Tag: covid variants

Growing the Beta Variant – Young Scientist Remembers the Day They Danced in the Lab

By Biénne Huisman

During South Africa’s COVID-19 hard lockdown, Dr Sandile Cele became the first to successfully grow the beta variant of SARS-CoV-2 in the lab. PHOTO: Rosetta Msimango/Spotlight

In a Durban laboratory in 2020, there was dancing and scientists jumping with joy when Dr Sandile Cele realised they had finally successfully “grown” the SARS-CoV-2 Beta variant. It was the holiday season and Cele and a few colleagues had sacrificed their Christmas to continue research at an otherwise deserted laboratory.

The Beta variant (501Y.V2) was first detected in the Eastern Cape in October 2020 and was announced to the public on 18 December that year.

“It was December 2020 and Tulio [Professor Tulio de Oliveira] had just flagged the beta variant and we had been struggling trying to grow it, really struggling for about two weeks,” says Cele. “But then as a scientist, you have to think outside the box and eventually it [the virus] did catch on. I was with Professor Alex Sigal that day in the laboratory. We were so excited. There was a lot of dancing in the lab, jumping up and down…”

The 35-year-old’s work on the Beta and Omicron variants helped propel South Africa to the forefront of COVID-19 research. Cele is the scientist credited with growing both Beta and Omicron in record time as the world reeled under lockdown pressure. Last year, he was awarded a special ministerial Batho Pele excellence award for his contribution to COVID-19 research in South Africa.

The moment of greatest fulfilment

Speaking to Spotlight, Cele says growing the beta variant was the moment of greatest fulfilment in his career so far.

“It was just a crazy, crazy moment. Like, you know when you are with your superior, usually you meet on a basis of respect. I mean, you talk seriously. They ask a question, you answer, and so on. But [at] that moment, all that got thrown out the window. We were celebrating. So yes, it was really special.”

At the time, they were leaping with joy inside PPE (personal protective equipment), including specialised masks, double gloves, plastic sleeves, and boots. Cele points out that due to all the safety measures in place, infection risk was smaller in their lab than at an average mall.

He was working inside a state-of-the-art biosafety level 3 (BSL-3) laboratory at the Africa Health Research Institute (AHRI). The laboratory is on the third floor of the University of KwaZulu-Natal’s medicine building. In the same eight-storey glass and face brick building, on the first floor, de Oliveira had been studying virus samples for genetic clues at KRISP, the KwaZulu-Natal Research and Innovation Sequencing Platform, from where the discovery of Beta and Omicron was first announced.

How he did it – growing the beta variant

Cele explains that viruses are isolated or “outgrown” by infecting cells in the laboratory, using swab samples from infected individuals.

“Growing a virus simply means isolating it from an infected host (humans) and making more of it in the lab for research purposes,” Cele explains. “You cannot study a virus within an infected person, especially a new virus. You need to have it in the lab for identification and clarification. Usually, you get small quantities from an infected person, thus you have to expand or grow – or make more of it – for research.”

Photo by Shvets Production on Pexels

However, the beta variant had not responded like previous SARS-CoV-2 variants. At the time, Cele found a creative solution using both human and monkey cell lines. First, he infected human cell lines with the beta variant, incubating the assay for four days. Then he used the infected human cell lines to infect monkey cell lines, which successfully lead to production of the virus.

Their moment of triumph arrived when they noticed the monkey cell lines starting to die, meaning that the virus was growing. The isolated virus could then be used in the laboratory to run experiments, like testing vaccine efficacy.

“Looking at the cells under the microscope, you can see them starting to die,” he says. “That they’re not happy. That they have been infected, which then obviously needed to be confirmed.”

While Cele’s Durban mentors – de Oliveira and Sigal – kept the public abreast of research developments, the young scientist kept his head down, pouring over his microscopes. “The world was going crazy, everything was crazy, but I had work to do,” he says.

‘a rising star’

During the interview, Cele readily shares anecdotes and laughs often.

From Ndwedwe, a rural area forty kilometres north of Durban, Cele joined Sigal’s laboratory team at the AHRI in 2014, where he studied HIV drug resistance and later COVID-19. His PhD obtained from UKZN in 2021, focused specifically on understanding the beta variant and its escape from antibodies.

“Actually, Professor Alex Sigal really took a chance on me,” he says. “Because on that post for a laboratory technologist, they stipulated that they wanted someone with three years experience. And I had only been doing my internship [at the Technology Innovation Agency] for eight months.”

But Sigal’s faith paid off, and he subsequently praised Cele in national press interviews on COVID-19. “Sandile is a rising star who spent all his holidays in a laboratory,” Sigal told journalists in January 2021.

