Coronavirus Research Tracking - 8 April
Effectiveness of four and three vaccine doses, infection dynamics, viral recombination, long Covid, preparing for the next pandemic, Sweden's public health response
This week, more studies on the effectiveness of four and three mRNA vaccine doses. Also, infection dynamics during different waves in the UK, prevalence of long Covid in the UK, recombination between variants, cardiac problems associated with long Covid, future therapies, and a strong critique of Sweden’s pandemic response.
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.
4th dose gives good protection against severe Covid in older people for at least 6 weeks
Compared with three doses a fourth Pfizer/BioNTech in over 60 year olds provides stronger protection against severe Covid for at least six weeks. However, protection against infection after four doses declined over the same period. The fourth dose was given at least four months after the third, and the Omicron variant was the dominant variant during the study.
The incidence rate for confirmed infection was 2-fold lower, and the rate of severe disease was 3-fold lower in the fourth week after receiving the fourth dose. There may be some behavioural differences between those who decided to get a fourth dose and those who didn’t. The paper was published in the New England Journal of Medicine.
Three Pfizer doses provides a much stronger immune response against Omicron than two doses
Three Pfizer/BioNTech vaccine doses provide much stronger neutralisation of the Omicron variant than two doses, or a prior infection. After three doses, neutralisation was 30-fold higher than for two doses.
In other tests, only 11 of 18 mono- or polyclonal antibody treatments demonstrated activity against Omicron, with only three having the same level of potency as against an earlier variant. The paper was published in Science Translational Medicine.
Third mRNA dose also generates a strong immune response in young people
A German study found that the effectiveness of mRNA booster vaccinations against Omicron infections in adolescents (12-17 year olds) was high, over 85%. Compared to 18 to 59 year olds, effectiveness against mild symptomatic infections waned less over the 15 weeks after the third dose. Protection against more serious illness was maintained for all age groups, although modest waning was seen for those under 60. The paper has not yet been peer reviewed.
Two Pfizer doses plus Omicron infection generates a good immune response
Being infected with Omicron after two Pfizer/BioNTech doses generates an immune response that is able to neutralise the Omicron variant as well as earlier variants of concern. This study shows that this is due to the Omicron infection expanding pre-existing memory B cells, rather than generating new memory B cells.
The authors suggest a booster vaccine based on the Omicron spike protein may be more effective than booster doses from the original vaccine. Serum samples were collected just a few weeks after an Omicron infection, so other immune responses may develop later. The paper has not yet been peer reviewed.
Strong immune response in Maori and Pacific people after two Pfizer doses
The Pfizer/BioNTech vaccine generated similarly strong immune responses for Maori, Pacific people and other ethnicities in New Zealand. However, antibody levels were lower in participants with diabetes. Neutralisation ability against the Omicron variant was greatly reduced, with two-thirds of serum samples having not having measurable activity.
The study assessed immune responses for one month after the second dose. Infection levels were low during the study so real life effectiveness of the vaccine was not assessed. The paper has not yet been peer reviewed.
Omicron infections relatively common in triple vaccinated Swedish health care workers
A Swedish study found high levels (22%) of infection in triple vaccinated healthcare workers. They were infected with BA.1, BA.1.1 or BA.2 variants. Viral load peaked on day 3 of the infection, with live virus detectable for up to 9 days after infection was confirmed. Higher antibody levels did not seem to prevent infection, but they were associated with lower viral load and a shorter time to clear the virus. Most of the infected participants reported only common cold-like symptoms.
The healthcare workers received two doses of either the Pfizer or AstraZeneca vaccines (or one dose of each), with the third dose being the Moderna vaccine given six months later. Many of the participants also had had a SARS-CoV-2 infection before being vaccinated, indicating the ability of Omicron and its subvariants to evade some immune responses. Participants were mostly young, healthy and female. The paper has not yet been peer reviewed.
Multiple exposure to Covid antigens improves T cell diversity
T cell types diversify the more exposures someone has to viral antigens. This can come from multiple vaccinations and from infections before or after vaccination. The T cell profiles differ for those infected before vaccination and those infected afterwards. The study examined cases of up to three exposures. The paper was published in Nature Immunology.
Infection dynamics of different variants
The UK REACT-1 study examines the dynamics of successive variant waves between May 2020 and March 2022. It describes the two peaks of the BA.1 and BA.2 waves between January and March, with very high infection rates in March, despite high levels of vaccination. At the end of March about 1 in 16 people (over 6% of the population) were infected, and the infection level was 40% higher than for the January Omicron wave.
A combination of greater transmissibility of BA.2 and removal of Covid restrictions in February probably account for this level of infection. Rates of hospitalisations and deaths increased significantly in March, especially among older people. The paper has not yet been peer reviewed.
Recombination between variants
Several recent papers have reported recombinations between variants or subvariants. Examples are:
In Hong Kong between BA.1 and BA.2
In Europe between Delta and Omicron.
A diagram on Twitter also illustrates where in the viral genome different recombinations have occurred.
Cardiac impairments in long Covid patients
Cardiac impairment was found in 20% of patients with long Covid at 6 months, and the impairment was still present in half of those six months later. The cardiac problems were mostly not myocarditis. Impairments were detected using cardiac magnetic resonance. They were not detectable using the usual blood biomarkers, so the problems may be overlooked.
Cardiac impairment was found in some patients who did not have severe Covid-19. Males were more likely to have cardiac impairments, even though long Covid was more common in women in the study. The study involved 534 patients with long Covid. The paper has not yet been peer reviewed.
Nearly 3% of people in the UK may have long Covid
The UK Office of National Statistics estimates that 1.7 million people in private households report that they have long Covid symptoms. This represents 2.6% of the population. They classified long Covid as symptoms that persist more than one month after an infection, and not attributable to other factors. Self-reported incidence of long Covid varied for different variants. Two-thirds of those reporting long Covid said that it limited their daily activities “a lot”.
Fatigue was the most common symptom (in 51% of those reporting symptoms), followed by shortness of breath, loss of smell and muscle pains. Long Covid was more frequently reported by women, 35-to-49 year olds, and those with disabilities, or living in deprivation. Health-sector and social care workers, and teachers, reported long Covid symptoms more frequently. The results are based on self-reporting rather than clinical diagnoses.
A paper published in the Proceedings of the National Academy of Sciences discusses the possibilities for future therapeutics for Covid-19, and subsequent pandemics. Challenges include improving patient datasets, prioritising research on microbes with known pandemic potential, finding therapies that prevent hospitalisation, and developing a clinical trial system that is able to start within days of promising therapeutics being identified.
Sweden’s pandemic response
Sweden’s pandemic strategy, especially the goal to rapidly develop herd immunity, is strongly criticised in a paper published in Humanities and Social Sciences Communications. It says that the public were kept in ignorance of basic facts about transmission, the Public Health Agency lacked infectious disease expertise, and undermined trust in those with such expertise. The country’s Covid-related death rate per capita was 10 times higher than Norway’s in 2020.
The paper also criticises political leaders elsewhere who were not transparent in their decision-making and did not consistently seek and apply expert advice. The authors suggest that in future pandemics the “scientific method be re-established.”
WHO’s slow response to aerosol transmission
A news article in Nature discusses why it took so long for the World Health Organisation to conclude that transmission through aerosols was the main means for infection. It notes that the WHO is traditionally conservative and that SARS-CoV-2 did not spread like most respiratory viruses. Critics suggest that its reliance on scientific consensus prevented it from responding more quickly to emerging evidence. However, the article concludes that the WHO may become more precautionary in its advice in future infectious disease outbreaks.