Coronavirus Research Tracking - 22 July
Vaccine effectiveness in children, and in males vs females, Omicron's selective advantages, pre-existing immunity, alleles that increase Covid risk, NZ transmission patterns
This week, the effectiveness of the Pfizer vaccine against Omicron in younger children, cross-reactive antibodies produced by BA.4, and differences in immune responses to vaccines in men and women.
In non-vaccine research, dissecting the effects of individual Omicron mutations, Covid protection provided by previous colds, genetic factors that increase the risk of developing more severe Covid, one monoclonal antibody that works relatively well for all variants, the risk of community transmission as more people come to NZ, and the advantages of wastewater surveillance.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Pfizer vaccine effective against Omicron in younger children
A Singaporean study found that two doses of the Pfizer/BioNTech vaccine provided good protection against Omicron in children aged 5-to-11 years, at least soon after vaccination. Effectiveness against PCR-confirmed infection after two doses was 65.3%, and effectiveness against hospitalisation was 82.7% when assessed at least a week after the second dose.
Effectiveness against hospitalisation after one dose was only 42.3%. The study was conducted between January and April 2022. The paper was published in the New England Journal of Medicine.
BA.4 variant produces cross-reactive antibodies
A South African study reports that, unlike BA.1, the BA.4 variant results in the development of neutralising antibodies that cross-react with other variants. Cross-reactivity of the BA.4 variant was similar to that seen for the Beta variant. Antibodies from Delta and BA.1 infections showed lower levels (10-to-100 fold less) of cross-reactivity. Cross-reaction was seen in both unvaccinated and vaccinated adults.
The authors suggest a second generation vaccine that uses the Beta, BA.4, or BA.5 spike sequence may provide better protection. Small numbers of people were involved in the study. The paper has not yet been peer reviewed.
Omicron is more effective at cell infection than most earlier variants
The Omicron (BA.1) variant shows similarly high levels of infectivity as the Delta variant, but a 15-fold higher level of immune avoidance. This study used virus-like particles containing the spike protein from different variants. Omicron and Delta had nearly a five-fold higher cultured cell infectivity level than particles with the original spike protein.
Antisera from vaccinated individuals and those with a prior infection showed poor neutralisation ability against Omicron, compared with earlier variants.
This study also showed that of five monoclonal antibodies tested, only two, sotrovimab and bebtelovimab, were effective in neutralising Omicron.
Complete viruses may behave differently than the virus-like particles. The paper was published in Proceedings of the National Academy of Sciences.
Sex differences in vaccine responses
A recent review examined the sex differences to the influenza and Covid vaccines. For influenza vaccines, older women tend to have stronger immune responses. and show higher levels of vaccine effectiveness. But they also tend to report more adverse events after vaccination, compared with older men. For mRNA Covid vaccines, older women usually show a stronger immune response after the first but not the second vaccine dose.
However there is insufficient data to infer if there are substantial differences between the sexes at different ages and frailty for mRNA vaccine effectiveness, or vaccine safety. The paper proposes a roadmap to address the knowledge gaps. The paper was published in Frontiers in Aging.
Non-vaccine-related papers
Studying the individual effects of Omicron mutations
The effect of individual mutations from Omicron variants have been examined in a functional analysis. Forty eight mutations found in the spike protein of the BA.1 and BA.2 variants were individually introduced into the Wuhan variant’s spike protein. Their effects on infectivity, immune evasion and other functions were then studied.
Some individual mutations enhanced BA.1 & BA.2 infectivity, while others reduced it. Other mutations were shown to increase immune cell recognition or binding. The study used pseudoviruses rather than the complete virus, and combinations of mutations were not investigated. The paper was published in Cell Host & Microbe.
Pre-existing immunity to SARS-CoV-2
A study found that CD4+ T cells from earlier common cold coronavirus infections provided immunity to SARS-CoV-2 in young adults (18-to-35 years). Only 32 people were included in the study, and the time since a prior cold infection was unknown. The paper was published in Cell Host & Microbe.
Pre-existing T cells that provide protection against SARS-CoV-2 were also found in another study. Analyses indicate that these T cells may have been generated in response to skin and/or gut microbes. Further research is needed into this. The paper was published in Science Immunology.
Genetic associations with developing more severe Covid-19
The combination of two specific alleles for the human OAS1 gene (which produces an antiviral protein) is associated with increased risk of hospitalisation with Covid-19. These alleles prevent the correct expression of the gene, leading to reduced clearance of the virus. This deficiency can be compensated for by giving the patient an interferon.
This combination of alleles has a frequency of 57% in the general European population, 59% in East-Asian individuals, and 15% in individuals of African ancestry. These two alleles do not appear to be present in Neanderthals. Other alleles that increase the risk of severe Covid may be present in non-European populations. The paper was published in Nature Genetics.
One monoclonal antibody appears to be effective against most variants
A short letter in The Lancet Infectious Diseases points out that only one monoclonal antibody, bebtelovimab, is effective against all known SARS-CoV-2 variants. However, it has not been submitted to medicine regulators for approval for clinical use outside of the US. The authors advocate for making it available outside of the USA, especially for immunocompromised people.
A paper published in the New England Journal of Medicine also reports the effectiveness of bebtelovimab against the BA.2.12.1, BA.4, and BA.5 variants. The antiviral drugs remdesivir, molnupiravir, and nirmatrelvir also showed some effectiveness against these variants.
Tracing new variant transmission as NZ travel restrictions ease
As international travel restrictions ease, there has been a strong relationship between the number of passengers arriving daily in NZ and the appearance of variants in the community. This study, based on analysis of over 10,000 viral genomes, found that in the first quarter of 2022 there were several introductions of the BA.1 and BA.2 variants. Between April and June, BA.2.12.1, BA.4, and BA.5 were more common. It is estimated that for about every 5,000 passenger arrivals there is one new border to community transmission for Omicron variants.
Another surge in cases later this year is predicted, as more people come to NZ, vaccine immunity wanes, and new variants emerge. The paper has not yet been peer reviewed.
An improved wastewater sampling method
New wastewater sampling and analytical methods were able to detect new variants up to two weeks before they were found in patients in and around a US university campus. Wastewater sampling is less subject to some of the biases associated with testing people. However, it may not always provide early detection of variants if those infected with them commute into but don’t live within the area.
Only one wastewater treatment site was included in the study. Variants at very low frequencies may not be detected in wastewater sampling. The paper was published in Nature.