Coronavirus Research Tracking - 19 August
Vaccine safety & effectiveness, new vaccine, long Covid, asymptomatic prevalence, antibody therapies, modelling future infections
This week, vaccine safety and effectiveness for pregnant women, a new vaccine that shows potential for longer lasting protection, and vaccines don’t appear to promote the emergence of new variants.
In non-vaccine research, more studies of the prevalence of long Covid, cognitive impacts of the pandemic on toddlers, a promising antibody cocktail therapy, asymptomatic infection prevalence, optimal rapid antigen test strategy, and modelling future variant scenarios.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Pregnant women can have a lower risk of adverse vaccine events than non-pregnant women
A Canadian study found that pregnant vaccinated women had a lower risk of significant vaccine-related adverse effects than a matched group of non-pregnant vaccinated women. Adverse effects were assessed in the seven days after the first or second vaccine dose. Women receiving the Moderna and Pfizer/BioNTech vaccines were included in the study.
There was a greater risk of an adverse reaction in pregnant women after the second Moderna dose than after one dose, or one or two doses of the Pfizer vaccine. The paper was published in The Lancet Infectious Diseases.
Vaccination improves outcomes for pregnant women, and their babies
A large US study found that vaccinated pregnant women were significantly less likely to become infected than unvaccinated pregnant women. For participants that did become infected, those who were vaccinated were less likely to develop more severe symptoms. Vaccination did not lead to poorer birth outcomes.
The study involved 86,000 pregnant women, with the vaccinated group having received one of the mRNA vaccines. A third vaccine dose improved maternal-foetal outcomes relative to two doses. There were a range of socio-economic and health differences between the vaccinated and unvaccinated mothers, which the study tried to account for. The paper has not yet been peer reviewed.
New vaccine shows promise of longer lasting protection
Durable protection against Omicron was found in macaques who had been given a subunit nanoparticle vaccine that had an adjuvant. Two doses of the vaccine with the receptor binding domain of the Wuhan strain resulted in high levels of neutralising antibodies for at least one year.
Improved cross-reactive neutralisation (against both SARS-CoV-2 variants, and other coronaviruses) was found when a third vaccine dose, containing the Beta variant receptor binding domain, was given six to 12 months after the first. Protection against lung infection was still 65% six months after the third dose, compared to unvaccinated animals.
Only 5-6 animals were used in each trial. The paper was published in Science Translational Medicine.
A paper in Nature Nanotechnology discusses the potential for nanoparticle-based vaccines to protect against SARS-CoV-2 variants. A key feature is that they can be rapidly adapted to address new variants.
Significant differences in viral shedding between some variants
Viral shedding in the small aerosols was greater for the Alpha, Delta, and Omicron variants than for less transmissible variants. Viral particles in some of the aerosol samples were able to infect cell lines, indicating that they remained infectious. Vaccinated people also shed infectious virus.
There was considerable variation between individuals in the quantity of virus in aerosols. The study is based on 93 people with infections.
The authors suggest that viral loads in saliva may be a better predictor of infectiousness than loads in nasal swabs. Based on comparisons with influenza virus, they also suggest that SARS-CoV-2 evolution could still lead to greater aerosol shedding. The paper has not yet been peer reviewed. The study was also highlighted in a news article in Nature.
Vaccination may not stimulate development of new variants
A study suggests that vaccination does not enable the emergence of new variants. The study examined over 2,000 genome sequences from Hong Kong, and looked at sequence variations within infected individuals. Alpha, Delta, and Omicron variant infections had higher within-host mutation rates &/or nucleotide diversity than other variants examined.
Vaccination with the Pfizer/BioNTech or CoronaVac vaccines was associated with higher viral mutation rates in variants of concern. However, mutations that changed amino acids were found to be less common. The authors conclude that indicating purifying selection is occurring, reducing the risk of protein changes that aid immune evasion or greater infection efficiency. The paper has not yet been peer reviewed.
Non-vaccine-related papers
Long Covid prevalence
A Dutch study estimated that the prevalence of long Covid was 12% in adults. Assessments were made 90 to 150 days after an infection. Symptoms could include chest pain, breathing difficulties, muscle pain, loss of taste or smell, tingling extremities, feeling hot and cold alternately, and general tiredness. This assessment took account of some of the symptoms also occurring in people without, or prior to, Covid-19.
The study involved 76,000 participants. Asymptomatic cases were not reported. Not all Covid-related symptoms were recorded for those without or before Covid. The paper was published in The Lancet.
