Coronavirus Research Tracking - 18 February
Booster doses, Omicron risks, long Covid, antiviral therapies, communication strategies
This week, several papers looking at the effects of three, or four, vaccine doses, the immune benefits of at least one vaccine dose if infected, and reduced risks of long Covid with either prior or subsequent vaccination.
More data on antiviral therapies, Omicron subvariants, possible common Omicron symptoms, and post-pandemic lessons from the past.
The tracker is shared with the COVID-19 Vaccine Media Hub.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Three Pfizer doses restores protection against infection
A study from a US healthcare system (and funded by Pfizer) reports that three doses of the Pfizer/BioNTech vaccine restored high levels of effectiveness against infection.
The effectiveness against infection of two doses declined from 85% one month after vaccination down to 49% after seven months or more. One month after a third dose effectiveness increased to 88%. Stronger protection against infection after three doses was higher than two doses for those over 65.
The third dose was given about seven months after the second dose. Waning effectiveness against hospitalisation was not seen after two doses, except for immunocompromised people. The study was undertaken when the Delta variant was dominant. The paper was published in The Lancet Regional Health Americas.
Substantial decline in neutralising activity against Omicron a month after second mRNA vaccine dose
mRNA vaccine-induced neutralising antibody activity declines substantially in the six months after the second dose. Levels of neutralising antibodies were lower in those who received the Pfizer/BioNTech vaccine compared with those who had the Moderna vaccine.
A significant decline in neutralising activity against the Omicron variant was found three-to-four weeks after second doses for both mRNA vaccines. In contrast to results seen for other variants, a post-vaccination infection did not improve neutralising ability against Omicron. The authors recommend three doses of mRNA vaccines to improve immune responses.
The study is based on healthcare workers, who may not be representative of the general population. T cells and other immune responses were not studied. The paper was published in Science Translational Medicine.
Moderna vaccine booster may be more effective than Pfizer/BioNTech
A Spanish study found that a booster dose of the Moderna vaccine was more effective than the Pfizer/BioNTech vaccine in preventing an Omicron infection. In the month after receiving the booster the effectiveness of the Moderna vaccine was 52.5%, compared with 46.2% for Pfizer/BioNTech.
Participants had initially been vaccinated with the AstraZeneca/Oxford, Moderna, Pfizer/BioNTech, or Johnson & Johnson/Janssen vaccines. The greatest protection (58.6%) was seen for two doses of the AstraZeneca followed by a Moderna booster. Effectiveness was greater if the booster was given more than six months after the last dose. People over 40 were included in the study. The paper has not yet been peer reviewed.
Fourth mRNA dose may restore rather than improve immune responses
A fourth dose of the Pfizer/BioNTech and Moderna vaccines may just restore antibody levels, rather than boosting them higher than a third dose. The fourth dose, given about four months after the third, did not prevent some participants from developing mild or asymptomatic Omicron infections. Viral loads were also high in the infected cases.
There were no significant adverse effects after a fourth dose. Participants were Israeli healthcare workers, with 274 receiving a fourth dose. The paper has not yet been peer reviewed.
Omicron-specific booster vaccines not significantly better in animal trials
A news article in Nature discusses the results of recent tests of Omicron-specific vaccines. Early results, using small numbers of animals, indicate a single booster dose of such a vaccine does not produce a markedly different immune response than boosting with vaccines developed for early strains. Pfizer and Moderna have started larger clinical trials on people.
Stronger immune response if Omicron infected people are also vaccinated
A South African study found that unvaccinated people infected with Omicron are likely to have less protection against subsequent infection from other variants, compared with a vaccinated person.
Antibody neutralising activity against several Variants of Concern was stronger in sera taken from people who had been vaccinated then been infected with Omicron, compared with samples from unvaccinated people with an Omicron infection.
The study only involved sera from 20 unvaccinated and seven vaccinated people with Omicron infections. The paper has not yet been peer reviewed.
A single vaccine dose after infection greatly improves immunity
A large Israeli study found that having a single Pfizer/BioNtech vaccine dose after an infection substantially decreased the risk (82% lower rate) of subsequent infection, compared to not being vaccinated. Risk of symptomatic infection was also lower.