Last year, the Bill and Melinda Gates Foundation invited Cele to present his findings at the Grand Challenges Annual Meeting in Brussels. This was his first time abroad. “It was my first time traveling outside South Africa and my first time talking in front of so many people. I presented my go-to talk – based on a paper I did on COVID-infection and HIV – and it went well,” he says.

Earlier this year, Cele was named one of Mail & Guardian’s 200 trailblazing young South Africans in the technology and innovation category. At the time, he could not attend the gala event as he was at the University of Nairobi in Kenya for training relating to a project involving HIV research for the Aurum Institute. Cele started a new job at the Aurum Institute in Johannesburg in March.

Over Zoom, Cele is speaking from his new home in Johannesburg. He is wearing a fluffy blue robe over his clothes, laughing as he says how cold Johannesburg is coming from Durban.

A sudden death

In Ndwedwe, Cele was one of ten boys born to his father, who was away from home often for work. Describing his mother as “a busy lady”, Cele says she was the one who shaped his young everyday life. Growing up in a mud hut without electricity and running water, he recalls how his mother would get up early every morning to prepare vetkoek, which she sold at a local school, and to boil water so her children could have a bath before leaving for school.

In the afternoons, he would look after his father’s goats and play soccer. He says that as a child he preferred herding goats to cows, as goats grazed for only about five hours, whereas cows took all day to eat their fill. From Grade 9 on, he attended school in Durban, at Overport Secondary School.

A childhood memory that inspired him? “Before my mother died, she sat us down and said one day I will be gone and I want you to know there are no shortcuts in life. Work hard and look after one another and you will be okay.”

His mother’s death was sudden, following complications from minor surgery.

“Like, I came back from school on a Friday only to find my father wasn’t around and had left a note… On the Saturday morning, I found out my mother had passed. And I think she went for, I don’t know, an operation or something. But as a kid, I guess they didn’t tell us because they thought it was something minor; that she would get operated [on], then go back home. I’m not really sure what happened. So, yes, it was a sudden death.”

The year after his mother died, Cele’s matric marks suffered. He says his final grade 12 marks had been 48% for maths, 53% for physics, and 66% for biology.

“I wasn’t really studying, I couldn’t really concentrate,” he says. “There was a lot going on when I was doing my matric. My mother passing away… and also the move from a rural school to the city where we were taught in English, everything in English.”

Cele came to study biology quite at random. He applied to study at UKZN only in October of his matric year – with admissions to most of the university’s courses having closed the previous month. He picked one of the last remaining options, which had been biology.

Soon, the young student started excelling. Cele obtained his BSc Biomedical Sciences degree with a Dean’s commendation and his Honours in Medical Microbiology, summa cum laude. He completed his Masters in Biochemistry with an upper-class pass.

To the Mail and Guardian, he shared advice he would give to his younger self: “Do not be afraid, you are a force to be reckoned with.”

Cele’s driving passion is to advance public healthcare, which he will continue to do at the Aurum Institute – an organisation that amongst others does research into Africa’s tuberculosis and HIV response. Cele has a ten-year-old son who lives in Durban.

Note: The Bill and Melinda Gates Foundation is mentioned in this article. Spotlight receives funding from the foundation, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons licence.

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Don’t Panic About New SARS-CoV-2 Variant, Experts Say

By Biénne Huisman

COVID-19 has largely dropped out of the headlines, but the virus that causes it is still circulating. We ask what we should know about a new variant of SARS-CoV-2, the state of the COVID-19 pandemic in 2025, and the lack of access to updated vaccines in South Africa.

In the leafy Johannesburg suburb of Sandringham, the National Institute for Communicable Diseases (NICD) bears a deceptive facade. Do not be fooled by its sleepy campus, clustered face brick buildings and shade-cloth parking, this government facility is home to state-of-the-art biosafety laboratories and some of South Africa’s top virologists, microbiologists and epidemiologists. Here, 71 scientists are tasked daily with laboratory-based disease surveillance to protect the country from pathogen outbreak events.

On 5 March 2020, then health minister Dr Zweli Mkhize announced South Africa’s first COVID‑19 infection at an NICD press briefing. At the time, the NICD was an obscure acronym for many – but that quickly changed as the institution became central to the country’s pandemic response.

While the COVID-19 pandemic may have waned, the NICD hasn’t stopped monitoring.

That is because there remains a global public health risk associated with COVID-19. The World Health Organization (WHO) states: “There has been evidence of decreasing impact on human health throughout 2023 and 2024 compared to 2020-2023, driven mainly by: 1) high levels of population immunity, achieved through infection, vaccination, or both; 2) similar virulence of currently circulating JN.1 sublineages of the SARS-CoV-2 virus as compared with previously circulating Omicron sublineages; and 3) the availability of diagnostic tests and improved clinical case management. SARS-CoV-2 circulation nevertheless continues at considerable levels in many areas, as indicated in regional trends, without any established seasonality and with unpredictable evolutionary patterns.”

