SARS-CoV-2 viruses (yellow) infecting a human cell (blue). Photo by CDC on Pexels
Researchers at the Medical University of Vienna and the Medical University of Innsbruck discovered that SARS-CoV-2 hijacks three important host proteins that dampen the activity of the complement system, a key component of early antiviral immunity. This significantly impairs viral clearance which may affect the course of both acute COVID infections and post-COVID sequelae. The study was recently published in the journal Emerging Microbes & Infections.
An early and effective immune response is crucial for resolving viral infections and preventing post-infectious complications. The complement system, a pivotal element of antiviral immunity, is a cascade of proteins found in the bloodstream and at mucosal sites, such as the respiratory tract. Activated through three different pathways, complement facilitates the clearance of virus particles by directly inducing their destruction (lysis). To prevent bystander damage to host cells, complement is rapidly inactivated by a set of host molecules referred to as complement regulatory proteins. The new study led by Anna Ohradanova-Repic and colleagues from the Center for Pathophysiology, Infectiology and Immunology at the Medical University of Vienna in collaboration with the team of Heribert Stoiber from the Institute of Virology at the Medical University of Innsbruck shows that SARS-CoV-2 hijacks three of these regulatory proteins, CD55, CD59 and Factor H, and thereby successfully shields itself from complement-mediated lysis.
Hijacking host proteins for effective complement resistance
By propagating SARS-CoV-2 in human cells the researchers discovered that the virus particles acquire the cellular proteins CD55 and CD59. Further experiments showed that SARS-CoV-2 also binds to Factor H, another complement regulatory protein that is primarily found in the bloodstream. Confronting the virus particles with active complement revealed that they are partially resistant to complement-mediated lysis. By removing CD55, CD59 and Factor H from the virus surface or inhibiting their biological functions, the researchers could successfully restore complement-mediated clearance of SARS-CoV-2.
“Through hijacking these three proteins, SARS-CoV-2 can evade all three complement pathways, resulting in reduced or delayed viral clearance by the infected host,” Anna Ohradanova-Repic, the leader of the study explains. Because complement is intricately linked with other components of the immune system, this not only affects virus elimination but can also cause significant inflammation, a core feature of both severe COVID-19 and Long COVID. “Uncovering immune evasion mechanisms that allow the virus to linger within the host for longer, deepen our understanding of the acute and long-term impacts of SARS-CoV-2 infection,” says first author Laura Gebetsberger.
An analysis of data in the UK Biobank has found that COVID infection may increase the risk of myocardial infarction (MI), stroke and death from any cause for up to three years for people with and without cardiovascular disease, according to new research published in the American Heart Association’s peer-reviewed journal Arteriosclerosis, Thrombosis and Vascular Biology (ATVB).
“We found a long-term cardiovascular health risk associated with COVID, especially among people with more severe COVID cases that required hospitalisation,” said lead study author James Hilser, M.P.H., Ph.D.-candidate at the University of Southern California Keck School of Medicine in Los Angeles. “This increased risk of heart attack and stroke continued three years after COVID infection. Remarkably, in some cases, the increased risk was almost as high as having a known cardiovascular risk factor such as Type 2 diabetes or peripheral artery disease.”
Previous research has shown that COVID increases the risk of serious cardiovascular complications within the first month after infection. This study examined how long the increased risk lasted and whether it subsided after recovering from COVID infection.
Researchers reviewed health and genetic data in the UK Biobank for more than 10 000 adults, including approximately 8000 who had tested positive for SARS-CoV-2 from February 1 to December 31, 2020 and about 2000 who tested positive for the virus in a hospital setting in 2020. A group of more than 200,000 adults who had no history of COVID infection during the same time frame in the UK Biobank were also reviewed for comparison. None of the participants were vaccinated at the time of infection because COVID vaccines were not yet available in 2020.
The analysis found:
During the nearly 3-year follow-up period, the risk of heart attack, stroke and death was more than two times higher among adults who had COVID, and nearly four times greater among adults hospitalized with COVID, compared with the group with no history of COVID infection.
People hospitalized with COVID, without cardiovascular disease or without Type 2 diabetes, had a 21% greater risk of heart attack, stroke and death compared to people with cardiovascular disease and without COVID infection.
There was a significant genetic interaction among the non-O blood types and hospitalisation for COVID. People with severe COVID infections had an increased risk of heart attack and stroke, however, that risk was even higher in people who had non-O blood types (those with blood types A, B or AB).
