Coronavirus Research Tracking - 3 June
Comparing vaccines, hybrid immunity, Omicron variants, Paxlovid, mask effectiveness
This week, comparing immune responses to four different vaccines, and immune effects of mixing or matching different vaccines. A prior infection plus vaccination leads to quicker immune responses after another infection, and modelling an infection wave as immunity wanes.
Real word comparisons of Paxlovid effectiveness, viral clearance in cancer patients, and modelling the significance of superspreaders. Plus, breaking focus, what’s not yet known about the Monkeypox outbreaks.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Comparing immune responses between vaccines
The immune responses to four vaccines (Moderna, Pfizer, Johnson & Johnson, & Novavax) have been compared over six months. The mRNA vaccines were more immunogenic. There were also some differences in the frequency of different types of memory B cells between vaccines. CD4+ T cell responses to Novavax were similar to those for the mRNA vaccines. While the Johnson & Johnson vaccine induced relatively lower, immune responses to this vaccine were comparatively more stable, consistent with previous studies.
For the mRNA vaccines antibody levels declined quickly, but B cell and T cell responses were comparatively stable. Effectiveness of the vaccines against viral variants was not assessed. Twelve people who received Novavax provided sera, while 30 people for each of the other vaccines were included in the study. All had relatively mild infections. The paper was published in Cell.
Effects of mixing and matching vaccine doses
A review of 53 previous studies found only small differences in effectiveness against infection between vaccines after three doses. This held for whether a single vaccine was used, or two different ones were used. However, having at least one mRNA dose provides slightly greater protection if an adenovirus-based vaccine is used, especially for reducing the risk of hospitalisation. The results were similar for different viral variants, Omicron excluded. Further studies on vaccine effectiveness against Omicron are underway.
Immunity in people over 65 was substantially boosted when they received any combination of three doses, compared with the immune response after two doses. It was harder to determine which vaccines or vaccine combinations provided the greatest effectiveness in this group against hospitalisation.
For immunocompromised patients, the number of doses rather than the vaccine type is also more important in boosting their immune response. The authors recommend that an mRNA vaccine is given as the third dose. The paper was published in The BMJ.
In another study, an mRNA dose after a single Johnson & Johnson/Janssen dose provided nearly the same level of effectiveness against an Omicron infection as three mRNA doses. The article was published in the New England Journal of Medicine.
A third study reports that one AstraZeneca/Oxford dose followed by a Pfizer/BioNTech dose produced a stronger immune response than two AstraZeneca or Pfizer doses, or one Johnson & Johnson dose. The combination vaccination was also more effective at neutralising the Omicron (BA.1) variant, with neutralising antibody levels up to 10 times higher a month after second doses. The paper has not yet been peer reviewed.
Prior infection plus vaccination leads to a quicker response after a subsequent infection
People with a prior infection plus vaccination had more rapid immune responses to another infection than those who were vaccinated and not previously infected. The timing and magnitude of the immune response for vaccinated-only participants depended on the variant they were infected by. Immune responses to an Omicron infection were generally more variable, and delayed by several days, compared to a Delta infection.
The study involved 33 individuals, with 75% having had a prior infection. Symptoms were relatively mild following a post-vaccination infection. The paper was published in Immunity.
Comparing antigenic differences between Omicron sub-lineages
While the BA.2.12.1 sub-lineage is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than the BA.2 subvariant, the BA.4/5 sub-lineage is 4.2-fold more resistant. The antigenic distance between these sub-lineages and BA.2 is similar to that seen between Delta and the original SARS-CoV-2. The paper has not yet been peer reviewed.
Modelling the effect of waning immunity
A New Zealand modelling study that included waning immunity predicts a rising wave of re-infections in the second half of this year. The size and timing of the re-infection wave is strongly dependent on how fast immunity wanes. The model is based on reported cases, and so may underestimate the amount of infection-based immunity. The transmissibility of recent (or new) variants will also affect the real world pattern.
