Coronavirus Research Tracking - 17 June
Omicron & immune evasion, nasal vaccine, re-infection rates, public health communications
This week, hybrid immunity and effectiveness against Omicron, original antigenic sin limiting effectiveness against Omicron, and a nasal vaccine is effective in early animal trials.
In other research, high levels of re-infections in England, brain inflammations associated with Covid-19, persistence of symptoms with flu not just Covid-19, and testing the effectiveness of different messages to promote physical distancing.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
No difference in infection risks for BA.1 and BA.2
The risk of a symptomatic infection did not differ between BA.1 and BA.2 sub-variants for those who had an earlier infection and/or had been vaccinated in Qatar. A previous non-Omicron infection reduced the risk of a BA.1 or BA.2 infection by 50%.
Two vaccine doses (given at least 8 months earlier) did not prevent BA.1 or BA.2 infections. However, a prior infection followed by two vaccine doses provided a similar level of protection as just a prior infection, reflecting longer lasting immunity generated by an infection.
A third vaccine dose (without an earlier infection) reduced risk by 60%, but that may be due to participants having received the booster within the last two months. Three doses plus prior infection provided about 80% effectiveness.
Effectiveness against hospitalisation and death for all combinations of prior infections and vaccinations was more than 70% for both BA.1 and BA.2. Results were similar for both mRNA vaccines. The paper was published in the New England Journal of Medicine.
Original antigenic sin and Omicron
The immunity provided by antibodies and T cells from pre-Omicron infections was boosted after three vaccinations in healthcare workers. However, this immune response was less effective against the BA.1 variant. Sera from vaccinated workers who had no prior infections also showed stronger immune responses against earlier variants when infected with Omicron, even though their immune response to the Omicron infection was weak.
This is an example of what is called ‘original antigenic sin’, or antigenic imprinting. An immune system response to a second distinct variant of a pathogen can be less effective because the immune memory produces antibodies and T cells that are better at targeting the original variant. This probably explains (at least in part) why re-infections after an Omicron infection could be more common.
The authors suggest this could also mean that an Omicron-based booster vaccine may be relatively ineffective against new variants. The paper was published in Science.
In another study, children and adolescents with prior infections also had lower cross-reactive immunity to Omicron. The authors noted that original antigenic sin may be a factor. However, sera from vaccinated (but not previously infected) young people had stronger neutralisation activity against variants including Omicron. Participants had mild to severe infections. The paper was published in Nature Communications.
Limited cross-neutralisation of other Omicron variants after a BA.1 infection
A study of the efficacy of neutralising antibodies following a BA.1 infection found they were much less effective against BA.2, BA.4 and BA.5 variants. This is consistent with some previous research, reflecting the distinct mutation patterns between BA.1 and the other sub-variants. The authors suggest that a vaccine based on the BA.1 variant may provide little protection against newer variants. The paper has not yet been peer reviewed.
Intranasal vaccine more effective in mice
An experiment in mice found that a live, replication-deficient recombinant virus vaccine was more effective when given intranasally than intramuscularly. The inhalable form induced greater immunity and resulted in more rapid clearance of the virus from the lungs and respiratory tract. Only small numbers of mice were used in the experiments. The paper was published in Proceedings of the National Academy of Sciences.
Re-infections after BA.1 infection not unusual in England
A study reports that 18% of people with Omicron infections in England had been previously infected. However, reporting re-infections varied widely between age groups and location. This probably reflects both differences in testing in communities, and differences in exposure risks. Waning immunity as well as immune avoidance by Omicron contribute to re-infections.
The paper also estimates that at least 70% of people in England may have been infected with SARS-CoV-2. The authors conclude that periodic re-infection will be likely as new variants emerge. The paper has not yet been peer reviewed.
Covid associated with inflammations in the brain
Some brain damage in mice with mild Covid has been linked to high levels of a cytokine. The cytokine stimulates inflammation that can disrupt neuron functions, particularly in the hippocampus. This cytokine has also been found in humans with long Covid, and may contribute to cognitive impairment.
