Coronavirus Research Tracking - 28 May
Vaccine & mask effectiveness, antibody memory, viral loads, Covid burdens, new therapies and sensors, other viruses of concern
This week, the effectiveness of vaccines and masks continues to be reinforced, additional evidence for long term immune memory, and some antibodies that can increase infectivity. Also, studies of variation in viral loads and the health burdens of Covid-19, promising antibody therapies, using citizen science to create a supercomputer, rapid and accurate sensors for viral detection, and other cross-species viral infections.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Infection after vaccination is rare
By the end of April around 101 million people in the US had been completely vaccinated, but only 10,262 cases (0.01%) of post-vaccination infection were reported. Ten percent of these so-called breakthrough cases were hospitalised (though 29% were not due to Covid-19), and 2% died (though not all from Covid-19). The report was published in the Morbidity and Mortality Weekly Report.
Need to keep surveillance for asymptomatic infections after vaccination
Monitoring for asymptomatic infections following vaccination is likely to be required. A small study found a variety of variants infected people who had received the Pfizer/BioNTech vaccine. The people were either asymptomatic or had very mild symptoms, indicating the benefits of vaccination. However, a new mutation was found in one of the people, highlighting the importance of ongoing surveillance. The paper has not been peer reviewed.
Vaccine effective against B.1.617.2
High levels of effectiveness against the B.1.617.2 variant were seen following two doses of the AstraZeneca/Oxford or Pfizer/BioNTech vaccines. Analysis of thousands of cases in the UK found that after one dose the effectiveness was 20% lower than for the B.1.1.7 variant, but the difference after two doses was much smaller. The paper has not been peer reviewed.
A possible indicator of immunity
Identifying a measure that correlates with immunity has been challenging up until now. A recent study has found that the level of antibody neutralisation can provide a good indication of the level of protection. It used data from several studies to model the relationship between neutralisation titers and protection from infection or severe disease.
Assuming neutralisation titers decline linearly the authors predict that while booster vaccine shots may be needed to prevent infections, there could be long term protection from severe disease without a booster. A limitation of this study is that a variety of different assays and trials were used, rather than a standardised method. The study was published in Nature Medicine.
Long lived immune memory cells found
Long lived bone marrow plasma cells have been found that produce antibodies against the spike protein. They were detected in 15 of 19 convalescing Covid-19 patients who had relatively mild symptoms seven or eight months earlier. Such bone marrow cells are known to generate antibody producing cells against specific pathogens years after the original infection.
This suggests that there may often be long lasting immune responses against the virus, although the extent of immunity is unknown. Whether they are also present in people who had more serious Covid-19 is also currently uncertain. The research was published in Nature.
Infection-enhancing antibodies detected
Some antibodies that target a specific site in the N-terminal domain of the spike protein enhance infectivity. This was through improving the binding of the spike protein to the ACE2 receptor. These antibodies were present in patients with both mild and severe Covid-19, but were more common in those with severe symptoms. However, the enhancing antibodies do not work when high levels of neutralising antibodies are present. The paper was published in Cell.
A small proportion of people have very high viral loads
An analysis of 25,000 swab samples and cell infection studies in Germany found that about 8-9% of people had very high viral loads, and so may be highly infectious. Thirty six percent of these cases were asymptomatic, pre-symptomatic, and mildly symptomatic cases. Peak shedding was estimated to be around four days after viral shedding commenced, and 1 to 3 days before symptoms (if any) appear. The research was published in Science.
Viral loads also vary between variants. P.1 infections tend to have 10-fold higher viral loads than variants which they replaced, a study in Nature reports.
Covid burdens
A review of 45 studies, involving nearly 10,000 patients, examined the prevalence of persistent Covid-19 symptoms. Persistent symptoms were common, with 72.5% of patients reporting at least one symptom 60 days after symptom onset. Shortness of breath, fatigue and sleep disorders were the most common. However, there is a lack of consistency in study designs and study length, so more standardised studies are needed. The review was published in JAMA Network Open.