Health impacts of a re-infection wave are expected to depend on the number of older people and those with poorer existing health who become infected again. The paper has not yet been peer reviewed.
Expert reaction to this papers was provided on the Science Media Centre’s website.
Vaccine mandates boosted vaccination rates
Substantial increases in the number of people getting their first vaccine dose occurred in the weeks following the introduction of vaccine mandates in Canada, France, Italy and Germany. At a province or region level there was variability in how much vaccination rates increased, and the causes of this need further study. The paper was published in Nature Human Behaviour.
Real world assessments of Paxlovid
A large Israeli study found Paxlovid reduced hospitalisations and deaths in Covid patients over 65, but had little effect on disease severity for those between 40 and 65. The study was undertaken during the Omicron wave.
There was a 67% reduction in Covid-19 hospitalizations and an 81% reduction in Covid-19 mortality in the older group. For the under 65’s the lack of a clear benefit from Paxlovid may be due to overall lower severity of symptoms from Omicron. The paper has not yet been peer reviewed.
A Hong Kong study also reports the effectiveness of Paxlovid in reducing disease severity from Omicron. The risk of death was reduced by 75% and hospitalisation by 31%. Age and vaccination status did not have significant effects on treatment outcomes.
The effectiveness of molnupiravir was lower and less consistent. Over 1 million non-hospitalised Covid-19 people were included in the study, with just over 5,000 patients receiving Paxlovid, and another 5,000 receiving molnupiravir. The paper has not yet been peer reviewed.
BA.2 has reproduction advantage in upper respiratory tract
In cell cultures the BA.2 variant replicated much more effectively in nasal and bronchial tissues than other variants, which probably contributes to its greater infectivity. This was assessed at 33 degrees C, mimicking the temperature in the upper respiratory tract. The paper has not yet been peer reviewed.
Viral clearance in cancer patients depends on coordinated immune responses
A study of cancer patients with Covid found that delayed viral clearance was associated with prolonged symptoms. B cells and CD4+ T cells were important in stimulating rapid viral clearance. The study illustrates the importance of interactions between humoral and cellular immune responses.
Effectiveness of viral clearance differed between different cancers. The paper was published in Cancer Cell.
Most people infected may show some Covid symptoms, even if only for a short time
A meta review of studies of symptomatic and asymptomatic infections concludes that the majority of cases seem to have some Covid symptoms, even if briefly. Asymptomatic cases appeared to be less infective than those with symptoms. However, the review also notes considerable variability between studies, so it is not possible to determine a reliable estimate of asymptomatic cases.
Many studies only assessed the presence of symptoms at a single point in time. The analysis did not look at symptomatic and asymptomatic cases for different variants separetly. The paper was published in PLOS Medicine.
Mask wearing has a significant impact on reducing transmission
A global study examining mask wearing used a model to calculate that it led to a 19% reduction in viral transmission. The study examined reported mask wearing, rather than the introduction of mask mandates (which didn’t necessarily increase mask wearing much).
Analyses took account of other interventions, and differences in mobility. The study relied on survey data, and the quality of masks was not assessed. The paper was published in the Proceedings of the National Academy of Sciences.
Model indicates the significance of superspreaders
A modelling study indicated that 80% of secondary infections in indoor settings may come from just 4% of index cases. Viral load was found to be the most important factor influencing secondary infections [but see previous research that found viral load may not accurately predict infectious viral levels].
Having high ventilation rates and mask wearing significantly reduced transmission in the model. The paper was published in Physics of Fluids.
How the Omicron sub-lineages get there “names”
A news article in Nature discusses the naming of Omicron sub-lineages, and what is required for them to be designated variants of concern.
In other news, Nature identifies four important questions not yet answered about Monkeypox outbreaks - how did they start, have there been genetic changes in the virus, can the outbreaks be contained, and is the virus spreading differently in current outbreaks?
Bird flu outbreaks
Nature also discusses the large number of avian influenza outbreaks in both farmed and wild birds. Better surveillance is needed, as is better collaboration between public health and animal health researchers and organisations.