Some of the inflammatory responses in mouse brains after Covid infection were similar to those observed after an influenza infection, but inflammation was more widely distributed after Covid. The mouse experiments used the ancestral SARS-CoV-2 strain. The effects of vaccination on brain inflammation after infection are not yet known. The paper was published in Cell.
Hypotheses for long Covid
A news article in Science discusses evidence and uncertainties for three hypotheses for the cause of long Covid. Very small blood clots, lingering virus, and a disrupted immune system have all been proposed as factors leading to persistent symptoms. It is probable that multiple factors may be involved in long Covid.
Many human genes associated with risk of developing severe Covid-19
More than 1,000 genes across 19 cell types in lungs were found to be associated with severe Covid symptoms. These 1,370 genes accounted for 77% of the single nucleotide polymorphisms that have been associated with severe Covid cases. Artificial intelligence was used to analyse the large data set.
Further analyses found that maturation of one particular Natural Killer cell was disrupted in severe Covid-19 cases, suggesting that insufficient production of some cytokines, leading to uncontrolled viral replication in the lungs, may be a key factor in severe Covid.
Cells and tissues from 5,000 severe Covid cases were compared with samples from 1.3 million control cases. The study utilised cells and tissues mostly from patients of European ancestry. The paper was published in Cell Systems.
Persistent symptoms not just associated with Covid-19
A Dutch study found that persistent symptoms are not just caused by Covid-19, but occur in other lower respiratory tract infections too. The reported quality of life a year after a moderately severe lower respiratory tract infection was similar for those where the infection was due to SARS-CoV-2 and where another infection was involved. Many in both groups reported persistent symptoms. The paper has not yet been peer reviewed.
Persistence of viral RNA
A paper reviews the incidence of viral RNA persisting after an infection. In many cases the viral RNA does not stimulate or maintain symptoms, and is not infectious. However, in some cases symptoms may persist or infectious particles are produced. The factors that result in viral persistence require more research. The paper was published in PLOS Biology.
WHO preliminary report into origin of the virus
The WHO has produced a preliminary report from the Science Advisory Group investigating where the virus may have originated. The report states that further attention needs to be given to the lab-origin hypothesis, and doesn’t yet make conclusions about which origin scenario is more likely.
A news item in Science canvassed scientific opinion on the report. There were a range of views. Some were disappointed that no conclusion had yet been reached (notably from advocates of a zoonotic origin), while others thought that caution was reasonable for this preliminary report. The report authors noted in a press conference that all politics can’t be kept out of the investigation.
A call for better monitoring of zoonotic outbreaks
A paper advocates for the establishment of multidisciplinary teams to be supported for long-term monitoring for zoonotic (animal to human) outbreaks. This would explore the causes and mechanisms of the current SARS-CoV-2 and Monkeypox outbreaks, but also help improve understanding of future epidemics that come from wildlife.
The list of disciplines the authors identify for the teams does not include social science capabilities, which seems to be a weakness given the role deliberate or accidental human-wildlife encounters play in outbreaks. The paper was published in Veterinary Quarterly.
Effectiveness of social distancing messages is influenced to a degree by message tone
A study involving 89 countries examined the effectiveness of different messages promoting social distancing. Messages that promoted personal agency and reflective choices reduced feelings of defiance, compared with restrictive or shaming messages.
However, neither supportive nor shaming messages affected intentions to follow social distancing requirements. The authors discuss a variety of factors that may explain this. They include the numerous other messages participants will have seen outside of the study, and work or social commitments that prevent physical distancing.
Personal motivations (based on values) and perceptions of risks were a better predictor of behaviour than the type of message they were exposed to in the study. The paper was published in the Proceedings of the National Academy of Sciences.
Rapid diagnostic test for immunity being developed
A rapid PCR test could be used for widespread testing of immunity. The test measures the prevalence and quantity in blood samples of a mRNA transcript that correlates with T cell activation following SARS-CoV-2 infection.
The test is undergoing further development, and has not yet been authorised for use. The paper was published in Nature Biotechnology.