In an analysis of published prospective studies of people of all ages with confirmed SARS-CoV-2 infection who were followed for at least 12 months, pre-existing allergic conditions were linked to higher risks of experiencing long-term symptoms associated with COVID, or ‘Long COVID’.
The analysis, which is published in Clinical & Experimental Allergy, identified 13 relevant studies (with a total of 9 967 participants) published between January 1, 2020 and January 19, 2023.
Although the data as a whole from the studies suggested that individuals with asthma or rhinitis might be at increased risk of long COVID after SARS-CoV-2 infection, the evidence for these associations was very uncertain. Therefore, more robust epidemiological research is needed to clarify the role of allergy in the development of Long COVID.
“We need a better, harmonised definition of what is considered Long COVID for epidemiological studies of this sort. Regardless we will be updating our analysis once further studies have been published in the next few months,” said corresponding author Christian Apfelbacher, PhD, of the Institute of Social Medicine and Health Systems Research, in Germany.
When you think of Japan in the age of COVID, you might imagine a crowd of people wearing masks. But many of them are still wearing masks after the pandemic has ended. In an article published this month in the International Journal of Disaster Risk Reduction, a researcher from Osaka University analysed mask use before and after the government of Japan downgraded the legal status of COVID. Results showed that many people continue to wear masks for socio-psychological reasons – including reasons related to ‘relief’ and ‘norm’.
Of course, the obvious motivation for mask use is disease prevention. In the first half of 2020, masks were recommended worldwide because they help to prevent COVID transmission. Japan has since had one of the highest rates of mask usage throughout the pandemic.
However, on May 5, 2023, the World Health Organization declared the end of COVID as a global health emergency. Furthermore, on May 8, Japan downgraded the legal status of COVID to the same level as seasonal influenza.
Michio Murakami, the study’s author, notes, “The online survey shows that 59% of Japanese participants are still wearing masks, even after the downgrading of the legal status of COVID. That is only slightly down from 67%, which was before the downgrading.”
The surveys were conducted among people aged 20 to 69 in Japan. The first survey was performed in April 2023, before the policy changes, while the second was performed after the changes in June 2023. A total of 291 participants completed both surveys.
So what reasons, besides disease prevention, might lead people to continue wearing masks? “One common socio-psychological reason involves what we call ‘relief’. This means that wearing a mask can help relieve anxiety for many people,” explains Murakami. “There’s a second sociological reason, too: a ‘norm’. This refers to when people think they should wear a mask because they see others wearing masks,” he explains. People that have this trait are more likely to wear a mask when others around them are wearing masks, unsurprisingly.
Murakami was also able to document correlations between mask-usage motivations and actual mask usage. For instance, citing psychological reasons for mask use in April was correlated with actually wearing a mask later on in June. Furthermore, wearing a mask in April was associated with citing infection avoidance as a reason to wear masks in June.
“So many Japanese people prefer to wear masks,” notes Murakami. “This study helps us understand why people might do so, even in light of reduced infection risk.”
Professor Shabir Madhi has been appointed as an honorary Commander of the Most Excellent Order of the British Empire (CBE) by King Charles III.
Wits Professor of Vaccinology Shabir Madhi led the Oxford University sponsored Oxford/AstraZeneca Covid-19 vaccine clinical trials in South Africa
Wits University and the University of Oxford contributed scientifically to informing the public health response to the Covid-19 pandemic in South Africa and globally.
Madhi receives the Order in recognition of his services to science and public health in a global pandemic.
Madhi led South Africa and the continent’s first Covid-19 vaccine trials in 2020/2021 as founder and Director of the South African Medical Research Council (SAMRC) Wits Vaccines and Infectious Diseases Analytics (Wits VIDA) Research Unit.
An internationally recognised leader in his field, the National Research Foundation A-rated scientist was involved in multiple clinical and serology epidemiology studies on Covid-19, in addition to his research on vaccines against other life-threatening diseases.
