Women have long been known to outlive men. But new research published in JAMA Internal Medicine shows that, at least in the United States, the gap has been widening for more than a decade. Among the factors driving the trend are the COVID pandemic and the opioid overdose epidemic.
The study, led by UC San Francisco and Harvard T.H. Chan School of Public Health, found the difference between how long American men and women live increased to 5.8 years in 2021, the largest since 1996. This is an increase from 4.8 years in 2010, when the gap was at its smallest in recent history.
The pandemic, which took a disproportionate toll on men, was the biggest contributor to the widening gap from 2019–2021, followed by unintentional injuries and poisonings (mostly drug overdoses), accidents and suicide.
“There’s been a lot of research into the decline in life expectancy in recent years, but no one has systematically analysed why the gap between men and women has been widening since 2010,” said the paper’s first author, Brandon Yan, MD, MPH, a UCSF internal medicine resident physician and research collaborator at Harvard Chan School.
Life expectancy in the US dropped in 2021 to 76.1 years, falling from 78.8 years in 2019 and 77 years in 2020.
The shortening lifespan of Americans has been attributed in part to so-called “deaths of despair.” The term refers to the increase in deaths from such causes as suicide, drug use disorders and alcoholic liver disease, which are often connected with economic hardship, depression and stress.
“While rates of death from drug overdose and homicide have climbed for both men and women, it is clear that men constitute an increasingly disproportionate share of these deaths,” Yan said.
Interventions to reverse a deadly trend
Using data from the National Center for Health Statistics, Yan and fellow researchers from around the country identified the causes of death that were lowering life expectancy the most. Then they estimated the effects on men and women to see how much different causes were contributing to the gap.
Prior to the COVID pandemic, the largest contributors were unintentional injuries, diabetes, suicide, homicide and heart disease.
But during the pandemic, men were more likely to die of the virus. That was likely due to a number of reasons, including differences in health behaviours, as well as social factors, such as the risk of exposure at work, reluctance to seek medical care, incarceration and housing instability. Chronic metabolic disorders, mental illness and gun violence also contributed.
Yan said the results raise questions about whether more specialised care for men, such as in mental health, should be developed to address the growing disparity in life expectancy.
“We have brought insights to a worrisome trend,” Yan said. “Future research ought to help focus public health interventions towards helping reverse this decline in life expectancy.”
Yan and co-authors, including senior author Howard Koh, MD, MPH, professor of the practice of public health leadership at Harvard Chan School, also noted that further analysis is needed to see if these trends change after 2021.
“We need to track these trends closely as the pandemic recedes,” Koh said. “And we must make significant investments in prevention and care to ensure that this widening disparity, among many others, do not become entrenched.”
Although pets are generally perceived as having a positive impact on well-being, a new study has found that there was no association between well-being and owning a pet during the COVID pandemic. This finding, published in the Personality and Social Psychology Bulletin, was in spite of pets owners reporting that pet ownership improved their lives.
There is a general understanding that pets have a positive impact on one’s well-being. A new study by Michigan State University found that although pet owners reported pets improving their lives, there was not a reliable association between pet ownership and well-being during the COVID-19 pandemic.
The study assessed 767 people over three periods in May 2020. The researchers took a mixed-method approach that allowed them to look at several indicators of well-being while also asking people in an open-ended question to reflect on the role of pets from their point of view. Pet owners reported that pets made them happy. They claimed pets helped them feel more positive emotions and provided affection and companionship. They also reported negative aspects of pet ownership like being worried about their pet’s well-being and having their pets interfere with working remotely.
However, when their happiness was compared to nonpet owners, the data showed no difference in the well-being of pet owners and nonpet owners over time. The researchers found that it did not matter what type of pet was owned, how many pets were owned or how close they were with their pet. The personalities of the owners were not a factor.
“People say that pets make them happy, but when we actually measure happiness, that doesn’t appear to be the case,” said William Chopik, an associate professor in MSU’s Department of Psychology and co-author of the study. “People see friends as lonely or wanting companionship, and they recommend getting a pet. But it’s unlikely that it’ll be as transformative as people think.”