The risk of heart attack and stroke was about 65% higher in adults with non-O blood types compared to those who had type O blood. A preliminary analysis did not show that Rh (positive or negative) blood type interacted with severe COVID, the authors noted.
“Worldwide, over a billion people have already experienced COVID infection. The findings reported are not a small effect in a small subgroup,” said co-senior study author Stanley Hazen, M.D., Ph.D., chair of cardiovascular and metabolic sciences in Cleveland Clinic’s Lerner Research Institute and co-section head of preventive cardiology. “The results included nearly a quarter million people and point to a finding of global health care importance that may translate into an explanation for a rise in cardiovascular disease around the world.”
Study details, background and design:
Health data was from the UK Biobank, a large-scale study of 503,325 adults living in the United Kingdom who were 40 to 69 years of age at enrollment between 2006 and 2010. The in-depth health and biomedical information was collected for participants registered in the UK National Health Service with a UK general practitioner (similar to a primary care physician in the U.S.).
This analysis included health data for 10,005 adults who tested positive for the COVID virus or were hospitalized with COVID between February 1, 2020, and December 31, 2020. An additional 217,730 peers enrolled in the UK Biobank who did not have COVID during the same time period were included. In the analysis, all participants were matched as closely as possible for demographics and similar health conditions.
Major adverse cardiovascular events (heart attack, stroke and all-cause death) were evaluated for long-term risk, through October 31, 2022, approximately 3 years later.
“This interesting paper is really two studies in one,” said Sandeep R. Das, M.D., M.P.H., MBA, FAHA, co-chair of the American Heart Association’s COVID-19 CVD Registry committee and director for quality and value in the cardiology division for UT Southwestern Medical Center in Dallas. “First, the authors show that having been hospitalized with COVID is a marker of increased cardiovascular risk, on par with having a pre-existing diagnosis of cardiovascular disease. Although proving direct cause and effect is very difficult to tease out in a study that only analyses past data collected for other purposes, this finding is important because it suggests a history of prior COVID hospitalization, even without a history of CVD, should be considered to initiate and possibly accelerate CVD prevention efforts. Whether severe COVID infection has a direct impact on the vascular system is an interesting area for study as well,” Das said.
“The second ‘study’ in this paper looks at the relationship between ABO blood type and COVID outcomes. They show that something located close to the genetic home of ABO blood type is associated with different degrees of susceptibility to COVID. This is really fascinating, and I look forward to seeing scientists tease out what the specific pathway may be.”
The study had several limitations, including that the data was from patients who had the original strain of the COVID virus before vaccines were widely available in 2021. Additionally, the researchers noted that UK Biobank information on medication use was not specific to the beginning of the pandemic in 2020 or the date that patients were infected with SARS-CoV-2. Also, because the majority of participants in the UK Biobank are white, additional research is needed to confirm that these results apply to people with diverse racial and ethnic backgrounds.
“The results of our study highlight the long-term cardiovascular effects of COVID infection. Given the increased risk of heart attack, stroke and death, the question is whether or not severe COVID should be considered as another risk factor for CVD, much like Type 2 diabetes or peripheral artery disease, where treatment focused on CVD prevention may be valuable,” said co-senior study author Hooman Allayee, Ph.D., a professor of population and public health sciences at the University of Southern California Keck School of Medicine in Los Angeles. “The results suggest that people with prior COVID infection may benefit from preventive care for cardiovascular disease.”
Even when participants knew they had placebos, their COVID anxiety reduced
Photo from Pixabay CCO
A study out of Michigan State University found that non-deceptive placebos, or placebos given with people fully knowing they are placebos, effectively manage stress – even when the placebos are administered remotely.
Researchers recruited participants experiencing prolonged stress from the COVID pandemic for a two-week randomised controlled trial. Half of the participants were randomly assigned to a non-deceptive placebo group and the other half to the control group that took no pills. The participants interacted with a researcher online through four virtual sessions on Zoom. Those in the non-deceptive placebo group received information on the placebo effect and were sent placebo pills in the mail along with instructions on taking the pills.
The study, which appears in Applied Psychology: Health and Well-Being, found that the non-deceptive group showed a significant decrease in stress, anxiety and depression in just two weeks compared to the no-treatment control group. Participants also reported that the non-deceptive placebos were easy to use, not burdensome and appropriate for the situation.
“Exposure to long-term stress can impair a person’s ability to manage emotions and cause significant mental health problems, so we’re excited to see that an intervention that takes minimal effort can still lead to significant benefits,” said Jason Moser, co-author of the study and professor in MSU’s Department of Psychology. “This minimal burden makes non-deceptive placebos an attractive intervention for those with significant stress, anxiety and depression.”
