Coronavirus Research Tracking - 3 September - Vaccine edition

Vaccine effectiveness, waning immunity, impacts on long Covid, booster shots

This week we again have separate issues on vaccine and non-vaccine papers. Continuing research on effective of vaccines against infections and hospitalisations, and waning immunity. Plus, the benefit of getting vaccinated even if previously infected, how vaccines may reduce risk of Long Covid, and ethical and scientific perspectives on booster shots.

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

Hospitalisations higher for Delta than Alpha variant infections

In the UK unvaccinated people infected with the Delta variant were about twice as likely to be hospitalised as those with the Alpha variant. This was based on hospitalisations within 2 weeks of diagnosis. For both the Alpha and Delta variants, just over 2% of infections resulted in hospitalisations. However, the adjusted risk of hospitalisation was greater for those with the Delta variant.

Hospitalisation rates for those who had at least one vaccination dose were lower than for unvaccinated people with Covid-19. There were too few infected vaccinated cases to compare whether hospitalisation risks differed between those infected with the Delta or Alpha variants after vaccination. 

The study involved 43,000 Covid-19 patients with infections between March and May. The paper was published in The Lancet Infectious Diseases.

An editorial in the same issue discusses the study. It notes that those infected by the Delta variant were on average younger, and more frequently were of Asian ethnicity than those infected by the Alpha variant. This makes it difficult to determine associations between infection, morbidity and mortality between the variants.

Vaccine effectiveness

A study of vaccinated and unvaccinated healthcare workers in Israel found infection levels were much lower in the former. Of the 5,312 vaccinated workers who were tested post-vaccination only 27 (0.5%) tested positive, compared with 69 of the 690 (10%) of the unvaccinated workers. The infected vaccinated workers were more likely to have been living with an infected person. The paper was published in JAMA Network Open.

A US study found that unvaccinated adults are 17 times more likely to be hospitalised than vaccinated adults. Vaccinated people hospitalised with Covid-19 were on average about 13 years older, and have several underlying conditions, than the unvaccinated hospitalised group. The research examined over 67,000 hospitalisations in the first half of 2021. The paper has not yet been peer reviewed

Declines in vaccine effectiveness

A US study of vaccine effectiveness against symptomatic infection in healthcare workers found a rapid decline in July. Between March and June effectiveness was stable, at around 90%, but in July it declined to 65.5%. This is attributed to a combination of waning immunity and the greater infectivity of the Delta variant.

Vaccinated participants received one of the two mRNA vaccines. Unvaccinated healthcare workers had a much greater likelihood of becoming infected. The paper was published in The New England Journal of Medicine.

A Qatari study found that the effectiveness against infection of the Pfizer/BioNTech vaccine peaked at 72% about five weeks after the second dose. There was rapid decline after 15 weeks. Effectiveness against symptomatic infection was greater than for asymptomatic cases, but both declined over time.

The population in Qatar is relatively young, so some of the results may not be the same in countries with different demographic profiles. However, consistent with other studies, effectiveness against severe Covid-19 was more stable, remaining at around 95% for about six months. The paper has not yet been peer reviewed.

New data from Israel further demonstrated waning immunity following Pfizer/BioNTech vaccination. When assessed in July, vaccine efficacy against infection for fully vaccinated people over 60 was 73%  for those vaccinated in the second half of March. For those vaccinated during the second half of January efficacy was 57%. Similar differences were seen for other age groups. 

Vaccine efficacy against severe Covid-19 decreased less, from 91% to 86% for the over 60s. The paper has not yet been peer reviewed

Differences in antibody responses between the two mRNA vaccines

In a direct comparison the Moderna vaccine was found to generate a stronger antibody response than that produced after the Pfizer/BioNTech vaccine. The authors suggest that this may be due to the higher mRNA content in the Moderna vaccine. Vaccine levels were only measured at six and 10 weeks after the second doses, so whether these differences persist over the longer term are unknown. 