A US CDC National Center for Health Statistics household survey reports that about 34% of adults with Covid-19 had experienced long Covid symptoms lasting 3 months or more. Unlike the Dutch study there were no matched controls, so the survey may overestimate prevalence.
A news article in Science reports on the study included in last week’s tracker of low cortisol levels in some people with long Covid. It notes that several potential therapies could be tried to see if they boost cortisol levels. Eric Topol also discusses long Covid in his latest Ground Truths blog.
Cognitive development in young children impaired during pandemic
A US study found that the cognitive development of children under three was adversely affected during the first two years of the pandemic. Scores in a range of verbal and non-verbal tests were lower for toddlers during the pandemic than for toddlers tested in the decade before.
The causes of the decline are uncertain, though the authors suggest that the learning environment for young children was fundamentally affected. Reduced social contact during the pandemic may be one factor affecting cognitive development, but further research is needed. Follow-up of the toddlers is also required to determine if there are long lasting effects.
The study was relatively small, so the results may not be generalisable. The authors note though that other studies have reported pandemic effects on cognitive development in infants too. The paper has not yet been peer reviewed.
Antibody therapeutics
Three cross-neutralising antibodies have been developed to form a therapeutic cocktail against Covid-19. When given at a relatively high dose the three antibodies provided synergistic neutralising capability against a pseudovirus with the Omicron variant (B.1.1.529) spike protein. When given to hamsters there was better resistance to immune evasion and effective protection against the Beta variant.
The authors suggest that therapeutic antibody cocktails are likely to become a common treatment in the future. The paper was published in PNAS.
N95-type masks more effective than surgical ones
A Swiss study found that healthcare workers wearing FFP2 (similar to KN95 & N95) masks were less likely to become infected than workers wearing surgical masks. The risk of infection was calculated to be about 40% lower for those consistently wearing the respirator-type mask.
The study also reported that the risk of infection increased as cumulative exposure to patients increased. But the greater effectiveness of FFP2 masks remained. Vaccination also reduced infection risk. Nearly 3,000 healthcare workers were involved in the study, who self-reported the type(s) of masks they wore. It was not reported whether the N95-type masks were properly fitted. The paper was published in JAMA Network Open.
Asymptomatic Omicron infections may be very common
A small study found that over half of participants were not aware that they had had an Omicron infection. Staff and patients at an academic medical centre were taking part in a longitudinal seroconversion study. Fifty six percent of 210 who had antibodies to the virus during the Omicron wave had not noticed any infection symptoms.
The authors suggest that such a high frequency of unawareness of infection status would have contributed to Omicron’s spread. Larger studies are needed to more accurately assess asymptomatic prevalence in communities. The paper was published in JAMA Network Open.
BA.2.75 characteristics
The BA.2.75 sub-variant was better able to escape antibody neutralisation than BA.2. However, evasion was substantially less than the BA.4 & BA.5 sub-variants. Immune evasion was tested using sera from double- or triple-vaccinated healthcare workers and people hospitalised after an Omicron infection.
Two spike protein mutations in BA.2.75 were shown to increase resistance to neutralisation, while another increased susceptibility. This suggests compensatory mutations in the spike protein may improve infectivity, but also reduce immune evasion. Sera from only a small number of people were used. The paper has not yet been peer reviewed.
Two day intervals between rapid antigen tests is desirable
A study found that taking two rapid antigen tests two days apart is more reliable when someone has Covid symptoms. The rapid antigen tests were compared with PCR results. More than 90% of symptomatic cases were detected after two tests during the first week of symptoms. For asymptomatic cases, three tests, each two days apart, detected 79% of infections. The paper has not yet been peer reviewed.
Modelling multiple future scenarios
An Australian study modelled 64 future SARS-CoV-2 variant scenarios to identify optimal policy responses in the face of uncertainty. It can be used to compare health and economic benefits and burdens from different policy choices.
The model takes account of differences in infectivity, immune evasion, long Covid prevalence, and pathogenicity, and examines public health measures and impacts on transmission, health services, and GDP. The paper concluded that significant ongoing morbidity and mortality will occur due to the virus over the next few years.
Unsurprisingly, the study found that more stringent public health measures will benefit the health system, but have detrimental impacts on the economy. It also found that making N95, and similar, masks more widely available would have only modest effects on infection rates over use of surgical and cloth masks.
The authors suggest that multivalent vaccines (targeting two or more variants) were likely to be increasingly important as the pandemic continues. The model only took account of one new variant over the next 18 months. The paper has not yet been peer reviewed.