A study of COVID transmissions in a Taiwanese quarantine hotel revealed that SARS-CoV-2 can spread through cracks in walls and floors, according to findings published in Emerging Infectious Diseases.
The researchers investigated a cluster of SARS-CoV-2 infections in a quarantine hotel in Taiwan in December 2021. This happened amidst a succession of outbreaks in quarantine hotels involving the Omicron variant. The cluster involved three patients who lived in nonadjacent rooms on different floors, and who had no direct contact during their stay.
All three had tested negative by RT-PCR for SARS-CoV-2 within 72 hours before arrival to Taiwan and by deep-throat saliva RT-PCR upon arrival at the airport. None had left their rooms at any point during the stay in the hotel. No other guest or staff member at the hotel had tested positive since the month prior to the start of the investigation.
By directly exploring the space above the room ceilings, the researchers revealed residual tunnels, wall defects, and truncated pipes between their rooms. To see how the rooms were interconnected, they performed a simplified tracer-gas experiment, using ethanol. Aerosol transmission through structural defects in floors and walls in this poorly ventilated hotel was the most likely route of virus transmission.
This event demonstrated the high transmissibility of Omicron variants, even across rooms and floors, through structural defects. “Our findings emphasise the importance of ventilation and integrity of building structure in quarantine facilities,” the authors concluded.
“I think I’m in trouble,” came the message through to Professor Veronica Ueckermann one evening during the first surge of COVID-19 in South Africa in the winter of 2020. It was a distressed call made by a 48-year-old theatre nurse who worked alongside Ueckermann in the ICU frontline. Ueckermann, who is also a professor of internal medicine at the University of Pretoria and an ICU specialist, shifted into high gear with other doctors to save their colleague who was diagnosed with COVID-19.
They succeeded.
But what they didn’t know then was that months later the nurse would be ailing from ongoing medical symptoms put down to the catch-all of long-COVID.
“It’s a case study, but it was also very close to my heart,” says Ueckermann, who has become a specialist and researcher on the long-term effects of COVID. She recently presented on long-COVID during a webinar of the South African Academy of Family Physicians. “The nursing sister had numerous comorbidities, including a raised BMI, diabetes, hypertension, and asthma. When her symptoms didn’t get better, the hospital just wanted to have her medically boarded because they couldn’t be sure when she would be well enough to work again,” says Ueckermann.
She is cautious too, pointing out that there’s still little definitively known about long-COVID and new research is only in its infancy. Much of the difficulty lies in the wide-ranging symptoms and how individuals are affected. There are also varying recovery times, different underlying conditions and susceptibilities, and the reality that many people are simply not diagnosed. It makes the term “long-COVID” an umbrella term for everything from brain fog or mental confusion and fatigue to depression and shortness of breath and chest pains. Others also describe general body aches and continued loss of smell and taste.
The post-COVID condition
In October 2022, the World Health Organization (WHO) released a factsheet that states that between 10% and 20% of people who are diagnosed with COVID-19 continue to have symptoms beyond three months of first getting ill and develop what the WHO refers to as post-COVID condition. Many more people say symptoms plague them still even after nearly two years.
“The condition can be debilitating, causing disabling symptoms and functional deficits. It can significantly impact people’s ability to work, engage and participate fully in family and community life. Mental health effects can directly result from long-COVID, but may also develop due to prolonged suffering and distress caused by the condition,” reads the WHO factsheet.
The WHO’s recommended treatment, however, is non-specific, stating: “Post-COVID-19 condition can be supported with help from their families, peers, employers, and the community and they can also benefit from tailored rehabilitation.”
According to the National Institute for Communicable Diseases (NICD), “Every long-COVID patient is different, as such, every patient will need treatment specific to their symptoms which can be managed by their family doctor or clinic. There are no drugs to prevent long-COVID. Long-COVID is not a contraindication to vaccination, and COVID-19 vaccination may even sometimes improve long-COVID symptoms. Long-COVID is treated by slow, stepwise rehabilitation, and appropriate management of symptoms.”
Greater awareness and education needed
Ueckermann agrees with the WHO’s call for greater awareness and education so patients feel heard and supported. Many people resort to joining online support groups through platforms like Facebook. They share their challenges and stories and give each other support when they feel misunderstood and frustrated that they can’t get well and doctors can’t help. Ueckermann says there needs to be help for patients’ individual needs because not finding solutions will add to mounting pressure on the healthcare system.
