Delta variant set to dominate at the Olympics

A paper predicts that the Delta variant will become the dominant form of the virus in Japan in early July. This is based on estimates of the reproductive rates of several variants currently circulating in Japan. The study calculated that the Delta variant has 1.356 times higher transmissibility than the Alpha variant there. The paper has not yet been peer reviewed.

Vaccinations holding off severe Covid-19 in the UK

The UK government’s 1 July Coronavirus update shows that while infections are increasing again (largely due to the Delta variant), hospitalisations and deaths are showing more modest increases. The lower levels of serious Covid-19 cases is attributed to vaccination. Eighty five per cent of their adult population have had at least one vaccine dose, and two thirds are now fully vaccinated.

Vaccine effectiveness against variants

After two doses the Pfizer/BioNTech vaccine can generate very high levels of antibodies, suggesting even reduced neutralisation activity against some variants still provides protection.

A study of 180 vaccinated Finnish healthcare workers found that neutralisation of the Beta variant is five-fold lower than for the Alpha variant and an earlier strain. However, neutralisation concentrations were still much higher than seen for unvaccinated people who had relatively mild Covid-19, and so some degree of protection is expected. The paper was published in Nature Communications.

The AstraZeneca/Oxford vaccine generates lower levels of neutralising antibodies against a range of variants, compared to the BioNTech/Pfizer vaccine. This probably makes it less effective against preventing infection from variants of concern. However, it is uncertain at this stage whether severity of disease or mortality risk will be affected. The paper was published in The Lancet.

Sera from people who had received both doses of the Moderna vaccine showed little reduction in neutralisation activity against the Alpha variant. The Beta, Delta and Gamma variants showed greater reductions (2 to 8-fold) in neutralisation compared to “wild type” SARS-CoV-2. The greatest reductions were seen for the Beta variant and a variant of interest (A.VOI.V2) first identified in Angola.

Vaccine effectiveness was not measured, but the authors (who work at Moderna) consider that the high antibody levels generated by the vaccine mean that the vaccine should still be effective against the variants. The paper has not yet been peer reviewed.

The Delta variant has significantly reduced neutralisation from sera obtained from recipients of the Pfizer/BioNTech and AstraZeneca/Oxford vaccines. Neutralisation activity was reduced four-to-five fold for the B.1.617.1 and B.1.617.2 (Delta) variants, compared to an early Wuhan isolate. This reduction is slightly lower than that seen for the Beta variant.

The AstraZeneca/Oxford vaccine produced lower neutralising antibody levels than the Pfizer/BioNTech vaccine. However, hospitalisation rates of vaccinated people are remaining very low, so reduced antibody and neutralisation levels still provide some protection. The paper has not yet been peer reviewed.

Uncertainty over whether Alpha variant causes more deaths

The Alpha variant (B.1.1.7) is associated with more serious disease, but it is still uncertain if it leads to greater mortality. The authors of this study note that it only involved 60 patients, and they estimate that at least 234 for each group is desirable to assess the differences in mortality between the Alpha and earlier variants. The paper was published in The Lancet Infectious Diseases.

Novavax trials very promising

In a trial involving 14,000 participants the Novavax vaccine showed  89.7% protection against SARS-CoV-2 infection, and had high efficacy against the Alpha variant (86.3%, compared to 96.4% for non-Alpha). Following the first and second doses headache, muscle pain, and fatigue were common symptoms, but there were no serious adverse effects to the vaccine. The paper was published in the New England Journal of Medicine.

Effects of age on Pfizer/BioNTech vaccine effectiveness

In Israel the effectiveness of the Pfizer/BioNTech vaccine was very high, although slightly lower for over 75’s, and those with hypertension, diabetes or obesity. The study of 1.6 million people, aged over 16, found that overall the adjusted vaccine effectiveness for protection was 93.0% for infection, 93.4% for hospitalisation, and 91.1% for mortality.

For people over 75 effectiveness against infection was 81%. In people with hypertension, diabetes or obesity vaccine effectiveness in preventing infection was 89-90%. The vaccine effectiveness values were slightly lower than those reported in previous studies, probably due to the broader types of people included in this study. The paper has not yet been peer reviewed.

A separate study also shows an age effect. People over 80 vaccinated with the Pfizer/BioNTech vaccine had much lower serum neutralisation and binding antibody abilities than younger people, probably placing them at greater risk of infection.

The ability to neutralise the Alpha, Beta and Gamma variants in the over 80s is also much lower than for a wild type version of the virus, particularly after only one vaccine dose. There was, though, detectable neutralisation of these variants after older people had received the second vaccine dose. The paper was published in Nature.

Evidence for longer term protection following vaccination

More evidence is emerging of longer term protection following immunisation. In one paper high frequencies of spike protein-binding germinal centre B cells and antibody secreting plasmablasts were found in lymph nodes for at least twelve weeks after the second dose of the Pfizer/BioNTech vaccine. These cells generate more antibody producing cells during reinfection, so provide long lasting immune responses.

The study only involved 14 patients, and the persistence of T follicular helper cells that stimulate the germinal centres still needs to be investigated. The paper was published in Nature.

Evidence of long-lasting immune memory is also provided by a South Korean study of 101 patients. Memory T cell responses specific to Covid-19 were maintained for at least 10 months after infection. Memory T cells were found in patients regardless of the severity or presence of Covid-19 symptoms. The paper was published in Nature Communications.

Viral mutations and T cell recognition

A paper highlights that the relatively few studies of T cell responses to SARS-CoV-2 makes assessing immune responses incomplete. This study showed that a single specific amino acid change in the viral spike protein results in a loss of recognition by CD8 T cells that target a common viral epitope. To reduce risks of vaccine escape the researchers advocate for the development of vaccines that target multiple viral proteins, or several variants of the spike protein. The paper has not yet been peer reviewed.

