Coronavirus Research Tracking - 10 September

Vaccine effectiveness, Delta variant risk, vaccine safety, vaccine hesitancy, antigen tests, innate immunity, nasal swabs, and toilet risks

This week vaccines and infectiousness, differing results for Delta hospitalisation risks, effectiveness of a third dose, vaccine safety studies, and what influences vaccine hesitancy. In non-vaccine studies, rapid antigen tests, children’s strong innate immunity, the low risk from public toilets, and episodic mutation rates.

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

Vaccinated people may be less infectious

Infected vaccinated people shed infectious viral particles for shorter periods of time, and in lower amounts, than unvaccinated people with SARS-CoV-2. This study found that the virus in vaccinated people was also more easily detected in saliva than in nasopharyngeal swabs, indicating its distribution may be more limited than in unvaccinated people.

Symptoms in vaccinated participants were also usually less severe, consistent with previous research. This may mean that vaccinated but infected people may have a lower risk of infecting others. 

However, the study is based on only 23 people, of which only six were fully vaccinated. Viral variants in the study were Alpha and Gamma, and vaccinated participants had received the Johnson & Johnson/Janssen vaccine. The paper has not yet been peer reviewed

Different results in two studies of hospitalisation risks from Delta

A short research letter reported a higher hospitalisation rate for people infected with the Delta variant, compared to the Alpha, in Denmark. For Alpha 3.8% of 66,000 people were hospitalised. For Delta 6.9% of 636 cases were hospitalised between January and early July. This is consistent with an earlier UK study (see last week’s Tracker). The paper was published in The Lancet Infectious Diseases

However, a Norwegian study did not find a difference in hospitalisation rates. Nearly 8,000 cases of Delta infections and 12,000 of Alpha were compared between May and August. Overall 1.7% of cases were hospitalised.

Partial vaccination was calculated to reduce hospitalisation risk by 72%, and full vaccination by 76%, although confidence intervals in both cases range from 60% to just over 80%. People vaccinated with either of the two mRNA vaccines or the AstraZeneca/Oxford vaccine were included in the study.

The authors discuss factors that may account for different results between studies. These include when the studies were done (early or later in the Delta wave), differences in analytical methods, and the capacity of public and clinical health systems. The paper has not yet been peer reviewed

Three variants of concern evade humoral responses 

The Alpha, Beta and Gamma variants are less well controlled by antibodies from previously infected or vaccinated people. Sera from people who required hospitalisation or had been vaccinated with the Pfizer/BioNTech vaccine demonstrated stronger neutralisation ability against these variants than those with mild infections. The Beta and Gamma variants were better able to avoid neutralisation. The paper was published in Science Advances

Adverse reactions to mRNA vaccines are rare

The two mRNA vaccines are not associated with increased risks to a range of serious health conditions. This is based on analyses of over 6 million vaccinated people. It compared adverse effects in the first three weeks after vaccination with their occurrence over the next three weeks (when it was assumed adverse effects were not vaccine related).

There were just 55 cases of anaphylaxis within a day of a vaccine dose. Nearly all of these cases were women. The study did not examine conditions not reported to medical centers, so less serious health effects were not evaluated. Confidence intervals for some of the condition-specific results are broad, so the significance of results could change with additional information. The paper was published in JAMA.

Pfizer/BioNTech vaccine safe for most people with allergies

An Israeli study found that most people with allergies can be safely vaccinated with the Pfizer/BioNTech vaccine. It used medical histories and a questionnaire to identify those with the highest risk of allergic reactions to the vaccine. 

Out of 429 high risk people who were vaccinated under medical supervision, 2% had allergic reactions to either the first or second dose. The reactions were treatable and all quickly recovered. The authors suggest that medical centres use this approach to identify those most at risk. The paper was published in JAMA Network Open.

Strength of natural vs vaccine-based immunity

A news article in Science discusses reasons why SARS-CoV-2 infection may provide stronger immunity than a vaccine. It is based on the Israeli study included in the 27 August Tracker. The news article notes that deliberately becoming infected to develop stronger immunity comes with many risks, such as developing serious disease. Consequently, vaccination rather than infection is the less risky strategy to strengthen immune protection.

Third vaccine dose effective, at least in the short term

A third dose of the Pfizer/BioNTech vaccine can reduce the odds of infection by 48-68% one to two weeks after the shot. In the third week the effectiveness was 70-84%. The third dose showed no improved protection in the first week.

