Coronavirus Research Tracking - 10 June
BA.4 & BA.5, new Moderna booster, Paxlovid, long Covid, new therapies
This week, immune evasion by the BA.4 & BA.5 sub-lineages, and qa good immune response for Moderna’s new vaccine with the Omicron spike protein.
In non-vaccine papers, identifying possible new therapies, the potential for resistance development against Paxlovid, several papers on long Covid symptoms, the increased risks of various health conditions after a Covid-19 infection, and improving indoor ventilation.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
BA.4 and BA.5 sub-lineages can evade BA.1-stimulated neutralising antibodies
A BA.1 infection after vaccination increased neutralisation of BA.1, BA.2, and earlier variants of concern, but not of BA.4 or BA.5. The Pfizer/BioNTech vaccine was the most commonly received one by participants in the study. The BA.1 infection appears to expand existing B memory cells that are not able to recognise the distinct receptor binding sites in BA.4 and BA.5. The paper was published in Science Immunology.
Similar results were also found in a study published in Cell.
Severity of Omicron infections generally less than for the Delta variant
BA.1 and BA.2 infections were found to have a 40% lower risk of severe symptoms and death than a Delta infection. The study calculated the risks of hospitalisation, the need for intensive care, mechanical ventilation, and death. Patients with Omicron infections also usually had shorter hospital stays.
Differences between the two variants were most notable for unvaccinated people. Vaccination resulted in a more substantial fall in risk of severe Covid for those with Delta infections. The paper was published in Nature Medicine.
Moderna’s Omicron booster vaccine has encouraging trial results
A press release from Moderna stated that a Phase 2/3 trial of an updated version of their vaccine which includes the Omicron (BA.1) spike sequence. It was given as a 3rd dose to 437 participants. Antibody and neutralising antibody levels were significantly higher than in those who received a third dose of the original Moderna vaccine. Results of the trial will be published later. The company says it will use the new version as a booster in the coming northern autumn.
Systems biology used to identify possible new therapies
A systems biology approach was used to identify differences in gene expression in immune cells from hospitalised Covid-19 patients. In patients who died, mRNA metabolism, RNA splicing, and interferon signalling pathways were more active than in patients who recovered. The results allowed the researchers to identify three drugs that could be used to reduce these genetic disruptions.
Only seven patients were involved in the study, three of whom died. Clinical trials of the three drugs are already underway, by other research teams, to assess their individual effectiveness in treating Covid-19. The paper was published in Science Advances.
Potential for viral resistance to develop against Paxlovid
Cell culture experiments demonstrated that SARS-C0V-2 can develop resistance to Paxlovid. This was due to mutations in the main protease gene. Resistance to Remdesivir was not observed, so a combination treatment may be a possibility to reduce the risk of drug resistance. The paper has not yet been peer reviewed.
Similar results were reported in another study. Although the authors noted that resistance took some time to develop. Both papers stress the need to monitor for the development of resistance to Paxlovid. The paper has not yet been peer reviewed.
Long Covid studies
An analysis of studies estimates that globally over 144 million people could have Covid symptom clusters three months after an infection. This was estimated to represent just under 4% of infections. After one year 15% may still have symptoms. However, the confidence intervals in the study are broad. The paper has not yet been peer reviewed.
A review and meta-analysis of 21 earlier studies estimated that 25% of children and adolescents had Covid symptoms lasting at least 4-to-12 weeks. The most prevalent were mood symptoms (16.5%), fatigue (9.7%), and sleep disorders (8.4%).
There was no standard definition what constituted Covid symptoms between studies, most depended on self-reporting by children or their carers, and bias in those choosing to participate in the studies could not be excluded. The paper has not yet been peer reviewed.
A persistent disruption to the sense of smell after Covid-19 was found to be associated with good recovery from other Covid symptoms. Such olfactory dysfunction was found to be common in young women with no comorbidities.
However, the study included a high proportion of younger healthy women, and infections were mostly from the first year of the pandemic. The authors suggest that there may be several distinct long Covid phenotypes, of which this is one. The paper has not yet been peer reviewed.
A study of 74 people with long Covid and their physical activity found that an individual's symptoms varied considerably over time. There was also no strong correlation between a person’s symptoms and their level of physical activity.
Only one third of the participants managed more than 1 hour of moderate or vigorous physical activity per week. Symptoms and physical activity were self-reported. Most participants were while, middle-aged, well educated women. The paper has not yet been peer reviewed.
The US NIH has started a study utilising machine learning to better understand long Covid symptoms. A blog from the NIH summarises other recent studies of long Covid that have used artificial intelligence.
Heart and kidney problems associated with more severe cases of Covid
Cardio-renal injuries were found in most patients hospitalised with Covid after they were discharged. Injuries included myocarditis and acute kidney injury. These contributed to their decreased quality of life after infection, and may lead in some cases to greater demand for health support. During the 14 months after hospitalisation one in seven patients with Covid in the study died or were rehospitalized, and two in three patients required additional outpatient care. The study involved 159 people with Covid (average age 55), and 29 without. The paper was published in Nature Medicine.
Lung, kidney and olfactory damage seen in hamsters and people with Covid-19
Covid-19 caused more pulmonary and kidney damage and disruption of gene expression than an Influenza A infection, at least in hamsters. Covid also affected olfactory tissues, particularly by increased inflammation or changes in gene expression. Similar results were found in tissue samples from Covid-19 patients.
In the hamsters, olfactory changes were associated with a decreased sense of smell, which persisted for at least a month after the infection was cleared. Only a small number of hamsters were used to assess olfactory damage and the effects on behaviour. The paper was published in Science Translational Medicine.
Diabetes risk after Covid can also be higher
There can also be a greater risk (59%) of developing type 2 diabetes after having Covid-19. This was based on an analysis of four earlier studies, with risk assessed at one month after infection. Controls were matched people with no Covid-19 or with Influenza. Differences in methods and populations between the studies means that further research is needed. The paper was published in Primary Care Diabetes.
Bacterial differences between people with mild and severe Covid-19
A small study found that some bacteria were more, or less, abundant in people with severe Covid-19 than those with mild symptoms. Bacterial taxa from saliva and nasopharyngeal swabs were identified using 16S rRNA sequencing. The authors note that microbial community composition can vary substantially between people, so further studies are required. The paper has not yet been peer reviewed.
Predicting future lineages from distinctive new mutation clusters
The distinctiveness of a new set of mutations can predict future changes in prevalence of newer (sub)lineages. This study develops a way to quantify distinctiveness, and recommends close monitoring of new lineages that are quite distinct from others in that population. The study’s distinctiveness metric did not take account of all factors that may enable, or prevent, increased transmissibility or immune evasion. The paper has not yet been peer reviewed.
A new antibody diagnostic device developed
A portable microfluidic device to measure antibody levels has been developed. It is easy to use, low-cost and has high sensitivity. It may be suitable for use at clinics, border control, and other testing stations. The paper was published in Science Advances.
Improving indoor air circulation
A viewpoint published in JAMA discusses effective ways to improve air circulation indoors. It describes some lower cost and short-term options, as well as costlier structural changes. It also notes methods that can be used to measure effectiveness of changes.