Vaccine-related papers

Pfizer/BioNTech vaccine safe and effective for 5-to-11 year olds

A clinical trial of the Pfizer/BioNTech vaccine found that it was safe and effective for 5-to-11 year olds. Fifteen hundred children received two 10-μg mRNA doses of the vaccine, given 21 days apart (adult doses are 30-μg) and were monitored for two months after vaccination. Effectiveness against infection was calculated to be 90.7%.

No serious adverse effects were observed. Reported systemic effects of the vaccine, such as fever, were lower among vaccinated children than older children and adults. The paper was published in the New England Journal of Medicine.

Declining effectiveness against infections over time

A large study of US Veterans found that vaccine effectiveness against infection declined from 88% to 48% between February and October. This was an overall assessment of three vaccines. The effectiveness of the Johnson & Johnson/Janssen vaccine declined the most, from 86% down to 13%. The Moderna vaccine was 58% effective by the end of September, and the Pfizer/BioNTech 43%.

Overall effectiveness against preventing death from the Delta variant was nearly 82% for those under 65, and 72% for older veterans, with a slight decline over time. Janssen vaccine effectiveness was lower than the mRNA vaccines. The paper was published in Science.

AstraZeneca vaccine not as effective as Pfizer’s

A UK study found that the risk of a breakthrough infection was 43% higher for those receiving the AstraZeneca/Oxford vaccine, compared to the Pfizer/BioNTech vaccine. This was linked to lower levels of anti-spike antibodies generated by the AstraZeneca/Oxford vaccine. With both vaccines the antibodies began to decline three weeks after full vaccination.

Anti-spike antibody levels correlated with the degree of protection against infection. For people receiving the AstraZeneca vaccine it took about three months for their antibody levels to reach the threshold of increased risk of infection, compared with about five months for those vaccinated with the Pfizer vaccine. The paper has not yet been peer reviewed.

More evidence for stronger immunity from infection plus vaccination

Another study reports that a prior infection followed by one dose of the Pfizer/BioNTech vaccine can generate a broader and stronger immune response than two vaccine doses in uninfected people. This UK study of several hundred healthcare workers focussed on T cell responses.

After a single dose, T cell levels were five times higher in those with a prior infection. People who were fully vaccinated, but uninfected, had T cell levels slightly lower than those with an earlier infection and one vaccine dose. Antibody levels were also higher after one dose for those with a prior infection, consistent with other studies.

In tests of sera, neutralisation activity against the Beta variant was much stronger in those with a prior infection and a single vaccine dose than in those with one dose and no infection. The paper was published in The Lancet Microbe.

Vaccines may not reduce viral loads

Vaccination did not reduce viral loads or viable virus particles in people subsequently infected, a US study found. This implies infected vaccinated people may be as infectious as uninfected people, but the study did not test this.

Vaccinated participants had received one of the two mRNA vaccines or the Johnson & Johnson/Janssen vaccine. The paper does not compare the effects of different vaccines on viral loads or infectivity. It also did not measure whether vaccinated people were able to clear the virus more quickly than unvaccinated people (as has been reported in other studies). The paper has not yet been peer reviewed.

Protein-based vaccines in development

A news article in Nature discusses the protein-based vaccines undergoing clinical trials. These include Novavax. Protein-based vaccines have been used for decades, with good effectiveness and safety track records. They are typically slower to produce than the RNA and adenovirus-based vaccines.

The Covid-19 protein vaccines have promising trial data, and the risk of side effects appears to be very low. The logistics of distributing and using them is relatively simple, and they are also comparatively inexpensive to produce. Consequently, they have great potential for use in lower income countries, and for people who may be more at risk of adverse reactions. Protein vaccines may also prove useful as booster doses following on from other vaccines.

Lessons for Covid vaccinations and therapies from flu vaccinations

A perspective published in the New England Journal of Medicine looks at the history of influenza infections to assess the future of Covid vaccinations. It points out that the value of flu vaccinations is not in eliminating outbreaks, but in reducing transmission and the severity of symptoms.

The article notes that most predictions about the shape of a “post-Covid world” have been inaccurate. This is due, the authors suggest, to the speed at which we are still gathering information.