Thus, while SARS-CoV-2 is still circulating, it is clearly not making remotely as many people ill or claiming nearly as many lives as it did four years ago. Asked about this, Foster Mohale, spokesperson for the National Department of Health, says “there are no reports of people getting severely sick and dying due to COVID-19 in South Africa at the current moment”.

‘Variant under monitoring’

As SARS-CoV-2 circulates, it continues to mutate. The WHO recently designated variant NB.1.8.1 as a new variant under monitoring. There is however no reason for alarm. Professor Anne von Gottberg, laboratory head at the NICD’s Centre for Respiratory Diseases and Meningitis, tells Spotlight that NB.1.8.1 is not a cause for panic, particularly not in South Africa.

Von Gottberg says no cases of the new variant has been detected in South Africa. She refers to her unit’s latest surveillance of respiratory pathogens report for the week of 2 to 8 June 2025. It states that out of 189 samples tested, 41 (21.7%) cases were influenza, another 41 (21.7%) cases were respiratory syncytial virus (RSV), and three (1.6%) cases were earlier strains of SARS-CoV-2.

These figures suggest much greater circulation of influenza and RSV in South Africa than SARS-CoV-2. Over the past six months, 3 258 samples were tested, revealing 349 (10.7%) cases of influenza, 530 (16.3%) cases of RSV, and 106 (3.3%) cases of SARS-CoV-2. Since most people who become sick because of these viruses are not tested, these figures do not paint the whole picture of what is happening in the country.

As of 23 May 2025, the WHO considered the public health risk of NB.1.8.1 to be “low at the global level”, with 518 iterations of the variant submitted from 22 countries, mainly around Asia and the Pacific islands.

The WHO report states: “NB.1.8.1 exhibits only marginal additional immune evasion over LP.8.1 [first detected in July 2024]. While there are reported increases in cases and hospitalisations in some of the WPR [Western Pacific Region] countries, which has the highest proportion of NB.1.8.1, there are no reports to suggest that the associated disease severity is higher as compared to other circulating variants. The available evidence on NB.1.8.1 does not suggest additional public health risks relative to the other currently circulating Omicron descendent lineages.”

Combating misinformation

Von Gottberg says that the NICD plays a critical public health communication role in combating misinformation and warns against alarmist and inaccurate online depictions of NB.1.8.1, the Omicron-descendent lineage dubbed “Nimbus” by some commentators.

“There’s fake news about NB.1.8.1 going around on social media,” she says. “For example, supposed symptoms. I have been trying to look for articles and have not seen anything from [reliable sources],” she says. “In fact, there is no information about whether there are any differences in symptoms, because there are so few cases and it is not causing more severe disease.”

Von Gottberg implores members of the public to check information sources. “We try hard – and the Department of Health does the same – to put media releases out so that accurate information is shared. What we ask is that all our clients, the public, verify information before they start retweeting or resending.”

COVID-19 vaccines in South Africa

The WHO recommends that countries ensure continued equitable access to and uptake of COVID-19 vaccines. They also note that the currently approved COVID-19 vaccines are expected to remain effective against the new variant. But contrary to WHO advice, newer COVID-19 vaccines are not available in South Africa and continued access to older vaccination seems to have ceased. When Spotlight called two branches of two different major pharmacy retailers in Cape Town asking for available COVID-19 vaccines, the answer at both was that they have none.

Several recently approved COVID-19 vaccines are being used in other countries but are not available in South Africa. These include Moderna’s updated mRNA boosters, approved in the United States and parts of Europe, Novavax’s Nuvaxovid vaccine, approved in the United States, and Arcturus Therapeutics’s self-amplifying mRNA vaccine Zapomeran, approved in Europe. Self-amplifying mRNA vaccines has the additional capacity to induce longer lasting immune responses by replicating the spike-proteins of SARS-CoV-2.

None of these vaccines are under review for registration in South Africa, according to the South African Health Products Regulatory Authority (SAHPRA). Vaccines may not be made available in the country without the green light from SAHPRA. “It may be advisable to contact the owners of the vaccines to obtain clarity on whether they intend to submit for registration,” says SAHPRA spokesperson Yuven Gounden.

Spotlight on Friday sent questions to Moderna, Novavax, and Arcturus, asking whether they plan to submit their vaccines for registration with SAHPRA, and if not, why not. None of the companies responded by the time of publication.

Von Gottberg explains that vaccines can only become available in South Africa if their manufacturers submit them to SAHPRA for approval. “So, if a vaccine provider, a vaccine manufacturer, does not want to sell in our country because they do not see it as a lucrative market, they may not even put it forward for regulation so that it can be made available.”

