Coronavirus Research Tracking - 5 March
Vaccine efficacy, transmissibility and immune avoidance in variants
This Research Tracker covers papers on vaccine efficacy and impacts, T-cell responses to newer variants, the effects on transmissibility and immune avoidance of particular variants or mutations, delayed vaccination reactions, rapid antigen tests, and gender differences in response to viral infections.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Interactive vaccine tracker website
Another interactive vaccine tracker site allows you to monitor global roll-out as well as trials. It allows you to monitor vaccine equity by comparing roll out in high, middle and low income countries.
What does vaccine efficacy mean again?
A letter in The Lancet Infectious Diseases criticised an editorial in the Journal for getting the definition of 95% vaccine efficacy wrong. It does not mean that 95% of vaccinated people will be protected.
Instead, efficacy is a measure of the different rates of infection between the vaccinated and unvaccinated groups in the trial - the percent fewer cases seen in the vaccinated group compared to the unvaccinated or placebo group.
For the Moderna and Pfizer Phase 3 clinical trials the 95% efficacy value means that only about 0.05% of vaccinated people are expected to become infected if 1% of a similar but unvaccinated group became infected.
This is nicely illustrated in a New York Times article.
Reduced cases in elderly seen for Pfizer and AstraZeneca vaccines
The first doses of the Pfizer and AstraZeneca vaccines have reduced symptomatic cases and Covid-19 hospitalisations of people over 70 years old in England. Based on results to date the Pfizer vaccine reduced the risk of death in older people by about 85%. The paper has not yet been peer reviewed.
Comparing vaccines still difficult
The site YourLocalEpidemiologist provides an update (as of 28 Feb) of results for six of the vaccines. It notes that is not currently possible to compare effectiveness between vaccines because of differences in trials and studies. The most useful aspect to focus on at the moment are rates of severe Covid-19 (particularly hospitalisations and deaths).
A commentary in Nature notes that studies are being designed to compare the effectiveness of different vaccines. It highlights the need to be able to combine data from these studies, or to design them so comparisons on effectiveness can easily be made.
Novavax Phase 2 trial shows some protection from B.1.351 variant
Initial results from a Phase 2 clinical trial (not yet peer reviewed) of the Novavax vaccine (NVX-CoV2373) in South Africa indicate that it provides some protection against the B.1.351 variant. About 30% of participants had evidence of earlier infections (before B.1.351 was widespread), and prior infection did not provide protection against reinfection (assumed to be with the B.1.351 variant). Vaccine efficacy was calculated to be 49.4% (up to 45 days after the second dose), with the efficacy being higher (60%) for those without HIV.
T-cells react to new variants
As the Tracker has previously noted, most papers about immune responses to the current variants of concern have focussed on antibodies.
A new paper, not yet peer reviewed, tests the abilities of CD4+ and CD8+ T-cells from convalescent patients and vaccinated donors to recognise peptides from different SARS-CoV-2 variants. Overall, the reactivity of the T-cells was similar between the early Wuhan strain and the new variants (B.1.1.7, B.1.351, P.1 and CAL.20C [a variant first identified in California]).
An earlier paper, published in Cell Reports Medicine, found that CD4+ and CD8+ T-cells populations from the plasma of convalescent Covid-19 patients recognise many parts of the virus, rarely overlapping with antibody binding sites.
B.1.1.7 variant
A paper published in Science calculates that the B.1.1.7 variant has a 43–90% higher reproduction number in England than earlier variants. This was based on analyses of frequencies of variants over time using a database of 150,000 genome sequences. Similar increased levels of transmission have also been observed in Denmark, Switzerland, and the United States.
A paper published in Cell reports that B.1.1.7 has some resistance to a variety of potent monoclonal antibodies. However, the variant could still be neutralised.
A paper in Cell Host & Microbe also reports reduced neutralisation (about 2-fold compared to an earlier D614G variant) to sera from previously infected people, and those who had been vaccinated with the Moderna or Novavax vaccines. Resistance to two monoclonal antibodies was greater, but four other antibodies that bind to the receptor-binding domain were not affected.