The risk of reinfection even without the vaccine was low (about 1%). Reinfection risks were calculated based on reinfections at least 3 months after the first infection. People who had an infection plus two vaccine doses were not included in the study. During the study the Delta variant was dominant. The study involved over 100,000 members of a healthcare service. The paper was published in the Annals of Internal Medicine.
mRNA vaccines create robust immune responses over six months
mRNA vaccines generate persistent germinal cells that lead to production of antibodies with stronger binding abilities to SARS-CoV-2. The frequency of some of the high affinity antibodies increased over six months, indicating that the mRNA vaccines induce robust and relatively long lasting immune responses. The paper was published in Nature.
Long Covid risks reduced if vaccinated
A review by the UKHSA concluded that vaccinations can reduce the risk or incidence of long Covid. The review examined 15 studies, seven of which looked at the incidence of long Covid in people vaccinated before getting infected, seven looked at the effect of vaccination on symptoms after infection, and one study looked at both issues.
For those vaccinated before getting infected, people were less likely to report long Covid symptoms over the next six months.There is also some evidence that long Covid symptoms are reduced in infected people who are subsequently vaccinated. The review notes that biases in who does and doesn’t get vaccinated can influence the results. The paper has not yet been peer reviewed.
Vaccination programmes can be improved by communicating hope
Using hope as part of a health communication strategy can be effective. A US experiment compared the effectiveness of a hope-focussed visual aid versus a fear-based one for increasing vaccinations. The paper was published in Scientific Reports.
Non-vaccine-related papers
Covid-pill performs well in clinical trial
A clinical trial of the Covid pill Paxlovid found it to be effective in reducing the risk of developing more severe Covid-19. Compared with a placebo, the risk was 89% lower when Paxlovid (chemical name nirmatrelvir) was given with ritonavir within three days of symptom onset. There was also a 10-fold decrease in viral load.
There were no serious safety concerns, although diarrhoea, vomiting and/or altered taste (dysgeusia) were more common in Paxlovid-treated patients than those receiving a placebo. The paper was published in the New England Journal of Medicine.
Antiviral therapies being used against SARS-CoV-2
A review of antiviral treatments for Covid-19 summarises the effectiveness of the 12 therapies currently (or recently) being used. It also discusses the challenges of developing new antivirals. The paper was published in Cell Reports Medicine.
Beware of false dichotomies when considering mitigation measures for schools
A paper from the US discusses the false dichotomies often raised in debates of mitigation methods in schools. It suggests that many suggested dilemmas (such as harms from mitigation measures vs harms from infection) are not real, and that keeping schools open is compatible with reducing transmission. The paper has not yet been peer reviewed. [Published in March in Cell Reports Medicine]
Omicron subvariant distinct from original
The BA.2 subvariant of Omicron is quite different genetically and virologically from the BA.1 variant. They appear to be antigenically distinct, and BA.2 can more quickly replicate in cultured nasal cells, and stimulate more cell fusions than the BA.1 subvariant. The former’s effective reproduction number was calculated to be 1.4 times higher than BA.1.
In hamsters BA.2 was also more pathogenic than BA.1, resembling earlier variants. The authors suggest more attention should be paid to the BA.2 variant. Further research is needed to determine if the laboratory experiments provide an accurate assessment of infections in people. The paper has not yet been peer reviewed.
Common Omicron symptoms
A Norwegian study identified the six most common symptoms of an Omicron infection in vaccinated people following a Christmas party outbreak. Based on 81 infected people the most common symptoms were cough (83%), followed by runny/stuffy nose (78%), fatigue or lethargy (74%), sore throat (72%), headache (68%) and fever (54%). One infected person was asymptomatic, and 91% of cases had at least three symptoms. The paper was published in Eurosurveillance.
Covid-19 may lead to significant damage of the placenta
SARS CoV-2 infections can cause placental damage, harming or killing the baby. This is based on autopsies of 68 placentas from infected women. The degree of placental damage seen in these cases was much greater than seen for other perinatal infections. The paper was published in Archives of Pathology & Laboratory Medicine.
Double infections can occur
In Australia two people with kidney disease had infections of both Delta and Omicron variants at the same time. Based on sequencing data, these two cases were not connected. There was no evidence that the variants had recombined to form a new variant, but the cases highlight the potential for co-infection, particularly in immunocompromised people. The paper has not yet been peer reviewed.
Policy makers shouldn’t ignore post-pandemic health impacts
A news article in Nature cautions against ignoring long lasting Covid-19 conditions. It discusses the impacts of earlier influenza, polio, and other disease outbreaks. It notes that awareness about disabilities improved after polio and led to some improvements for those with disabilities. Long Covid, the article suggests, could lead to further social improvements if the long term consequences are not ignored.