Professor of Vaccinology at the University of the Witwatersrand, Shabir Madhi, says the major concern with the lack of licensed SARS-CoV-2 vaccines in South Africa is that “high-risk individuals remain susceptible to severe COVID-19, as there is waning of immunity”.

“High-risk individuals should receive a booster dose every 6-12 months, preferably with the vaccine that is updated against current or most recent variants,” he says.

Von Gottberg has similar concerns. “My hope as a public health professional is that these vaccine manufacturers take us seriously as a market in South Africa and in Africa, very importantly, and put these vaccines and products through our regulatory authorities so that they can be made available both in the public and in the private sector for all individuals who are at risk and should be receiving these vaccines,” she says.

Gounden notes that should a public health need arise, “SAHPRA is ready to respond in terms of emergency use approval.”

Concerns over vaccine expert dismissals in the United States

Earlier this month in the United States, Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. fired all 17 members of the Advisory Committee on Immunisation Practices (ACIP) – an expert body responsible for recommending vaccines for 60 years. He then appointed eight new members, some known for vaccine skepticism.

Commenting on this, Von Gottberg says: “I am hoping there will be those who will think about what he [Kennedy] is doing and question it. It is an unusual situation in the United States, you cannot call it business as usual.”

In an article published in the Journal of the American Medical Association, former ACIP members voice grave concerns over the dismissals. “Vaccines are one of the greatest global public health achievements. Vaccine recommendations have been critical to the global eradication of smallpox and the elimination of polio, measles, rubella, and congenital rubella syndrome in the US. They have also dramatically decreased cases of hepatitis, meningitis, mumps, pertussis (whooping cough), pneumonia, tetanus, and varicella (chickenpox), and prevented cancers caused by hepatitis B virus and human papilloma viruses. Recent scientific advancements enabled the accelerated development, production, and evaluation of COVID-19 vaccines…,” they write.

The article also questioned the announcement by Kennedy Jr. on X that he had signed a directive to withdraw the recommendation for COVID-19 vaccination in healthy children and healthy pregnant people.

“[R]ecent changes to COVID-19 vaccine policy, made directly by the HHS secretary and released on social media, appear to have bypassed the standard, transparent and evidence-based review process. Such actions reflect a troubling dis-regard for the scientific integrity that has historically guided US immunisation strategy,” the authors warn.

Von Gottberg adds: “We hope that this anti-vax, the denialism of vaccines and the good they do, won’t come to South Africa.”

In addition, she cautions public healthcare professionals to take heed of this discourse. “We must take seriously that people have questions, and that they want to see us doing things correctly, transparently, always telling people of our conflicts of interest, being very upfront when things are controversial, when it’s difficult to make decisions,” she says. “So I think what this teaches us is not to be complacent in the way we talk and write about vaccines, discuss vaccines, and we must take our clients, the public out there seriously and hear their voices, listen to their questions.”

Republished from Spotlight under a Creative Commons licence.

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New Antibodies Potentially Effective Against All SARS-CoV-2 Variants

Image by Fusion Medical on Unsplash

SARS-COV-2 has been very good at mutating to keep infecting people – so good that most antibody treatments developed during the pandemic are no longer effective. Now a team led by Stanford University researchers may have found a way to pin down the constantly evolving virus and develop longer-lasting treatments.

The researchers discovered a method to use two antibodies, one to serve as a type of anchor by attaching to an area of the virus that does not change very much and another to inhibit the virus’s ability to infect cells. This pairing of antibodies was shown to be effective against the initial SARS-CoV-2 virus that caused the pandemic and all its variants through omicron in laboratory testing. The findings are detailed in the journal Science Translational Medicine.

“In the face of an ever-changing virus, we engineered a new generation of therapeutics that have the ability to be resistant to viral evolution, which could be useful many years down the road for the treatment of people infected with SARS-CoV-2,” said Christopher O. Barnes, the study’s senior author, an assistant professor of biology.

An overlooked option

The team led by Barnes and first author Adonis Rubio, a doctoral candidate in the Stanford School of Medicine, conducted this investigation using donated antibodies from patients who had recovered from COVID-19. Analysing how these antibodies interacted with the virus, they found one that attaches to a region of the virus that does not mutate often.

This area, within the Spike N-terminal domain, or NTD, had been overlooked because it was not directly useful for treatment. However, when a specific antibody attaches to this area, it remains stuck to the virus. This is useful when designing new therapies that enable another type of antibody to get a foothold and attach to the receptor-binding domain, or RBD, of the virus, essentially blocking the virus from binding to receptors in human cells.

