Vaccine-related papers

Comparing the effectiveness of three vaccines

An Argentinian study compared the effectiveness of three vaccines, rAd26-rAd5 (Sputnik V), AstraZeneca/Oxford, and BBIBP-CorV (Sinopharm), in those over 60. The Sputnik and AstraZeneca vaccines were more effective in reducing the risk of infection than the Sinopharm vaccine.

All showed a high level of effectiveness in preventing death from Covid-19, with the Sinopharm being slightly less effective (85%, compared with 93- 94%).

The vaccines were less effective in older people, especially those over 80. The Sputnik and AstraZeneca are viral vector vaccines, while the Sinopharm is an inactivated virus vaccine. All are two dose vaccines. Two doses substantially increased effectiveness against infection, but a single dose provided at least 80% effectiveness against dying. The paper was published in The Lancet.

A comment on the study was also published in The Lancet.

Two or three Pfizer doses effective in preventing hospitalisation in over 70s

A Finnish study found vaccine effectiveness against hospitalisation was still high (87%) in those over 70 up to three months after a second dose. Most had received the Pfizer/BioNTech vaccine. Effectiveness increased to 96% two months after a third dose. Effectiveness against ICU admissions was similarly very high (above 90%) for two and three doses.

In Finland the second vaccine dose was given 12 weeks after the first, so a larger gap than most other countries. The paper has not yet been peer reviewed.

Four doses may be more effective for older people

In Israel a fourth Pfizer/BioNTech dose resulted in a two-fold lower rate of infection in older people than in those who had received three doses. The risk of developing severe symptoms was four-fold lower.

The fourth dose was given at least four months after the third, and effects assessed 12-23 days after vaccination. The longer term protection provided by a fourth dose is still to be assessed. The paper has not yet been peer reviewed.

However, a small study of Israeli healthcare workers indicates that maximum immunogenicity is generated by three mRNA vaccine doses, with a fourth dose only restoring antibody levels. Neutralising antibody levels three weeks after the fourth dose reached similar levels as peak levels after the third dose. Viral loads in those infected after a fourth dose were often high.

Only 174 healthcare workers received a fourth dose in the study. T cell responses were not investigated. Participants were relatively young and healthy, so the results may not be generalisable. The paper was published in the New England Journal of Medicine.

Vaccines effective in 5-to-11 year olds

Data from the US CDC indicates that unvaccinated 5-to-11 year olds are three times as likely to have Covid-related hospitalisations as those which had received two vaccine doses. Greater protection is seen for vaccinated adults.

Why hybrid immunity can be more effective

People infected and subsequently vaccinated have a different immune profile than those who are vaccinated and not infected. When looking at antibody responses after two mRNA vaccine doses the previously infected have greater quantities of receptor binding domain-specific plasma antibodies that are better able to neutralise a range of viral variants. They also have more of certain types of memory B cells. These differences are reduced or disappear after a third vaccine dose.

However, distinct T cell types produced by infection are not generated by vaccination even after three doses, and this may count in part for the stronger protection against symptomatic infection often generated from hybrid immunity.

The study only looked at immune cells in peripheral blood, and responses only three weeks after a third vaccine dose. Fifty four vaccinated people were included in the study. The paper was published in Cell.

Non-vaccine-related papers

Global Covid death toll may be three times higher than official estimates

While Covid-related deaths have been reported to be around 6 million, a study suggests that the actual number could be up to 18 million. This is based on an analysis of mortality reports from 74 countries in 2020 and 2021. Estimates of excess deaths that could be attributable to Covid-19 were then made. Country variability in reporting mortality data can affect the results. The paper was published in The Lancet.

The Economist magazine also examines excess deaths during the pandemic in many countries. It uses graphs and other visuals.

Immunological consequences of Covid-19

A review of what we know about the immunology and pathology of Covid-19 was published in Science. This is a “fill your boots” paper that summarises most current knowledge of the immune aspects of Covid-19, including long Covid.

Recombinations between variants

More papers are identifying, or inferring, recombinations between different variants or subvariants.

A US analysis of nearly 20,000 infections found 20 cases of co-infection of both the Delta and Omicron variants. In one of these cases there was evidence of recombination between the variants within the person (though it was rare among the genomes sequenced from that individual).

In addition, two independent cases of infection with recombinant viruses containing both Delta and Omicron mutations were found. They did not find these recombinants in any other samples, which the authors interpret as indicating lower transmissibility or viability.

The authors ruled out the possibility of sequencing artefacts for the recombinant genomes. The paper has not yet been peer reviewed.