The researchers explored several reasons why there is not a difference between the well-being of pet owners and nonpet owners. One of them being that nonpet owners may have filled their lives with a variety of other things that make them happy.
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.
A study published in the journal Nature Cardiovascular Research shows that SARS-CoV-2 can directly infect the arteries of the heart and cause the fatty plaque inside arteries to become highly inflamed, increasing the risk of heart attack and stroke. The findings may help explain why certain people who get COVID have a greater chance of developing cardiovascular disease, or if they already have it, develop more heart-related complications.
In the National Institutes of Health (NIH)-funded study, researchers focused on older people with atherosclerotic plaque, who died from COVID. However, because the researchers found the virus infects and replicates in the arteries no matter the levels of plaque, the findings could have broader implications for anybody who gets COVID.
“Since the early days of the pandemic, we have known that people who had COVID have an increased risk for cardiovascular disease or stroke up to one year after infection,” said Michelle Olive, PhD, acting associate director of the Basic and Early Translational Research Program at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “We believe we have uncovered one of the reasons why.”
Though previous studies have shown that SARS-CoV-2 can directly infect tissues such as the brain and lungs, less was known about its effect on the coronary arteries. Researchers knew that after the virus reaches the cells, the body’s immune system sends in macrophages to help clear the virus. In the arteries, macrophages also help remove cholesterol, and when they become overloaded with cholesterol, they morph into a specialised type of cell called foam cells.
The researchers thought that if SARS-CoV-2 could directly infect arterial cells, the macrophages that normally are turned loose might increase inflammation in the existing plaque, explained Chiara Giannarelli, MD, PhD, associate professor in the departments of medicine and pathology at New York University’s Grossman School of Medicine and senior author on the study. To test their theory, Giannarelli and her team took tissue from the coronary arteries and plaque of people who had died from COVID and confirmed the virus was in those tissues. Then they took arterial and plaque cells – including macrophages and foam cells – from healthy patients and infected them with SARS-CoV-2 in a lab dish. They found that the virus had also infected those cells and tissues.
Additionally, the researchers found that when they compared the infection rates of SARS-CoV-2, they showed that the virus infects macrophages at a higher rate than other arterial cells. Cholesterol-laden foam cells were the most susceptible to infection and unable to readily clear the virus. This suggested that foam cells might act as a reservoir of SARS-CoV-2 in the atherosclerotic plaque. Having more build-up of plaque, and thus a greater number of foam cells, could increase the severity or persistence of COVID.
The researchers then looked at the predicted inflammation in the plaque after infecting it with the virus. They observed the release of inflammatory cytokines, also known to promote the formation of even more plaque. The cytokines were released by infected macrophages and foam cells. The researchers said this may help explain why people who have underlying plaque buildup and then get COVID may have cardiovascular complications long after getting the infection.
“This study is incredibly important as it adds to the larger body of work to better understand COVID,” said Olive. “This is just one more study that demonstrates how the virus both infects and causes inflammation in many cells and tissues throughout the body. Ultimately, this is information that will inform future research on both acute and Long COVID.”
Though the findings conclusively show that SARS-CoV-2 can infect and replicate in the macrophages of plaques and arterial cells, they are only relevant to the original strains of SARS-CoV-2 that circulated in New York City between May 2020 and May 2021. The study was conducted in a small cohort of older individuals, all of whom had atherosclerosis and other medical conditions; therefore, the results cannot be generalised to younger, healthy individuals.
Bada Pharasi, CEO of The Innovative Pharmaceutical Association of South Africa (IPASA)
Lessons from the COVID-19 pandemic have underlined the importance of continued investment into pharmaceutical innovation and R&D to not only bring life-saving medications to those in need, but to improve public health outcomes, writes Bada Pharasi, CEO of The Innovative Pharmaceutical Association of South Africa (IPASA).
