Coronavirus Research Tracking - 29 January
Antagonistic antibodies, vaccine impacts, immune responses to new variants
This week’s Research Tracker is the last regular general ‘rona research update. It covers papers about autoantibodies, vaccine effectiveness and risks of adverse reactions, neutralising the recent viral variants, infection risks of young people and men, and animal species that can potentially be infected by SARS-CoV-2.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Types of tests in New Zealand
The NZ Ministry of Health has published information on the three types of tests that it is using - a PCR test on nose swabs, a saliva test, and an antibody test.
How genomic sequences are being used to study infection patterns and dynamics
Over a quarter of a million SARS-CoV-2 genomes have been sequenced. A perspective published in Science describes how genome data is being used to understand the dynamics of infection and evolutionary changes.
Severe Covid-19 associated with antagonistic antibodies
Three papers report how antibodies produced in response to Covid-19 can target host cells and tissues rather than the virus, leading to more severe disease.
Antibodies that are “autoreactive”, attacking the patient’s own tissues, appear common in cases of severe Covid-19, an unpublished study reports. Out of 52 people with severe or critical conditions 44% had autoantibodies. The authors suggest that two molecules may be able to be used as markers to identify which patients may develop autoimmunity.
Another study (also not yet peer-reviewed) of 194 SARS-CoV-2 infected patients found that, compared with uninfected people, they had “dramatic” increases in autoantibody reactivities. These autoantibodies were shown to prevent immune signalling and change the composition of immune cells, leading to disruption of immune responses and impaired control of the virus. Experiments in mice found that some of the autoantibodies lead to more severe disease.
Research published in Nature found that patients with severe Covid-19 have antibodies that prevent an effective antiviral response. The small study, involving 21 patients with mild or severe Covid-19, showed that for those with severe disease the immune system did not produce the protective cell populations found in patients with mild Covid-19.
The latter patients showed a coordinated pattern of interferon-stimulated gene expression. Patients with severe cases produced very high anti-SARS-CoV-2 antibody titers and had lower viral loads compared to mild disease, but also produced antibodies that block production of cells that express interferon-stimulated genes.
Overviews of antibody responses to infections
A paper in Cell Death & Differentiation gives a short overview of the antibody response induced by an infection. It also describes how monoclonal antibodies are produced, and the attempts to induce potently neutralizing antibodies by vaccination.
A primer on B cell memory was published in Immunity.
Using models to test vaccine prioritization strategies
A modelling study published in Science examined five vaccination strategies. It assumed that the vaccine would be approved for all age groups, but didn’t take account of non-age related differences in disease severity.
To minimise Covid-19 deaths the modelling showed that vaccinations of those 60 years and older should be prioritised. To minimise virus transmission, priority should be given to 20-49 year olds. Targeting those who were seronegative marginally improved impact, while reducing inequities.
Encouraging early signs for effectiveness of Pfizer vaccine in Israel
Preliminary results (reported in a Nature news item) from Israel (based on 200,000 vaccinated older people) indicate that people over 60 receiving the Pfizer-BioNTech vaccine are 33% less likely to test positive for the virus two weeks after the first shot than people who had not been vaccinated.
Allergic reactions to Pfizer’s and Moderna’s vaccines are rare
A report in JAMA Network identifies that out of 1,893,360 people receiving the first dose of the Pfizer-BioNTech vaccine there were only 21 reported cases (0.001% or 11 cases per million doses administered) of anaphylactic reaction to it.
The US CDC reports that out of 4,041,396 people receiving the first dose of the Moderna vaccine there were just 10 cases of anaphylaxis (0.0002%, or 2.5 cases per million doses administered), nine of which happened within 15 minutes of vaccination. No deaths due to anaphylaxis were reported in either study.
Ability of the immune system and vaccinations to control new variants
Several studies have appeared over the last week that look at the immunity implications of the UK (B.1.1.7) and South African (B.1.351) viral variants. (See also last week’s tracker for other studies).
The papers examine how well antibodies from earlier infections, monoclonal antibodies, and/or plasma from vaccinated people are able to neutralise new variants (or pseudoviruses with some of the mutations) compared to earlier variants.
A limitation is that these studies have tested plasma from relatively few people, so results may change as more tests are conducted.
While reduced abilities to neutralise variants may seem concerning, in some cases the decline in immunity still appears adequate to control infections.
Derek Lowe’s blog post published by Science Translational Medicine explains the significance of some of the recent papers. He emphasises that “it definitely looks like vaccination can still handle the variant forms of the coronavirus that we are seeing – but that we also have to be on our guard.”
Earlier infections may provide less protection against new South African variant
A not yet peer-reviewed paper found that antibodies from earlier infections were less effective at neutralising two B.1.351 variants (called 501Y.V2 in the paper). Sera from only six people were tested. Samples from different people showed different levels of reduced neutralising activity, ranging from six to 200 fold, with one sample showing no neutralisation ability against B.1.351.
Moderna’s vaccine able to neutralise UK and South African variants
Testing sera from small numbers of people and other primates vaccinated with Moderna’s vaccine demonstrated that neutralising antibodies in the sera remain effective against pseudoviruses that have the spike mutations seen in the B.1.1.7 variant. Pseudoviruses use parts of other viruses to present particular parts of the SARS-CoV-2 in laboratory tests.