An article in Nature describes the health and disability burdens that Covid-19 is creating. They authors estimate that as much as 30% of the health burden may be due to Covid-induced disabilities, rather than through deaths. Better measures of disease burden are required to understand the impact of Covid-19, and other diseases.
A rare Covid-19 condition in children - Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 - was found to go away after about six months. The UK study involved 46 children (average age 10 years). Only one showed inflammation after six months, and many had other symptoms resolved during that time. However the children often required ongoing physical and mental health support. The study was published in The Lancet Child & Adolescent Health.
Monoclonal neutralising antibody therapies
A detailed review of monoclonal neutralising antibodies describe those in use or in clinical trials and evidence for effectiveness against variants. Some of the barriers to development or wide spread use of monoclonal antibodies are also noted. The paper was published in Cell.
Inhalable nanobody therapy
An inhalable nanobody was shown to prevent serious disease and stop viral replication in infected Syrian hamsters. The early stage trials involved small numbers of hamsters. Nanobodies are antigen binding sites from small antibodies found in llamas and related species. The study was published in Science Advances.
Citizen science creates supercomputer to model virus folding
A distributed computing project involving over one million people was used to model the folding of the virus. It used the folding@home platform, where a network of computers are used to perform calculations. The authors claim that this is the first “exascale” computer, meaning that more than 1 exaflop of computing power was used (one quintillion - 1018 - floating-point operations per second). The simulation of structural changes during infection may lead to new targets for therapies. The paper was published in Nature Chemistry.
Mask effectiveness
Another study has demonstrated the effectiveness of masks in reducing transmission. The modelling study looked at the size distribution of small particles produced during breathing, speaking, coughing and sneezing with and without masks. It concluded that simple surgical masks can be effective in reducing transmission when viral loads are relatively low.
More specialised masks will be required when there are very high viral loads indoors, such as in hospitals with many Covid-19 cases. Mask wearing combined with social distancing and good ventilation can greatly reduce infection risks. The research was published in Science.
A review of 21 studies found that mask-wearing policies can reduce population-level burdens of Covid-19. The paper, not yet peer reviewed, has been submitted to The Lancet.
Good chip, good dog
A distinct odour produced by asymptomatic people or those with mild Covid-19 can be detected by sensors and trained dogs. The organic semi-conducting sensors had very high levels (at least 98%) of sensitivity and specificity, while six dogs had lower, but still very good, sensitivity (82 to 94%) and specificity (76-92%).
The authors suggest that the sensors could be used in rooms or aircraft, while two dogs could be used to assess 300 people (ie, a plane load) in about 30 minutes, with infections subsequently confirmed with PCR tests. However, the dogs have only been tested on odour samples from clothing and not on people so far. The paper has not yet been peer reviewed.
In another study, a nanobody attached to a transistor created a very sensitive and accurate virus sensor, comparable to the PCR test but taking only minutes. The proof of concept is published in Nature Biomedical Engineering.
Other zoonotic events
Another coronavirus has been found to infect humans. This was determined from old infections of eight children in Malaysia who had pneumonia. The coronavirus appeared to be a recombination between several coronaviruses - dog, cat and possibly pig. There is no evidence that the virus can be transmitted from human to human, but it highlights the risks of the emergence of new zoonotic coronaviruses. The paper was accepted, but not yet published, by Clinical Infectious Diseases. A news item in Science also discusses this study.
Outbreaks of a H5N8 avian influenza virus have been reported in wild and domesticated birds over the past decade in Europe, the Middle East and Asia. Many outbreaks have been reported in the past year, and tens of millions of birds have died, or needed to be killed. Seven Russian poultry workers also became infected last year, but did not become sick or transmit the virus to other people. The Covid-19 pandemic has reduced surveillance of such outbreaks, so monitoring needs to increase. The paper is published in Science.