being vaccinated.

This study, involving over 500 people, is consistent with other studies. It did not assess memory B cells (nor T cells), but earlier research found these do not decline over the short term. Currently it is uncertain what level of antibodies provides protection from infection or more severe disease, so the significance of the decline is unknown. Further research on larger groups, including multiple sampling over time from the same individuals, is required. The paper was published in The Lancet.

A correlate of protection for the Moderna vaccine

Spike-protein-specific antibody levels generated by the Moderna vaccine correlate with the level of virus replication control in the respiratory tract in primates. There was a strong correlation between levels of binding antibodies and neutralisation activity.

Perhaps more importantly, different levels of antibodies may provide similar levels of protection in different parts of the body. A lower antibody level was required in the lower respiratory tract than in the upper for viral control. Limitations of the research included the fact that the primates only develop mild Covid-19 disease, and recent variants of concern were not tested. The paper was published in Science.

Overcoming barriers to vaccination

The biggest barrier to Covid-19 vaccination may be getting people to schedule their first vaccination. Based on randomised controlled trials in the US, text reminders for booking vaccination appointments were particularly effective if they provided a “sense of ownership” to the recipient. That is, making people feel the vaccine has just become available for them, and urging them to “claim their date.”

In the study 90% of people who made a first appointment showed up for it. Additional information aimed at reducing vaccine hesitancy did not improve response rates. Further research is needed to find what information (and how it is presented) would reduce vaccine hesitancy.

The research found differences in the results of stated intentions following online experiments and actual behaviours, and the authors advocate for conducting real world pilot tests before scaling up vaccination strategies. The paper was published in Nature. The research is also summarised in a Nature News & Views article.

In another study, an intervention that gets participants to imagine a Covid-related scenario helped change perceptions or risk, and reduced risky infection-related behaviours. The scenario provides numerical information. The effect persisted for a week or more. Contrary to expectations, personal and impersonal scenarios appeared to be equally influential, although the researchers suggest personalisation may be better for correcting underestimation of risk.

The intervention took 10 minutes and is suited for on-line distribution. Not everyone changed behaviours after the exercise. A study limitation is that it relied on self-reporting of behaviours. The paper was published in the Proceedings of the National Academy of Sciences.

Factors that led to rapid vaccine development in the US

An article published in Immunity reviews how US government initiatives helped connect public and private sector expertises and infrastructure to speed up vaccine development and distribution. It identifies lessons learned in pandemic preparedness. It notes that the successful vaccines were not developed by chance, but were based on a decade or more of research on vaccine antigen design and new vaccine platform technologies.

An important factor in the rapid distribution of vaccines was early investment by the government in commercial-scale manufacturing before clinical trials were completed. This allowed large scale production to proceed very quickly after regulatory approvals were given. However, the paper also identifies where there is still room for improvement in optimising emergency manufacturing capacity.

Non-vaccine-related papers

REGEN-COV therapy trials continue to provide positive results

The two monoclonal antibody therapy REGEN-COV can provide good protection against infection, and reduce duration of symptoms if infected. This Phase 3 clinical trial, involving 1,500 participants (with half receiving a placebo), found that the therapy decreased the overall risk of infection (symptomatic and asymptomatic) by two thirds.

For those with symptomatic infections, the period with symptoms was on average two weeks shorter for those who had previously been given REGEN-COV, and the period of highest viral load decreased from about 9 days to three. No serious adverse effects from the drug were observed. The paper was published in the New England Journal of Medicine.

Wastewater monitoring finds new variants, but origins unclear

A New York study detected new viral lineages in wastewater samples. Sequencing of the spike protein gene detected mutations rarely observed in clinical samples. When included in a pseudovirus,some of these mutations allowed infection of mouse and rat cells, and/or were more resistant to some receptor binding domain neutralising monoclonal antibodies. It is uncertain if the novel lineages are derived from people or have come from other mammals in the city. The paper has not yet been peer reviewed.

Variants may have little effect on T cell effectiveness

Variants of concern do not appear to disrupt overall T cell responses to infection. Memory CD4 and CD8 T cells that recognise early viral strains also recognise Alpha, Beta, Gamma and CAL.20C variants. These T cells are generated both by natural infections and mRNA vaccines. Variants of concern were able to evade only 7% of CD4 and 3% of CD8 epitopes, indicating strong T cell responses to variants.

T cells play a stronger role in reducing disease severity than in preventing infection.  The study focused on overall T cell responses not specific T cells, and did not examine T cells produced in response to recent variants of concern. The paper was published in Cell Reports Medicine.

Neutralisation potency can improve over time

Neutralisation antibody potency increases over the months following infection. Memory B cells accumulate mutations over time, leading to production of more diverse sets of antibodies. This study found that this leads to increased binding affinity, potency and breadth of recognition for antibodies targeting the receptor binding domain, restricting options for viral escape. The paper was published in Immunity.

Risks of the Lambda variant of interest may be being under appreciated

Lambda, a variant of interest in South America, appears to show a level of infectivity similar to that seen for the Delta variant. The term Variant of interest is used to identify variants with mutations that may increase infectivity, disease severity, or resistance to vaccines, but further information is still required.

This paper associates Lambda’s potentially greater infectivity with the spike protein mutations T76I and L452Q. Other mutations increase (by about 1.5-fold) resistance to some neutralising antibodies. The authors suggest that it’s current label of “Variant of interest” may create complacency about its potential risks. The paper has not been peer reviewed.

Closer study of the olfactory bulb recommended

A review of previous research suggests that the olfactory bulb should be monitored more closely for SARS-CoV-2 infection. It suggests that a chronic or permanent olfactory problem following infection could be an indicator for an increased likelihood of long term neurological disorders, although this requires further research. The paper was published in The Lancet Neurology.

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