From treatments for cancer, cardiovascular diseases and more recently, the COVID-19 vaccine, the pharmaceutical industry has made significant progress in the development of over 470 medications in the last 10 years alone.1
While the innovative pharmaceutical process typically takes between 10 and 15 years from discovery to regulatory approval2 – owing to factors including immense R&D costs, regulatory compliance, and the protection of patents3 – the fast-tracked development and approval of COVID-19 vaccines laid bare the need for pharmaceutical companies to be prepared to mitigate the risk of future outbreaks – and this means continued investment in innovation and R&D.
The pandemic underlined the need for countries to be prepared for outbreaks on the horizon. To ensure we can meet the next challenge, pharmaceutical innovations must match the pace at which diseases mutate. This kind of innovation is non-negotiable and requires continued investment as a safeguard against losing lives and endangering South Africa’s fragile healthcare system.
As we are in the midst of a cholera epidemic, as well as the recent measles outbreak,4 it’s important to continue driving innovation to treat diseases, with medicines developed by innovative pharmaceutical companies benefiting millions across the country every day.
This is evidenced by mortality rates for HIV/AIDS and TB in the country falling by 59.2% and 55.7% between 2007 and 2017, with at least 60 new medicines currently in the R&D pipeline to treat TB.5
While patents in pharmaceutical innovation protect the originators’ intellectual property, it is important that innovative medications be developed to ensure a continuous pipeline of access to generics once the patent has lost its exclusivity. This will drive consumer accessibility and affordability of life-saving treatments and medications that may otherwise be unattainable for many.
As we continue racing against the proverbial clock in protecting against current and future diseases, pharmaceutical companies should continue to invest in innovation and R&D to outsmart existing dreaded diseases, and provide agility and preparedness should the next unknown pandemic threaten. Our health, and lives, depend on it.
People often say whether they feel like their immune system is ‘down’ – but could there be some truth to this? A recent study showed that when freshly vaccinated people self-assessed the strength of their immune response, their estimates correlated well to their measured antibody levels. They were even more accurate when their immune response was weak. The results were published in the journal Biological Psychology.
At the University of Konstanz, Stephanie psychologist Dimitroff researches the connection between our brain and our immune system. “Listen to your body,” she concludes from her study. “The field of medicine is moving towards greater patient orientation. Our findings support the idea that patients’ self-perceptions provide valuable clues about their state of health. Physicians should listen to them more.”
Communication between the immune and nervous systems
One part of our brain, the insula, receives information from the body and gives us a basic impression of its condition, which until now was assumed to be quite general in nature. Stephanie Dimitroff’s study now suggests that our brain can perceive the body’s condition more specifically than previously thought. Is it possible that our brain can assess the state of our immune system?
“Of course, our brain does not count antibodies. But our immune system is intrinsically connected to the central nervous system,” Dimitroff explains. “The immune system is regulated via this connection. And our brain also receives information from the immune system.”
This communication between the immune system and the central nervous system is key for our sense of well-being or illness. “It is important to know here: When we feel ill, for example, we have a cold, this feeling is caused quite significantly by the immune system’s communication with the central nervous system,” says Dimitroff. “The brain receives signals that something is wrong with the body and causes the feeling of illness as a result.”
The same flow of information between the immune and nervous systems can generally also take place when the body is not ill. This means it could be possible that this communication process gives us an impression of our immune system even when we are healthy. Stephanie Dimitroff’s study investigates whether this is actually the case.
Results of the study
The study looked at people who had received the COVID-19 vaccine. This group of participants was chosen because a particularly large number of people received the vaccine in the summer of 2021, when the study was conducted. 166 people between the ages of 18 and 59 participated in the study.
After vaccination, the participants in the study were able to assess surprisingly well how strongly their immune system was positioned to fight the respective illness. This was especially true for people who had developed only a few antibodies. In fact, 71% of participants who did not feel well protected after vaccination also had a below-average immune response. “Our most notable finding is that those who felt they had not produced high levels of antibodies after vaccination were often correct in their assessment.”
