Coronavirus Research Tracking - 26 August
Booster timing, hybrid immunity, self-replicating vaccines, viral evolution trends, Paxlovid, Ivermectin
This week, trying to decide when it’s best to get a booster, more research finding that prior infection plus vaccination can provide better protection against Omicron (for a few months at least), and self-replicating vaccines may be more effective than non-replicating ones.
In non-vaccine research, the virulence of future variants can’t be predicted, but variant incubation periods have been decreasing. Paxlovid and molnupiravir are effective for Covid patients 65 years or older, while another study confirms Ivermectin is ineffective in treating Covid. And beliefs about pathogen transmission pathways can be hard to change, even with good evidence.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Booster options
A Nature news explainer discusses different, or emerging, vaccine boosters, and when may be the best time to receive them. There is a medical consensus that people should wait at least four months before having a booster vaccine dose.
Second doses for children
Another news item in Nature considers how long children should wait before receiving a second vaccine dose. A longer interval is known to improve immune responses in adults, but there is less evidence for the effect in children. Medical opinion is usually of the view that in the middle of a large outbreak waiting longer for a second dose is outweighed by the risk of becoming infected.
Omicron and immunological imprinting
An Omicron infection in unvaccinated and vaccinated adults leads to a better neutralising antibody response against Omicron variants. Similarly, those with Delta infections tend to produce antibodies that better neutralise that variant.
The authors of this study suggest that a vaccine with the Omicron spike protein would be more effective against Omicron variants, although they didn’t test this. They also aren’t sure if a bivalent vaccine, containing the Omicron and another variant’s spike protein would be more effective.
The study was based on people hospitalised with Covid-19. The paper has not yet been peer reviewed.
A similar result is reported in another study. Unlike infections with some previous variants, an Omicron infection after vaccination does not usually generate antibodies able to neutralise a range of variants. The authors of this study concluded that this is due to immunological imprinting, where immune responses to the infection are largely based on those generated by the vaccine (or a previous infection).
However, BA.1 infections after vaccination generated neutralising antibodies in the nasal mucosa. A previous study found that mRNA and adenovirus-based Covid vaccines do not generate appreciable antibodies in the mucosa. So, hybrid immunity may generate stronger responses where the virus usually infects.
As has been found in previous studies, this study also identified an antibody from earlier infections that was able to neutralise Omicron sub-variants. The paper has not yet been peer reviewed.
A previous infection reduces Omicron infection risk over the next few months
A study reports that a recent infection, or a booster vaccine dose, reduces the risk of an Omicron infection. About six months after an infection the risk of a reinfection increases substantially. The risk of hospitalisation due to an Omicron infection was also reduced for those with hybrid immunity.
The health records of nearly 400,000 people were included in the analyses. Differences in social distancing, mask wearing, and health policies were not taken into account. The paper has not yet been peer reviewed.
A self-replicating vaccine may provide more effective protection
A study in hamsters found that a replicating adenovirus-based vaccine provided stronger immune protection than a non-replicating version. The replicating form produced larger amounts of the SARS-CoV-2 spike protein, and higher levels of antibodies.
When vaccinated animals were challenged with SARS-CoV-2, those who had the replicating vaccine had lower viral loads and lung damage.
The replicating vaccine does not produce infectious viral particles. Only small numbers of hamsters were tested. The paper was published in Science Advances.
Non-vaccine-related papers
Virulence of future variants can’t be predicted
A UK analysis found that there was no consistent pattern in increasing or decreasing severity as different variants emerged. This indicates that it is not possible to predict whether subsequent variants will be more or less pathogenic. The paper has not yet been peer reviewed.
Virus incubation period became shorter over the pandemic
A meta-analysis found that the SARS-CoV-2 incubation period shortened as the pandemic progressed. For the Alpha variant the mean incubation period was 5.0 days, with the period declining with subsequent variants, down to 3.42 days for Omicron.
The review is based on 142 studies. Differences in populations and methods between the studies makes a precise assessment of changes in incubation period difficult. The paper was published in JAMA Network Open.
Micro blood clots and long Covid
A news article in Nature discusses evidence for and against very small blood clots being a factor in some long Covid cases. However, it is not yet clear if these clots could be the cause or just a symptom of long Covid.
Paxlovid is effective for those 65 and older
An Israeli study found that people 65 or older with Covid-19 were less likely to be hospitalised if they received Paxlovid. The risk of hospitalisation for the Paxlovid group was about one-third that for those who weren’t treated with the anti-viral. In contrast, the hospitalisation risk for 40-to-64 year olds was not reduced by Paxlovid.
The study was based on medical records, rather than a direct trial, and so not all factors that could influence the results could be excluded. The study was published in the New England Journal of Medicine.
A study in Hong Kong found that both molnupiravir and Paxlovid reduced deaths, and disease progression, in older Covid-19 patients. Viral load also decreased more quickly in those receiving the antivirals.
The mean age of participants was close to 80 years, and the antivirals provided no substantive benefit to those under 65. The study was published in The Lancet Infectious Diseases.
Ivermectin and two other treatments ineffective against Covid-19
A randomised trial found that Ivermectin, Metformin, and Fluvoxamine provided no significant benefit to Covid-19 patients. Ivermectin is an anti-parasitic drug, Metformin is used to treat diabetes, and Fluvoxamine is used in the treatment of some mental health conditions. These medicines have been used by some to treat Covid-19 based on modelling that indicated they could have anti-viral properties.
The effects on blood oxygen levels, emergency department visit, hospitalisation, or death were assessed. Severity of symptoms, compared with a placebo, was also not affected.
All patients were overweight or obese, with the median age being 46. The study was published in the New England Journal of Medicine.
An associated editorial in the same issue recommended that physicians stop prescribing ineffective Covid-19 treatments.
Improving social data and use collection before another pandemic
An opinion published in Nature emphasises the need for improved data collection on people’ mobility and social behaviours to be better prepared for subsequent pandemics. It notes how such data, often collected from mobile phone information, proved useful in understanding transmission and the impacts of public health measures for Covid-19.
However, the data were often fragmented and incomplete, limiting its reliability and usefulness. Privacy concerns can also prevent or discourage such data collation and use. The author recommends that we start thinking now about how to collect and use such data more rigorously and ethically before another pandemic arrives.
Belief perseverance and pathogens
A historical perspective on how the idea of airborne transmission of disease has developed, and been resisted, over the last 100 years is given in the journal Indoor Air. The authors emphasise the role of “belief perseverance”, where views don’t change despite accumulating evidence, in resisting new ideas. The authors suggest that Covid-19 has helped change perspectives on disease transmission pathways.
An April commentary in The Lancet listed the top 10 lines of evidence that support airborne transmission of SARS-CoV-2.