Coronavirus Research Tracking - 12 February
Vaccine hesitancy, impact of one vaccine dose, vaccine control of variants, other therapeutics, and viral evolution in an immunocompromised patient
This week’s Research Tracker covers papers about vaccination hesitancy, the immune boosting impacts of mRNA vaccines, promising therapeutics under development, how viral load affects transmission, reduced viral loads following Pfizer vaccination, and a case study of viral evolution in an immunocompromised patient.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Another Vaccine Tracker
Bloomberg has also developed a vaccine tracker. This goes into more detail than The Economist’s one highlighted last week.
Factors that influence vaccine hesitancy
Several recent papers have examined what is influencing vaccination decisions.
Similarities and differences between vaccine rejectors and hesitants
A survey in France, published in The Lancet Public Health, found similarities in characteristics between those who refused vaccines and those who were hesitant about being vaccinated. Both groups tended to be female, middle-aged, have a lower level of education, a history of avoiding previous vaccinations, and an absence of chronic medical conditions.
Those hesitant about vaccinations were concerned about vaccine efficacy and safety, the country where the vaccine was made, and having to go to a mass vaccination centre rather than their doctor for the vaccination.
The authors suggest that giving greater priority to vaccinating younger people who are more likely to accept vaccines than the middle aged could enable herd immunity to be achieved more quickly.
Misinformation has an impact on vaccination decisions
A study published in Nature Human Behaviour reports that in September 2020 6% of 4,000 people in the UK surveyed stated that they would definitely not get vaccinated, while in the USA 15% said that they wouldn’t. About 40% in both countries indicated they were unsure about getting vaccinated.
The researchers then looked at how misinformation affected vaccination decisions. Compared to factual information, misinformation led to a 6% decline in intent to be vaccinated. Factors such as age, gender, socio-economic status, level of education, ethnicity, religion and political affiliation can influence whether misinformation affects a person's decision about vaccination.
Misinformation that was more “scientific-sounding” (such as referencing scientific articles) had a stronger influence on reducing participants intent to be vaccinated.
An encouraging change in vaccination attitude in the US
The US CDC reports that, based on national polls, between September and December last year there was a decline (from 38.1% to 32.1%) in the proportion of people indicating that they would not be getting vaccinated (Note that the September figures don’t match the results for the study above due to different surveys and sample sizes).
There was an increase (39.4% to 49.1%) in those stating that they were very likely to get vaccinated. However, age, gender, ethnicity, socio-economic status and location still influence decision-making.
Be careful with your language when communicating about Covid-19 science
A paper in Public Understanding of Science found that using aggressive or insulting language (words like “stupid” and “idiot”) to people reluctant to follow scientific recommendations doesn’t help, particularly if they don’t feel like they have much in common with the communicator.
On the other hand, for those who feel they have a closer connection to the communicator a more aggressive communication style, while not necessarily supported, can make Covid-19 risks seem more important and urgent.
mRNA vaccines boost immune responses in previously infected people
Three as yet not peer-reviewed papers report that people who have previously recovered from Covid-19 show strong increases in IgG and/or neutralising antibody activity after a single dose of either the Moderna or Pfizer mRNA vaccines. The studies all involve small numbers of people and so are indicative rather than definitive.
Two of the studies - here and here - report that the increase in IgG antibody response in previously infected people who received a single dose of the Moderna or Pfizer mRNA vaccines was higher than uninfected people who had one dose of the vaccine.The authors conclude that giving previously infected people one vaccine dose would increase the availability of the mRNA vaccines without undermining immune responses.
The third paper reports that in previously infected people the neutralising antibody strength in sera increased 1,000-fold after they received a single dose of the Moderna or Pfizer vaccines, compared to antibody activity levels before receiving the vaccine. This increase in neutralising activity was seen for both the original Wuhan variant and the B.1.351 variant from South Africa.
Small to modest declines in vaccine effectiveness against variants
Research just published in Nature found that plasma from both naturally infected and vaccinated (two doses of either the Moderna or Pfizer vaccine) people had reduced levels of neutralising activity against some viral mutations. This was based on testing pseudoviruses that had the E484K, N501Y or K417N:E484K:N501Y combination mutations seen in recent variants. Neutralising activity was reduced by up to a three fold compared to earlier viral variants.
Fourteen of 17 potent monoclonal antibodies were also less effective at neutralising pseudoviruses with these mutations. The authors note the need for periodic modifications of the mRNA vaccines for them to remain effective.
Similar results were seen in another study published in Nature Medicine that looked at just the Pfizer vaccine.
A pre-print paper reports that convalescent plasma from patients infected before recent variants emerged was still able to neutralise newer variants, although with a slightly decreased potency. Sera from people vaccinated with the Pfizer vaccine were about seven times more potent at neutralising an older D614G variant than convalescent plasma from unvaccinated people.
