Vaccine-related papers

“Booster” doses

A third vaccine dose was found to be effective against symptomatic infection for those over 50, regardless of what vaccine they had initially received. This UK study gave a Pfizer/BioNTech dose to those who had previously received two doses of either the Pfizer or AstraZeneca/Oxford vaccine.

Compared to unvaccinated participants, effectiveness 20 weeks after the second Pfizer or AstraZeneca doses were 62.5% and 44.1%, respectively. Two weeks after the third dose, effectiveness was 93.1% for those originally vaccinated with AstraZeneca, and 94.0% for those who received the Pfizer vaccine. The paper has not yet been peer reviewed.

A News & Views article in Nature Medicine discusses recents studies demonstrating the benefits of vaccine booster doses. It also highlights some of the uncertainties of additional doses, such as how long the benefits may last, as well as implications for equitable access to vaccines.

Waning effectiveness

A Finnish study of healthcare workers found waning effectiveness against infection between three and six months after vaccination. This occurred for the two mRNA and the AstraZeneca/Oxford vaccines. Effectiveness declined from 80-90% in the first two months down to 60% between three and six months.

Effectiveness against hospitalisation remained high, nearly 90%, over 10 months. The study didn’t correct for more at risk people getting vaccinated earlier, nor the increase in the interval between doses later in the vaccination program. The paper has not yet been peer reviewed.

Comparing vaccines

A Mongolian study found that antibody responses to the Sputnik V and Sinopharm vaccines were much lower against a range of viral variants than those seen for the Pfizer/BioNTech vaccine. The AstraZeneca/Oxford vaccine generated intermediate responses.

The results are based on 196 vaccinated participants. A limitation is that this was an observational study, where differences between those receiving the different vaccines could not be excluded. The paper was published in Cell Host & Microbe.

Novavax + flu vaccines = safe & effective

A randomised clinical trial found that the Novavax vaccine is safe and effective when given with the flu vaccine. Two flu vaccines were included in the trial, and their humoral immune responses were not affected by giving them with Novavax. IgG responses were slightly lower for the Novavax when given with a flu vaccine, but this did not appear to have a large impact on efficacy.

Novavax efficacy was 87.5% amongst 18-65 year olds when given with a flu vaccine, compared with 89.8% for those who just received Novavax.  The paper was published in The Lancet Respiratory Medicine.

Neutralising antibody levels may provide a good predictor of protection against infection

Concentrations of neutralising antibodies were found to be predictive of the level of immune protection against infection from variants following vaccination. This is based on a meta-analysis of 24 studies, involving eight vaccines.

This study concludes that within one year of vaccination efficacy against infection from the Delta variant will probably be less than 50%.

There are too few appropriate studies to reliably predict immune protection against severe Covid-19 from neutralisation activity data. The paper was published in The Lancet Microbe.

IgG levels are correlated with protection

A UK study found that anti-spike IgG levels correlate with protection from infection. This was found for both the Pfizer/BioNTech and AstraZeneca/Oxford vaccines, with the second doses substantially boosting levels. Antibody levels were higher for the Pfizer vaccine. IgG levels declined faster in older people, men, and those with existing health conditions.

A 8-12 week gap between AstraZeneca doses increased antibody levels, but not their half-life. However, for the Pfizer vaccine peak levels did not change, but half-life increased. Antibody half-life was greatest in those who had a prior infection and were fully vaccinated.

In people without a prior infection, at least a 67% level of protection lasted for at least 2-3 months after two doses of the AstraZeneca vaccine, and 6-15 months for those who had the Pfizer vaccine. For unvaccinated people who had been infected, the paper estimates that level of protection may last 1-2 years, despite peak IgG levels being lower. This indicates peak antibody level isn’t the only indicator of the degree of protection. The paper has not yet been peer reviewed.

Vaccination reduces the risk of long Covid

A US study of 16,000 vaccinated people who subsequently became infected found that the risk of developing long Covid was lower than for unvaccinated patients. This was assessed at six months after infection. Symptoms associated with long Covid were observed in vaccinated patients even if the initial infection did not require hospitalisation.

The study is based on health records from military veterans, so is biased towards older males The paper has been submitted to Nature, but has not yet been peer reviewed.

Effects of vaccination in communities

In the US increasing vaccination rates correlate with decreased infections and Covid-related deaths. In counties where vaccination rates were higher than 40% every percentage increase in vaccination reduced the county’s infection risk by 1.5% and deaths by 2.9%. In counties with vaccination levels below 40%, increasing vaccination did not have a significant effect on county-wide risk.

The analyses also indicated that increasing vaccination rates from 40% to 80% in a county could reduce infection cases by 45%, and deaths by 67%.

Not all Covid cases would have been reported, and there were differences in how counties or states tested and reported cases. The paper has not yet been peer reviewed.  

Effect of vaccine mandates and passports

A Canadian study reviewing previous studies concludes that vaccine mandates and vaccine passports are very effective in increasing vaccination rates. However, it finds that the impact of excluding unvaccinated people from some settings depends on the level of vaccination.