“Because of COVID disruptions, many cancers are now presenting at later stages. There are cases of TB and other illnesses that were neglected. And now we have long-COVID that requires diagnosis after diagnosis for exclusion so all of this drives up costs,” she says.
lung There are other associated costs for people who cannot work or are performing sub-optimally trying to work while feeling unwell. Children affected by long-COVID do worse at school and lose interest in their sports and other activities that they used to enjoy, she says.
Last year, Spotlight reported on a dedicated long-COVID clinic at Groote Schuur Hospital in Cape Town. As far as we could establish, such specialised long-COVID clinics are very rare in South Africa.
“Long-COVID remains inaccurately defined and as a result, standard treatment guidelines for the condition as a whole have not yet been developed,” says Foster Mohale, Spokesperson for the National Department of Health. “However, standard treatment guidelines to address the symptoms and conditions associated with long-COVID are in place,” he says. “These guidelines guide assessment and treatment, and provide criteria for referral from primary healthcare to more specialised services.”
Mohale adds that the burden of disease is of “enormous concern and needs to be better understood and quantified”. But says the department’s data shows that visits by adults to public sector primary healthcare facilities remain below pre-pandemic levels, which suggests that any increase in the burden of disease has not resulted in an increased burden on health services. He also emphasises the need to have up-to-date vaccinations, adding that “people who are vaccinated are less likely to develop long-COVID”.
Research ongoing
Ueckermann says it’s a positive development that as awareness is growing, so are studies, including studies by the Medical Research Council and many of the country’s universities. She says scientists are looking at everything from the role of green tea extracts and the use of SSRIs (Selective serotonin reuptake inhibitors) that are commonly used to treat depression.
“These are all ongoing studies, so we have to wait to see the data coming through but it’s promising that everyone is trying to understand exactly what this long-COVID is and the most important thing is that we continue making this a greater area of priority in healthcare,” she says. It matters for the growing number of patients, or for her colleague who she says still needs help to get from “doing better,” to fully recovered.
Daily COVID vaccinations have more or less plateaued since July. At the peak of the vaccination drive, South Africa was administering up to 240 000 vaccine doses a day. But this number has dropped to just over 5000 a day. Less than half of these are first doses and a third are booster shots.
The government still hasn’t reached its target of 67% adult vaccination, which it wanted to achieve by the end of 2021. Half of the adult population in South Africa is currently vaccinated. Among adults 60 years or older, nearly 73% have been fully vaccinated.
GroundUp visited the District Six Community Day Centre, a government clinic, in Cape Town. We asked for a COVID vaccine and were directed to a small room on the first floor, where one of us waited over 1.5 hours to get a vaccine (though two of us were vaccinated considerably quicker – about 30 minutes). This wasn’t because there was a long queue.
The nurse administering the vaccines was busy treating patients elsewhere in the clinic. The person logging the vaccines on the computer system told GroundUp that on average, 12 people a day come to the clinic for vaccines.
GroundUp visited a Clicks store in Cape Town where, three months ago, vaccines were still being administered. But they no longer do COVID vaccines.
The government’s dedicated Coronavirus website has a list of “active vaccination sites”, many of which are no longer active, and the “Find My Jab” page has completely different information.
Meanwhile, people are still getting ill from the virus. About 2000 new cases are reported each week, but according to the National Institute for Communicable Diseases (NICD) only 16% of cases are being detected. Testing sites are also few and far between.
Professor Glenda Gray says that the vaccine has done a good job at reducing deaths, serious illness and hospitalisations. Official daily deaths and hospitalisation rates are low in relation to previous waves. In the past four weeks, 125 deaths from COVID were reported.
The real number of deaths is likely much more than this. A weekly report published by the Medical Research Council and the University of Cape Town calculates the number of excess deaths – the deaths above the historical average before COVID: there have been close to 50 000 excess deaths so far this year. While in earlier waves the researchers were able to estimate that 85% to 95% of these excess deaths were due to COVID, the changing nature of the epidemic has made it much harder to estimate how many of this year’s excess deaths are due to COVID.
More than 85% of COVID infections in the country are from the Omicron BA.5 variant, which is widespread and infectious but usually causes very mild illness.
To prevent serious illness and death, getting the vaccine and booster shots are still recommended. Gray says that it is especially important for immunocompromised people, such as people living with HIV, to get vaccinated.
