Coronavirus Research Tracking - 24 September

Vaccinating the under 12s, Moderna and other vaccines' effectiveness, prior infection plus vaccination, fertility and vaccines, years lost due to Covid, Remdesivir trials, AI

This week Pfizer’s data on vaccinating 5 to 11 year olds, papers on the effectiveness of the Moderna vaccine, the effectiveness of several vaccines against different variants, the immunity boost from natural infection, and the need for more research on whether vaccination affects menstruation.

Non-vaccine research includes years of life lost due to Covid, mixed results for Remdesivir, infectiousness of the Delta variant, an artificial intelligence success, paranoia and its influences, and underestimating infections from bats.

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

Pfizer/BioNTech vaccine appears effective in young children

Pfizer has announced some of the results of its clinical trial for vaccinating 5 to 11 year olds. It is a press release rather than a paper. Children received smaller doses (10 micrograms rather than the standard 30 micrograms) than adults. They developed similar concentrations of neutralising antibodies as 16 to 25 year olds. There were no significant safety concerns, but the trial is too small to identify rare side effects, such as myocarditis.

Effectiveness of Moderna vaccine

Several recent studies are indicating that the Moderna vaccine has slightly greater effectiveness than the Pfizer/BioNTech vaccine.

A US study found that the Moderna vaccine was more effective than the Pfizer/BioNTech and Johnson & Johnson/Janssen vaccines in preventing hospitalisations. Between March and August effectiveness of the Moderna vaccine was 93%, compared with 88% (Pfizer) and 71% (Johnson & Johnson).

For the Pfizer vaccine, which has been used for a longer period, effectiveness declined (to 77%) after four months. The study followed adults for up to 6 months. Immunocompromised people were not included in the study. The paper was published in Morbidity and Mortality Weekly Report.

A Phase 3 trial of the Moderna vaccine showed that five months after the second dose vaccine efficacy in preventing Covid-19 symptoms was 93.2%. Effectiveness at preventing serious disease was efficacy in preventing severe disease was 98.2%, while there was 63% effectiveness in protecting against asymptomatic infection. The paper was published in The New England Journal of Medicine.

Waning effectiveness of both mRNA vaccines in older people after 5 months

Data from Humetrix, provided in an online presentation, indicates that the effectiveness of both mRNA vaccines against infection declines after several months, at least in older people. The study involved 5.6 million people aged 65 years and older.

Breakthrough infection rates were twice as high 5 to 6 months after vaccination, compared to 3 to 4 months post-vaccination. Breakthrough infections were more common in those over 85. The data and methods haven’t yet been peer reviewed.

IgG antibodies may indicate the level of protection for Moderna vaccine

The levels of spike-specific IgG antibodies produced in response to the Moderna vaccine are a correlate of protection in Rhesus macaques. Lower concentrations are more effective at controlling infection in the lower respiratory tract than in the upper respiratory tract. 

When these antibodies were given to Syrian hamsters they did not develop disease after SARS-CoV-2 infection. Study limitations include the fact that Covid-19 disease in macaques is milder than that seen in people, and the study was relatively short so longer term protection was not assessed. The paper was published in Science.

At least three vaccines provide good protection against severe Covid from a range of variants

A short review notes that several of the vaccines are effective in substantially reducing severe disease for several variants. Effectiveness against infections from some variants is more variable. The best data is available for Pfizer/BioNTech, AstraZeneca/Oxford and the Moderna vaccines. The paper doesn’t discuss the effects of waning immunity. The paper was published in Cell.

Natural infection plus vaccination results in very strong immune response

A SARS-CoV-2 infection followed by an mRNA vaccination results in stronger memory B cell development and more potent neutralisation. This leads to strong neutralisation of a range of variants of concern even if the initial infection occurred before the appearance of the variants. 

The immune response in uninfected but vaccinated participants was weaker but improved over 12 months. The authors suggest that additional vaccine shots for the uninfected may lead to stronger and broader protection. The study involved only small numbers of participants (43 with prior infections). The paper was published in Immunity.

Another study also suggests natural infection followed by vaccination may provide broader protection against variants. This study created a spike protein with up to 20 naturally occurring mutations. In lab tests neither sera from previously infected people nor from vaccinated people could neutralise the pseudovirus. 

However, neutralisation was effective when sera from infected then vaccinated people was used. This combination is thought to increase the diversity of antibodies. The results are based on only 14 people who were infected then vaccinated, and are lab-based tests. The paper was published in Nature.

In an outbreak in a US prison 93% of unvaccinated and 70% of fully vaccinated prisoners became infected. Of the four hospitalisations, three were unvaccinated. Those at lowest risk of becoming infected were those who had a previous infection and had subsequently been infected, although the numbers of previously infected prisoners was low. The paper was published in Morbidity and Mortality Weekly Report.

A review of nine studies concluded that the protection provided from a natural infection is at least equivalent to that from vaccination. There was a small additional immunity boost for previously infected people who then got vaccinated. The authors note that data on effectiveness of vaccinations and natural immunity is rapidly increasing, so the conclusions may change. The paper has not yet been peer reviewed.

Vaccine effectiveness against Alpha and Delta variants may be equal

A Dutch study found that vaccine effectiveness against hospitalisation was the same for the Alpha (94%) and Delta (95%) variants. Overall vaccine effectiveness against ICU admissions was 97%. The study included cases between April and August 2021.