The researchers are particularly hopeful in the ability to remotely administer the non-deceptive placebos by health care providers.
“This ability to administer non-deceptive placebos remotely increases scalability potential dramatically,” said Darwin Guevarra, co-author of the study and postdoctoral scholar at the University of California, San Francisco, “Remotely administered non-deceptive placebos have the potential to help individuals struggling with mental health concerns who otherwise would not have access to traditional mental health services.”
Researchers in Belgium have discovered a new population of macrophages, important innate immune cells that populate the lungs after injury caused by respiratory viruses. These macrophages are instrumental in repairing the pulmonary alveoli. This groundbreaking discovery promises to revolutionise our understanding of the post-infectious immune response and opens the door to new regenerative therapies.
Respiratory viruses, typically causing mild illness, can have more serious consequences, as shown during the COVID pandemic, including severe cases requiring hospitalisation and the chronic sequelae of “long Covid.” These conditions often result in the destruction of large areas of the lungs, particularly the alveoli responsible for gas exchanges. Ineffective repair of these structures can lead to ARDS or a permanent reduction in the lungs’ ability to oxygenate blood, causing chronic fatigue and exercise intolerance.
While the role of macrophages during the acute phase of respiratory viral infections is well known, their function in the post-inflammatory period has been largely unexplored. This study by the GIGA Institute at the University of Liège reveals that atypical macrophages, characterised by specific markers and transiently recruited during the early recovery phase, play a beneficial role in regenerating pulmonary alveoli.
Led by Dr Coraline Radermecker and Prof. Thomas Marichal from the Immunophysiology Laboratory, the study was conducted by Dr Cecilia Ruscitti and benefited from the ULiège’s advanced technological platforms, including flow cytometry, fluorescence microscopy, and single-cell RNA sequencing. “Our findings provide a novel and crucial mechanism for alveolar repair by these atypical macrophages,” explains Coraline Radermecker. “We have detailed their characteristics, origin, location in the damaged lung, the signals they require to function, and their role in tissue regeneration, specifically acting on type 2 alveolar epithelial cells, the progenitors of alveolar cells.” The scientific community had overlooked these macrophages because they express a marker previously thought to be specific for another immune cell population, the neutrophils, and because they appear only briefly during the repair phase before disappearing.
“Our study highlights the reparative role of these macrophages, countering the prevailing idea that macrophages following respiratory viral infections are pathogenic,” adds Thomas Marichal. “By targeting the amplification of these macrophages or stimulating their repair functions, we could develop therapies to improve alveolar regeneration and reduce complications from serious respiratory infections and ARDS.”
To illustrate, consider the lungs as a garden damaged by a storm (viral infection). These newly discovered macrophages act like specialised gardeners who clear debris and plant new seeds, enabling the garden to regrow and regain its vitality.
Pro Secure fails in bid to stop Special Investigating Unit going after it to recover millions of rands
Photo by J Castellon on Unsplash
A company accused of unlawfully benefiting from a multi-million rand contract to supply personal protective equipment (PPE) during the Covid pandemic, has failed in a bid to quash a summons issued against it by the Special Investigating Unit to recover the money.
Pro Secure raised several objections to the formulation of the case against it in the papers. But Special Tribunal Judge Kate Pillay has dismissed the company’s objections and ordered the company to pay the costs.
The SIU investigation uncovered irregularities in the Limpopo Department of Health’s appointment of service providers including Pro Secure, Clinipro and Ndia Business Trading, which resulted in about R182-million irregular and wasteful expenditure. The SIU initiated action against Pro Secure, alleging the company had made “secret profits”, and also instituted civil proceedings against the former head of health in the province, Dr Thokozani Florence Mhlongo.
In October 2022, the SIU secured an order from the Special Tribunal, effectively freezing Mhlongo’s pension fund until the outcome of the civil action against her. Mhlongo resigned in June that year while facing disciplinary charges.
In its application to the Tribunal, Pro Secure challenged the SIU’s legal standing, the fact that the Limpopo health department was not a party to the SIU action. Pro Secure also claimed that there was no allegation that its bid for the contract was not lawful.
Judge Pillay found there was no substance to any of the company’s arguments.
She said the particulars of claim in the civil action set out how Pro Secure had received a payment “significantly exceeding their initial bid”.