“Sadly, the virus has done a far better job of generating immunity than our government, which continues to be maddeningly slow at getting the vaccine out,” says Professor Francois Venter, infectious diseases clinician and head of Ezintsha at Wits University.
Although being infected by and recovering from the virus does provide a level of immunity, getting a vaccine still greatly improves one’s protection against the virus.
“I think we were all hoping once we had immunity from either infection or a vaccine or two, it would be enough. But from what we are seeing internationally, new waves of COVID, while not killing people in the numbers we saw in 2020 and 2021, are still making people very sick,” Venter says.
Dr Nicholas Crisp, Deputy Director-General of the National Department of Health, is the coordinator of the national vaccination drive. He agrees the current status of the vaccination drive is “very disappointing”.
He says the vaccination program is being integrated into primary health care, targeting areas geographically where communities or segments of a community are not vaccinated.
To monitor and manage the pandemic, Crisp says the government is continuing with daily testing, gene sequencing and wastewater sampling. Crisp says that the government is preparing for the future of COVID as well as other potential pandemics.
Future variants of the virus could be more dangerous. “As long as there is transmission, there is going to be mutation,” Gray told GroundUp. How the virus mutates in the future is yet to be seen.
In the US, new bivalent vaccines designed to target the Omicron variant are already available. But, Gray says, there is not yet sufficient evidence that these work better than the current vaccines.
According to Crisp, the government is not considering any new vaccines. “We are not buying vaccines this year and may not buy vaccines next year,” he says.
South Africa still has 8 million doses of the Pfizer vaccine and 10 million doses of the Johnson and Johnson vaccine. He says paediatric Pfizer vaccines will be purchased with some of the credit that South Africa has with the Covax facility. These will be given to children who are immunocompromised.
According to a study published in JAMA Pediatrics, cases of young people seeking care for eating disorders greatly increased in the months of the pandemic.
Eating disorders (EDs), such as anorexia nervosa and bulimia nervosa, impact a wide range of individuals. In the developmental stages of adolescent and young adulthood, EDs – especially restrictive ones – can have particularly negative impacts. Furthermore, EDs commonly co-occur with other mental health conditions which can influence the trajectory of illness. Individuals with EDs have greater mortality rates, partly due to increased suicidality.
EDs requires intensive specialist care, which is not often available in many settings. A rise in rates of anxiety and depression have been attributed to the COVID pandemic, as well as a worsening of ED. Possible reasons for this include uncertainty about the future, disruptions in daily routines, inconsistent access to food, more time spent in triggering environments, influence from the media, and changes in access to treatment.
Reports from hospitals indicated increasing numbers of diagnoses and hospital admissions for ED, but there was little geographically widespread data.
Therefore, the researchers set out to investigate trends in patient volume for inpatient medical hospitalisation as well as volume of patients seeking outpatient subspecialty care, both before and after the pandemic.
The researchers used an an observational case series design to compare changes in volume in inpatient and outpatient ED-related care at 15 sites between January 2018 and December 2021.
Before the COVID pandemic, the relative number of pooled inpatient ED admissions were increasing over time by 0.7% per month. After onset of the pandemic, there was a significant increase in admissions over time of 7.2% per month through April 2021, then a decrease of 3.6% per month through December 2021. Before the pandemic, relative outpatient ED assessment volume was stable over time, with an immediate 39.7% decline in April 2020. Thereafter, new assessments increased by 8.1% per month through April 2021, then decreased by 1.5% per month through December 2021. The nonhospital-based ED program did not demonstrate a significant increase in the absolute number of admissions after onset of the pandemic but did see a significant increase of 8.2 additional inquiries for care per month in the first year after onset of the pandemic.
“Given inadequate ED care availability prior to the pandemic, the increased postpandemic demand will likely outstrip available resources. Results highlight the need to address ED workforce and program capacity issues as well as improve ED prevention strategies.”
Patients with nasopharyngeal cancer are often treated with immunotherapy. It was previously feared that, due to its immune response stimulation, COVID vaccination could reduce the success of cancer treatment or cause severe side effects. A recent study published as a “Letter to the editor” in the journal Annals of Oncology now gives the all-clear on this matter. What’s more, the study showed that cancer drugs actually worked better after vaccination with the Chinese vaccine SinoVac than in unvaccinated patients.
Many cancer cells are capable of subverting the body’s immune response. They do this by acting on the PD-1 receptor, they effectively shut down these endogenous defence forces. Drugs can be used to block PD-1 receptors. This enables the immune system to fight the tumour more effectively.