An illustration of the bispecific antibodies the Stanford-led research team developed to neutralise the virus that causes COVID-19. Named “CoV2-biRN,” these two antibodies work together by attaching to different areas of the virus.
The bispecific antibodies target two areas of the virus: One attaches to the “NTD,” or Spike N-terminal domain, an area on the virus that does not change very much. This allows the second antibody to attach to the “RBD,” or receptor-binding domain, essentially preventing the virus from infecting human cells. | Christopher O. Barnes and Adonis Rubio using Biorender stock images

The researchers designed a series of these dual or “bispecific” antibodies, called CoV2-biRN, and in laboratory tests they showed high neutralisation of all the variants of SARS-CoV-2 known to cause illness in humans. The antibodies also significantly reduced the viral load in the lungs of mice exposed to one version of the omicron variant.

More research, including clinical trials, would have to be done before this discovery could be used as a treatment in human patients, but the approach is promising – and not just for the virus that causes COVID-19.

Next, the researchers will work to design bispecific antibodies that would be effective against all coronaviruses, the virus family including the ones that cause the common cold, MERS, and COVID-19. This approach could potentially also be effective against influenza and HIV, the authors said.

“Viruses constantly evolve to maintain the ability to infect the population,” Barnes said. “To counter this, the antibodies we develop must continuously evolve as well to remain effective.”

Source: Stanford University

New SARS-CoV-2 Variant BA.2.86 not as Resistant to Antibodies as First Feared

Image by Fusion Medical on Unsplash

Researchers studying the new SARS-CoV-2 variant BA.2.86 have found that the new variant was not significantly more resistant to antibodies than several other circulating variants. Their study, published in The Lancet Infectious Diseases, also showed that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86.

The recently emerged BA.2.86 is very different from any other currently circulating variants. It includes many mutations in the spike gene, reminiscent of the emergence of Omicron.  The virus uses the viral spike to infect cells and is the main target for our antibodies.  When the spike mutates, it comes with the risk that our antibodies are less effective against this new ‘variant’, and therefore that our protection from infection is reduced and that vaccines may need to be updated.

“We engineered a spike gene that matches that of the BA.2.86 variant and tested the blood of Stockholm blood donors (specifically those donations made very recently) to see how effective their antibodies are against this new variant. We found that although BA.2.86 was quite resistant to neutralising antibodies, it wasn’t significantly more resistant than a number of other variants that are also circulating”, says Daniel Sheward, lead author of the study and Postdoctoral researcher in Benjamin Murrell’s team at Karolinska Institutet.

An important question is whether upcoming updated vaccines that are based on the XBB variant will boost protection against BA.2.86.  To determine whether antibodies triggered by infection with XBB may be effective against this new variant, Ben Murrell’s team also compared samples taken before and after XBB spread in Sweden.

“We also found that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86. However, BA.2.86 was resistant to all available monoclonal antibody therapeutics that we tested,” says Daniel Sheward.

Public health agencies need to know what the current level of immunity to this new variant is, and whether the vaccines are sufficient must be updated.  Monoclonal antibodies also represent an important option for some patient groups, such as the immunocompromised – for the clinicians, it’s important to know which if any, monoclonal antibody therapeutics will be effective against the variants that are circulating.  

“I think the main message is that there is currently no reason to be alarmed over this new variant and that it’s probably a good idea to get a booster vaccine when they are offered.  However, another ‘omicron-like’ event is also a reminder that we shouldn’t get complacent”, says Benjamin Murrell, Principal researcher at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

Source: Karolinska Institutet

How SARS-CoV-2 Evolved Past its Own Weaknesses

Image from Pixabay

New research suggests that the first pandemic-accelerating mutation in the SARS-CoV-2 virus evolved as a way to correct vulnerabilities that were caused by the mutation that started the SARS-CoV-2 pandemic.

Published in Science Advances, this new evidence addresses important biological questions about two key mutations in the virus’ surface spike protein, say the researchers. It suggests that a spike protein mutation called D614G, which emerged a few months after the virus began spread among humans, was not an adaptation to humans. Instead, the mutation was an adaptation to the major changes that happened in the spike gene just before the pandemic, changes which allowed spread via respiratory transmission.

“This study has revealed that the first two genetic alterations in the evolution of the spike protein in SARS-CoV-2 are connected by their function, and this knowledge can improve our understanding of how the spike protein works and how the virus evolves, with important implications for vaccine design and effectiveness of COVID antibodies,” says Stephen Gould, professor of biological chemistry at the Johns Hopkins University School of Medicine, whose lab was studying the basic biology of the virus’s spike protein when the study began.

The initial mutation in the virus, Gould says, is known by scientists as the “furin cleavage site insertion mutation.”

Research by other scientists across the world has shown that this mutation enabled the virus’s spike protein to be cut and primed it for rapid infection of cells lining the airway.