P.1 variant
Modelling of infections in Manaus, Brazil between November and January estimates that the P.1 (or 20J/501Y.V3) variant may be 1.4 – 2.2 times more transmissible than other lineages (at least in that population). It may also be able to evade the immunity created by earlier effections 25 to 61% of the time. The paper hasn't yet been peer reviewed.
A separate paper, also not peer reviewed, reports that the P.1 variant is 6.5-fold more resistant to neutralisation by convalescent plasma, and 2.2 to 2.8-fold more resistant to sera from people vaccinated with the Moderna or Pfizer vaccines. The potency of several monoclonal antibodies was reduced between two- and 17-fold.
B.1.351 variant
Laboratory experiments indicate that the B.1.351 (or 501Y.V2, originally reported from South Africa) variant is not more transmissible than the 614G variant in human cell lines, but it is more resistant to 12 of 17 neutralising antibodies, and to sera from convalescing patients.
The research, published in Cell, used pseudoviruses and linked the resistance to the E484K and N501Y mutations in the receptor-binding domain. Introducing the K417N mutation (not found in the B.1.351 variant) increased susceptibility to polyclonal antibodies.
Another article in Cell reports that when tested against 20 monoclonal antibodies the B.1.351 variant was much more difficult to neutralise than strains from which it is descended.
The E484K mutation plays a significant role in immunity evasion
The role of E484K in disrupting neutralisation activity was confirmed in a computer modelling paper that has not yet been peer reviewed. A range of other mutations in the receptor-binding domain were shown to enhance ACE2 binding. Several key mutations appear to be able to disrupt antibody binding while not affecting ACE2 binding.
An article in Nature Medicine reports that pseudoviruses containing the E484K spike mutation are less susceptible to some potent monoclonal antibodies, as well as sera from previously infected people and those vaccinated by the mRNA vaccines.
Delayed local reactions to Moderna vaccine
A letter in the New England Journal of Medicine describes delayed reactions in 12 people vaccinated with the Moderna vaccine. The reactions emerged four to 11 days after the first injection and were usually large regions of rashes and/or swelling around the injection site. They disappeared between two and 11 days after they appeared. The cause was due to a delayed hypersensitivity reaction. Nine of the 12 produced a similar or lesser reaction after the second injection.
Effect of transmission mechanism on retail customer control strategies
A modelling paper published in PNAS finds that retailer strategies to reduce infections differ if transmission is largely via close contact (through droplets), or “wake” transmission over larger distances through aerosols.
If close contact is the primary mechanism then one-way movement of customers in aisles is likely to be effective in reducing transmission. With aerosol transmission, controlling customer density and ensuring an even flow of customers will be necessary. The latter will have a greater negative impact on customer traffic, and potentially shop earnings.
Rapid antigen diagnostic tests still need to improve
Antigen diagnostic tests are intended to detect viral fragments in the first week after symptom development when viral loads are at their highest. If accurate and reliable they have the potential to identify infections early.
However, a living systematic review (not yet peer reviewed) of reports on antigen rapid diagnostic tests found that the highest test sensitivity was 81.7%. This is below the sensitivity of the PCR tests on nasal swabs. Sensitivity was also lower when viral load was lower.
The authors also found that all the antigen diagnostic reports had biases, and some had a lack of independence from test makers. They recommend better standardisation of tests and how the results are reported.
An individual account of the impact of “long Covid”
A personal perspective of the impact of “long Covid” in a young person (in their 20’s) in Ireland is described in The Lancet Respiratory Medicine. After experiencing a mild infection last April she is still unable to return to work as a nurse due to continuing fatigue.
Different immune responses to viral infections between men and women
A good summary of the nature and causes of different immune responses to viral infections in males and females is in The Scientist. Females tend to have stronger immune responses to viruses, but this can increase the risk of autoimmune diseases later in life.