Non-vaccine-related papers

Pfizer’s Covid pill

Derek Lowe, in his blog for Science, discusses Pfizer’s data on it’s Covid pill (Paxlovid) that uses a protease inhibitor. Trials report an 89% reduction in hospitalisation or death if the pill is taken within three days of symptom onset.

He also considers that combining Merck’s molnupiravir with Paxlovid could provide a very effective treatment that would be very difficult for the virus to develop resistance to.

Excess years of life lost due to Covid-19

A study estimated that 28 million “excess years of life” were lost in 31 countries due to Covid-19 in 2020. Excess years of life is the difference between the observed and expected life expectancy.

New Zealand, Taiwan and Norway had an increase in life expectancy, while there was no change in life expectancy in Denmark, Iceland, and South Korea. Russia had the greatest decline in life expectancy. The reasons for changes, or not, were not examined. The paper was published in The BMJ.

Human genetic variations associated with Covid-19 risks

A human chitinase protein that increases the production of ACE2 protein was found to become more abundant in older people. This could lead to greater infectivity since the the viral spike protein binds to the ACE2 protein. This may, the authors suggest, partly explain the increased severity of Covid-19 in older people.

The authors also suggest that the virus may have inadvertently co-opted the body’s healing and repair system to aid infection, since chitinase is produced in response to cell damage. The chitinase protein may provide a useful target for Covid-19 therapies. The paper was published in JCI Insight.

Another genetic variation has also been found to be associated with a greater risk of developing severe Covid-19. This is a single nucleotide polymorphism that increases the expression of a transcription factor-like gene (LZTFL1). This is associated with a two-fold greater risk of respiratory failure in Covid-19 patients.

This genetic variant is associated with a set of other variations in a part of Chromosome 3. This set of mutations is much more common in people of South Asian ancestry than European ancestry. The paper was published in Nature Genetics.

Predicting the effects of mutations

A method that allows assessment of the effects of SARS-CoV-2 mutations in all the viral proteins has been developed. Using the method showed that mutations in the nucleocapsid protein leads to improved mRNA packaging, increasing the virus’ replication efficiency, and consequently transmission..

The authors suggest the method will also be useful for testing antiviral therapies. The paper was published in Science.

Factors that influence transmission

A short letter discusses the four factors involved in viral transmission. These are the time from being infected to becoming infectious; individual variability in infectiousness; the time from infection to symptom development; and the time between symptom onset in the infector and someone they infect (serial interval).

These are usually estimated, but often with considerable uncertainty. This then leads to inaccurate estimates of the viral reproductive number (R0) and the effectiveness of testing and other public health measures.

The authors recommend better coordination of studies to more accurately estimate transmission parameters, particularly in complex situations where there are varying levels of immunity, vaccinations, and different variants. The paper was published in Nature Medicine.

Delta variant 70% more transmissible than Alpha

Household transmission rates were 70% higher for the Delta variant than the Alpha variant in an English study. Households where the index case had Asian ethnicity tended to have higher transmission rates. The study corrected for a range of factors, including age, vaccination status, and ethnicity. However, some information, such as ages within households, was lacking, and this can influence transmission rates. The paper was published in The Lancet Regional Health Europe.

The role of children in spreading infection

A Chinese study reports that children under 12 were important spreaders in an outbreak with over 200 cases. Two children of the index case passed the infection onto school contacts, which resulted in further transmission within and between households and workplaces.

Infected under 12 year olds had milder symptoms than older infected people, and developed antibodies more slowly. The authors suggest that this may result in children under 12 being infectious for a longer period than older children (and adults). The paper has not yet been peer reviewed.

The rapid rise in Covid mis- and disinformation

A working paper on Covid mis- and disinformation from Te Punaha Matatini was released this week. It has already received wide coverage in the media, particularly the finding of recent rapid rises and changes in tone of disinformation. It defines misinformation as false information not created with the intention of hurting others. Disinformation is false information created to cause harm.

Modelling isolation risks

Another paper from Te Punaha Matatini models the risk of an infectious overseas traveller causing a community outbreak. It looks at different border control strategies and levels of vaccine coverage. It found that home isolation presents a substantially greater risk than managed quarantine. However, frequent testing of those in home isolation can reduce this risk. The paper has not yet been peer reviewed.

Immunology 101

A YouTube video from Kurzgesagt provides a good simple overview of how the immune system works.

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