Coronavirus Research Tracking - 12 August
hybrid immunity, electronic health records, long Covid, BA.2.75, wastewater monitoring, rapid diagnostics
This week, hybrid vs vaccine immunity, better use of electronic health records, and the improving understanding about long Covid. Also, the characteristics of BA.2.75, the broader public health utility of wastewater surveillance, new rapid saliva tests, and estimating the prevalence of coronavirus spillover events from bats to people.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Vaccine and hybrid immunity effectiveness
An Italian study found that two mRNA vaccine doses did not neutralise BA.4 or BA.5, but that antibodies generated after a third dose did. Neutralisation of these sub-variants was also found for people who had an earlier infection and subsequently received two mRNA vaccine doses.
Antibodies generated by vaccination targeted different parts of the spike protein than those from an earlier infection. Hybrid immunity resulted in a more diversified set of antibodies. Four hundred and eighty two monoclonal antibodies from vaccinated &/or infected people were tested. The paper has not yet been peer reviewed.
A UK study also found a similar expanded neutralisation ability after three vaccine Pfizer doses or a prior infection and two doses. It also reported that a longer interval between first and second doses (8-to-12 weeks vs 3 weeks) increases antibody diversity, but this difference was largely lost after a third dose. The third dose was given 6-to-8 months after the second. Only small numbers of participants were involved. The paper has not yet been peer reviewed.
Hybrid immunity studies are also summarised in an article In Nature Reviews Immunology.
Improved use of electronic health records for assessing variant and vaccine impacts
A commentary in the New England Journal of Medicine highlights the need to have better integration of electronic healthcare records. This would improve monitoring of the clinical course of Covid infections, variants, and vaccine effectiveness for particular population groups over time. The article notes that Israel did this to inform who should get additional vaccine doses and when.Several health system gaps that need to be closed (at least in the US) are identified that would improve integration.
Non-vaccine-related papers
Long Covid - phenotypes, prevalence, & treatment
A recent study found that people with long Covid have distinct immune phenotypes, when compared to uninfected people and those who did not develop long Covid. Differences included the types and/or numbers of specific B and T cells. Antibodies to SARS-CoV-2 and herpes virus antigens were also higher in those with long Covid.
Cortisol levels in plasma were significantly lower in long Covid patients, and were the best predictor of long Covid. However, cortisol levels are affected by other infections or diseases, so by itself may not be generally reliable as a predictor of long Covid. The authors propose a set of soluble biomarkers (decreased cortisol, increased interleukin-8 and galectin-1 [a carbohydrate-binding protein]) that may provide a reliable specific diagnosis for long Covid.
Participants with long Covid were compared to matched groups without long Covid. The study had relatively small numbers in each comparison group, so a larger study is required to confirm the results and conclusions. The paper has not yet been peer reviewed.
A commentary in The Lancet summarises some of the studies into long Covid. It concludes that current evidence indicates that long COVID is common and can persist for at least 2 years after an infection. However, severely debilitating long Covid appears to be rare. There is a need to improve long Covid definitions due to the range of symptoms, and to inform personalised treatments.
A news article in Nature discusses why treatments for long Covid have been slow to emerge. A key factor is the complexity of symptoms and uncertainty about the cause(s) of long Covid. It notes that at least 26 trials of treatments are now underway, but many are small or not well designed.
BA.2.75 characteristics
An analysis of the BA.2.75 variant suggests that it may pose a greater risk than BA.5. It fuses more strongly to the ACE2 receptor than other Omicron sub-variants, and is able to escape immune responses generated by a BA.5 infection. BA.2.75 replicated more efficiently than BA.2 in alveolar epidermal cells, but not in airway cells. In hamsters, BA.2.75 generated greater lung inflammation and damage than other Omicron sub-variants.
However, BA.2.75 remains sensitive to remdesivir, Paxlovid, and molnupiravir. Whether BA.2.75 will outcompete BA.5 is unknown at this stage. The study used pseudoviruses to assess viral characteristics. The paper has not yet been peer reviewed.
Summary information on the BA.5 and BA.2.75 sub-variants is also provided in the BMJ. A news article in Nature also discusses recent analyses of BA.2.75, and the absence of increased hospitalisation rates or deaths associated with it.
Wastewater monitoring potential
An editorial in Nature Microbiology discusses the advances that wastewater monitoring of SARS-CoV-2 has made over the last two years. It advocates that it should also be routinely applied to monitoring other infectious diseases, antibiotic resistance, and chemical contaminants.
Modelling Covid impacts in lower income countries
A modelling study examined the impact of Covid-19 in low- and middle-income countries. Demographics, social contacts, comorbidities, health system capacity, and mitigation strategies were all considered. While case numbers and deaths can’t be accurately predicted for countries, the study indicated that moderate changes in behaviours could substantially reduce excess mortalities.
The authors also noted that, more than wealthier countries, lower- and middle-income countries also have to balance Covid responses alongside interventions against other diseases. The paper was published in Science.
Rapid saliva tests developed
A lab-on-a-chip test can simultaneously detect both viral RNA and antibody levels in saliva. The chip is relatively inexpensive, very sensitive & specific, and could be used at point-of-care facilities, providing results in 2 hours. It was tested on saliva samples spiked with RNA and antibodies, and further testing, and regulatory approvals, are required. The paper was published in Nature Biomedical Engineering.
A separate research team has developed a saliva-based test that can provide results in one hour. It is a nucleic acid-based test that fluoresces when the virus is present. It correctly identified 31 of 33 SARS-CoV-2 positive samples, and all 30 of the negative samples.
The test utilises loop-mediated isothermal amplification, and may also be suitable for use at point-of-care facilities. Further development and testing is still required. The paper was published in Nature Biomedical Engineering too.
Bat coronavirus spillover infections into humans may be relatively common
Modelling of bat SARS-related coronaviruses in Southeast Asia estimated that spillover infections into humans are relatively common, but undetected. Using viral seroprevalence in people, it estimated that 66,000 people are annually infected by bat coronaviruses. Hotspots for the bat coronaviruses are also identified. The paper was published in Nature Communications.