Vaccination against COVID also stimulates the immune response, involving the PD-1 receptor. “It was feared that the vaccine would not be compatible with anti-PD-1 therapy,” explains Dr Jian Li of the Institute of Molecular Medicine and Experimental Immunology (IMMEI) at the University Hospital Bonn. “This risk is especially true for nasopharyngeal cancer, which, like the SARS Cov-2 virus, affects the upper respiratory tract.”
Researchers from the Universities of Bonn and Shanxi in the People’s Republic of China investigated whether this concern is justified. More than 1500 patients treated in 23 hospitals from all over China participated in the analysis. Such multi-centre studies are considered to be particularly informative because the participants are very diverse and, moreover, the results are not distorted by regional characteristics.
Better response to cancer therapy
A subset of 373 affected individuals had been vaccinated with the Chinese COVID vaccine SinoVac. “Surprisingly, they responded significantly better to anti-PD-1 therapy than the unvaccinated patients,” explains Prof. Dr. Christian Kurts, Director of IMMEI. “Furthermore, they did not experience severe side effects more often.” The researchers cannot say why the treatment was more successful after vaccination. “We assume that vaccination activates certain immune cells, which then attack the tumor,” says Prof. Dr. Qi Mei of Shanxi University Hospital. “We will now investigate this hypothesis further.”
Nasopharyngeal cancer is quite rare in this country. In southern China and other countries in Southeast Asia, however, the disease is widespread. One of the suspected reasons for this is the frequent use of air conditioning in the hot and humid regions. Nutritional factors also appear to play an important role. In Taiwan, nasopharyngeal cancer is now considered one of the leading causes of death among young men.
COVID patients placed on ventilators can take a long time to regain consciousness. New research published the Proceedings of the National Academy of Sciences now shows that these delays may serve a purpose: protecting the brain from oxygen deprivation.
The existence of such a brain-preserving state could explain why some patients wake up days or even weeks after they stop receiving ventilation, and it suggests that physicians should take these lengthy recovery times into account when determining a patient’s prognosis.
In their study, investigators connect the pattern seen among those who have survived severe COVID with similar delays known to occur in a small fraction of cardiac arrest patients.
“The delayed recoveries in COVID patients are very much like the rare cases we’ve documented in previous research. In this new paper, we describe a mechanism to explain what we’re seeing in both types of patients,” said study co-senior author Dr Nicholas D. Schiff, a neurology professor at Weill Cornell Medicine.
He suggests that this mechanism is the brain protecting itself, pointing to animals, most notably painted turtles, that can tolerate extended periods without oxygen.
More than a decade ago, Dr Schiff and his colleagues first observed these delays among comatose cardiac arrest patients who received cooling therapy to reduce brain damage caused by a loss of blood flow. In one such case, a 71-year-old patient took 37 days to awaken, before ultimately making a near-complete recovery.
During the pandemic, Dr Schiff performed neurology consultations for COVID patients, and he soon began seeing similar, delayed awakenings occurring when patients were taken off ventilators and stopped receiving movement-limiting sedatives.
In a separate analysis of a large cohort of COVID patients from Weill Cornell Medicine and two other major U.S. medical centres, Dr Schiff and his colleagues, including co-author of the current paper, Dr Emery N. Brown, professor of anaesthesia at Harvard Medical School, found that a quarter of patients who survived ventilation took 10 days or longer to recover consciousness. The more oxygen deprivation they suffered while on the ventilator, the longer that delay.
In the prior study of cardiac patients, the researchers recorded a distinctive pattern in brain activity, one also seen in patients under deep anaesthesia. (Recordings from COVID patients are extremely limited.) Dr Schiff read that a similar pattern had been seen in the brains of painted turtles, which can withstand up to five months without oxygen under ice in the winter. To do so, they activate the same inhibitory system within the brain targeted by anaesthetics given to human cardiac and COVID patients but in novel ways developed by evolutionary specialisations.
Drs Schiff and Brown propose that, by chance, the same protective response emerges in the patients.
“It is our theory that oxygen deprivation as well as practices in the ICU, including commonly used anaesthetics, expose elements of strategies that animals use to survive in extreme conditions,” Dr Schiff said.
“These observations may offer new insights into the mechanisms of how certain anaesthetics produce unconsciousness and new approaches for ICU sedation and for fostering recovery from disorders of consciousness,” Dr Brown added.
