It is easy to get swamped by all the research on coronavirus. New Zealand’s Science Media Centre is keeping track of much of it so you don’t have to. The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre New Zealand.

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Vaccine-related papers

Vaccines may generate a stronger immune response than natural infections

The mRNA vaccines result in higher levels of antibodies than natural infections. Vaccine-generated antibodies also showed greater specificity towards SARS-CoV-2. Natural infections produced a greater proportion of antibodies that bind weakly to SARS-CoV-2 and cross-reacted with other human coronaviruses.

The consequences of producing cross-reactive antibodies for Covid-19 severity is currently unclear. The study involved only small numbers of serum samples from naturally infected (10) and vaccinated (23) people. The paper has not yet been peer reviewed.

A study of real-world infection supports this, at least for older males. The study examined infections in US military veterans after they had received mRNA vaccines or recovered from earlier infections. Vaccinated veterans 65 or older were less likely to become infected, hospitalised or die from Covid-19 than unvaccinated veterans who had recovered from an earlier infection.

However, for those under 65, while vaccinated veterans had a lower risks of infection and hospitalisation, these were not significantly different from natural infection.

Ninety percent of participants were male, but included a range of ethnicities. The authors state “Death is an important competing risk as one must survive the first infection to become at risk again for another infection.” The paper has not yet been peer reviewed.

But natural infections may stimulate a greater diversity of antibodies

mRNA vaccinations generate more potent neutralising antibodies than natural infections. However, this study indicates that the greater potency is mostly against the original Wuhan strain, which the vaccines are based on.

In contrast, a broader range of antibodies can be produced by natural infections. While they may have lower potency their diversity can lead to greater effectiveness against new variants. The authors caution that booster vaccine doses based on the current vaccines may not improve the breadth of antibodies. Further research on the is required. The paper was published in Nature.

T cell declines after vaccination  

Most lab studies of waning vaccine immunity have looked at antibodies. A small study reports that certain types of T cell levels can also decline over six months following receiving the Pfizer/BioNTech vaccine. Only 12 people were included in this analysis.

The study also looked at declining antibody reposnes. Among 47 participants, neutralising antibody responses against a range of variants were substantially lower (about 7-fold) six months after full vaccination compared with levels at three weeks. Binding IgG antibody levels also declined about 7-fold over the six months. The paper has not yet been peer reviewed.

Binding and neutralising antibody levels decrease at different rates after Pfizer/BioNTech vaccination

In Israel after vaccination the level of IgG antibodies in healthcare workers decreased at a consistent rate, but levels of neutralising antibodies decreased rapidly over the first 3 months and then more slowly.

Six months after the second dose, neutralizing antibody titers were substantially lower among men than women, in those over 65 compared to younger people, and in immunocompromised workers.

The authors note that for measles and some other vaccines there is usually a more gradual decline in neutralising antibody levels over time. They also reference research that indicates antibody declines following natural infections are slower. Whether the antibody dynamics in this study reflect the type of vaccine used requires further research.

The study involved just under 5,000 people, making it (I think) the largest SARS-CoV-2 antibody study published so far (about 700 had neutralising antibodies assessed). The study did not include vaccinated workers who subsequently became infected, so comparisons between antibody levels and real-world infection risks were not made. The paper was published in The New England Journal of Medicine.

mRNA vaccine effectiveness against infection

A short letter (not peer reviewed) in The New England Journal of Medicine calculated mRNA effectiveness against infection by examining cumulative incidence of infections in vaccinated and unvaccinated groups. The authors estimated 16 infection events per 1000 person-years in the vaccinated group and 210 events per 1000 person-years in the unvaccinated group. Waning effectiveness is not considered.

Protection against infection after Pfizer/BioNTech vaccination may decline within months

Another study from Israel found that SARS-CoV-2  infections and hospitalisations increased as time since vaccination increased. When assessing infections in July, people over 60 who were fully vaccinated in March (ie, 4 months earlier) were 1.6 times more protected against infection and 1.7 times more against severe Covid than those vaccinated in January (6 months earlier).

Similar trends were seen for young age groups. The study involved nearly 5 million people vaccinated with Pfizer/BioNTech. The interval between vaccine doses in Israel is usually around 3 weeks. The paper has not yet been peer reviewed.  

In the 3 September Tracker we included a non-peer reviewed paper from Qatar describing a rapid decline in effectiveness against infections but high and stable level of protection against severe Covid-19. This has now been published in The New England Journal of Medicine.

Evidence that vaccination reduces transmission, at least for a period

Vaccinations decreased transmissions for both the Alpha and Delta variants, a large UK study reports. Although this effect waned over 3 months. Both the Pfizer/BioNTech and AstraZeneca/Oxford vaccines reduced the likelihood of an infected vaccinated person infecting close contacts. The vaccines were more effective at reducing transmission of the Alpha variant compared to the Delta variant The authors propose that this is due to the Delta variant being more infectious.

The Pfizer vaccine resulted in a greater reduction in transmission risk than the AstraZeneca vaccine. The effects waned over time, with the degree of reduction greater for the Delta variant.

