Coronavirus Research Tracking - 28 October
bivalent vaccine effectiveness, vaccines & long Covid, therapies, and conspiracy gateways
This week in vaccine research, why we don’t (yet) have vaccines that prevent SARS-CoV-2 infections, bivalent vaccines stymied by immune imprinting, and vaccines may have little effect on reducing the number of persistent symptoms a person develops.
In non-vaccine research, a review of available Covid therapies, pathogenicity is influenced by the viral ORF6 region, the effect of Covid public health measures on other infectious diseases, and Covid conspiracies as an entree to believing in other conspiracy theories.
Note: This is the final regular edition of the Coronavirus Research Tracking weekly newsletter.
The Research Tracker has been prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Obstacles in the way of vaccines that prevent infection
A paper published in Immunity discusses the challenges in developing vaccines that can prevent SARS-CoV-2 infections in the first place. Strong and broadly neutralising antibody responses are required, which none of the vaccines currently available generate. Preventing infection requires a rapid and strong humoral response in the upper respiratory tract, but this type of mucosal immunity is difficult to create with vaccines.
However, a paper just published in Science found a strong immune system response in mice and hamsters to an intranasal vaccine. A subunit vaccine containing the spike protein was given intranasally two weeks after they had received an intramuscular Pfizer/BioNTech vaccine. A longer interval between the doses was also effective.
Compared with two Pfizer doses the intrasal vaccine booster reduced Covid severity in mice infected with the virus after vaccination. Vaccinated hamsters had cleared the virus more quickly than hamsters that had two intramuscular vaccine doses. This suggests the vaccine may help reduce transmission. Further work and testing on the intranasal vaccine is required.
Bivalent vaccines don’t appear to be more effective than the originals
Bivalent Pfizer and Moderna vaccines appear to be no more effective against BA.5 than the original vaccines. The bivalent vaccine contained the spike protein sequences of the original Wuhan version and the BA.5 variant. Neutralising antibody levels against BA.5 were similar for both the monovalent and bivalent vaccines. T cell responses also did not significantly differ.
The authors conclude, in agreement with an earlier study of a BA.1 bivalent vaccine, that immune imprinting caused by the original vaccines probably limits humoral immune responses to subsequent similar vaccines.
The study involved only 15 people who had at least two or three doses of the original Pfizer, Moderna, and/or Johnson & Johnson vaccines, and 18 who had a bivalent version and two or three previous monovalent vaccine doses. The paper has not yet been peer reviewed.
Earlier viral variants are associated with a greater range of persistent Covid symptoms
Pre-Omicron infections are associated with more long lasting symptoms. Vaccination was not found to be associated with a reduction in the number of longer lasting symptoms following an Omicron BA.1 infection. The study compared symptoms in groups with a wild-type, Alpha, Delta, or BA.1 infection to group that was uninfected. Some of the uninfected participants displayed some of the conditions seen in Covid cases (such as fatigue, breathlessness, and pains).
Eighteen months after a wild-type infection individuals reported significantly more “post acute sequelae of Covid” symptoms, and had a higher fatigue score and a lower self-reported health score than the control. Those with Alpha or Delta infections also reported more symptoms 6 months post infection, but fewer than for the wild-type group. In contrast, those assessed 3 months after an Omicron infection reported fatigue, exhaustion or muscle/limb pain only slightly more commonly than uninfected participants. Their self-reported health scores were not different from the control group.
The study involved nearly 3,000 healthcare workers, who were mostly young, healthy females. The paper has not yet been peer reviewed.
Non-vaccine-related papers
A review of Covid therapies
A review published in Nature Reviews Nephrology examines the therapies developed, or repurposed, to treat Covid-19. It highlights the number of therapies and how many were developed very quickly. The review also notes that people with kidney diseases are usually not included in clinical trials, which is of concern because they are often some of the most vulnerable to developing severe Covid-19.
State of knowledge about Covid effects on blood vessels
A review published in Acta Pharmacologica Sinica looks at what biomarkers are useful for detecting Covid-induced damage in endothelial cells, and what treatments can be effective. The endothelium, which is the lining of blood vessels, has a critical role in maintaining the body’s homeostasis. When disrupted a range of other organs can be affected. While existing therapies can be effective, the review suggests that development of endothelial-specific therapies could be very beneficial.
Other parts of the viral genome that affect pathogenicity
Most research has focused on the spike protein as a key factor in the virus’ pathogenicity. However, the protein from the ORF6 region also affects pathogenicity. It disrupts transport between the cell’s nucleus and cytoplasm, and so affects gene expression and reduces antiviral responses. Hamsters infected with the virus lacking the ORF6 region had less lung damage and lost less weight than animals infected with the normal virus, but viral load was not affected.The paper has not yet been peer reviewed.
The effect of Covid restrictions on the spread of other infectious diseases
A study in England found that during the pandemic public health measures reduced the transmission of several other infectious diseases. England removed all restrictions were removed in July 2021. Out of 22 diseases (or disease groups), 8 had lower levels of incidence compared to before the pandemic, 10 had comparable levels, and only four were more common. These latter were chickenpox (for which there is a vaccine but it is not generally given), herpes simplex virus, skin & subcutaneous tissue infections, and infectious intestinal diseases.
The authors conclude that the public health restrictions did not result in greatly reduced population immunity to many infectious diseases. The paper has not yet been peer reviewed.
[A 2021 New Zealand study reported that the prevalence of respiratory viral infections were also greatly reduced in the winter of 2020.]
Chewing gum to reduce transmission
An antiseptic chewing gum was found to reduce viral loads in exhaled air samples. Reductions were around 90% when measured 30 to 120 minutes after chewing. There was, though, considerable variability between individuals. The gum was chewed for 15 minutes before testing. This was a pilot study with only nine infected adults tested. The paper was published in Infection.
Covid conspiracy theories as a gateway other conspiracy beliefs
Belief in Covid-19 conspiracy theories may lead on to belief in other specific or more general conspiracy theories. This supports a “gateway conspiracy” hypothesis, where belief in one conspiracy can make it more likely to go on to believe in other supposed conspiracies.
This study is based on US and UK surveys. The US surveys found that belief in a Covid-19 conspiracy was associated with an increased belief in fraud in the 2020 election and general conspiracy beliefs six months later. The UK surveys also found that belief in Covid-19 conspiracy theories was also associated with a subsequent increase in conspiratorial thinking about six months later.
The authors note this is consistent with other studies. They propose that belief in a specific conspiracy theory may set off a sequence of psychological processes (such as reduced trust in institutions) that guide people to being receptive toward a wider variety of conspiracy theories.
The US study recruited 501 participants via the Mechanical Turk, so may not be generally representative. Only 21% participated in the six month follow-up survey. The UK study involved 2,025 initial participants, with 51% taking part in later surveys. The paper was published in PLoS One.