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New variants of COVID-19 may prolong the duration of the virus

11 August 2021 | Story André Damons | Photo Anja Aucamp

Prof Burt read more — Prof Felicity Burt from the University of the Free State (UFS) and the National Health Laboratory Services (NHLS) holds an NRF-DST South African Research Chair in Vector-borne and Zoonotic Pathogens Research. She is also an expert on arbovirology in the UFS Division of Virology.

New variants of severe acute respiratory coronavirus 2 (SARS-CoV-2) have the potential to influence the size and duration of waves of infection and may prolong the duration of COVID-19’s stay with us. Despite the development of vaccines and the technology available to adapt vaccines in the future to address the emergence of new variants, it is extremely unlikely that COVID-19 will ever be eradicated.

The emergence of new variants has illustrated the importance of continually monitoring circulating variants for changes in viral proteins associated with cell binding (in other words, influencing entry of the virus into a cell) and immune responses (which would influence vaccine efficacy and reinfections).

Prof Felicity Burt from the University of the Free State (UFS) and the National Health Laboratory Services (NHLS), who holds an NRF-DST South African Research Chair in Vector-borne and Zoonotic Pathogens Research, says the current vaccines are effective against severe disease, but do not prevent transmission. Hence, complete eradication of the virus is unlikely, as the virus will continue to circulate at low levels in the population even if high levels of vaccine coverage are achieved. Prof Burt is also an expert on arbovirology in the UFS Division of Virology.

“To date, the only pathogen that has been eradicated globally is the smallpox virus. This was achievable because of a highly efficacious vaccine and because smallpox caused a disease that was readily recognisable, enabling rapid isolation of afflicted patients. In contrast, a virus such as SARS-CoV-2 that can cause asymptomatic infections in which the person is unknowingly infected and able to shed and transmit the virus, is probably impossible to eradicate,” explains Prof Burt.

Development of affordable treatment options remains important

The current vaccines are, however, able to reduce the severity of the disease until a vaccine is available that prevents complete transmission of SARS-CoV-2; therefore, the development of affordable treatment options remains important. Novel therapeutics, such as an antiviral drug that interrupts replication of the virus, or monoclonal antibodies that neutralise the virus, would go a long way to contribute to the treatment of infections.

“Currently, monoclonal antibody therapy is available in higher-income countries. Monoclonal antibodies mimic our natural antibody response, targeting specific regions of the virus, neutralising the virus, and stopping it from entering cells. Monoclonal antibodies have been used to treat other viral infections such as Ebola; however, they have significant limitations due to cost, availability, and high specificity, meaning that mutations in emerging variants could influence their efficacy. They are unlikely to be an affordable option in lower-income countries.”

Mutations become problematic

According to Prof Burt, viruses have a propensity to acquire mutations, or changes, in their genetic make-up during replication, and as expected, this virus has changed during the pandemic and will inevitably continue to mutate.

“These mutations become problematic if they influence the way the virus is transmitted between people, or if the disease profile changes and the virus causes a more severe disease, or if the changes result in a virus that is not recognised by the body's immune response. In other words, the virus is capable of hiding from, or can escape, the immune response that a person has developed as a result of a previous natural infection or from vaccination.

“If the virus has changed such that an existing immune response does not recognise it, then a person can become reinfected. Hence, changes in the ability to escape immunity are considered to confer an advantage to the virus. Although there are changes in all regions of the viral genes, we are concerned with changes that occur in the gene that codes for the spike protein. This protein is responsible for binding and entry of the virus into cells, hence changes in the spike protein that allow the virus to more readily enter cells are considered to be an advantage to the virus.”

Variants of interest vs variants of concern

Prof Burt says there is now some evidence suggesting that antibodies produced in response to the Beta variant – the dominant variant during the second wave in South Africa – are less efficient at neutralising the Delta variant of the virus. In addition, there is evidence suggesting that the Delta virus can replicate to higher levels in the body, resulting in a higher viral load. Although the kinetics of each variant are still not completely understood, the combinations of higher viral load, and the potential for reinfections to occur will likely contribute towards a larger wave of infection.