By contrast, participants who assessed their immune response as good were not always right. However, all of those who had a particularly strong immune response also reported feeling well protected.
Alternative interpretations
For Stephanie Dimitroff, however, it is still too early to draw any final conclusions. The psychologist is considering other possible causes, including the placebo effect. This is because communication between the brain and the immune system runs in both directions. The signals from our brain can therefore also influence our immune system. People who firmly believe in vaccination or are basically optimistic could thus actually develop a better immune defence (placebo effect) and also feel better protected. It is therefore possible that belief in the effectiveness of a vaccine is what improves its efficacy, and this could also explain the high accuracy of the self-assessments.
“Our results suggest that it is quite likely that people have a real ability to assess their own health. However, I cannot rule out that there is a combination of effects at play, including the placebo effect and/or feelings of optimism,” Dimitroff says. In her view, it would make sense to repeat the study in order to confirm the results and rule out alternative causes.
The Health Justice Initiative today reported an important court victory in their attempts to lift the veil of of secrecy over government’s vaccine procurement contracts. The result is a court ruling which orders the Department of Health to disclose these contracts, which will shed light on important questions such as whether these vaccines were purchased at inflated prices and unfavourable terms. They detail the court victory in a press release:
Health Justice Initiative v The Minister of Health and Information Officer, National Department of Health (Case no 10009/22).
Today, South African courts upheld the principles of transparency and accountability when our government procures health services using public funds. The Pretoria High Court ruled in our favour in our bid to compel the National Department of Health to provide access to the COVID-19 vaccine procurement contracts. The Court ordered (per Millar J) that all COVID-19 vaccine contracts must be made public within 10 days.
This is a massive victory for transparency and accountability. The contracts concern substantial public funds, and the contracting process has been marred by allegations that the government procured vaccines at differential, comparatively inflated prices and that the agreements may contain onerous and inequitable terms including broad indemnification clauses, export restrictions, and non-refundability clauses.
This significant moment comes as we begin to emerge from the devastation of the COVID-19 pandemic. It sets an important precedent, especially as our government pursues National Health Insurance (NHI). With increasing reports of corruption within the healthcare sector, we cannot have a healthcare system shrouded in secrecy. Procurement must be held in check, as it will involve powerful multinational companies, particularly from the pharmaceutical industry.
The secrecy surrounding COVID-19 vaccine procurement at the height of the pandemic continues to be a global issue, not just limited to SA – it is important to know what was agreed to in our name at the behest of powerful vaccine manufacturers who have been reported to have bullied governments in the Global South especially, insisting on contracts that ultimately made them huge profits, without maximum accountability and openness. Therefore, this judgment can be leveraged by other countries to demand open contracting in their jurisdictions.
We believe that in the current Pandemic Treaty negotiations, where worrying attempts are being made to water down transparency, this judgment will support Pandemic Preparedness measures by bolstering provisions on transparency and accountability in these negotiations.
This case demonstrates that all governments should and can be held accountable when spending public funds, this also includes the parties it entered into contracts with. It is in the public interest to know what was agreed to. The judgment has affirmed that today.
We look forward to the Department of Health’s cooperation by making available all the records HJI requested within the time period set out in the judgment (10 court days from 17 August 2023).
Research led by the University of Bristol has found that long COVID is not caused by an immune inflammatory reaction to COVID. Emerging data shows that immune activation may persist for months after contracting COVID. In this new study, published in eLife, researchers wanted to find out whether persistent immune activation and ongoing inflammation response could be the underlying cause of long COVID.
To investigate this, the Bristol team collected and analysed immune responses in blood samples from 63 patients hospitalised with mild, moderate or severe COVID at the start of the pandemic and before vaccines were available. The team then tested patients’ immune responses at three months and again at eight and 12 months post hospital admission. Of these patients, 79% (82%, 75%, and 86% of mild, moderate, and severe patients, respectively) reported at least one ongoing symptom with breathlessness and excessive fatigue being the most common.