These results, from Israel, are based on two types of analyses, involving over 30,000 people who received a third dose about 7 months after the second. Of the more that 150,000 who had two vaccine doses, 5.5% became infected during the study, compared with 3.6% of those who had had three doses. Longer term effects are being monitored. The paper has not yet been peer reviewed

Moderna vaccine effectiveness

In a large real-world study the Moderna vaccine had 87.4% efficacy against infection and 95.8% against hospitalisation. Over 350,000 vaccinated people were matched with 350,000 unvaccinated people in California. The vaccine was more effective at preventing symptomatic than asymptomatic infection, but efficacy was still 72% for the latter. The study also found that a single vaccine dose may boost protection for those with a previous infection. The paper has not yet been peer reviewed

AstraZeneca/Oxford vaccine less effective against Delta infection

An Indian study found that the AstraZeneca/Oxford vaccine was less effective against preventing infections of the Delta variant than the Alpha. This was based on 130 infected healthcare workers. Lab studies demonstrated the Delta variant was six-fold less sensitive to neutralisation by sera from patients who had recovered from infection, and 8-fold less sensitive to sera from vaccinated people, compared with an earlier Wuhan strain. 

The Delta variant was also more efficient than Alpha in replicating in respiratory cell cultures. This is attributed to a difference in the structure of the spike protein’s receptor binding domain. The paper was published in Nature.

First DNA vaccine approved

India has approved the world’s first DNA vaccine for use on people (for any disease). A news item in Nature discusses the significance of the approval, and prospects for other DNA vaccines.

The ZyCoV-D vaccine is applied to the skin without requiring an injection. In clinical trials it demonstrated 67% effectiveness against symptomatic Covid-19. DNA vaccines are easier to produce than RNA vaccines, and can be stored at warmer temperatures, making production and distribution cheaper and simpler.

Vaccine hesitancy in marginalised groups

In the UK two broad themes were found to be associated with vaccine hesitancy in minority ethnic people. The first is a history of marginalisation and discrimination. This decreases trust in government and health services. The second was a lack of clear guidance and opportunities for two way discussions about vaccine safety. Government messages often did not reach many communities. The paper was published in The Lancet Infectious Diseases.

Vaccine passports

The BMJ has published a map of countries or regions that currently provide “vaccine passports” or similar records of vaccination status. These have usually been developed for domestic uses rather than international travel. The brief article notes that there is little or no coordination between these certification schemes, which will create difficulties.

Antibodies not innate immunity stops the virus in mice

In some elegant mice experiments it was shown that antibodies, rather than innate immunity, are responsible for eradicating SARS-CoV-2. Antibodies generated in response to an earlier infection or vaccination showed the same effect. CD4 T cells played a role in viral clearance by supporting antibody production. Measuring specific antibody levels or activity may provide a suitable correlate of protection. The paper was published in Science Immunology.

Non-Vaccine-related papers

Rapid antigen tests 

Given NZ’s current interest in more rapid Covid-19 diagnostic tests, a February article in Nature is useful. It discussed the advantages and disadvantages of rapid antigen tests. These are non-PCR tests that detect parts of the virus. They are useful early in the infection cycle when the virus is rapidly reproducing and producing infective particles. 

There are a large number of such tests available, but the sensitivity and specificity of the tests vary, so choice of test and when to use it are critical decisions. Results of independent testing are published by FIND.

Children’s innate immune system more effective in controlling the virus

Children’s innate immune system is probably a key reason why they are less likely to develop Covid-19. Their innate immune responses (which result in more general attacks on pathogens) respond more quickly than in adults, suppressing the virus. The article published in Nature, summarises a number of studies that have examined infections in children.

Most people develop an immune memory of SARS-CoV-2 after infection

A review of 54 existing studies calculated that 90% of infected people developed immune memory of SARS-CoV-2. This lasted for at least 6 to 8 months. Based on the available data a previous infection reduced the odds of a subsequent infection by 81%.

Some of the studies in the analysis were small, and different variants were involved. No studies later than February 2021 were included, so the impact of the Delta and other more recent variants are not included. Differences in immune memory responses to variants were not studied. The paper has not yet been peer reviewed

Nasal swabs make you more likely to sneeze

Taking nasopharyngeal swabs can increase the risk of coughing or sneezing. That probably isn’t too surprising, but it is based on a structured study not anecdotes. About 20% of those having swabs taken coughed or sneezed in the study, which could increase infection risk. Strategies to reduce the risk of infection from such aerosols during sample collection are described. The paper has not yet been peer reviewed

Low risk of infection from well-maintained public toilets

A review of studies of disease transmission linked to public toilets concludes that the risk of becoming infected with SARS-CoV-2 is low. Thirty eight studies were included. It found that only a few cases of infection from bacteria or viruses have been linked to public toilets, and these were associated with faecal-oral transmission rather than from aerosols. 

Good hand washing & drying, along with regular toilet cleaning and maintenance, and adequate ventilation will keep risks of infections from public toilets low. The study was published in Science of the Total Environment.

Episodic mutation rates in variants

The emergence of variants of concern may be linked in part to episodic increases in evolutionary rates. Based on models, a four-fold increase was estimated for the four variants of concern. This is probably caused by selection during chronic infections. The paper has not yet been peer reviewed

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