She said that according to the SIU, the request for quotation sent by the department was for 5000 automated hand sanitisers. Pro Secure had submitted a quote for 5000 white electronic hand disinfectant dispensers and for 5000 liquid sanitisers, the total amount being just over R7-million. Ultimately, the company had delivered 30 000 dispenser holders at R420 per unit and 900 000 litres of hand sanitiser at R170 a litre and had been paid almost R162-million.
In a statement, SIU spokesperson Kaizer Kganyago said: “This ruling supports the SIU’s stance on the irregular procurement of PPE by the Limpopo Department of Health during the pandemic.”
A rare autoimmune disease has been newly described as a COVID-related syndrome, following an investigation by the University of California San Diego School of Medicine and Leeds University.
It started when Pradipta Ghosh, MD, a professor in the Departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, received an email from Dennis McGonagle, PhD, professor of investigative rheumatology at the University of Leeds in the UK. This was the beginning of an international collaboration, one that uncovered a previously overlooked COVID-related syndrome and resulted in a paper in eBioMedicine, a journal published by The Lancet.
McGonagle asked if she was interested in collaborating on a COVID-related mystery. “He told me they were seeing mild COVID cases,” Ghosh said. “They had vaccinated around 90 percent of the Yorkshire population, but now they were seeing this very rare autoimmune disease called MDA5 – autoantibody associated dermatomyositis (DM) in patients who may or may not have contracted COVID, or even remember if they were exposed to it.”
McGonagle told of patients with severe lung scarring, some of whom presented rheumatologic symptoms – rashes, arthritis, muscle pain – that often accompany interstitial lung disease. He was curious to know if there was a connection between MDA5-positive dermatomyositis and COVID.
“DM is more common in individuals of Asian descent, particularly Japanese and Chinese,” Ghosh said. “However, Dr McGonagle was noting this explosive trend of cases in Caucasians.”
“But that’s the least of the problem,” Ghosh said. “Because he said, ‘Oh, and by the way, some of these patients are progressing rapidly to death.'”
Ghosh is the founding director of the Institute for Network Medicine at UC San Diego School of Medicine, home to the Center for Precision Computational Systems Network (PreCSN – the computational pillar within the Institute for Network Medicine). PreCSN’s signature asset is BoNE – the Boolean Network Explorer, a powerful computational framework for extracting actionable insights from any form of big-data.
“BoNE is designed to ignore factors that differentiate patients in a group while selectively identifying what is common (shared) across everybody in the group,” Ghosh explained. Previous applications of BoNE allowed Ghosh and her team to identify other COVID-related lung and heart-afflicting syndromes in adults and children, respectively.
As a rheumatologist, McGonagle specialises in inflammatory and autoimmune conditions. Ghosh said that McGonagle’s roster of patients, all within the UK’s National Health System (NHS), helped to facilitate the investigation.
“The NHS has a centralised health care database with comprehensive medical records for a large population, making it easier to access and analyse health data for research purposes,” Ghosh explained.
Ghosh and McGonagle put together a team to probe what they found was indeed an entirely new syndrome.
The study began with McGonagle lab’s detection of autoantibodies to MDA5 – an RNA-sensing enzyme whose functions include detecting COVID and other RNA viruses. A total of 25 patients from the group of 60 developed lung scarring, also known as interstitial lung disease. Ghosh noted that the lung scarring was bad enough to cause eight people in the group to die due to progressive fibrosis. She said that there are established clinical profiles of MDA5 autoimmune diseases.
“But this was different,” Ghosh said. “It was different in behaviour and rate of progression – and in the number of deaths.”
Ghosh and the UC San Diego team explored McGonagle’s data with BoNE. They found that the patients who showed the highest level of MDA5 response also showed high levels of interleukin-15.
“Interleukin-15 is a cytokine that can cause two major immune cell types,” she explained. “These can push cells to the brink of exhaustion and create an immunologic phenotype that is very, very often seen as a hallmark of progressive interstitial lung disease, or fibrosis of the lung.”
BoNE allowed the team to establish the cause of the Yorkshire syndrome – and pinpoint a specific single nucleotide polymorphism that is protective. By right of discovery, the group was able to give the condition a name: MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with COVID. It’s MIP-C for short, “Pronounced ‘mipsy,'” Ghosh said, adding that the name was coined to make a connection with MIS-C, a separate COVID-related condition of children.
Ghosh said that it’s extremely unlikely that MIP-C is confined to the United Kingdom. Reports of MIP-C symptoms are coming from all over the world. She said she hopes the team’s identification of interleukin-15 as a causative link will jump start research into treatment.