Dr Laura Rivino, the study’s lead author, explained: “Long Covid occurs in one out of ten COVID cases, but we still don’t understand what causes it. Several theories proposed include whether it might be triggered by an inflammatory immune response towards the virus that is still persisting in our body, sending our immune system into overdrive or the reactivation of latent viruses such as human cytomegalovirus (CMV) and Epstein Barr virus (EBV).”
The team found patients’ immune responses at three months with severe symptoms displayed significant dysfunction in their T-cell profiles indicating that inflammation may persist for months even after they have recovered from the virus. Reassuringly, results showed that even in severe cases inflammation in these patients resolved in time. At 12 months, both the immune profiles and inflammatory levels of patients with severe disease were similar to those of mild and moderate patients.
Patients with severe COVID were found to display a higher number of long Covid symptoms compared to mild and moderate patients. However, further analysis by the team revealed no direct association between long COVID symptoms and immune inflammatory responses, for the markers that were measured, in any of the patients after adjusting for age, sex and disease severity.
Importantly, there was no rapid increase in immune cells targeting SARS-CoV-2 at three months, but T-cells targeting the persistent and dormant Cytomegalovirus (CMV) – a common virus that is usually harmless but can stay in your body for life once infected with it – did show an increase at low levels. This indicates that the prolonged T-cell activation observed at three months in severe patients may not be driven by SARS-CoV-2 but instead may be “bystander driven” ie driven by cytokines.
Dr Rivino added: “Our findings suggest that prolonged immune activation and Long COVID may correlate independently with severe COVID. Larger studies should be conducted looking at both a larger number of patients, including if possible vaccinated and non-vaccinated COVID patients, and measuring a larger range of markers and cytokines.
“Understanding whether inflammation and immune activation associate with Long COVID would allow us to understand whether targeting these factors may be a useful therapy for this debilitating condition.”
Patients who had heart attacks during the first COVID lockdown in the UK and Spain are predicted to live 1.5 and 2 years less, respectively, than their pre-COVID counterparts. That’s the finding of a study just published in European Heart Journal – Quality of Care and Clinical Outcomes.
“Restrictions to treatment of life-threatening conditions have immediate and long-term negative consequences for individuals and society as a whole,” said study author Professor William Wijns of the Lambe Institute for Translational Medicine, University of Galway, Ireland. “Back-up plans must be in place so that emergency services can be retained even during natural or health catastrophes.”
Research has shown that during the first wave of the pandemic, about 40% fewer heart attack patients went to hospital as governments told people to stay at home, fear of catching the virus, and the stopping of some routine emergency care. Compared to receiving timely treatment, heart attack patients who stayed at home were more than twice as likely to die, while those who delayed going to the hospital were nearly twice as likely to have serious complications that could have been avoided.
Heart attacks require urgent treatment with stents (called percutaneous coronary intervention or PCI) to open the blocked artery and restore blood flow. Delays, and the resulting lack of oxygen, lead to irreversible damage of the heart muscle and can cause heart failure or other complications. When a large amount of heart tissue is damaged, potentially fatal cardiac arrest results.
This study estimated the long-term clinical and economic implications of reduced heart attack treatment during the pandemic in the UK and Spain. The researchers compared the predicted life expectancy of patients who had a heart attack during the first lockdown with those who had a heart attack at the same time in the previous year. The study focused on ST-elevation myocardial infarction (STEMI), where a coronary artery is completely blocked. The researchers also compared the cost of STEMIs during lockdown with the equivalent period the year before.
A model was developed to estimate long-term survival, quality of life and costs related to STEMI. The UK analysis compared the period 23 March (when lockdown began) to 22 April 2020 with the equivalent time in 2019. The Spanish analysis compared March 2019 with March 2020 (lockdown began on 14 March 2020). Survival projections considered age, hospitalisation status and time to treatment using published data for each country. For example, using published data, it was estimated that 77% of STEMI patients in the UK were hospitalised prior to the pandemic compared with 44% during lockdown. The equivalent rates for Spain were 74% and 57%. The researchers also compared how many years in perfect health were lost for patients with a STEMI before versus during the pandemic.