In a separate study CD8 T cell epitopes that showed limited mutation across a range of coronavirus spike proteins were identified. These can help inform the development of a pan-coronavirus vaccine. The paper was published in Cell.

The benefits of being vaccinated after being infected

Two more studies have shown the significant boost in neutralising antibody levels that people with previous infections see after one vaccine dose.

Pre-vaccination sera from recovered Covid-19 patients neutralised the Wuhan-Hu-1 variant (from early in the pandemic) and sporadically neutralised the Beta variant (B.1.351). After receiving a single dose of either the Pfizer/BioNTech or Moderna vaccine their sera had neutralising titres against all variants (and SARS-CoV-1) elevated by up to 1000-fold. The second vaccine dose did not significantly elevate neutralising antibody levels. The paper was published in Science.

Similarly, in a second study a single dose of the Pfizer/BioNTech vaccine substantially boosted immune responses in healthcare workers previously infected with the early Wuhan viral variant. T cell and memory B cell responses were enhanced, and neutralising antibodies were effective against the Alpha and Beta variants. In contrast, workers who had not been infected but had one dose of the vaccine showed poor neutralisation ability against these variants, and T cell responses were variable. The paper was also published in Science.

A perspective on these two papers was also published in Science, although only the summary is free to access.

Vaccination alone won’t get rid of the virus

Modeling by Te Pūnaha Matatini suggests that for more infectious Covid-19 variants very high levels of vaccination will be required to achieve “herd immunity.” For protection against the Alpha variant they calculate 83% of the population would require vaccination, while 97% would be needed to stop the spread of the Delta variant.

The model assumes that few other public health measures are in place to control spread, which is not likely to be the case. This means that actual vaccination levels could be lower and outbreaks could still be controlled when combined with other public health measures.

The model doesn’t yet take account of unequal access to vaccines, differences in health outcomes between different groups or communities, or changes in immunity over time. The model will be further refined to inform policy. The paper has not yet been peer reviewed.

Correlates of protection

High levels of particular IgG antibodies and neutralisation antibody titres were found to be indicators of protection from mild symptomatic infections. The study, which analysed sera from 171 vaccinated participants who subsequently became infected and 1404 who didn’t, assessed efficacy of the vaccine 28 days after the second dose. Values for the specific antibody levels and neutralisation titres that provide 80% vaccine efficacy against symptomatic infection were calculated.

Antibody levels were found not to be a good predictor of protection against asymptomatic infections. The authors suggest that the antibody and neutralisation values they determined could be applied to other vaccines to estimate effectiveness, though this needs to be tested. The paper has not yet been peer reviewed.

Different trajectories of immunity

More sophisticated sampling of immune responses following infections is revealing the individual variability in these responses, and the implications for immunity to subsequent infections and variants.

A study in the UK analysed a range of immune response features for six months from 78 UK healthcare workers. Both humoral and cellular responses were monitored, and high and low immune responding groups were identified. For people with asymptomatic infections their immune responses were generally low after infection. This may make them more susceptible to reinfection (though this wasn’t tested). For symptomatic infections immune responses were often stronger early on.

Modelling identified “high responders” who are likely to have durable and protective immunity for at least six months after infection. These high responders showed strong responses for a range of antibody properties, along with strong T cell responses. The paper suggests that immune responses early in the infection may prime the immune system for one of several trajectories which determines subsequent levels of protection. The paper has not yet been peer reviewed.

Post-Covid effects

Studies of  long Covid have tended to focus more on people who have had moderate or worse symptoms a recent paper suggests. It studied 242 patients who had relatively mild symptoms. It found that fatigue, myalgia, decreased appetite and sleep disturbances were reported by at least 20% of the participants three months after having Covid-19. Females and those with comorbidities were much more likely to report some of the post-infection symptoms. The paper was published in Scientific Reports.

Covid-19 increased the risk of fatigue and sleep problems, but not mental illnesses, a UK study of 226,000 people has found. An increase in mental illnesses (or what the paper refers to as psychiatric morbidity) was not strongly associated with infection because increases were also seen in those who were not infected. The pandemic has, though, resulted in a large increase in the rate of psychotropic drug prescriptions, particularly for antipsychotic and benzodiazepine medications. The paper has not yet been peer reviewed.

How SARS and Covid-19 disrupt lung cell gene expression

A News and Views article in Nature summarises a paper describing changes in lung epithelial cell gene expression when they are infected with SARS-CoV-2 or SARS-CoV-1. It notes similarities in how these two viruses can escape immune responses, and also how the results identify potential antiviral compounds.

Different risk factors are associated with severe Covid-19 and with Covid-associated death

Patient characteristics most strongly associated with being admitted to intensive care with Covid-19 may not be the same as those that pose the greatest risk of dying from Covid-19. A  study of patients in England found that obesity was the comorbidity that posed the highest risk for admission to an intensive care unit, but did not seem to have a significant influence on mortality. Several factors related to clinical practices may explain this.

Deaths due to Covid-19 were found to be more strongly associated with immunosuppression due to disease, type-2 diabetes, chronic respiratory disease, increasing age. Males were more likely to be admitted to ICUs and to die. The paper was published in PLOS Computational Biology.

Another promising point-of-care test being developed

A rapid point-of-care test that detects several SARS-CoV-2 proteins was found to have high sensitivity and specificity. Using microfluidics it detects antibodies targeting the spike S1 and nucleocapsid proteins, and the receptor binding domain. The paper was published in Science Advances.

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It is easy to get swamped by all the research on coronavirus. New Zealand’s Science Media Centre is keeping track of much of it so you don’t have to. The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre New Zealand.

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