Coronavirus Research Tracking - 23 September
Vaccine effectiveness against Omicron, myocarditis, new therapies, genetic risk factors, Omicron infection & fatality rates
This week in vaccine research, effectiveness of different vaccines against Omicron sub-lineages, and an autoantibody associated with some vaccine-related myocarditis cases.
In non-vaccine research, greater risks of neurological disorders after having Covid-19, long Covid cases with severe fatigue, potential new therapies for SARS-CoV-2, human genotypes associated with more severe Covid outcomes, comparing Omicron infection and fatality rates to other variants, and the need for better surveillance measures in Africa.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Vaccine effectiveness against Omicron
A review of vaccination studies found that neutralisation of Omicron variants was significantly lower than for other variants. Following primary doses, neutralisation was usually at least 10-fold lower than for the original Wuhan variant. After a booster, neutralisation of Omicron variants was generally 6-to-7-fold lower. For the BA.4/5 variants reduction in neutralisation ability was even greater.
This held for different types of vaccines, although mRNA vaccines performed better against Omicron than protein subunit vaccines. However, there was considerable variation in neutralisation levels between studies.
Most studies involved mRNA vaccines and the BA.1 Omicron sub-lineage. Neutralisation was usually assessed about one month after the vaccine dose. The review included 153 studies. The paper has not yet been peer reviewed.
Bivalent Moderna vaccine booster shows promise against Omicron
A phase 2/3 trial of a bivalent Moderna vaccine indicated that it could provide stronger protection against Omicron variants than the original vaccine. The vaccine (with the Wuhan and BA.1 spike protein sequences) was given as a fourth dose and compared to responses after a fourth dose of the original vaccine. Neutralising antibody levels were higher in recipients of the bivalent vaccine.
Effectiveness of the vaccine has not yet been fully assessed. The fourth dose was given about four months after the third. Adverse reactions to the bivalent vaccine were similar to those from the original vaccine. The paper was published in the New England Journal of Medicine.
An association between an autoantibody and myocarditis after vaccination
A small study found that autoantibodies were in the majority of younger people who had myocarditis after vaccination, but rarer in older people. Out of 40 vaccinated people with myocarditis, 12 had antibodies that targeted the interleukin-1 receptor antagonist (IL-1RA). Nine of the cases were in people under 21. The antibody was also found in two out of 214 adults vaccinated but without myocarditis,. However, unlike the myocarditis cases, the IL-1RA was not hyperphosphorylated. The paper was published in the New England Journal of Medicine.
Non-vaccine-related papers
Increased risks of neurological disorders a year after having Covid-19
A large US study, involving health data from military veterans, found increased risks of a range of neurological disorders one year after having had Covid-19. This included strokes, cognition and memory disorders, and migraines. Age did not have a significant influence on risks. Risks and burdens varied for specific neurological conditions, and risks and burdens of the condition were generally substantially lower for those who did not require hospitalisation.
Most participants were not vaccinated, and the study is based on infections before the Omicron waves. The data is dominated by white males, so the results may not be representative of the whole population. The paper was published in Nature Medicine.
Long Covid
A Dutch study found that people experiencing severe fatigue as part of long Covid also had many other symptoms, and persistent low grade inflammatory responses. As with other studies, symptom similarities were noted with people with ME/chronic fatigue syndrome.
At least one quarter of those with severe fatigue had signs of depression. Many of the long Covid participants without severe fatigue showed some improvement after one year.
The study compared people with long Covid experiencing fatigue with others who had long Covid symptoms but not fatigue. A comparative group who did not experience long Covid was not included. The paper has not yet been peer reviewed.
Finding new Covid-19 therapies
Screening of 2,500 small molecules identified two FDA-approved anti-inflammatory drugs that appear effective against Covid-19. One in particular was particularly effective at inhibiting both inflammasomes (multiprotein signalling platforms formed in response to infections) and SARS-CoV-2 replication in cell assays. The compound, called NIC, is already being tested in several Covid-19 clinical trials. The paper was published in Science Advances.
A potential inhibitor of SARS-CoV-2 infection
A short peptide has been shown to be a very effective inhibitor of infection for all current main variants. The peptide prevents correct folding of the spike protein. Effectiveness varies between variants, with inhibition of the Omicron variant 10-fold lower, compared to Alpha and Delta variants. However, the peptide is much more potent than other similar peptides tested. Further refinement of the peptide is planned.
Tests of effectiveness were based on cell and viral infection assays. The paper was published in PNAS.
Variants of a human gene are associated with worse Covid-19 outcomes
The Apolipoprotein E (APOE) gene has several variants, some of which appear to be associated with poorer Covid-19 outcomes. Mice (particularly males) with the human APOE variants 2 or 4 had more rapid Covid disease progression and poorer survival than mice with APOE3. Mice with APOE2 or 4 also had higher viral loads. Early immune responses to the virus appear to be weaker in mice with APOE2 and APOE4.
Analysis of APOE genotypes in the UK Biobank also indicated that a homozygous APOE4 genotype was associated with a 2-fold higher risk of Covid-19-related death than patients homozygous for APOE3. About 3% of the world population are homozygous for APOE2 or APOE4.
The APOE gene is known to modulate immune processes, and APOE4 is a risk factor for development of Alzheimer’s disease. The study concluded that APOE genotype may influence Covid-19 outcomes, rather than being the sole factor determining disease progression. Older age and being male also influence outcomes. Testing Covid-19 patients for their APOE genotype may, though, help identify patients at higher risk of more severe outcomes. The paper was published in Nature.
Omicron’s comparative infection and case fatality rates
An analysis of infections in the UK found that case fatality rates in adults for the Omicron variant were lower than those for earlier variants. However, hospitalisation and death rates increased later in the Omicron wave (February to May), compared to the earlier Omicron period. This was particularly noticeable for those 75 years and older.
The study also noted that ethnic and socio-economic factors are associated with vaccination status (none, two, or three vaccine doses) and exposure risks, and these need to be taken into account when determining vaccine effectiveness. The paper has not yet been peer reviewed.
An analysis of reinfections in Denmark found that reinfection with the same variant was rare, except for Omicron. Over 90% of reinfections involved an Omicron sub-lineage. Before Omicron, reinfection by the same variant was estimated to be 0.3%, while for Omicron sub-lineages it was 4.6%. Omicron reinfections tended to occur within just a few weeks. The high rate of Omicron reinfection was attributed to the distinctiveness of the BA.1, BA.2 and BA.5 spike proteins. The paper has not yet been peer reviewed.
More sequencing and other surveillance measures still needed in Africa
Whole genome sequencing of SARS-CoV-2 has increased substantially in Africa over the past two years, but more investment in surveillance there is still needed. Sequencing data showed that different African regions had different patterns and dynamics for variants of concern. For example, some variants have been more prevalent in some regions than others. Factors that account for these differences are uncertain at this time.
Testing and reporting of cases varies widely both between and within African countries. The paper was published in Science.
A compendium of SARS-CoV-2 variants
covSpectrum is a website that allows scientists to track and compare older and new SARS-CoV-2 variants. Collections of particular variants have already been assembled by researchers, and new collections can be created.