When patients fail to regain consciousness for an extended time, physicians may recommend withdrawing life-supporting care. This threshold is typically set at 14 days or less for cardiac patients, while no such guidelines exist for COVID.
In light of this new research, however, so long as they lack brain injuries, physicians should avoid making negative projections about these patients’ potential to recover, note the researchers.
The European Medicines Agency (EMA) recommended that heavy menstrual bleeding should be added to the product information as a side effect of unknown frequency of the mRNA COVID vaccines Comirnaty (Pfizer/BioNtech) and Spikevax (Moderna).
Heavy menstrual bleeding may be defined as bleeding characterised by an increased volume and/or duration which interferes with the person’s physical, social, emotional and material quality of life. Cases of heavy menstrual bleeding have been reported after the first, second and booster doses of Comirnaty and Spikevax.
The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) assessed this safety signal after reviewing the available data, including cases reported during clinical trials, cases spontaneously reported in Eudravigilance and findings from the medical literature.
After a review of the available data, the PRAC concluded that there is at least a reasonable possibility that the occurrence of heavy menstrual bleeding is causally associated with these vaccines and therefore recommended the update of the product information.
The available data reviewed involved mostly cases which appeared to be non-serious and temporary in nature.
There is no evidence to suggest the menstrual disorders experienced by some people have any impact on reproduction and fertility. Available data provides reassurance about the use of mRNA COVID vaccines before and during pregnancy. A review carried out by EMA’s Emergency Task Force showed that mRNA COVID vaccines do not cause pregnancy complications for expectant mothers and their babies, and they are as effective at reducing the risk of hospitalisation and deaths in pregnant people as they are in non-pregnant people.
Red mitochondria in airway cells become coated with green SARS-COV-2 proteins after viral infection: Researchers discovered that the virus that causes COVID-19 damages lungs by attacking mitochondria. Credit: Stephen Archer
Viruses and bacteria have a very long history. Because viruses can’t reproduce without a host, they’ve been attacking bacteria for millions of years. Some of those bacteria eventually became mitochondria, synergistically adapting to life within eukaryotic cells (cells that have a nucleus containing chromosomes).
Ultimately, mitochondria became the powerhouses within all human cells.
This is the story of how a team, assembled during the pandemic, recognized the mechanism by which these viruses were causing lung injury and lowering oxygen levels in patients: It is a throwback to the primitive war between viruses and bacteria – more specifically, between this novel virus and the evolutionary offspring of bacteria, our mitochondria.
SARS-CoV-2 is the third novel coronavirus to cause human outbreaks in the 21st century, following SARS-CoV in 2003 and MERS-CoV in 2012. We need to better understand how coronaviruses cause lung injury to prepare for the next pandemic.
How COVID-19 affects lungs
People with severe COVID-19 pneumonia often arrive at the hospital with unusually low oxygen levels. They have two unusual features distinct from patients with other types of pneumonia:
First, they suffer widespread injury to their lower airway (the alveoli, which is where oxygen is taken up).
Second, they shunt blood to unventilated areas of the lung, which is called ventilation-perfusion mismatch. This means blood is going to parts of the lung where it won’t get sufficiently oxygenated.
We already knew that mitochondria are not just the powerhouse of the cell, but also its main consumers and sensors of oxygen. Mitochondria control the process of programmed cell death (called apoptosis), and they regulate the distribution of blood flow in the lung by a mechanism called hypoxic pulmonary vasoconstriction.
This mechanism has an important function. It directs blood away from areas of pneumonia to better ventilated lobes of the lung, which optimizes oxygen-uptake. By damaging the mitochondria in the smooth muscle cells of the pulmonary artery, the virus allows blood flow to continue into areas of pneumonia, which also lowers oxygen levels.
It appeared plausible that SARS-CoV-2 was damaging mitochondria. The results of this damage – an increase in apoptosis in airway epithelial cells, and loss of hypoxic pulmonary vasoconstriction – were making lung injury and hypoxaemia (low blood oxygen) worse.
Our discovery, published in Redox Biology, explains how SARS-CoV-2, the coronavirus that causes COVID-19 pneumonia, reduces blood oxygen levels.
We show that SARS-CoV-2 kills airway epithelial cells by damaging their mitochondria. This results in fluid accumulation in the lower airways, interfering with oxygen uptake. We also show that SARS-CoV-2 damages mitochondria in the pulmonary artery smooth muscle cells, which inhibits hypoxic pulmonary vasoconstriction and lowers oxygen levels.