Unless there are very high levels of vaccination (above 90%), large numbers of people may need to be excluded to have a meaningful impact on transmission. The authors emphasise the need to consider the cost of exclusions. The studies included were all from periods when there were a range of public health measures in effect. Effects may differ when there are fewer or less stringent public health measures. The paper has not yet been peer reviewed.

Non-vaccine-related papers

Covid pills

A news item in Nature discusses the Merck and Pfizer Covid antiviral pills. It notes that further research on effectiveness and safety are still required, as are studies on combination treatments. It also highlights concerns that wealthy countries stockpiling these two therapies will limit distribution in poorer countries.

Neutralisation activity and T cell effectiveness may decline over 12 months for those who had mild Covid

A year after infections, antibodies against the virus are usually still detectable in people who had mild Covid. However, neutralisation activity, particularly against variants of concern, was considerably reduced.

In addition, while viral-specific T cell levels remained high, their functionality against newer variants was substantially reduced, at least based on one method of testing. Consequently, the level of immunity from natural infections after one year is likely to be low when new variants are encountered. The paper has not yet been peer reviewed.

Cytokine link to long Covid

A German study reports that specific cytokine responses are associated with long Covid. The most common symptoms of people in the study were fatigue, shortness of breath, and concentration difficulties. High levels of the cytokines Interleukin 1ß, Interleukin-6 and Tumour Necrosis Factor-α were more commonly found in those with long Covid symptoms.

These cytokines can generate a self-perpetuating cycle of inflammatory responses, which may lead to some of the long lasting symptoms. The paper has been submitted to The Lancet, but has not yet been peer reviewed.

Incidence of long Covid varies between regions, but can be substantial

A systematic review of long Covid studies found that overall 43% of Covid cases developed long Covid symptoms, with 57% of hospitalised patients developing long Covid. Forty studies, accounting for nearly one million individuals from a range of countries, were included. Fatigue was the most common long lasting symptom. Higher incidences of long Covid symptoms were reported in females and those with pre-existing asthma.

Across the studies examined there was considerable variation in the prevalence of cases. Asian countries appear to have higher incidences of long Covid than Europe or the USA.

Not all the studies used the same definition for designating long Covid, or assessed it at the same time after infection. The paper has not yet been peer reviewed.

Real-time monitoring of mental health using helpline data

An analysis of 8 million calls to healthlines in 19 countries found that calls peaked about six weeks after initial outbreaks and were 35% higher than pre-pandemic levels. Increases were driven largely by fear and loneliness. Pandemic-related issues appeared to replace pre-pandemic issues such as relationship and economic problems, violence and suicidal thoughts.

In a more detailed analysis of calls in France and Germany suicide-related calls increased when control measures became more stringent but decreased when income support was extended. This suggests that financial relief relieved some of the anxiety and stress. The authors highlight how information from helplines can provide near real-time tracking of mental health. The paper was published in Nature, and a news & views article on the study is in the same issue..

Including variation in social behaviour can improve epidemic models

A model that incorporates heterogeneity in social behaviours can improve the accuracy of pandemic modelling. The model assumes that individual behaviours will vary over time, rather than be constant, which changes the risk of infection and transmission. The model produces both the waves and plateaus of infections seen in pandemics.

The study found that this “Stochastic Social Activity” model better matched predicted death rates in the US than the traditional Susceptible-Infected-Removed (SIR) epidemiological model. The paper has not yet been peer reviewed.

Effectiveness of masks and social distancing

A meta-analysis found that mask wearing and physical distancing significantly reduce infection risks. Based on six studies, mask wearing can halve the risk of infection, although there is considerable variability between studies. The effect of mask type could not be investigated.

Across five studies physical distancing reduced infection risk by 25%, although some individual studies report much greater reductions in risks. Handwashing can also reduce risk, but the effect was not significant based on available data.

The paper notes the difficulty in assessing effectiveness of individual public health because each study differs and there are usually a range of public health measures implemented at the same time. The paper was published in the BMJ.

Masks on cruise ships are not enough

A simulation study using data from cruise ships found that mask-wearing alone would have little impact on reducing transmissions. This is due to the majority of contacts occurring in the dining rooms and sports areas, where mask wearing is less common. Vaccinations and rapid antigen testing, along with masks, were found to substantially reduce transmission risks on cruise ships. The paper has not yet been peer reviewed.

Uncertainty about the ‘flu as lockdowns ease

A US study warns about the potential for a large resurgence in influenza as Covid-19 related public health measures are relaxed. It notes that since the incidence of flu has been decreased globally due to Covid it is difficult to predict what flu strains will re-emerge, and so flu vaccines may not be as effective.

On the other hand, the authors also note that since flu strains have not been as able to circulate as well as previously they may not have a bigger impact as anticipated. This is because the opportunities to evolve and avoid immune responses have been reduced. The paper was published in the Journal of Infectious Diseases.

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