While this initial mutation was essential in helping SARS-CoV-2 efficiently slip into human cells, the mutation’s effects weren’t all good, says Gould, as it cut the spike protein structure into two separate pieces.

According to Gould, this change disrupted other functions of the spike protein, creating evolutionary pressure for a second mutation to correct the disrupted functions of the spike protein while keeping the initial mutations’ rapid infection benefits .

In early 2020, researchers from the University of Toronto discovered a subsequent SARS-CoV-2 mutation, called D614G; however, its precise function was not known.

Gould, first author and graduate student Chenxu Guo, and the research team set out to understand the D614G mutation and its effect.

Working with dozens of blood samples from patients with COVID-19 hospitalized in April 2020 at the Johns Hopkins Hospital, Gould’s team isolated antibodies for the spike protein from the patients’ blood samples. Then, they used these antibodies to track the location of spike proteins in human cells genetically engineered to produce the spiky surface molecules.

They found that the D614G mutation redirects the spike protein and pulls the virus from the surface of human cells into a tiny compartment within the cell called a lysosome, which the spike protein reprograms into storage containers that are used to release infectious virus particles from the cell.

In addition, the D614G mutation caused a three-fold drop in the abundance of spike proteins at the cell surface.

“With less spike protein on the surface of virus-infected cells, it may be more difficult for the immune system to identify and kill those virus-containing cells,” says Gould.

The researchers caution that the study does not provide information about the still-debated origins of the virus. However, their work suggests that the two mutations likely arose in rapid succession.

The researchers are new examining whether spike protein mutations in more recent virus strains affect spike protein trafficking, studying the identity of the human proteins that deliver spike proteins to lysosomes, and researching how spike proteins convert lysosomes into compartments that release more virus.

Source: John Hopkins Medicine

Children’s Nasal Epithelium Protective against Older COVID Variants

Photo by Kelly Sikkema on Unsplash

An Australian study published in PLOS Biology suggests the nasal epithelium of children inhibits infection and replication of the ancestral strain of the SARS-CoV-2 virus and also the Delta variant, but not the Omicron variant.

Children are in general less susceptible to COVID, with a lower infection rate and milder symptoms than adults. However, the factors driving this apparent paediatric resistance to COVID infections remained unknown.

In order to better understand infection and replication of SARS-CoV-2 in children, Kirsty Short at University of Queensland, and colleagues, obtained samples of primary nasal epithelium cells from twenty-three healthy children aged 2–11 and fifteen healthy adults aged 19–66 in Australia. They exposed the cells of adults and children to SARS-CoV-2 and then observed the infection kinetics and antiviral responses in children compared to adults.

The researchers found that ancestral SARS-CoV-2 replicated less efficiently and was associated with a heightened antiviral response in the nasal epithelial cells of children. This lower viral replication rate was also observed with the Delta variant, but not the Omicron variant.

Study limitations included a small sample size, so future clinical studies will be needed to validate these preliminary findings in a larger population and to determine the role of other factors, such as antibodies in protecting children from SARS-CoV-2 infection. Additionally, paediatric protection from emerging variants has yet to be quantified.

The authors wrote, “We have provided the first experimental evidence that the paediatric nasal epithelium may play an important role in reducing the susceptibility of children to SARS-CoV-2. The data strongly suggest that the nasal epithelium of children is distinct and that it may afford children some level of protection from ancestral SARS-CoV-2.”

Short added, “We use nasal epithelial cells from children and adults to show that the ancestral SARS-CoV-2 and Delta, but not Omicron, replicate less efficiently in paediatric nasal epithelial cells.”

Source: Science Daily

SARS-CoV-2 Variants are Evolving to Evade Human Interferons

SARS-CoV-2 infecting a human cell
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID

Researchers have investigated how antiviral proteins called interferons interact with SARS-CoV-2. The study, published in PNAS, focuses on how the innate immune system defends against this coronavirus, which appears to be adapting to evade this interferon response.

The study was the result of a collaborative effort, including the laboratories of Mario Santiago, PhD, associate professor of medicine and Eric Poeschla, MD, professor of medicine, both at the University of Colorado School of Medicine.

While the adaptive arm of the immune system robustly deals with infection by generating antibodies and T cells, the innate arm forms an earlier, first line of defence by recognising conserved molecular patterns in pathogens.

“SARS-CoV-2 just recently crossed the species barrier into humans and continues to adapt to its new host,” said Prof Poeschla. “Much attention has deservedly focused on the virus’s serial evasions of neutralising antibodies. The virus seems to be adapting to evade innate responses as well.”

The type I Interferon system is a major player in antiviral defence against all kinds of viruses. Virus-infected cells release type I interferons (IFN-α/β), which warn the body of the intrusion. Secreted interferons cause susceptible cells to express powerful antiviral mechanisms to limit viral growth and spread. The interferon pathway could significantly reduce the levels of virus initially produced by an infected individual.