“The World Health Organisation (WHO) and international partners characterise emerging variants as variants of concern (VOC) or variants of interest (VOI). Although there are multiple new variants globally, only a small proportion of these meet the definition. The Lambda variant, initially recognised in South America, is deemed a VOI. This is a level below VOC, indicating that it has mutations that are known or have the potential to affect the characteristics of the virus and that the prevalence is increasing in multiple countries over time. Currently, Lambda is not a concern in SA. In contrast, a VOC has the same characteristics as a VOI, but in addition, has one or more of the following: increased transmissibility or is associated with change in disease severity or clinical presentation, or the public health and social measures are less effective against the variant,” says Prof Burt.

Vaccines will likely need to be adapted to accommodate future variants

It is impossible to predict which variants may emerge next, explains Prof Burt. “Fortunately, although the current vaccines may not prevent mild disease, they have all been shown to reduce the incidence of severe disease and fatalities. The technology for adapting vaccines is available – but of course – if a vaccine has to be adapted, it will take some time for that to be available. As this virus is now well established globally and will continue to evolve over the years, it is likely that, in the future, vaccines will be required to be adapted to accommodate circulating variants.”

“Although there is some reduction in vaccine efficacy against the currently circulating variants, there are fortunately high levels of protection against severe disease and hospitalisation in people who have received the single-dose Johnson & Johnson vaccine or both doses of the Pfizer vaccine. In other words, they are fully vaccinated,” says Prof Burt.

Despite reduced effectiveness and potential for vaccine breakthrough, it is still important for people to be vaccinated, as it reduces viral load and duration of virus shedding. Less viral replication means that the virus has less chance to mutate, with less chance of new variants emerging.

News Archive

Inaugural lecture: Prof Robert Bragg, Dept. of Microbial, Biochemical and Food Biotechnology

2006-05-17

Attending the inaugural lecture were in front from the left Prof Robert Bragg (lecturer at the Department of Microbial, Biochemical and Food Biotechnology) and Frederick Fourie (Rector and Vice-Chancellor). At the back from the left were Prof James du Preez (Departmental Chairperson: Department of Microbial, Biochemical and Food Biotechnology) and Prof Herman van Schalkwyk (Dean: Faculty of Natural and Agricultural Sciences). Photo: Stephen Collett

A summary of an inaugural lecture delivered by Prof Robert Bragg at the University of the Free State:

CONTROL OF INFECTIOUS AVIAN DISEASES – LESSONS FOR MAN?

Prof Robert R Bragg
Department of Microbial, Biochemical and Food Biotechnology
University of the Free State

“Many of the lessons learnt in disease control in poultry will have application on human medicine,” said Prof Robert Bragg, lecturer at the University of the Free State’s (UFS) Department of Microbial, Biochemical and Food Biotechnology during his inaugural lecture.

Prof Bragg said the development of vaccines remains the main stay of disease control in humans as well as in avian species. Disease control can not rely on vaccination alone and other disease-control options must be examined.

“With the increasing problems of antibiotic resistance, the use of disinfection and bio security are becoming more important,” he said.

“Avian influenza (AI) is an example of a disease which can spread from birds to humans. Hopefully this virus will not develop human to human transmission,” said Prof Bragg.

According to Prof Bragg, South Africa is not on the migration route of water birds, which are the main transmitters of AI. “This makes South Africa one of the countries less likely to get the disease,” he said.

If the AI virus does develop human to human transmission, it could make the 1918 flu pandemic pale into insignificance. During the 1918 flu pandemic, the virus had a mortality rate of only 3%, yet more than 50 million people died.

Although the AI virus has not developed human-to-human transmission, all human cases have been related to direct contact with infected birds. The mortality rate in humans who have contracted this virus is 67%.

