Vaccine-related papers

Effectiveness of a fourth Pfizer dose in the over 60s

Further research from Israel on a fourth Pfizer/BioNTech dose found a substantial reduction in risk of dying, compared with three doses, in those over 60. The adjusted hazard ratio was calculated to be 0.22, indicating a 78% reduction mortality rate for those infected after 4 doses.

The fourth dose was given at least four months after the third. Over 300,000 people received four doses in the study, and infection rates (from Omicron) were very high. Participants were monitored up to 40 days after the fourth dose. The paper has not yet been peer reviewed.

Eric Topol summarises recent studies on effectiveness of four doses in his Ground Truths newsletter.

Effectiveness against Omicron of three doses in the UK

In the UK the effectiveness against symptomatic infection from Omicron two to four weeks after a third dose ranged from 60% to 75%. Beyond 15 weeks effectiveness was 25% to 40%. Similar results were seen when either Pfizer/BioNTech or Moderna was the third dose, regardless of which vaccine (Pfizer, Moderna, or AstraZeneca) was originally given.

Effectiveness against hospitalisation for 18-64 year olds following an Omicron infection peaked at 82.4% shortly after a third dose and fell below 54% by 15 weeks. Effectiveness was higher for those 65 and older, going from 92.4% down to 76.9% after 15 weeks. The difference in effectiveness between older and younger hospital patients is, according to the report, likely to be due to how hospitals classify the cause of hospitalisation for different age groups.

The assessments were made in the UK Health Security Agency’s latest weekly Covid-19 vaccine surveillance report.

Pfizer vaccine effectiveness against Omicron in children

A study of 5-to-11 year olds found that the Pfizer/BioNTech vaccine reduced the risk of hospitalisation from the Omicron variant by two thirds. For 12-to-18 year olds, the vaccine was less effective in preventing hospitalisation following an Omicron infection (40%) than for the Delta (93%) variant. However, the risk of more critical symptoms was similarly low for both variants after vaccination.

Direct comparisons between under and over 12 year olds can’t be made. For the under 12’s, the hospitalised participants had received a second dose about one month before, while in the older adolescents the interval was on average five months. The vaccine formulation for younger children also differs from that given to the older age groups. The study included nearly 1,200 adolescents with Covid-19 and 1,600 without. The paper was published in the New England Journal of Medicine.

Potential differences in neutralisation of three Omicron subvariants after three Pfizer doses

Neutralisation of the BA.1, BA.2 and BA.3 variants after three Pfizer doses was 3-to-6-fold lower than for the original Wuhan strain, a study reports. Neutralising ability was assessed one month after the third dose. The BA.3 variant was less well neutralised than BA.1 and BA.2, although variation between serum samples was high. However, the authors recommend that close attention should be given to the BA.3 subvariant.

The BA.3 subvariant is currently not very common. The experiments were done by introducing the variant spike proteins into a modified virus, and testing frozen sera so the results may not be generalisable. Only a small number of serum samples were tested. The paper has not yet been peer reviewed.

BA.2 subvariant may be more strongly neutralised than BA.1

A small study in Hong Kong found that neutralisation of BA.2 was usually higher than BA.1. This was seen for sera from people with prior infections, and those who were vaccinated. However, the differences weren’t always statistically significant. The authors conclude that the high level of transmission seen for BA.2 must be due to factors other than immune escape. The paper was published in The Lancet Microbe.

More durable humoral immune response seen with prior infection followed by vaccination

Compared with uninfected vaccinated people, a prior infection followed by vaccination leads to a more durable humoral immune response. Antibody and memory B cells were monitored for up to six months after participants received two mRNA doses.

Antibodies targeting the receptor binding domain and the spike protein declined more over six months in the uninfected (“naive”) participants. A prior infection followed by vaccination may also provide a stronger immune response against subsequent variants of concern.

The Pfizer/BioNTech and Moderna vaccines generally generated similar immune responses. However, the Moderna vaccine led to a faster rise in the spike-specific IgG response, and may generate a broader suite of antibodies than the Pfizer vaccine.

The study was small, involving only 27 naive and 40 previously infected people. Consequently, further research is needed, especially in comparing immune responses to the  two vaccines. The paper was published in Cell Reports Medicine.

Subtle immune response differences between Pfizer and Moderna vaccines

There can be subtle immune response differences between the Pfizer/BioNTech and Moderna vaccines. Differences were found in both the abundance of particular antibodies, and functional differences in particular antibody types.

It is uncertain at the moment whether, or how, these differences affect the level or type of protection. What aspects of the vaccines may be involved in the immune differences is also uncertain.

Participants in the study were mostly healthy young female health care workers. The paper was published in Science Translational Medicine.

Non-vaccine-related papers

A potential new Covid-19 therapy

A new small compound can block SARS-CoV-2 infection of lung cells. Unlike other therapies which target the virus, this compound disrupts a human protease which is used by the virus for cell entry. The compound is a three amino acid peptide that binds to the protease, stopping the virus from interacting with it, and subsequently preventing virus-cell fusion.

Tests of the compound in cultured cells and mice indicate that very small doses are effective at reducing infections, and it works for a variety of variants of concern. In mice the compound when given within hours of an infection, reduced weight loss and other symptoms, and completely prevented death from infection. Only small numbers of mice were used in the experiments. The paper was published in Nature.

Ivermectin not found to benefit people with early stage Covid-19

A randomised controlled trial found that ivermectin taken soon after infection does not reduce the risk of hospitalisation. The paper was published in the New England Journal of Medicine.

Co-infection with other respiratory viruses may increase risk of death with Covid-19

Co-infection of SARS-CoV-2 and another respiratory virus can be associated with a greater risk of death. In the study co-infection was found in 8% of nearly 7,000 patients. Influenza or respiratory syncytial virus or adenoviruses were the other viruses detected.

Greater mortality was found in patients co-infected with SARS-CoV-2 and influenza, compared with only having SAR-CoV-2. Having influenza plus the SARS-CoV-2 virus also increased the risk of requiring mechanical ventilation.

Co-infection with adenovirus was also associated with greater mortality, but only in some of the analyses. Vaccination status for influenza was not recorded, and the study began before Covid vaccination programmes began. The paper was published in The Lancet.

Infected people could have several distinct viral strains

People infected with SARS-CoV-2 could be co-infected with other variants. Co-infections may in part explain the severity of some symptoms in some patients, the authors suggest.

The study is based on both modelling and sampling from patients. Analysis of genomes in databases identified single nucleotide polymorphisms. Simulations indicated that individual cases in the databases consisted, on average, of just over 3 variants. That is, they had sequences that differed by several single nucleotide polymorphisms. Modelling indicated these were more likely to be generated by separate viruses than by mutations from a single virus.

Sequencing 42 patients with Covid-19 identified 20 with polymorphisms that suggest co-infections. Further research is needed to establish that these are co-infections, and how prevalent they may be. The paper was published in the Computational and Structural Biotechnology Journal.

Dogs may be able to sniff out long Covid

A small study found that dogs could sometimes distinguish people with long Covid symptoms. Sweat samples were collected from 45 people with long Covid and from 188 uninfected people. Two dogs that had previously been trained to detect SARS-CoV-2 were used.

Half of the samples from participants with long Covid were identified by the dogs, while the dogs did not respond to any of the uninfected samples. The results suggest that Covid antigens may persist in some patients with long Covid.

Sample quality will have varied because participants took their own samples at home. Larger scale testing is required to determine if the method is sufficiently accurate and reliable. The paper was published in the Journal of Clinical Trials.

‍