“They are clinically viable therapeutic agents that have been studied for viruses like HIV-1 for years,” explained Prof Santiago. “Here we looked at up to 17 different human interferons and found that some interferons, such as IFNalpha8, more strongly inhibited SARS-CoV-2. Importantly, later variants of the virus have developed significant resistance to their antiviral effects. For example, substantially more interferon would be needed to inhibit the omicron variant than the strains isolated during the earliest days of the pandemic.”

The data suggests that COVID clinical trials on interferons, dozens of which are listed in clinicaltrials.gov, may need to be interpreted based on which variants were circulating when the study was conducted. Researchers say that future work to decipher which of SARS-CoV-2’s multitude of proteins might be evolving to confer interferon resistance may contribute in that direction.

Source: University of Colorado Anschutz Medical Campus

mRNA Vaccines Perform Better against Variants of Concern

Image from Pixabay

A comparison of vaccinations has demonstrated that mRNA vaccines perform better against variants of concern (VOCs) than viral vector vaccines. Although they all effectively prevent severe disease by VOCs, the research published in PLOS Medicine suggests that people receiving a viral vector vaccine are more vulnerable to infection by new variants.

The Pfizer-BioNTech and Moderna are mRNA vaccines, which deliver genetic code to the bodies’ cells, whereas Oxford/AstraZeneca and J&J are viral vector vaccines which uses a modified virus to deliver instructions. J&J is delivered as a single dose while the rest are administered two weeks apart.

Marit J. van Gils at the University of Amsterdam, Netherlands, and colleagues, took blood samples from 165 healthcare workers, three and four weeks after first and second vaccination respectively, and for J&J at four to five and eight weeks after vaccination. Samples were collected before, and four weeks after a Pfizer-BioNTech booster.

Four weeks after the initial two doses, antibody responses to the original SARS-CoV-2 viral strain were highest in recipients of Moderna, followed closely by Pfizer-BioNTech, and were substantially lower in those who received viral vector vaccines. Tested against the VOCs Alpha, Beta, Gamma, Delta and Omicron, neutralising antibodies were higher in the mRNA recipients than the viral vector recipients. Neutralisation ability against VOCs was reduced in all vaccine groups, with the greatest reduction against Omicron. The Pfizer-BioNTech booster increased antibody responses in all groups with substantial improvement against VOCs, including Omicron.

The researchers caution that their AstraZeneca group was significantly older, because of safety concerns for the vaccine in younger age groups. As immune responses tend to weaken with age, this could affect the results. This group was also smaller because the Dutch government halted use for a period.

Source: EurekAlert!

Scientists Pry Open Secrets of a Potent Antibody against COVID

Even as the structure of SARS-CoV-2 changes with different variants of the virus (grey), the J08 antibody (blue) can still bind it, Scripps researchers showed. Credit: Scripps Research

Scientists have revealed the secrets of a potent antibody against SARS-CoV-2 that was discovered in COVID survivors. The antibody has a broadly neutralising effect, and is able to retain its efficacy against a wide range of variants – though not Omicron.

In 2021, Scripps Research and Toscana Life Sciences scientists screened the blood of 14 COVID-19 survivors to find the most potent antibodies against the SARS-CoV-2 virus. One of the most promising finds, now in stage II/III trials, was an antibody dubbed J08, which seemed to be capable of both preventing and treating COVID. 

Now, the same group has visualised exactly how J08 binds to different SARS-CoV-2 variants in different conformations, explaining what makes the monoclonal antibody so potent. The research, published in Proceedings of the National Academy of Sciences, suggests that the J08 antibody’s flexibility will likely keep it effective against future COVID variants.

“Even though we can’t predict what variants of COVID will emerge next, understanding the details of J08 reveals what works against the virus, and perhaps how we can engineer antibodies to be even more potent,” explained senior author Andrew Ward, PhD at Scripps Research.

On exposure to a virus like SARS-CoV-2, the body creates a variety of antibodies that bind to different sections of the virus to clear it from the body. There is considerable interest in why certain naturally produced antibodies such as J08 more effective than others. In the months after Ward and his collaborators first identified J08, it became clear that the antibody, unlike many others, was potent against a variety of COVID variants.

The researcher mapped the three-dimensional structure of J08 as it bound to the spike protein of SARS-CoV-2. J08 was confirmed to successfully attach to the Alpha, Beta, Gamma and Delta variants, preventing replication. However, J08 attached to the Omicron variant about 7 times more slowly, and then quickly detached. About 4000 times more J08 was needed to fully neutralise Omicron SARS-CoV-2 compared to the other variants.