There are viruses out there that nobody has on their radar, but they suddenly appear and, like SARS-CoV-2, can trigger major epidemics. They only have a slight genetic difference from before, the exchange of genetic material between different virus species can lead to the sudden emergence of threatening pathogens with significantly altered characteristics. This is suggested by current genetic analyses carried out by an international team of researchers. Virologists from the German Cancer Research Center (DKFZ) were in charge of the large-scale study which appears in PLOS Pathogens.
“Using a new computer-assisted analysis method, we discovered 40 previously unknown nidoviruses in various vertebrates from fish to rodents, including 13 coronaviruses,” reports DKFZ group leader Stefan Seitz. With the help of high-performance computers, the research team, which also includes Chris Lauber’s working group from the Helmholtz Center for Infection Research in Hanover, has sifted through almost 300 000 data sets. According to virologist Seitz, the fact that we can now analyse such huge amounts of data in one go opens up completely new perspectives.
Virus research is still in its relative infancy. Only a fraction of all viruses occurring in nature are known, especially those that cause diseases in humans, domestic animals and crops. The new method therefore promises a quantum leap in knowledge with regard to the natural virus reservoir. Stefan Seitz and his colleagues sent genetic data from vertebrates stored in scientific databases through their high-performance computers with new questions. They searched for virus-infected animals in order to obtain and study viral genetic material on a large scale. The main focus was on so-called nidoviruses, which include the coronavirus family.
Nidoviruses, whose genetic material consists of RNA (ribonucleic acid), are widespread in vertebrates. This species-rich group of viruses has some common characteristics that distinguish them from all other RNA viruses and document their relationship. Otherwise, however, nidoviruses are very different from each other, i.e. in terms of the size of their genome.
One discovery is particularly interesting with regard to the emergence of new viruses: In host animals that are simultaneously infected with different viruses, a recombination of viral genes can occur during virus replication. “Apparently, the nidoviruses we discovered in fish frequently exchange genetic material between different virus species, even across family boundaries,” says Stefan Seitz. And when distant relatives “crossbreed,” this can lead to the emergence of viruses with completely new properties. According to Seitz, such evolutionary leaps can affect the aggressiveness and dangerousness of the viruses, but also their attachment to certain host animals.
“A genetic exchange, as we have found in fish viruses, will probably also occur in mammalian viruses,” explains Stefan Seitz. Bats, which — like shrews — are often infected with a large number of different viruses, are considered a true melting pot. The SARS-CoV-2 coronavirus probably also developed in bats and jumped from there to humans.
After gene exchange between nidoviruses, the spike protein with which the viruses dock onto their host cells often changes. Chris Lauber, first author of the study, was able to show this by means of family tree analyses. Modifying this anchor molecule can significantly change the properties of the viruses to their advantage – by increasing their infectiousness or enabling them to switch hosts. A change of host, especially from animals to humans, can greatly facilitate the spread of the virus, as the corona pandemic has emphatically demonstrated. Viral “game changers” can suddenly appear at any time, becoming a massive threat and – if push comes to shove – triggering a pandemic. The starting point can be a single double-infected host animal.
The new high-performance computer process could help to prevent the spread of new viruses. It enables a systematic search for virus variants that are potentially dangerous for humans, explains Stefan Seitz. And the DKFZ researcher sees another important possible application with regard to his special field of research, virus-associated carcinogenesis: “I could imagine that we could use the new High Performance Computing (HPC) to systematically examine cancer patients or immunocompromised people for viruses. We know that cancer can be triggered by viruses, the best-known example being human papillomaviruses. But we are probably only seeing the tip of the iceberg so far. The HPC method offers the opportunity to track down viruses that, previously undetected, nestle in the human organism and increase the risk of malignant tumours.”
Creative artwork featuring colourised 3D prints of influenza virus (surface glycoprotein hemagglutinin is blue and neuraminidase is orange; the viral membrane is a darker orange). Note: Not to scale. Credit: NIAID
By Elri Voigt for Spotlight
COVID-19-related factors resulted in several years of lower-than-normal rates of the flu, but experts say that is now something of the past. As this year’s flu season gets under way, Elri Voigt asks several local experts what their expectations are, which flu vaccines are available this year, and whether we should be concerned about new strains of bird flu.
While most people who get the flu experience only mild to moderate symptoms, some can get severe symptoms and even die, especially the very young and the old. As Spotlight previously reported, the influenza virus causes around 11 000 deaths per year in South Africa, with around 40 000 people hospitalised.
Dr Sibongile Walaza, a medical epidemiologist and the Head of Epidemiology at the Centre for Respiratory Disease and Meningitis at the National Institute for Communicable Diseases (NICD), says that it is difficult to predict what a flu season will look like beforehand.