“Apart from the obvious fears for the human population, this virus is a very serious poultry pathogen and can cause 100% mortality in poultry populations. Poultry meat and egg production is the staple protein source in most countries around the world. The virus is currently devastating the poultry industry world-wide,” said Prof Bragg.

Prof Bragg’s research activities on avian diseases started off with the investigation of diseases in poultry. “The average life cycle of a broiler chicken is 42 days. After this short time, they are slaughtered. As a result of the short generation time in poultry, one can observe changes in microbial populations as a result of the use of vaccines, antibiotics and disinfectants,” said Prof Bragg.

“Much of my research effort has been directed towards the control of infectious coryza in layers, which is caused by the bacterium Avibacterium paragallinarum. This disease is a type of sinusitis in the layer chickens and can cause a drop in egg product of up to 40%,” said Prof Bragg.

The vaccines used around the world in an attempt to control this disease are all inactivated vaccines. One of the most important points is the selection of the correct strains of the bacterium to use in the vaccine.

Prof Bragg established that in South Africa, there are four different serovars of the bacterium and one of these, the serovar C-3 strain, was believed to be unique to Southern Africa. He also recently discovered this serovar for the first time in Israel, thus indicating that this serovar might have a wider distribution than originally believed.

Vaccines used in this country did not contain this serovar. Prof Bragg established that the long term use of vaccines not containing the local South African strain resulted in a shift in the population distribution of the pathogen.

Prof Bragg’s research activities also include disease control in parrots and pigeons. “One of the main research projects in my group is on the disease in parrots caused by the circovirus Beak and Feather Disease virus. This virus causes serious problems in the parrot breeding industry in this country. This virus is also threatening the highly endangered and endemic Cape Parrot,” said Prof Bragg.

Prof Bragg’s research group is currently working on the development of a DNA vaccine which will assist in the control of the disease, not only in the parrot breeding industry, but also to help the highly endangered Cape Parrot in its battle for survival.

“Not all of our research efforts are directed towards infectious coryza or the Beak and Feather Disease virus. One of my Masters students is currently investigating the cell receptors involved in the binding of Newcastle Disease virus to cancerous cells and normal cells of humans. This work will also eventually lead to a possible treatment of cancer in humans and will assist with the development of a recombinant vaccine for Newcastle disease virus,” said Prof Bragg.

We are also currently investigating an “unknown” virus which causes disease problems in poultry in the Western Cape,” said Prof Bragg.

“Although disinfection has been extensively used in the poultry industry, it has only been done at the pre-placement stage. In other words, disinfectants are used before the birds are placed into the house. Once the birds are placed, all use of disinfectants stops,” said Prof Bragg.

“Disinfection and bio security can be seen as the ‘Cinderella’ of disease control in poultry. This is also true for human medicine. One just has to look at the high numbers of people who die from hospital-acquired infections to realise that disinfection is not a concept which is really clear in human health care,” said Prof Bragg.

Much research has been done in the control of diseases through vaccination and through the use of antibiotics. “These pillars of disease control are, however, starting to crumble and more effort is needed on disinfection and bio security,” said Prof Bragg.

Prof Bragg has been working in close co-operation with a chemical manufacturing company in Stellenbosch to develop a unique disinfectant which his highly effective yet not toxic to the birds.

As a result of this unique product, he has developed the continual disinfection program for use in poultry. In this program the disinfectant is used throughout the production cycle of the birds. It is also used to ensure that there is excellent pre-placement disinfection.

“The program is extensively used for the control of infectious diseases in the parrot-breeding industry in South Africa and the product has been registered in 15 countries around the world with registration in the USA in the final process,” said Prof Bragg.

“Although the problem of plasmid mediated resistance to disinfectants is starting to rear its ugly head, this has allowed for the opening of a new research field which my group will hopefully exploit in the near future,” he said.

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