Viral loads were not strongly correlated with transmission risks. The authors suggest that this is because load is usually only measured once when in reality viral levels vary over time, and the load at the time of transmission is not measured. The paper has not yet been peer reviewed. The article was also discussed in Nature.

Pfizer/BioNTech vaccine provides strong and relatively stable protection against severe disease for 6 months

Another study has shown that the Pfizer/BioNTech vaccine provides strong protection for all age groups (just under 90%) against hospitalisation for five months. Effectiveness against infections (from all variants) declined from a high of 88% a month of having two doses to 47% at six months.

The Delta variant did not appear to reduce vaccine effectiveness against hospitalisation, but effectiveness against infection was lower for this variant. The results are based on health records of three million people The paper was published in The Lancet.

Long Covid impacts reduced after vaccination

Vaccination reduced the severity and duration of long Covid, a French study reports. Effects were measured 120 days after vaccination, with 455 patients given the vaccine and 455 patients used as a control group. Vaccines involved were Pfizer/BioNTech, AstraZeneca/Oxford, Moderna, and Johnson & Johnson/Janssen.

The mean number of symptoms was 1.8 fewer for the vaccinated group (13 vs 14.8). Twice as many (16.6%) of the vaccinated group reported no Covid symptoms at 120 days (7.5% in the controls). Vaccinated participants also reported lower impacts on their lives compared to the unvaccinated participants. The paper has not yet been peer reviewed.

The UK reports that in September 1.1 million people (1.7% of the population) reported experiencing long Covid symptoms. This was an increase from 970,000 in August, reflecting continuing high levels of infection. The report hasn’t been peer reviewed.

Very low risk of myocarditis from Pfizer/BioNTech vaccine

Out of 2.5 million Pfizer/BioNTech-vaccinated people only 54 developed myocarditis within 42 days of their first dose. This represents an incidence of 0.002%, or 2 cases per 100,000 vaccinated. Males 16 to 29 were most likely to develop myocarditis, with an incidence of just over 10 per 100,000.

Three quarters of the cases were assessed as mild, and only one case was classed as serious. Patient follow-up stopped at 82 days post-vaccination. The paper was published in The New England Journal of Medicine.

An Israeli study also found that myocarditis incidence was low after vaccination, but still higher than prevalence in unvaccinated populations. Following vaccination it was most common in young men, 16-19 years old, and after the second dose. Incidence was calculated as 1 case per 26,000 vaccinated males (0.003%), and 1 per 218,000 females (0.0005%). The paper was published in The New England Journal of Medicine.

Non-vaccine-related papers

Molnupiravir Covid pill

Last week Merck announced in a press release that its therapy Molnupiravir reduced by 50% the proportion of patients who were hospitalised or died from Covid-19. The five day treatment is pill-based, so is much easier to administer than intravenous delivery for therapies such as Remdesivir. Results from the trial have not yet been published.

Earlier, a News and Views article in Nature Structural & Molecular Biology summarised findings for two studies involving Molnupiravir. The drug works by disrupting viral RNA and the article notes that further research is needed on the risk to host DNA.

An article in STAT notes that Merck has set the cost of the five day treatment at $700 per patient in the US, but is signing agreements with generic drug manufacturers to make the drug cheaper for lower income countries.

An analysis (not peer reviewed) calculated that the cost of production of the pills for the five day treatment was US$17.74.

Increased virulence of Delta variant

An analysis of over 200,000 Covid-19 patients in Ontario, Canada, found increased virulence associated with the Delta variant. This was based on adjusted frequencies of hospitalisations, ICU admittance and deaths associated with several variants.

Variants with the N501Y mutation were associated with higher risk of hospitalisation, intensive care, and death.There was a marked reduction in risk of hospitalisation and death for people who were partially or fully vaccinated.  The paper was published in the Canadian Medical Association Journal.

Similar results are reported in a study (not yet peer reviewed) from Washington State, USA.

Reinfection likely to be common if SARS-CoV-2 becomes endemic

Reinfection with SARS-CoV-2 is likely to become common if or when the virus becomes endemic. This is based on analyses of  evolutionary relationships and reinfections for other human coronaviruses. The analyses do not consider the effects of vaccination. Sixteen months was the median reinfection time calculated for SARS-CoV-2, about half that seen for other endemic human coronaviruses.

However, there was a  broad range of reinfection times for SARS-CoV-2, ranging from 3 months to 5 years after peak antibody response to the first infection. Estimates of reinfection times will improve as more data on SARS-CoV-2 infections and antibody responses accumulates. The paper was published in The Lancet Microbe.

More frequent testing needed for Delta outbreaks

A modelling study of surveillance testing at a US university found that twice-weekly testing is likely to be insufficient for the Delta variant. Testing every other day would be necessary to help control the spread of the Delta.

The authors recommend targeted testing of people in high risk settings and surveillance testing in lower risk settings, along with mandatory mask wearing (particularly N95-type masks), improved ventilation, social distancing, and improving vaccination coverage. The paper has not yet been peer reviewed.

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