Coronavirus Research Tracking - 21 October
mRNA vaccine effects, cognitive effects of Covid-19, assessing new variant pathogenicity
This week in vaccine research, how two or three mRNA doses affect Covid symptoms, the reduced immune response to the Pfizer vaccine in older people, a more rapid method to develop new mRNA vaccines, and prospects for future vaccines.
In non-vaccine research, the cognitive impacts of Covid-19, controversy over a hybrid virus study, a rapid method to assess pathogenicity of new variants, and a critique of two papers indicating the pandemic started in Wuhan markets.
Note: The Coronavirus Research Tracking will stop its regular weekly reports from the end of October. Particularly important research developments, or significant pandemic events may see the Tracker send out special editions.
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The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Impact of 2 and 3 mRNA vaccine doses
A study of frontline essential workers found that two or three mRNA vaccine doses led to lower viral loads &/or less severe Covid-19 symptoms, compared with unvaccinated workers. Asymptomatic infections from the Delta variant were more likely in vaccinated participants, but for Omicron there was a greater likelihood of a symptomatic infection in those who had three vaccine doses compared with an unvaccinated person. However, severity and duration of symptoms were reduced in the vaccinated groups.
The study involved 1,199 participants. Some group sizes were small when variant type and vaccine doses were accounted for, so larger studies are needed. Vaccinated participants had infections between 2 weeks and five months before an infection. The paper was published in JAMA.
Age-related immune responses to the Pfizer vaccine
A study demonstrated that immune responses to the Pfizer/BioNTech vaccine decrease with increasing age of the vaccinated. Both B and T cell responses declined in older people. Some spike-specific T cell responses were significantly lower in those over 65, compared with younger age groups. No significant differences in responses were found between the 22-to-40 and 41-to-65 old age groups.
In contrast, all age groups had similar immune responses to SARS-CoV-2 infections, indicating that the difference in immune response was related to the vaccine not to a generally weaker immune system in older people. The study involved 115 people, 66 of whom (with ages between 22 and 95) had two vaccine doses and no evidence of an infection. A larger study is required to confirm the results. The paper was published in Nature Aging.
A new rapid method to develop mRNA vaccines
A method to rapidly develop mRNA vaccines against new variants or other coronaviruses has been developed. It involves an improved method to rapidly clone and synthesise the spike protein gene from an infected person. The immunogenic response to this mRNA can then be tested in mice. The authors estimate that new vaccines could be developed in 4-to-5 weeks. The paper has not yet been peer reviewed.
Where next for Covid-19 vaccines?
A short feature in the BMJ discusses potential future vaccines. Possibilities include vaccines that target more than the spike protein, nasal vaccines, and pan-coronavirus vaccines. Nasal vaccines are being developed, but the level of financial support for them is much less than for the original vaccines, so may take sometime before they become widely available. Considerable work is needed to develop pan-coronavirus vaccines since clinical testing against a variety of coronavirus will take time, and widespread levels of immunity to SARS-CoV-2 variants will make it challenging to determine effectiveness..
Non-vaccine-related papers
Covid-19 and cognitive impacts
Covid-19 can have differential effects on cognitive functions. In this study processing speed, reasoning, verbal, and overall performance were worse after an infection compared with before. Poorer physical health due to more severe Covid-19 was associated with poorer cognitive function. However, short-term memory was not greatly affected by Covid-19.
The cognitive deficits were not associated with mental health status. Depression, anxiety, and reduced emotional well-being tended to co-occur and were not related to Covid-19 severity.
The study involved 478 adults, who were given 12 cognitive tests about one month after an infection. Some had been hospitalised, while others weren’t. Participants were self-selected, and the study may be biased towards those with a closer interest in their health. A causal link between cognitive function and infection couldn’t be proven. The paper was published in Cell Reports Medicine.
Hybrid variant virus research generates controversy
A news item in Science reports on a controversy about the creation of a hybrid SARS-CoV-2 virus and its testing in mice. The research (not yet peer reviewed) introduced the Omicron spike protein into an early variant. The hybrid was more lethal to mice than the original Omicron variant, but the study found that non-spike proteins also appear to influence pathogenicity.
Concerns have been raised that the researchers didn’t seek NIH approval for the study, but other scientists have noted that similar experiments by others have been done and didn’t require NIH approval. Some also noted that this type of mutation has already been seen in humans and was not as dangerous as variants such as Delta, so concerns about the risk of the experiment may be overblown.
Some commentators suggest the NIH rules are not very clear, and also that the authors of the paper could have communicated their research better. A review of such gain of function research is already underway in the US.
A potentially rapid method to determine pathogenicity and infectiousness of new variants
A system that can test specific actual and potential mutations in the spike protein may be a useful tool for determining the immune evasion and infectivity of new variants. Large numbers and combinations of mutations can be rapidly generated and tested in a pseudovirus.
Comparisons of immune evasion and infectivity of Delta and BA.1 variants were similar to those from other studies, indicating the method’s reliability. This approach can also be applied to assessments of other viruses. The paper has not yet been peer reviewed.
Viral origin debates
A paper has criticised the methodologies of two earlier studies into the origins of SARS-CoV-2. The latter papers were published in the same July issue of Science. The critique suggests that the models and assumptions used to map the spread from earlier cases were not appropriate, and some viral genome data was not included that could support an origin not associated with the Wuhan markets. The paper doesn’t address all of the lines of evidence presented in the earlier papers.
The critique does not propose a more likely origin but emphasises that the earlier papers are insufficient to conclude that the outbreak originated at the markets. A response by authors from the original papers that critiques this draft paper can be expected. The paper has not yet been peer reviewed.