Nicole Jennings, spokesperson for the South African Pharmaceutical company Pharma Dynamics, agrees. “Influenza is a global disease and the spread of the virus in other parts of the world can influence the trajectory of flu seasons in different regions. For now, it’s too early to make any predictions,” she says.
It is difficult to predict the trajectory of flu seasons ahead of time, Jennings says, because of a “complex interplay” of factors, including the fact that influenza viruses are constantly mutating. This makes it difficult to accurately predict which strains of the influenza virus will dominate and how they will behave.
“The level of immunity in the population can also vary from year to year due to factors, such as vaccination rates, previous exposure to similar strains and so forth,” she adds. “However, surveillance efforts, modelling and ongoing research conducted by the NICD can help the public to prepare for the cold and flu season as best possible.”
NICD guidelines published in April 2023 already stated that since the COVID-19 pandemic, there have been some changes in the timing of flu transmission.
The transmission reduction strategies – like masking and social distancing – during the pandemic had an impact on the rates of flu transmission and the duration of the flu season between 2020 to 2022, according to Dr Jocelyn Moyes, a medical epidemiologist at the Centre for Respiratory Disease and Meningitis at the NICD.
Back to normal?
Although the numbers were still much lower, it appears that the winter flu season’s peak had started to return to levels seen pre-COVID-19 in 2022 and 2023, Walaza confirms.
“In 2023, the flu season was a little bit longer than we’d seen before [COVID-19], but it started on time. So, in terms of the timing, it was similar to what we would see before COVID-19,” she says.
When exactly the winter flu season starts each year varies, Walaza says, but on average it can start anytime from the third week of April and can circulate until August. It has been known to go on longer though.
At the time of the interview, the NICD had only detected sporadic cases of flu but had not yet seen the sustained uptick in transmission which usually signals the start of the flu season. The latest surveillance data published by the NICD indicate that 108 cases of influenza had been detected so far this year. The real number of flu cases will be much higher since most cases of flu are not diagnosed.
This year’s vaccines
Walaza explains that the flu vaccine is updated each year based on the World Health Organization’s (WHO) recommendations. This is to ensure it provides protection against evolving influenza viruses seen in global surveillance programmes.
Photo by National Cancer Institute
Flu shots used in South Africa are inactivated influenza vaccines. This means they do not contain live virus and cannot cause flu.
In the public healthcare sector, the government this year procured the trivalent vaccine which protects against three strains of the influenza virus – two influenza A strains (H1N1pdm 2009 and H3N2) and one influenza B strain (known as the B/Victoria), Walaza says. These jabs should be in public health clinics by the first week of May.
In the private healthcare sector, she says a trivalent and a quadrivalent vaccine are available. The quadrivalent shot includes protection against a second influenza B strain (B/Yamagata), but that strain has not been seen circulating in a few years. These flu shots are already available in the private healthcare sector.
The level of protection provided by the flu shot varies and generally it ranges in effectiveness against infection from about 30% to 60%, according to Walaza, but importantly it protects against severe illness.
How effective this year’s flu shot will be depends on which influenza strain or strains circulate in the country. “The hope is that if an individual gets infected by any of those strains [in the vaccine], then that individual is protected or has some level of protection [against these strains] and will have some protection against severe illness” she says.
However, she adds, it’s difficult to predict how effective this year’s flu shot will be against preventing someone from getting the flu or experiencing symptoms of the flu. This is because there is always the chance that the strains which do circulate this season are different from the ones in the vaccine or have mutated so the shot becomes less effective.
Should we worry about bird flu?
At the start of April, the WHO reported that one case of avian influenza A (H5N1), one of the avian/bird flu viruses, had been detected in a person in the United States after they had come into contact with a cow who was presumed to be infected. This was the second human case of influenza A (H5N1) detected in that country, and the first case of a person being infected with this strain after coming into contact with a non-avian species.
So far, the risk to the general public is low, according to the WHO.
“Since the virus [avian influenza A (H5N1)] has not acquired mutations that facilitate transmission among humans and based on available information the WHO assesses the public health risk to the general population posed by this virus to be low and for occupationally exposed persons, the risk of infection is considered low-to-moderate,” the WHO statement said.
There are many subtypes of influenza A viruses, Moyes tells Spotlight, and avian influenzas are similar to human influenza A viruses. And so, she explains, there is always a possibility that these viruses mutate, enabling them to infect humans, or more importantly develop the ability to transmit effectively from one person to another. This could potentially cause a pandemic.