The analysis predicted that patients who had a STEMI during the first UK lockdown would lose an average of 1.55 years of life compared to patients presenting with a STEMI before the pandemic. In addition, while alive, those with a STEMI during lockdown were predicted to lose approximately one year and two months of life in perfect health. The equivalent figures for Spain were 2.03 years of life lost and around one year and seven months of life in perfect health lost.
The cost analysis focused on initial hospitalisation and treatment, follow-up treatment, management of heart failure and productivity loss in patients unable to return to work. For example, the cost applied to a STEMI admission with PCI was £2837 in the UK and €8780 in Spain. Heart failure costs were estimated at £6086 in year one and £3882 in all subsequent years for the UK. The equivalent figures for Spain were €3815 (year one) and €2930 (each subsequent year).
Professor Wijns said: “The findings illustrate the repercussions of delayed or missed care. Patients and societies will pay the price of reduced heart attack treatment during just one month of lockdown for years to come. Health services need a list of lifesaving therapies that should always be delivered, and resilient healthcare systems must be established that can switch to emergency plans without delay. Public awareness campaigns should emphasise the benefits of timely care, even during a pandemic or other crisis.”
South African scientists – notably, the team headed by Professor Tulio de Oliveira – were thrown into the global spotlight through their pivotal role in detecting and monitoring the emergence of new variants of SARS-CoV-2 – the Beta variant in 2020 and Omicron in 2021. De Oliveira is now at the University of Stellenbosch, but for much of the pandemic headed the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP).
The country’s advanced genomic sequencing capabilities and proactive surveillance efforts allowed for the early identification of the variants and the discoveries played a crucial role in alerting the global scientific community to the potential for viral mutations and the need for enhanced monitoring.
Now, scientists worldwide believe it is critical to continue investing in genomics to support disease control in public health in South Africa and the broader continent.
What is genomics?
The World Health Organization (WHO) defines genomic surveillance as “the process of constantly monitoring pathogens and analysing their genetic similarities and differences”. It is done through a method known as whole genome sequencing, which determines the entire genetic makeup of specific organisms or cell types. This method is also able to detect changes in areas of genomes, which can help scientists to establish how specific diseases form. The results of genomic sequencing can also be used in diagnosing and treating diseases.
Genomic sequencing enables scientists to read the DNA and RNA of pathogens and understand what they are and how they spread between people – and to develop vaccines and other measures to deal with them.
The US Centers for Disease Control (CDC) explains, “All organisms (bacteria, vegetable, mammal) have a unique genetic code, or genome that is composed of nucleotide bases (A, T, C, and G). If you know the sequence of the bases in an organism, you have identified its unique DNA fingerprint or pattern. Determining the order of bases is called sequencing. Whole genome sequencing is a laboratory procedure that determines the order of bases in the genome of an organism in one process.
“Scientists conduct whole genome sequencing by following these four main steps:
DNA shearing: Scientists begin by using molecular scissors to cut the DNA, which is composed of millions of bases (A’s, C’s, T’s, and G’s), into pieces that are small enough for the sequencing machine to read.
DNA barcoding: Scientists add small pieces of DNA tags, or bar codes, to identify which piece of sheared DNA belongs to which bacteria. This is similar to how a bar code identifies a product at a grocery store.
DNA sequencing: The bar-coded DNA from multiple bacteria is combined and put in a DNA sequencer. The sequencer identifies the A’s, C’s, T’s, and G’s, or bases, that make up each bacterial sequence. The sequencer uses the bar code to keep track of which bases belong to which bacteria.
Data analysis: Scientists use computer analysis tools to compare sequences from multiple bacteria and identify differences. The number of differences can tell the scientists how closely related the bacteria are, and how likely it is that they are part of the same outbreak…”
Time to expand
At a recent conference held at Stellenbosch University’s new state-of-the-art Biomedical Medical Research Institute, de Oliveira stressed that African and other experts should now build on their success in COVID-19 genomics to expand to other pathogens such as influenza, H5N1, and climate-amplified pathogens.