The vaccine-elicited antibodies were also more effective at neutralising the B.1.351 variant than convalescent plasma, but not as well as for earlier variants or the B.1.1.7 variant.
Pfizer/BioNTech vaccine may reduce viral loads
An Israeli study (not yet peer-reviewed) reports that virus levels in infected people (as judged by PCR tests) declined between early December and late January. Israel began vaccinations of older people on 20th December. Their study did not have records of who had been vaccinated, but they consider that the decline in viral loads in those over 60 in late January, while under 60’s loads were unchanged, is consistent with the hypothesis that the BNT162b2 vaccine reduces infection. They estimated that the vaccine reduced viral load up to 20 fold. This is likely to reduce levels of transmission.
Developing Variant-proof vaccines
A comment in Nature advocates the need for a vaccine design process that focuses on developing broadly neutralizing antibodies (or “pan-virus vaccines”) that enable protection from many viral variants.
Vaccine vs drug development
An article in the New York Times discusses why, compared with vaccine research, success in developing other therapies has been poor. It notes that in the US the government invested more than twice as much money in vaccines as drugs, and that this money went to only a few drug candidates. Many studies of other therapies were small and poorly organised and coordinated.
Anti-cancer drug shows promise as an anti-viral treatment
Two papers identify the potential therapeutic value of the anti-cancer drug Plitidepsin. A study published in Science found that it is 27.5-fold more potent than remdesivir against SARS-CoV-2. The drug proved more effective at reducing viral replication in both cell lines and mice.
A pre-print paper from the same research team reports that in cell-based tests plitidepsin is over an order of magnitude more potent than remdesivir against both an earlier SARS-CoV-2 variant and the B.1.1.7 variant.
A neutralizing antibody may be able to prevent infection and reduce tissue damage following infection
A neutralising antibody that is very effective at preventing SARS-CoV-2 binding to the ACE2 receptor is reported in a paper that has yet to be peer-reviewed. In lab tests it was able to block a range of variants, including the B.1.351 variant.
When tested on two rhesus macaques it was found to prevent infection with a Wuhan strain of SARS-CoV-2 and reduced lung damage when given to two macaques after they were infected. A Phase 1 clinical trial of the antibody is now underway.
Asthma drug can reduce hospitalisations
A small randomised trial reports that the asthma drug budesonide (a steroid) reduces hospitalisations of Covid-19 patients by 90%. Fevers and other symptoms also disappeared more quickly relative to patients receiving standard care. The paper has not yet been peer-reviewed.
Effect of convalescent plasma on virus evolution in an immunocompromised patient
A paper published in Nature studied SARS-CoV-2 evolution in an immunocompromised patient with a chronic infection. Viral genomes from the patient’s upper respiratory tract were sequenced over 101 days. The patient was treated with remdesivir for the first 57 days and there was little change in the virus sequences recovered.
However, after convalescent plasma treatment began there was a dramatic change in viral sequences, with one variant becoming dominant, and a two-fold decrease in antibody neutralisation. This variant declined when antibodies from the convalescent serum decreased, indicating complex host-viral dynamics.
The dominant variant had the spike protein mutations D796H and the deletion ΔH69/ΔV70. The D796H mutation reduced susceptibility to antibodies in the convalescent plasma, but by itself was associated with reduced viral infectivity. However, the deletion mutation conferred a two-fold higher infectivity than earlier virus variants, so the mutation combination resulted in little change in infectivity.
The authors note that the more diverse and stronger immune responses seen in non-immunocompromised patients means that this type of evolution is less likely to occur.
B.1.1.7 variant is more transmissible, and potentially more serious
A paper, not yet peer-reviewed, estimates that the B.1.1.7 variant is 43-82% more transmissible than earlier variants. Clear evidence for greater (or lesser) disease severity was not found, though the paper recognises that greater transmissibility will result in more hospitalisations.
It also includes a note that recognises that their analyses, which cover data up to Christmas 2020, are compatible with last week’s conclusion from NERVTAG (included in last week’s Tracker) that the variant may cause more severe disease. Further data and analyses are expected to clarify this.
Viral load affects transmission and symptom development
A Spanish study published in The Lancet Infectious Diseases found that people with higher viral loads were more likely to infect others. And, people with higher viral loads soon after infection were more likely to develop Covid-19 symptoms.
Severe Covid-19 is worse than the flu
An analysis published in the Canadian Medical Association Journal reports that early in the pandemic hospitalised Covid-19 patients had a greater risk of death (3.5 times) and ICU admission (1.5 times), and longer hospital stays (1.5 times) than those hospitalised due to influenza. This difference could partly be due to lower immunity against the novel coronavirus, but this hasn’t been proven. The bias towards males being at greater risk of severe Covid-19 is not seen with severe cases of influenza.
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