And a French study reports three recombinant “Deltacron (or “Deltamicron”) infections. The paper has not yet been peer reviewed.

Another study reports that the sequences of many Omicron subvariants can have sets of mutations shared with other subvariants and with some other variants that don’t match their phylogenetic lineages. The authors interpret this as evidence of recombination, possibly involving co-infections.

However, recombination is inferred rather than proven. The effects of these recombinations, or mutations, are unknown. The paper has not yet been peer reviewed.

Viral mutations in breakthrough infections

Sequencing of the spike protein region from vaccine breakthrough infections identified a range of mutations. The patients were infected with the Alpha variant, but some of the mutations were those also subsequently seen in Delta, Iota or Omicron variants, despite the samples being taken in early 2021.  

Samples were obtained from five patients who had received two doses of the Pfizer/BioNTech vaccine. Most of the mutations were also seen in unvaccinated patients infected at about the same time. The paper was published in The Journal of Clinical Infection.

More virulent variants still possible

A paper suggests that the relatively milder symptoms often associated with the Omicron variant was coincidental, and that more dangerous variants may yet emerge. The variants identified so far demonstrate that considerable variation can emerge quickly, with newer variants of concern coming from different viral lineages. The paper was published in Nature Reviews Microbiology.

Long Covid relatively common in young people

Meta-analyses of studies on long Covid in young people found that 25% of them experienced long Covid symptoms. The most common symptoms were mood-related, fatigue, and sleep disorders.

Risk factors associated with developing long Covid were older age, female gender, severe COVID-19, overweight/obesity, allergies, and other long-term co-morbidities. Follow-up times in the studies ranged from one to 13 months.

Twenty one studies (all observational), involving 80,000 young people with Covid, were included. The authors identified that all the studies are subject to biases, including lack of standardised long Covid definitions, recall biases, misreporting, not always reporting vaccination status, and lack of follow-up. The paper has not yet been peer reviewed.

Mild Covid can lead to air bubbles in the lungs

Small pockets of air bubbles were found to block the lungs of people who had long Covid symptoms, regardless of the severity of their initial Covid symptoms. Between one quarter and one third of the lung was affected.

A small percentage (7%) of people who had not had Covid also had such blockages. One hundred people who had Covid symptoms lasting more than 30 days were involved in the study. The long term persistence and consequences of these blockages are unknown. The paper is to be published in the journal Radiology.

Longer lasting inflammation may follow mild Covid

Mild Covid can lead to longer lasting inflammatory responses, due to genetic imprinting effects on some types of macrophages. Inflammatory responses, mediated by monocyte-derived macrophages, were detected at 3-to-5 months after the infection, but had disappeared by 12 months.

Sixty eight people (median age 37) with mild Covid were included in the study. The paper was published in Mucosal Immunology.

Using blood cell membranes to deliver vaccines and therapies

A study has demonstrated that red blood cell membranes with SARS-CoV-2 spike proteins attached generate antibodies in mice. This method may result in fewer side effects than current vaccines, and could also be used to deliver other therapies.

It also may be quickly adaptable, the authors suggest, to new variants and viruses. Only three mice were used in the trial. The paper was published in PLOS One.

New therapeutic targets

One of the SARS-CoV-2 non-structural proteins may be a good target for antiviral therapies. This is based on a study of the protein’s structure, and identification of sites where inhibitors could disrupt its functions. The protein plays a role in proofreading the RNA during replication. Therapies have not yet been tested on it. The paper has not yet been peer reviewed.

A possible link between gut microbes and Covid-19 immune responses

A small study found that the microbial diversity in faecal samples was lower in people with Covid-19.  There was also lower abundance of species in the Bifidobacterium group (known to have anti-inflammatory properties) in those with Covid. Comparisons were made between people exposed to the virus but not infected, and those who had an infection (and with a spectrum of symptom severity) .

The authors suggest that these declines before or after SARS-CoV-2 infection could have reduced immune responses, leading to symptomatic infections.

The study only identifies a correlation, and gut microbial diversity was not studied before infections, so further research is required. The paper has not yet been peer reviewed.

Evolution of SARS-CoV-2 in white-tailed deer

Alpha and Delta variants were found in white-tailed deer in Pennsylvania, with the Alpha variant persisting after it declined in people. The Alpha variant in deer had mutations not seen in people, indicating evolution within the deer.

Nineteen percent of 93 deer tested had SARS-CoV-2, with a greater proportion of road kill animals positive than those killed by hunters. If this percentage is representative of infections across the state, then millions of deer may be infected. Only seven viral genomes were sequenced. The paper has not yet been peer reviewed.

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