Whether this results in greater efficacy for the Moderna vaccines is also not yet known. Neutralising activity was not measured, nor were real world effects on virus infection and disease severity. [Previous research has found an association between neutralisation titre and level of protection.] The results are based on 1,600 vaccinated healthcare workers. The paper was published in JAMA.

Another study, published in JAMA Network Open, found antibody levels were lower in older adults who received the Pfizer/BioNTech vaccine compared to levels in younger adults recipients. There was no age difference in antibody levels for those vaccinated with the Moderna vaccine.

Vaccines benefit the previously infected

Infection with SARS-CoV-2 doesn’t guarantee “natural immunity”, a study has shown. Those who had mild or no symptoms were found tohave much lower levels of antibodies than those with multiple Covid-19 symptoms. 

Two doses of either mRNA vaccine were more effective at boosting antibody levels than one dose for those who had mild or no Covid-19 symptoms. In all cases antibody levels declined substantially by three months after vaccination with either mRNA vaccine. The research is based on only 27 fully vaccinated participants. The paper was published in Scientific Reports.  

Vaccinations can reduce risk of long lasting symptoms

A large UK study found that the risk of having long lasting (more than 28 days) symptoms following infection after full vaccination was half of that for unvaccinated people. Vaccinated people were more likely to be asymptomatic if infected, and less likely to be hospitalised.

Those becoming infected after vaccination were about two-thirds less like to be hospitalised, compared to unvaccinated people. Only 0.5% of those who had received the first vaccine dose became infected two weeks of more later, while only 0.2% of fully vaccinated people in the study became infected.

Older people and those living in deprivation were more likely to be infected after having the first dose of a vaccine (Pfizer/BioNTech, Moderna or AstraZeneca/Oxford). The results come from the ZOE COVID study, which has more female participants and fewer people from deprived communities. Covid-19 symptoms are also self-reported. The paper was published in The Lancet Infectious Diseases.

Vaccines safe and effective for those with some autoimmune diseases

In people with autoimmune diseases, a natural SARS-CoV-2 infection followed by a single vaccine dose results in a stronger immune response than uninfected patients with two vaccine doses. Antibody responses were 10-50 times higher in those who had an earlier infection and one vaccine dose. 

This is similar to the response seen in people without autoimmune disorders. However, the study is based on only 30 people vaccinated with the AstraZeneca/Oxford vaccine. The paper has not yet been peer reviewed

Booster shots

An editorial in The Lancet Infectious Diseases discusses booster doses and vaccine equity. After noting the moral and global public health imperatives for equitable vaccinations it references studies that show the economic return to high income countries from supplying vaccines to low and middle income countries.

The Director-General of the WHO has stated that they do not want to see widespread use of booster shots in healthy fully vaccinated people until there is greater global equity in vaccination rates.

An Israeli study found that giving a third Pfizer/BioNTech dose reduces the relative risks of infection and development of severe Covid-19. There was around a 10% reduction in the relative risk of infection and more than 10% reduction in risk of hospitalisation.

This was based on analysis of over 1 million vaccinated people aged 60 or more. The effect was assessed 12 days or later after the third dose. Boosters were given in July & August, 5 to 6 months after the second dose.

Limitations of the study were the short period of follow-up, differences in demographics of those receiving the booster shot and those who didn’t, and broad confidence intervals associated with reduction in severe disease. The paper has not yet been peer reviewed

Pfizer has released data that the company says indicate a third dose of its vaccine significantly increases neutralising antibody levels. They are submitting information to medicine regulatory agencies. The data and study have not yet been peer reviewed.

Monitoring IgG antibody levels may be a useful means for determining who may require a booster vaccine dose. This study found a hierarchy of antibody levels, where fully vaccinated people who had an infection before or after vaccination tended to have the highest antibody levels. Most of the vaccinated participants had received the Pfizer/BioNTech vaccine. The paper has not yet been peer reviewed

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