She tells Spotlight that over the last decade sporadic cases of human avian influenza have been described related to global outbreaks in birds. These cases have all been in people who have had very close contact – usually during the culling process – with sick birds. She advises that people involved in the management of avian influenza outbreaks take precautions, such as using appropriate personal protective equipment to prevent infection.
When asked whether people in South Africa need to be concerned about a potential bird flu outbreak, Walaza says so far, no cases of bird flu infection in humans – even during the recent widespread outbreaks in birds – have been identified in the country. But it is something that the NICD is aware of and surveillance for human cases during outbreaks of bird flu in the country is being conducted.
“What’s important though to note is that even when cases have been detected [in other countries] the risk of person-to-person transmission is extremely low,” she adds.
Launch of Cough Watch SA
Walaza tells Spotlight that most of the data gathered by the NICD on influenza is from surveillance in healthcare facilities, which means that not all cases of influenza are necessarily identified.
To gather additional data, the NICD is in the process of rolling out an additional digital surveillance system to detect influenza cases, called Cough Watch SA. This online web application allows the public to report influenza symptoms.
People who sign up are asked to provide basic demographic data like age and postal code. Participants will then be sent a weekly prompt asking if they’ve had any flu symptoms. If they have had symptoms, according to Walaza, then they will be asked to provide more information. This data will then be linked to the NICD database where it will be compared to other surveillance data to see if the platform could serve as an early warning system for a flu outbreak.
Cough Watch SA will be launched in the week of 7 May, says Moyes, who urged the public to help keep an eye on flu by signing up.
Professor Shabir Madhi of Wits University. Photo: supplied.
The Sabin Vaccine Institute presented the Albert B. Sabin Gold Medal to physician-researchers Keith Klugman and Shabir Madhi.
Nicole Basta, an associate professor at Canada’s McGill University and Canada Research Chair in Infectious Disease Prevention, received Sabin’s 2024 Rising Star Award.
The awards were made on 18 April 2024 at a ceremony in the National Academy of Sciences building in Washington D.C.
Formidable Wits alumni are world leaders in vaccinology
Klugman and Madhi received the Sabin Gold Medal, one of the highest recognitions for vaccinologists globally, for their seminal combined contributions to the development of vaccines against pneumonia and diarrhoeal disease – major causes of death in children in low- and middle-income countries (LMICs).
Klugman is a Wits University alumnus who received an honorary doctorate from his alma mater in 2023.
Madhi, also a Wits alumnus, is currently Professor of Vaccinology and Dean of the Faculty of Health Sciences at Wits University.
The Gold Medal is Sabin’s highest scientific honour. It has been given annually for more than three decades to a distinguished member of the global health community who has made exceptional contributions to vaccinology or a complementary field.
Klugman first met his then-graduate student Madhi at Wits University, where Klugman established, and Madhi expanded, a now globally renowned infectious diseases research institute. Apart from pneumonia, their work focused on maternal and children’s vaccines including influenza, respiratory syncytial virus (RSV), typhoid, and Group B streptococcus (GBS).
The evidence produced by these two awardees has and continues to inform the World Health Organization’s recommendations for vaccines. Klugman and Madhi’s research has helped pave the way for the introduction of lifesaving vaccines in public immunization programs – including the pneumococcal conjugate vaccine where their findings were pivotal in influencing vaccination policy in many low- and middle-income countries (LMICs).
Klugman’s efforts help prevent babies from dying of pneumonia
Fuelled by an early interest in science as a child in South Africa – in part due to a physician father – Klugman holds both a medical as well as a science doctorate degree from Wits University and was the first student in the school’s history to obtain them simultaneously.
He began his research career nearly five decades ago investigating the typhoid vaccine and has since distinguished himself as a formidable infectious diseases’ scientist.
Klugman is widely known for his work on pneumonia, which still kills a child under five every 43 seconds, many in the world’s poorest countries.
As the director of the pneumonia programme at the Seattle-based Bill & Melinda Gates Foundation, Klugman orchestrates strategic initiatives aimed at reducing deaths from pneumonia, RSV, neonatal sepsis, and meningitis.
He has authored hundreds of publications that have been cited over 50 000 times to date and has been elected to the National Academy of Medicine in the United States. He is also a professor emeritus of global health at Atlanta’s Emory University.
His scientific achievements aside, Klugman has long championed the need for the world’s poorest children to have equitable access to vaccines. While in South Africa he joined in Wits University’s struggle to allow access to the institution for all students.
