Coronavirus Research Tracking - 7 October
Four Moderna doses, myocarditis & long Covid risks after vaccination, mental health impacts, potent pan-variant antibodies & compounds
This week in vaccine research, four doses of the Moderna vaccine may not improve resistance to Omicron infections; differences in risks of developing myocarditis after 1, 2, or 3 mRNA doses; and, vaccination may reduce the risk of long Covid.
In non-vaccine research, impacts on mental health from the pandemic; people with rheumatic diseases may be more likely to develop long Covid if they had an earlier human coronavirus infection; older age can indirectly increase the risk of long Covid; and several potential new therapies may lead to variant-independent protections.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Three or four Moderna doses not greatly effective at preventing some Omicron sub-variant infections
Four doses of the original Moderna vaccine may not be very effective against infection from BA.5 and subsequent variants. Three doses of the Moderna vaccine provided good and relatively long lasting protection against the BA.1 variant, but was less effective against subsequent variants. A fourth dose provided moderate and short-lived effectiveness against infection from the later variants too. The fourth dose did, though, improve effectiveness against hospitalisation for BA.4/5 infections.
The authors suggest Omicron-specific boosters may be more effective against Omicron-related variants. The study included data from over 30,000 infected adults and 90,000 uninfected adults. Biases that affected infection-risk, and disease severity could not be fully excluded. The paper has not yet been peer reviewed.
Myocarditis risk after mRNA vaccination
A US study found that the incidence of myocarditis in the week after the first mRNA vaccine dose was 1 in 200,000, and 1 in 30,000 after the second. Incidence after a third dose was 1 in 50,000. Myocarditis was more likely in adolescent males, especially after the second and third doses.
Cases of myocarditis also occurred more than seven days after vaccination, but less commonly. The study analysed data from several million hospitalised vaccinated patients, aged five to 39 years old. Incidence of myocarditis was not assessed in a non-vaccinated control group. The paper was published in Annals of Internal Medicine.
Vaccination may reduce the risk of long Covid
Vaccinated adults who subsequently had a Delta or Omicron infection had a lower risk of developing long Covid, compared to unvaccinated people infected with the Wuhan variant. This Swiss study looked at the risk of long Covid in the six months after an infection. The number of vaccine doses, and time since vaccination had no apparent effect on risk of long Covid after an Omicron infection.
For unvaccinated people, the risk of developing long Covid was similar for Wuhan, Delta and Omicron infections. For vaccinated people, the estimated relative risk reduction was 52% for those with an Omicron infection, and 35% for those with a Delta infection.
The study is based on 1,350 people with an infection. It relied on self-reporting of symptoms, and the variant was inferred from time of infection. A bias towards participants who had long lasting symptoms could not be excluded. mRNA vaccines were the predominant vaccine type in the study. The paper has not yet been peer reviewed.
Non-vaccine-related papers
Mental health impacts from Covid-19
A review in Nature Medicine looks at how Covid-19 has affected mental health. A measurable increase in mental health disorders has not been found, but many of the studies have been small, and had different methodologies and participant groups. The variability between studies or subgroups is very high, and longer term consequences have not been well studied.
The review notes the need to give equal priority to mental and physical health, and the importance of establishing larger and longer term studies that take a multidisciplinary approach to mental health.
Prior human coronavirus infection may increase risk of long Covid in people with existing rheumatic diseases
A small study has found that an earlier infection with a human coronavirus is associated with subsequent long Covid in people with rheumatic diseases. Rheumatic patients with long Covid were found to have a distinct humoral immune response, compared to those with rheumatic diseases who did not develop long Covid. Part of their immune profile included a strong immune response against the OC43 coronavirus. The authors suggest that the immune profile could provide a marker for those at greater risk of developing long Covid.
Those who developed long Covid also had lower antibody responses to the Spike and S2 SARS-CoV-2 proteins. Most participants were vaccinated. However, the study only involved 43 people, 79% women, so further research is required. The paper has not yet been peer reviewed.