“With variants other than Omicron, this antibody binds quickly and doesn’t come off for hours and hours,” says co-first author Gabriel Ozorowski, a senior staff scientist in the Ward lab at Scripps Research. “With Omicron, we were initially happy to find that it still binds, but it falls off very quickly. We identified the two structural changes that cause this.”

The team showed that, for all the variants, J08 binds to a very small section of the virus – a section that generally stays the same even as the virus mutates. Moreover, J08 could attach in two completely different orientations, like a key that manages to unlock a door whether it is right side up or upside down. 

“This small, flexible footprint is part of why J08 is able to withstand so many mutations – they don’t impact the antibody binding unless they happen to be in this one very small part of the virus,” said co-first author Jonathan Torres, lab manager of the Ward lab at Scripps Research.

The Omicron variant of SARS-CoV-2, however, had two mutations (known as E484A and Q493H) that changed the small area of the virus that directly interfaces with J08, anchoring it in place. Ward and his collaborators found that if just one of these mutations is present, J08 can still bind and neutralise the virus strongly, but mutations in both are what make it less effective against the Omicron variant.

The researchers said the new results support the continued clinical trials of the monoclonal antibody based on J08.

“I think we’re pretty confident that future variants won’t necessarily have both of these two critical mutations at the same time like Omicron,” remarked Ozorowski, “so that makes us hopeful that J08 will continue being very effective.”

Source: Scripps Research

SA Doctors Report SARS-CoV-2 Mutations in a Patient with HIV

HIV Infecting a T9 Cell. Credit: NIH

In an article awaiting peer review, doctors in South Africa report on the case of a 22-year-old female with uncontrolled advanced HIV infection and a SARS-CoV-2 infection that lasted 9 months, during which time the virus accumulated more than 20 additional mutations. Antiretroviral therapy suppressed HIV and cleared the coronavirus within 6–9 weeks. 

One hypothesis for novel variants is that they arise in severely immunocompromised individuals. Being unable to clear the virus because of a weakened immune response results in a persistent infection, letting mutations accumulate – some of which may allow immune evasion. In one case, SARS-CoV-2 in a female leukaemia patient developed seven mutations over three months of infection.

The authors describe a case of persistent SARS-CoV-2 infection, lasting for at least 9 months, in a severely immunocompromised woman with HIV that had challenges with adherence to antiretroviral therapy.

In mid-September 2021, a female in her 20s was admitted to a tertiary hospital in Cape Town with a one-week history of sore throat, malaise, poor appetite and dysphagia. The patient was infected with HIV at birth. In January 2021, her antiretroviral therapy (ART) regimen had been changed to tenofovir, emtricitabine and efavirenz, but she had difficulty adhering. In August 2021 she moved from rural KwaZulu-Natal to Cape Town. She stated that she had not received a COVID vaccination.

“On physical examination, the patient was wasted but had no palpable lymph nodes,” the authors report. “She was awake and lucid, with no focal neurological deficits. She was not in respiratory distress with an oxygen saturation of 98% on room air. The cardiovascular and abdominal examinations, renal function, white cell count and liver enzymes were without abnormalities. Her CD4 count was 9 cells/μL and her plasma HIV viral load 4.60 log10 viral RNA copies/mL, indicating advanced HIV infection, poorly controlled by ART.

“During a prolonged hospital stay the patient experienced multiple complications requiring treatment. Following adherence counselling, antiretroviral therapy was reinitiated with a new regimen of tenofovir/efavirenz/dolutegravir a week after admission.” 

The patient tested positive for COVID on 25 September 2021, with genomic sequencing indicating the Beta variant. However, in October, the patient later revealed that she had tested positive for COVID in January 2021. On 25 November 2021, the patient’s HIV viral load was <50 copies/ml and a PCR test was negative for COVID. While there was no CD4 count performed, suppressed HIV replication and clearance of the SARS-CoV-2 infection suggest her immune system had recovered to some degree.

Phylogenetic analysis showed that the samples indicated an ongoing infection instead of re-infections. During the 9 months of infection, the virus acquired at least 10 mutations in the spike glycoprotein and 11 other mutations over and above the lineage-defining mutations for Beta.

The authors consider it unlikely that the novel variant described spread into the general population, and stress that it does not prove that any of the other novel variants originated from an immunocompromised host in this fashion.

Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants. They ascribed the detection of the case to good connections between sequencing laboratories, routine diagnostic laboratories and frontline clinicians.

The authors concluded that their experience “reinforces previous reports that effective ART is the key to controlling such events. Once HIV replication is brought under control and immune reconstitution commences, rapid clearance of SARS-CoV-2 is achieved, probably even before full immune reconstitution occurs. This underscores the broader point that gaps in the HIV care cascade need to be closed which will benefit other conditions and public health problems, too, including COVID.”