Attacking mitochondria
Coronaviruses damage mitochondria in two ways: by regulating mitochondria-related gene expression, and by direct protein-protein interactions. When SARS-CoV-2 infects a cell, it hijacks the host’s protein synthesis machinery to make new virus copies. However, these viral proteins also target host proteins, causing them to malfunction. We soon learned that many of the host cellular proteins targeted by SARS-CoV-2 were in the mitochondria.
How SARS-CoV-2 targets mitochondria to kill lung cells and prevent oxygen sensing. Credit: Brooke Ring, provided by Stephen Archer
Viral proteins fragment the mitochondria, depriving cells of energy and interfering with their oxygen-sensing capability. The viral attack on mitochondria starts within hours of infection, turning on genes that break the mitochondria into pieces (called mitochondrial fission) and make their membranes leaky (an early step in apoptosis called mitochondrial depolarization).
In our experiments, we didn’t need to use a replicating virus to damage the mitochondria – simply introducing single SARS-CoV-2 proteins was enough to cause these adverse effects. This mitochondrial damage also occurred with other coronaviruses that we studied.
We are now developing drugs that may one day counteract COVID-19 by blocking mitochondrial fission and apoptosis, or by preserving hypoxic pulmonary vasoconstriction. Our drug discovery efforts have already enabled us to identify a promising mitochondrial fission inhibitor, called Drpitor1a.
Our team’s infectious diseases expert, Gerald Evans, notes that this discovery also has the potential to help us understand Long COVID. “The predominant features of that condition – fatigue and neurologic dysfunction – could be due to the lingering effects of mitochondrial damage caused by SARS-CoV-2 infection,” he explains.
Bacteria are regularly attacked by viruses, called bacteriophages, that need a host to replicate in. The bacteria in turn fight back, using an ancient form of immune system called the CRISPR-cas system, that chops up the viruses’ genetic material. Humans have recently exploited this CRISPR-cas system for a Nobel Prize-winning gene editing discovery.
The ongoing competition between bacteria and viruses is a very old one; and recall that our mitochondria were once bacteria. So perhaps it’s not surprising at all that SARS-CoV-2 attacks our mitochondria as part of the COVID-19 syndrome.
Pandemic pivot
The original team members on this project are heart and lung researchers with expertise in mitochondrial biology. In early 2020 we pivoted to apply that in another field – virology – in an effort to make a small contribution to the COVID-19 puzzle.
Our discovery owes a lot to our virology collaborators. Early in the pandemic, University of Toronto virologist Gary Levy offered us a mouse coronavirus (MHV-1) to work with, which we used to make a model of COVID-19 pneumonia. Che Colpitts, a virologist at Queen’s University, helped us study the mitochondrial injury caused by another human beta coronavirus, HCoV-OC43.
Finally, Arinjay Banerjee and his expert SARS-CoV-2 virology team at Vaccine and Infectious Disease Organization (VIDO) in Saskatoon performed key studies of human SARS-CoV-2 in airway epithelial cells. VIDO is one of the few Canadian centres equipped to handle the highly infectious SARS-CoV-2 virus.
Our team’s super-resolution microscopy expert, Jeff Mewburn, notes the specific challenges the team had to contend with.
“Having to follow numerous and extensive COVID-19 protocols, they were still able to exhibit incredible flexibility to retool and refocus our laboratory specifically on the study of coronavirus infection and its effects on cellular/mitochondrial functions, so very relevant to our global situation,” he said.
Our discovery will hopefully be translated into new medicines to counter future pandemics.
According to a recent study published in Frontiers in Cardiovascular Medicine, the risk of developing myocarditis is seven times higher with a COVID infection than with the COVID vaccine, by scientists. Patients with myocarditis can experience chest pains, shortness of breath or an irregular heartbeat. In severe cases, the inflammation can lead to heart failure and death.
“Our findings show that the risk of myocarditis from being infected by COVID is far greater than from getting the vaccine,” said Dr Navya Voleti, a resident physician at Penn State College of Medicine. “Moving forward, it will be important to monitor the potential long-term effects in those who develop myocarditis.”
Typically resulting from viral infection, myocarditis is a known complication of SARS-CoV-2 infection, and heart complications have been associated with mRNA COVID vaccination – particularly myocarditis in teenage boys. However, the relative risk of myocarditis due to vaccines and infections had not been clearly established.
