Coronavirus Research Tracking - 16 April
Adverse vaccine reactions, updated vaccines, vaccine effectiveness, differences between variants, Covid-19 mortality
This Research Tracker includes reports on adverse vaccine reactions, early trials of a modified Moderna vaccine, vaccine neutralisation abilities, differences in vaccination rates between groups, pathogenicity of B.1.1.7 and P.1 variants, influence of race and gender on Covid-19 mortality, and a world mortality dataset
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Potential adenovirus-based vaccine link to rare blood clot risks
A case study published in the New England Journal of Medicine describes thrombosis and thrombocytopenia in a woman who received the Johnson & Johnson/Janssen Ad26.COV2.S vaccine. The symptoms appeared 14 days after vaccination, and the patient was still in critical condition at the time of publication.
The authors note that these rare thromboses have been reported for the AstraZeneca and Johnson & Johnson vaccines, which are both adenovirus-based vaccines. The possibility of a link between these types of vaccines and the condition needs further research.
New Zealand’s Medsafe is seeking additional information about the Janssen vaccine.
Medsafe reporting on adverse reactions to local Covid-19 vaccinations
Medsafe has started publishing overview reports of adverse reactions to Covid-19 vaccinations in New Zealand. Their 14 March report lists 215 adverse events so far (out of more than 22,000 doses), with six rated as serious. The serious cases include allergic reactions, and reactogenicity reactions. No potential safety issues have yet been identified.
Two updated forms of the Moderna vaccine do well against B.1.351 variant in mice trials
Updated versions of Moderna’s mRNA vaccine adapted for the B.1.351 variant show improved neutralisation of that variant in mice. One version has the B.1.351 spike protein sequence, and the other vaccine is a combination of the original mRNA and the B.1.351 version. The latter updated vaccine produced better neutralisation against a range of variants.
Tests also demonstrated that giving a the B.1.351 version as a booster after the original two dose vaccine also improved neutralisation activity. A limitation in the research is that mouse immune responses to the B.1.351 variant were not the same as for humans, so further research on other animals (such as hamsters and macaques) is required before proceeding to human trials. The paper has not yet been peer reviewed.
Two Chinese vaccines show good ability in neutralising B.1.351 variant
A letter in The Lancet Microbe reports that Sinopharm’s BBIBP-CorV and ZF2001 (from the Chinese Academy of Sciences) show only a slight decrease in their ability to neutralise the B.1.351 variant. The study tested sera from 24 vaccinated people and used live viruses rather than pseudoviruses.
Pfizer vaccine weaker at neutralising B.1.351 variant
Another study, using pseudoviruses, has demonstrated the effectiveness of the Pfizer/BioNTech vaccine in neutralising the wildtype and B.1.1.7 variants. Sera from vaccinated people showed stronger neutralisation ability than sera from previously infected patients.
Neutralisation of the B.1.351 variant was 6.8-fold lower. Experiments also confirmed previous studies that link resistance to neutralisation to the E484K mutation, and to a lesser extent K417N mutations. The paper was published in Cell Host & Microbe.
Moderna and Pfizer vaccines less able to neutralise P.1
The P.1 variant is more resistant to neutralisation by sera from 20 convalescent patients and 22 people vaccinated with either the Moderna or Pfizer vaccines. Resistance to neutralisation was also observed from some monoclonal antibodies.
The experiments used both pseudoviruses and authentic viruses. Pseudoviruses showed a greater resistance to neutralisation than the authentic viruses for convalescent sera, but not for vaccinee sera.
The E484K mutation appears to be the main factor involved in this resistance. The difference in resistance seen by P.1 and B.1.351 is probably due to mutations in the N-terminal domain of the spike protein. The paper has not yet been peer reviewed.
Field study demonstrates Pfizer vaccine is more effective against B.1.1.7 than B.1.351
Most of the studies on variant immune avoidance have so far been assessed by cell-based assays. A new case controlled study of vaccinated and unvaccinated people in Israel confirms that fully vaccinated people (with the Pfizer vaccine) are more likely to be infected by the variant B.1.351 than B.1.1.7 or earlier variants. However, infection with the B.1.1.7 variant was higher up to one week after receiving the second vaccine dose, so decisions to delay the second dose should be carefully considered. The study has not yet been peer reviewed.
A limitation of lab-based assessments of vaccine neutralisation of variants is that they do not assess disease severity. Earlier research reported in the Tracker finds that the leading vaccines do reduce disease severity for those who subsequently become infected with B.1.351.
Pfizer vaccine reduces asymptomatic infections
A study of 9,000 healthcare workers in the UK found that the first dose of the Pfizer/BioNTech vaccine led to a four-fold reduction (from 0.8% to 0.2%) in asymptomatic infections 12 or more days after the vaccination. The authors suggest that this may result in reduced transmission after the first vaccination dose, though masks and other precautions should still be taken. The research was published in eLife.