Older people may be more likely to develop long Covid
An international study found that long Covid was more likely in older people, but by itself age was not a good predictor. The greater incidence of comorbidities and the higher likelihood of developing severe Covid in older people were considered to be the key factors affecting the higher prevalence in older people.
Older patients were more likely to report having cough and joint stiffness as long Covid symptoms, while younger patients were more likely to report persistent headaches, chest pain, concentration impairment, and/or emotional distress.
The most common symptoms in older people were fatigue (38%) and dyspnea (breathing difficulties; 30%). But risk of fatigue and dyspnea were associated more strongly with female gender, obesity, and proximity to the infection, than age alone. In addition, dyspnea was associated with pre-existing respiratory difficulties and an inactive lifestyle.
Over 2,000 people, from Israel, Switzerland, Spain and Italy, were assessed for long Covid symptoms about 5 months after an infection. The paper was published in the International Journal of Infectious Diseases.
A compound that temporarily affects ACE2 receptor may be a potent inhibitor of infection and transmission
A compound that can temporarily change the ACE2 receptor structure, prevents SARS-CoV-2 infection. The compound, called NMT5, first binds to the virus and then transfers a nitrogen oxide group to the receptor, which changes shape. This could also prevent someone who is infected and taking the drug from infecting someone else. The authors suggest the compound could be developed into a variant-independent therapy.
In cell tests, the compound reduced infection by various variants by up to 95%. In hamsters it reduced viral loads 100-fold, and reduced lung damage. Further development and testing is required. The paper was published in Nature Chemical Biology.
New monoclonal antibodies show promise for variant-independent effectiveness
A potent monoclonal antibody may be able to neutralise all known variants, and sub-variants, of concern. It was derived from people in India who had been infected with the original Wuhan variant. The antibody binds to a highly conserved part of the virus’ receptor binding domain. Identification of this conserved region could help design new therapies and vaccines. The paper was published in Science Advances.
Another study identified two potent multi-variant antibodies from 12 other previously infected people. They bind to different regions of the receptor binding domain. In direct comparisons they were more effective than seven commercially available antibodies used to treat Covid-19. The two new monoclonal antibodies were especially effective against the Wuhan, Alpha, Beta, Delta, and the BA.1 and BA.2 Omicron sub-variants, and less so against BA.2.12.1 and BA.4. When the two new antibodies were used in combination they provided greater effectiveness against the range of variants tested in vitro.
When tested in hamsters the antibodies prevented weight loss and reduced viral loads when the animals were subsequently infected by the Wuhan or Delta variant. The NA8 antibody was more effective against Delta infections than the other antibody. Effectiveness in the hamsters was compared to animals given a general IgG antibody. Small numbers of animals were used in each experiment. The paper was published in Cell Reports.
The ORF8 region of the virus may disrupt aspects of genetic regulation in infected cells
A protein produced by the ORF8 region of the virus mimics histone proteins and disrupts epigenetic regulation. It affects the regulation of chromatin, which in turn disrupts gene transcription. The ORF8 locus appears to have multiple functions and impacts on host cells and tissues.
The research is based on the effects on cell lines. However, natural mutants of the virus with all or part of ORF8 missing have been associated with milder Covid-19. The paper was published in Nature.
Omicron variants are more antigenically distinct from the original SARS-CoV-2 than some bat and pangolins coronaviruses
Some Omicron sub-variants appear to be more antigenically distinct from the ancestral SARS-CoV-2 strain than some bat and pangolin coronaviruses. The animal coronaviruses were more effectively neutralised by sera from SARS-CoV-2 infected or vaccinated people than BA.1, BA.2 and BA.5. The authors concluded that this is due to strong selection on SARS-CoV-2 over the pandmeic due to human immune responses. The paper was published in Nature Microbiology.