The researchers conducted the largest study to date on the risk of developing myocarditis as a result of SARS-CoV-2 infection vs experiencing inflammation after COVID vaccination. The researchers compared vaccinated and unvaccinated COVIP patients to uninfected controls. The myocarditis risk was 15 times higher in COVID patients, regardless of vaccination status, compared to individuals who did not contract the virus.
Next, the researchers separately compared the rates of myocarditis in those who received the vaccines to those in unvaccinated individuals. According to the findings, the rates of myocarditis in people who were vaccinated against COVID were only twofold higher than in unvaccinated people.
Based on all the findings, the researchers concluded that the risk of myocarditis due to COVID was seven times higher than the risk related to the vaccines.
Investigators conducted a systematic review and meta-analysis of 22 studies published worldwide from December 2019 through May 2022. The studies included nearly 58 million patients who reported cardiac complications and belonged to one of two groups: the 55.5 million who were vaccinated against COVID compared to those who were not vaccinated (vaccination group), and the 2.5 million who contracted the virus compared to those who did not contract the virus (COVID group).
In the vaccination group, the researchers separately compared the risk of myocarditis for various COVID vaccines. The median age of the study population was 49 years; 49% were men; and the median follow-up time after infection or COVID vaccination was 28 days.
The researchers found that among those diagnosed with myocarditis after receiving the vaccine or having COVID, the majority (61%) were men. Of patients diagnosed with myocarditis in both vaccination and COVID groups, 1.07% were hospitalised and 0.015% died.
“COVID infection and the related vaccines both pose a risk for myocarditis. However, the relative risk of heart inflammation induced by COVID infection is substantially greater than the risk posed by the vaccines,” said Dr. Paddy Ssentongo, a resident physician in the Department of Medicine at Penn State Health Milton S. Hershey Medical Center and the lead author of the study. “We hope our findings will help mitigate vaccine hesitancy and increase vaccine uptake.”
The pharmaceutical industry is facing a serious challenge as it struggles to source enough non-human primates (NHPs) such as macaques for research and testing. Alongside demand created by HIV/AIDS research, the pandemic has tightened supplies of the animals further as China, a major supplier, has clamped down on exports.
Since NHPs have great genetic and physiological similarity to humans, scientists use these animals, most commonly rhesus macaques, to study medical conditions and conduct trials which are not yet possible in humans. In 2019, US scientists used 68 257 NHPs in research, according to US government data.
As a result of this shortage, many projects may not be able to be completed, according to industry insiders, with implications for medical research. Pre-pandemic prices of $11 000 per macaque have risen to $35 000.
In July last year, Nature reported that the US government pledged to increase funding to make primates available for clinical research. However, this would not do anything to address the current shortage.
To make room for more NHPs, the US National Institutes of Health (NIH) has invested about US$29 million to refurbish housing, build outdoor enclosures and making other infrastructure improvements at the US National Primate Research Centers (NPRCs), which it funds.
“A couple of years ago, we were feeling the pinch,” Nancy Haigwood, director of the Oregon NPRC in Beaverton, which houses about 5 000 non-human primates. But because of the pandemic, “we are truly out of animals”, she told Nature. “We’re turning away everyone.”
China had been a cheap source of cynomolgus macaques (Macaca fascicularis) since 1985, but in 2013 began to prioritise local research, restricting exports. Adding to this was soaring demand was sparked by multiple NIH grants awarded in 2016 to study HIV/AIDS, according to a 2018 report. Housing and feeding NHPs is costly, and NPRCs could not expand due to budget caps. The report warned of a coming shortage of various primates in coming years.
The situation has drawn the public’s attention – and opposition. Complaints made to airlines has resulted in many no longer carrying the animals, making transportation a major challenge. Air France was one of the last holdouts, and last year said it would stop carrying NHPs for research purposes.
With the arrival of the pandemic and the need for NHP research and testing, vaccine research was naturally prioritised, while trying to supply other projects as well.
When COVID hit, China completely suspended exports of macaques, hitting pharmaceutical companies hardest, which prefer that species for drug trials. Even if the export ban were to be lifted, the Chinese demand for macaques in research is so high that there would be few available for export: of 30 000 macaques that became suitable for use in research last year, 28 000 were used.
Other restrictions constrain the supply, such as a European Union requirement that all non-human primates for research come from self-sustaining colonies by November this year. The UK also carried through this directive following its exit from the EU.