Vaccination rates in England vary due to ethnic, socio-economic and mental health factors
An analysis of England’s NHS patient records found that there is considerable group variation in who has been vaccinated so far. Of the nearly 21 million vaccinated (out of 58 million patient records), substantially more white than black people have been vaccinated, and a lower proportion of the most deprived had been given vaccines. People with mental illnesses or learning disabilities were also under-represented in vaccination figures. The authors recommend greater targeting is required to improve vaccination rates in these undr-represented groups. The paper has not yet been peer reviewed.
Don’t stop social distancing straight after vaccination
A short communication in The Lancet Infectious Diseases uses a simple model to illustrate that an important measure to reduce the risk of SARS-CoV-2 escaping vaccine control is to keep the number of cases low. So, the article recommends that non-pharmaceutical interventions shouldn’t be removed quickly after a vaccination campaign.
Pre-existing T cells cross react with SARS-CoV-2, and are reactivated by Pfizer vaccine
Pre-existing CD4+ T cells can cross-react with the SARS-CoV-2 virus, and they are reactivated following the first dose of the Pfizer/BioNTech vaccine. The T cells were generated in response to earlier human coronavirus infections. Cross-reactivity was found to decline with age. The authors suggest that this cross-reactivity may explain why many have milder Covid-19 and why a single vaccine dose can often show high levels of effectiveness. The paper, from a German research consortium, has not yet been peer reviewed.
Asymptomatic infections linked to more balanced and coordinated immune response
People with asymptomatic infections develop an efficient and balanced antiviral response that provides protection without significant disease. The study found T cell responses between asymptomatic and symptomatic people were similar, except that interferon gamma (IFN-γ) and interleukin 2 (IL-2) were higher in asymptomatic cases. Asymptomatic patients also had more coordinated production of proinflammatory and regulatory cytokines. The research was published in the Journal of Experimental Medicine.
Mouse monoclonal antibodies developed that are effective against a range of variants
A study, not yet peer reviewed, created monoclonal antibodies in mice and found some were effective against a range of receptor binding domain variants. Some were able to reduce viral levels in infected mice and 12 out of 14 could neutralise both the B.1.1.7 and B.1.351 variants.
B.1.1.7 does not appear to be more pathogenic
The B.1.1.7 variant, while more transmissible, is not more pathogenic than earlier variants. The study of over 36,000 Covid app users in the UK also did not find that reinfection rates of the B.1.1.7 variant were higher than for other variants, indicating that high levels of immunity are generated against this variant. The research was published in The Lancet Public Health.
A cohort study of around 340 hospitalised patients also reports that the B.1.1.7 variant does not cause more severe disease. Those infected with B.1.1.7 have higher viral loads, which may in part explain the variants higher level of transmissibility. Patients with the B.1.1.7 variant were generally younger (under 60) than those who were infected with other variants. The research was published in The Lancet Infectious Diseases.
There have been conflicting results from studies of whether the B.1.1.7 variant causes more severe disease. An associated comment in The Lancet Infectious Diseases discusses the factors that contribute to different conclusions from different studies.
Showing where the mutations are in variants
Another useful graphical representation of the mutations in variants.
Brazilian failures in controlling the pandemic
An article in Science analysed the spread of Covid-19 in Brazil and concludes that overall there was a failure in implementing prompt, coordinated and equitable responses. This led to high and unequal infection and mortality rates.
Modelling of infections in Brazil estimates that the P.1 variant is 1.7 to 2.4-fold more transmissible than previously circulating variants. The study also estimated that a previous infection provides only 54-79% of the protection against P.1 as for non-P.1 variants in Brazil. P.1 most probably emerged in Manaus in chronically infected patients or immuno-compromised people. The research was published in Science.
Race as well as gender affect Covid-19 mortality
An analysis Covid-19 mortality in Georgia and Michigan the US found that sex disparities are not the same across different racial groups. Usually it is stated that men are at greater risk than women. However, the mortality rate for Black women in these states is higher than for White and Asian men. The paper highlights how race and gender influence outcomes, and the limitations of simple forms of reporting. The research was published in the Journal of General Internal Medicine.
World Mortality Dataset
A World Mortality Dataset has been created to estimate excess deaths due to Covid-19. A paper describing the dataset notes that countries differ in their accuracy of reporting. Overall, they estimate that the actual death toll may be 1.6 times higher than reported numbers indicate. The paper has not yet been peer reviewed.
Preparing for the next pandemic
A news article in Nature notes that previous warnings for pharmaceutical companies to develop and stockpile antiviral drugs. Traditionally there has been a “one bug, one drug” approach, but that needs to change to development of broader spectrum antiviral drugs. This is challenging, but a coalition or organisations is now working to develop broad spectrum therapies against coronaviruses and influenza viruses. The article also describes the variety of ways to thwart viruses.