John Sillitoe, the Director of the Genomic Surveillance Unit at the Wellcome Sanger Institute in the United Kingdom, agreed.
“It is important now to focus on endemic diseases so we can improve our understanding and control of endemic diseases. We should also be looking at TB, particularly with the increased prevalence in drug resistance and reduced response to drugs. For other African countries, malaria should be a key focus area. We know that drug resistance now is spreading into Africa from South East Asia and understanding the right combination of drugs to use is something that is easily identifiable through genomic surveillance.”
But surveillance is also about being ready for the next pandemic.
“There’s that classic line that, ‘diseases take no notice of national borders’,” Sillitoe said in an interview. “So, it is really important that we can get as wide a picture of surveillance as possible to identify something new emerging as soon as possible.”
Marco Salemi, Professor of Experimental Pathology at the Department of Pathology, Immunology, and Laboratory Medicine at the University of Florida College of Medicine, said Africa and the world need to be “proactive, rather than reactive” in the battle against future epidemics. He said the world is currently focused on monitoring the COVID-19 pandemic. “But we forget this is this huge reservoir of pathogens out there which we know so little about and which can become more and more of a threat, especially because of climate change – so we need to understand more about all these pathogens in the wild, in animals, and their potential to jump to humans, especially with the rate of globalisation on the planet … Events of zoonotic transmissions will become more and more frequent. We need to face it.”
Building capacity
De Oliveira is of the view that Africa could, in the next few years, potentially, “leapfrog over the rest of the world” in genomic surveillance, thanks to its success in COVID-19 genomics and its experience in using genomics to monitor other pathogens over the past 20 years.
We won’t be starting from scratch.
The use of genomics in infectious diseases started in the mid-eighties during the HIV epidemic, when scientists realised HIV was a complex virus that existed in many different sub-types. Scientists around the world started using genomic tools to sequence the HIV virus, track its origin, and trace the way the virus disseminated.
Genomics has, however, changed dramatically since the 1980s.
“There have been many attempts… to use genomics for public health purposes, but the key factor that was always missing was the ability to generate DNA sequencing in real-time,” said Salemi. “Real-time means there is an epidemic, with cases happening today – and we need to generate sequences within one or two days and then to analyse the genomic data and then to have actionable information that can be immediately transmitted to the public health authorities so that they can act within a few days.”
“Now the technological and computational limitations of the past few years have been overcome, and, as was clearly shown during the COVID-19 pandemic, we have machines that can generate literally thousands of sequences, like coronavirus sequences, in less than one day, or even within a few hours. At the same time, we have high-performance computer clusters, and super calculators that are capable of analysing this data in a very short time,” he said.
These technical advances would, of course, be of little value without people to use them and develop them further.
“Investment has been made on the continent in infectious disease surveillance and genomics surveillance specifically, and so we have lots of experts on the continent who know a lot about infectious diseases and how viruses work, and why it’s important to look at the genomics to trace when there is going to be a new outbreak,” says Professor Zané Lombard, Principal Medical Scientist in the Division of Human Genetics at the University of the Witwatersrand. “South Africa’s role during COVID-19 showcased what can happen quickly and effectively for public health interventions if you have the right experts with the right platform and expertise and infrastructure in place to do that kind of surveillance.”
De Oliveira and his team have worked closely with the Africa Centres for Disease Control and Prevention (Africa CDC) to scale genomic surveillance on the continent and have actively collaborated with other African countries to share expertise, resources, and genetic data in a bid to foster a continent-wide approach to genomic surveillance.
They have also helped set up large genomics facilities in Zimbabwe, Mozambique, and Botswana.
The Africa CDC, through its Pathogen Genomics Initiative (Africa PGI), has, for the past few years, been building a continent-wide genomic disease surveillance network. In 2019, when the PGI started its work, only seven of the African Union’s 55 member states had public health institutions with the equipment and staff to do genetic sequencing. Today, 31 African nations are able to do genetic sequencing for surveillance of COVID, malaria, cholera, Ebola, and other diseases.