“It is absolutely wonderful to be receiving this award, especially together with Shabir,” he says. “When I look down the list of previous awardees, I recognize the great majority of them, and it is extraordinary to now be numbered among them.”
Past award recipients include leaders of vaccinology and vaccine advocacy such as Drs. Barney Graham, Carol Baker, Bill Foege, Anne Gershon, Stanley Plotkin, and Kathrin Jansen.
Madhi’s research informed WHO recommendations on universal rotavirus vaccination
With a career spanning more than 25 years, Madhi, also from South Africa, is a trained paediatrician whose research continues to be instrumental in prioritising the rollout of vital vaccines and guiding global public health policies. At Wits University, he led clinical trials focused on respiratory and meningeal pathogens, including vaccines targeted at pregnant women and their unborn babies.
Madhi led the first study showing that a rotavirus vaccine could significantly prevent severe diarrhoea during the first year of life in African infants. That research served as a key piece of evidence for the WHO’s recommendation of universal rotavirus vaccination. In addition, he also led the first two COVID-19 vaccine trials in Africa, and a number of COVID-19 epidemiology studies which led to the first evidence suggesting that infection-induced immunity and vaccinations played a role in reducing severity of disease.
In addition to serving as Professor of Vaccinology and Dean of Health Sciences at Wits University, Madhi heads South Africa’s widely respected South African Medical Research Council (SAMRC) Vaccines and Infectious Diseases Analytics Research Unit (Wits VIDA). He is also the co-founder and co-Director of the African Leadership Initiative for Vaccinology Expertise (ALIVE).
He has co-authored hundreds of publications which have been cited over 59 000 times. Madhi is a recipient of numerous lifetime achievement awards in South Africa, as well being bestowed an Honorary Commander of the Order of the British Empire (CBE) from the British Government for his services to science and public health in a global pandemic.
“It is really humbling for me to be acknowledged for my contributions in the field of vaccinology along with those who have received the Gold Medal award,” says Madhi. “It makes me realise that the work my team and I have done is acknowledged by my peers as being of substance. Most significantly, we contributed to protecting lives in those settings where a majority of death and suffering occurs, and that is in LMICs.”
Amy Finan, Sabin’s chief executive officer, says, “I am honoured to award the Sabin Gold Medal to Dr Klugman and D. Madhi for their extraordinary work on vaccines that have saved lives in communities most in need of these interventions. Their pneumonia research has been particularly transformative in shaping our understanding of the disease and strengthening global health strategies to protect children from this vaccine-preventable disease.”
Researchers from Rutgers University in the U.S. believe that they are ahead in a race to find an oral COVID-19 treatment to supplement or replace the antiviral Paxlovid. Their report, published in Science, shows that an alternative medication, a viral papain-like protease inhibitor, inhibits disease progression in animals while also possessing an important advantage over Paxlovid – fewer prescription drug contraindications.
“COVID-19 remains the nation’s third leading cause of death, so there’s already a massive need for additional treatment options,” said Jun Wang, senior author of the study and associate professor at Rutgers. “That need will grow more urgent when, inevitably, COVID-19 mutates in ways that prevent Paxlovid from working.”
The Rutgers team hoped to make a drug that interfered with viral papain-like protease (PLpro), a protein that performs important functions in all known strains of COVID-19.
Creating such a drug required detailed information about PLpro’s structure, which Wang’s team got from the Arnold Lab at Rutgers’ Center for Advanced Biotechnology and Medicine (CABM).
Precise knowledge of PLpro’s structure enabled Wang’s team to design and synthesise 85 drug candidates that would bond to – and interfere with – this vital protein.
“The PLpro crystal structures showed an unexpected arrangement of how the drug candidate molecules bind to its protein target, leading to innovative design ideas implemented by professor Wang’s medicinal chemistry team,” said Eddy Arnold, who is a professor at CABM.
Laboratory testing established that the most effective of those drug candidates, a compound dubbed Jun12682, inhibited several strains of the SARS-CoV-2 virus, including strains that resist treatment with Paxlovid.
Oral treatment with Jun12682 on SARS-CoV-2-infected mice was shown to reduce viral lung loads and lesions while improving survival rates.
“Our treatment was about as effective in mice as Paxlovid was in its initial animal tests,” said Wang, who added the experimental drug appears to have at least one major advantage over the older drug.
“Paxlovid interferes with many prescription medications, and most people who face the highest risk of severe COVID-19 take other prescription medicines, so it’s a real problem,” Wang said.
“We tested our candidate Jun12682 against major drug-metabolising enzymes and saw no evidence that it would interfere with other medications.”