When tested against pseudoviruses with some or all of the mutations seen in the B.1.351 variant serum samples demonstrated lower neutralising activity, but they could still neutralise the viruses. The study has not yet been peer-reviewed.
Pfizer’s vaccine may have reduced neutralisation ability for the UK variant
A pre-print paper reports the results of testing the neutralising ability of sera from 23 people who had received the first dose of the first Pfizer/BioNTech vaccine. The study also tested immune responses to pseudoviruses that had some or all of the mutations in the spike protein seen in the UK variant. Experiments were done using a cell-based assay. Sera from people under 80 showed strong neutralisation activity against a pseudovirus that had the SARS-CoV-2 “wild type” spike protein.
The serum samples showed a similar ability to neutralise a pseudovirus with three of the spike mutations found in the UK variant. However, neutralisation activity decreased by up to six fold when tested against a virus will all eight of the B.1.1.7 spike protein mutations.
Another study (in pre-print) tested the sera from 20 people who received both doses of the Pfizer/BioNTech vaccine. Three engineered viruses that contained some of the spike mutations seen in the UK and/or South African variants were challenged. Small effects on neutralisation were observed.
All of the last three studies above involved pseudoviruses, which may respond differently than actual SARS-CoV-2 variants. The authors of all three note that more research is required to understand the impacts of viral variants and vaccine effectiveness outside of the lab.
Indian vaccine shows effectiveness against UK variant
Another small study (not peer-reviewed) tested sera from 38 people vaccinated with an inactivated SARS-CoV-2 vaccine that is under development (BBV152/COVAXIN). It showed similar neutralisation ability against the UK variant as against another variant present in India.
Mutations in UK and South African variants reduce antibody neutralisation abilities
Another not yet peer-reviewed study reports that the B.1.1.7 variant is “modestly” more resistant to neutralisation by plasma from convalescent patients (about 3 fold) and plasma from people who had received the Moderna or Pfizer vaccines (about 2 fold). Out of 20 convalescent plasma samples, 11 showed a decrease in neutralisation potency.
This study also tested the effectiveness of monoclonal antibodies (some of which are in use as treatments). Ten of 12 monoclonal antibodies were as effective against B.1.1.7 as earlier variants. The authors consider that the reduction in neutralisation ability against B.1.1.7 may have little impact on immune evasion or vaccination.
However, they were concerned about the greater ability of the B.1.351 variant to avoid neutralisation. Five of the monoclonal antibodies that target either the N-terminal domain or the receptor binding domain of the spike protein had greatly reduced potency.
The B.1.351 variant also demonstrated greater resistance to neutralisation by convalescent plasma (about 11-33 fold) and sera from vaccinated people (about 6.5-8.6 fold). The authors attribute the higher level of resistance to the E484K mutation seen in both the B.1.351 variant and some other variants (such as the Brazilian B.1.1.28 (or P1) variant).
Moderna and Pfizer have stated that they will be developing new booster shots of the vaccines that target newer variants.
Young people less likely to become infected
An analysis from the CDC shows that in the US children and adolescents (up to 17 years old) have had lower incidence and fewer severe Covid-19 than adults. Just over 16% of infections in the US were in young people 14-17 years old, while younger age groups accounted for 7 to 10% of cases. The CDC suggests that the risk for reopening child care centres and primary schools might be lower than opening highschools and tertiary institutions, but good infection mitigation practices will still need to be followed.
The analyses were done before the spread of the new variants.
Men more at risk than women
A large study of 96,473 individuals in the US, published in PLOS ONE, found adult males were more likely to develop complications from Covid-19. 14,992 (15.6%) tested positive for SARS-CoV-2, of whom 4,785 (31.9%) were hospitalized and 452 (9.5%) died. Independent of age men were more likely to test positive, and if hospitalised were more likely to develop complications, require ICU admission and mechanical ventilation, and to die. Men had about a 45% greater risk of dying in hospital than women. Comorbidities and high-risk behaviours do not explain the difference. (See last week’s tracker for a paper on potential reasons for this disparity).
NZ public toilets lacking good hand washing facilities
A New Zealand study (not yet peer-reviewed) of 400 public toilets found that 2.5% had no water for hand washing and 14.8% had no soap. Less than 30% of the toilets had no-touch hand-washing devices. Health messaging can also be improved in public toilets.
Spike protein able to bind to a broad range of mammalian ACE2 proteins
The ACE2 proteins of 22 mammal and bird species were tested in cell assays to see how well they bound to SARS-CoV-2. The research, published in PLOS Biology, found that bat and bird ACE2 proteins didn’t bind as strongly, while dog, cat, and cattle ACE2 proteins showed strong affinity. The authors conclude that the virus may developed the stronger affinity for ACE2 in an intermediate host before infecting people. The results also suggest the potential for the virus to infect a wide range of companion animals, livestock, and wildlife.
However, the authors note that while their assay shows strong binding in some species, it has proven harder to infect some of the species (such as dogs and pigs) experimentally.