It did not find evidence of waning immunity up to 20 weeks after full vaccination, although this result is less robust because of the low numbers of infected vaccinated people at different time points.   

During the study 5.7% of hospitalised Covid cases were fully vaccinated. Four vaccines were in use (Pfizer/BioNTech, AstraZeneca/Oxford, Moderna and Johnson & Johnson/Janssen). The study was not able to exclude people who had some degree of natural immunity from a previous infection. The paper has not yet been peer reviewed.

Uncertainty over vaccine effects on menstruation, but fertility not affected

An editorial in The BMJ discusses the need for more research on the effect Covid-19 vaccines may have on the menstrual cycle. Reports of changes to menstrual cycles after vaccination indicate that any effects are short-lived, but this is still not well studied. Covid-19 also can affect women’s periods. The article notes that there are biologically plausible mechanisms for how a stimulated immune system can affect the menstrual cycle.

The editorial also links to research that shows no effect of vaccinations on fertility. The British Fertility Association has also produced a fact sheet on Covid-19 vaccines and fertility.

Non-vaccine-related papers

Significant loss in quality of life from Covid-19

In the US the pandemic, up until March 2021, resulted in 6.6 million lost quality-adjusted life years (a measure of the health burden from infection). Nine million years of life lost for those aged over 25. The biggest losses were experienced in Black and Hispanic communities. 

For comparison, in 2019 in the US 6.8 and 5.3 million years of life were lost due to cancer and cardiovascular diseases, respectively. The paper was published in the Annals of Internal Medicine.

Remdesivir not effective for hospitalised patients

An international Phase 3 trial of Remdesivir found no clinical benefit for hospitalised patients. Effectiveness was assessed at 15 and 29 days after treatment. The paper was published in The Lancet Infectious Diseases.

In a press release Gilead, the company who developed Remdesivir, reports that another Phase 3 trial found that if the drug is delivered early (before hospitalisation) it can significantly reduce the risk of hospitalisation, at least in a group of high risk patients. The company says that more details will be provided at an infectious disease conference next week.

Few therapies under development for Covid-19

Therapies currently in development for Covid-19 are summarised in Derek Lowe’s blog for Science. There aren’t many, and results for most may not be available before the end of the year at the earliest.

Delta may be six times more infectious than Alpha

The Delta and Epsilon variants show higher levels of infectivity than the Alpha variant in lab tests. Delta was about six times more infectious than Alpha for samples with the same amount of viral RNA. Variability between individuals was large, but still showed higher viral loads and infectivity for the Delta and Epsilon variants. 

The study tested 165 viral samples, of which 21 were Alpha variants and 113 Delta variants. Clinical information for each sample (such as patient symptoms, age, PCR cycle count, etc), that could provide additional useful information, were not available. The paper has not yet been peer reviewed

Broad approach needed to assess variant risks

A paper in Nature Reviews Genetics reviews the key mutations affecting increased transmissibility and immune evasion in variants. Due to several of the mutations appearing independently in different variants the paper suggests that variant classification may need to change to reflect their mutation profile rather than the lineage from which they came from.

It also suggests that the best way to assess risks of new variants is to combine genomic surveillance with lab tests of antibody neutralising activity and vaccine efficacy studies. 

Artificial Intelligence proves useful in selecting people for Covid-19 tests

Artificial intelligence has been used in a range of Covid-19 research projects, but with not much success. This study from Greece, though, a method called reinforcement learning can be useful in selecting people to be tested at the border for Covid-19. The algorithm learns as more data becomes available. Demographic information and testing results from previous travellers were used to select those to test. 

The algorithm identified 1.85 times as many asymptomatic, infected travellers as random surveillance testing (and up to four times as many during peak travel periods). Traditional population-level epidemiological indicators (such as country of origin) were not very successful at identifying infected travellers.

To meet data privacy requirements the algorithm used a minimum amount of information on passengers, which limits its accuracy. The paper was published in Nature. A News and Views article in the same issue discusses the results. 

Paranoia, predictability and the pandemic

Paranoia can significantly increase when societal volatility increases and social rules are broken, particularly in cultures where rule following is valued. This conclusion comes from a US study that involved participants with different levels of paranoia (based on a standard test) undertaking different tasks where the rules sometimes changed without participants being told. The experiments were done before the pandemic, during a period of lockdown, and a period of reopening. Attitudes to mask wearing were also collected.

The study concluded that proactive leadership that tempered expectations of volatility reduced paranoia during lockdown. However, mask mandates enhanced paranoia during reopening by imposing a rule that was often violated. The authors suggest the results can help guide responses to future crises. The paper was published in Nature Human Behavior

Numbers of people infected by bat viruses probably very much greater than recorded

An average of 400,000 people a year may be infected with SARS-like coronaviruses in Southeast Asia. This is based on analyses of the home ranges of 23 bat species, human population densities, antibody prevalence, and human behaviours linked to contact with bats. 

The results suggest bat-to-human transmission may be more common than expected, and not picked up by routine surveillance programmes.  However, most of the infections do not appear to cause disease or persist. More data is required to improve risk assessments. The paper has not yet been peer reviewed

Another paper suggests that more research into bat immunology could improve therapies in humans. Bats usually show few if any symptoms from coronavirus infections. Only the abstract of the paper, published in Science Immunology, is open access.

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