De Oliveira said the continent’s experience in genomic surveillance of pathogens in Africa evolved to “unheard-of” levels during COVID. “We’ve been trying to advance genomic surveillance in Africa for the past two decades, and when the pandemic came, we had the right expertise to deal with viruses and respiratory pathogens such as tuberculosis, so we were able to pivot for SARS-CoV-2. In the end, South Africa and Africa became an example to follow for the whole world.
“All the investments we have made in genomic surveillance for COVID can now be leveraged and advanced to other areas of genomics in Africa… including for rare diseases, for cancer diagnostics, and human genomics. Finally, we have the tools and the equipment, as well as the support, to do advanced genomics in Africa, as we have dreamt of doing for the last twenty years.”
What it means in practical terms
Asked what it means, practically, to build capacity for genomics research, Lombard said one aspect is the establishment of strong laboratories. “Historically, if infrastructure was not available locally, researchers would partner with international labs and send their samples to have their sequencing done there. The problem with that was that expertise in using [that] technique was not being built locally,” she said. “It is really important to train the right people who know how to do the laboratory experiments but also to interpret the data correctly.
“It’s not only about building the infrastructure in the labs but also about training the individuals and making sure there are job opportunities locally for them,” she said.
Turning to the machines used in genomics, Lombard said, “The most popular machine these days is called a next-generation sequencer. These can read the whole DNA sequence of a virus.”
Salemi added, “Some of these sequencers are very large and some are even little portable boxes. Some can sequence thousands of samples at a time, while others are capable of sequencing a few dozen samples at a time. The samples, depending on the virus (or pathogen) being tested for, are taken from blood samples, nasal swabs, or sputum from patients, from faeces, urine, or from the skin.
“The BMRI (at Stellenbosch University) – which has the largest sample storage capacity in the southern hemisphere – can store five million samples at minus 80 degrees. If someone wants to build a lab that includes top-of-the-line computational capacity, it will cost anything from $40 million (over 700 million), but to start a small operation to do a few hundred sequences of a virus every week, $100 000 to $200 000 (roughly R17 million to R34 million) is enough, which has been done in many different African countries during the pandemic.”
Training is key
While all the scientists interviewed agreed that laboratories are important in building capacity for genomics research, they stressed that what is really needed is to train more individuals.
“More people need to be trained in genomics but also in bioinformatics, which is a really important component of this work. The technology component is becoming very smart and automated, but the data being generated is becoming more and more complex, with bigger data sets. Dealing with these,” Lombard said, “requires special data analysis skills and bioinformatics skills. The field of bioinformatics will need investment so that we can deal with the deluge of data that will come out.”
She said South African and other African universities are taking this skills need seriously, with many initiatives to offer undergraduate and post-graduate training programmes in these areas.
Salami agreed. “The most important part of building capacity is the human training. I find it naïve and sad when I hear politicians talking about building top-of-the-line laboratories, when, what they really need to do is to start building human capacity. Africa is an amazing reservoir (from which to build these skills) because 50 percent of the continent [are] people who are less than 30 years old. There are about 27 excellent laboratories all over Africa. We need to start creating a strong next generation of scientists.”
In support of this, de Oliveira is trying to raise 100 million dollars to implement real-time genomic research to enable the African continent to respond to new epidemics.
He said during COVID, the Network for Genomics Surveillance was founded and funded by the Department of Science and Innovation and the South African Medical Research Council (SAMRC). This funding was until 2021.
The Centre for Epidemic Response and Innovation, which is led by de Oliveira and forms part of the BMRI, is funded by the Africa CDC, the WHO, the Rockefeller Foundation, and the Elma Foundation. These funders support the work in South Africa and in other African countries, as well as the SA government. The BMRI was mostly funded by Stellenbosch University to the effect of R900 million, while the Department of Higher Education provided about R300 million. CERI occupies one floor of the BMRI.
In de Oliveira’s words, “This truly is the genome era for Africa.”