The first of (subsequently two) Wits University-led South African Covid-19 vaccine trials, Madhi led the Oxford/AstraZeneca Covid-19 vaccine clinical trials in South Africa, in association with the University of Oxford.
Professor Sir Andrew Pollard, Director of the Oxford Vaccine Group, University of Oxford, and Madhi’s UK counterpart in these Covid-19 vaccine trials, says of Madhi’s CBE appointment: “I am delighted that Professor Shabir Madhi CBE has been honoured by King Charles for his remarkable contributions to global public health and particularly for his extraordinary leadership in the midst of a global pandemic. It has been a huge privilege for me to work alongside him and his team on the development of the globally impactful Oxford-AstraZeneca vaccine.”
Over the course of the pandemic (2020-2022), Madhi had been an outspoken, articulate, and ardent advocate of Covid-19 vaccination as well as for increased access to these and other vaccines in Africa.
On his appointment as CBE, Madhi says: “The privilege of being conferred this honour is credit to the tremendous effort of the incredible Wits VIDA research team that I have the privilege of leading at Wits University – before, during and beyond the Covid-19 pandemic. As a collective, and together with colleagues at the University of Oxford and in South Africa, we are proud to have contributed scientifically to informing the public health response to the Covid-19 pandemic in South Africa and globally.”
Until now, the reason why some coronaviruses such as SARS-CoV-2 affect humans more severely than other seasonal ones has eluded scientists. Now, results published in Nature have provided a piece of the puzzle by identifying a gateway used by the seasonal coronavirus HKU1 to enter human cells. HKU1 binds to a different receptor than SARS-CoV-2, which may partly explain the difference in severity between these two coronaviruses.
Receptors provide a useful means of figuring out coronavirus transmissibility and pathology as part of surveillance work on viral evolution. Seven coronaviruses are known for their ability to infect humans. Four of these are generally mild: HKU1, 229E, NL63 and OC43, while the other three are more pathogenic: SARS-CoV-1, Mers-CoV and SARS-CoV-2.
The HKU1 virus was first identified in an elderly patient with severe pneumonia in Hong Kong in 2005. Like SARS-CoV-2, HKU1 mainly infects upper respiratory tract cells. However, it rarely affects the bronchi and alveoli in the lungs. The HKU1 virus causes colds and other mild respiratory symptoms. Complications may also occur, including severe respiratory tract infections, particularly in young children, the elderly and immunocompromised individuals. It is estimated that 70% of children are infected before the age of 6. In total, 75 to 95% of the global population has been exposed to HKU1, which is comparable to other seasonal human coronaviruses.
At the cellular level, coronavirus spike proteins are cleaved after binding to their receptors. This cleavage phenomenon is vital for viral fusion, entry and multiplication. Some coronaviruses (SARS-CoV-2 and NL63) use the ACE2 receptor as a gateway for entering cells. Until now, HKU1 and OC43 were the only coronaviruses with unknown receptors.
Through collaboration between scientists at eight Institut Pasteur units, it was possible to identify the TMPRSS2 enzyme as the receptor to which HKU1 binds to enter cells. Once binding has occurred, TMPRSS2 triggers fusion of HKU1 with the cell, leading to viral infection. Through a combination of techniques performed in vitro and in cell culture, the scientists demonstrated that the TMPRSS2 receptor has high affinity with the HKU1 spike, which is not the case for SARS-CoV-2.
“Once a receptor has been identified for a virus, it is possible to characterise target cells more accurately, while also gaining insights on viral entry and multiplication mechanisms and infection pathophysiology,” comments, Olivier Schwartz, co-last author of the study and Head of the Institut Pasteur’s Virus and Immunity unit.
“Our findings also shed light on the various evolution strategies employed by coronaviruses, which use TMPRSS2 either to bind to target cells or trigger fusion and viral entry,” adds Julian Buchrieser, co-last author of the study and scientist in the Institut Pasteur’s Virus and Immunity unit.
These human-pathogenic viruses’ use of different receptors probably affects their degree of severity. Receptor levels vary among respiratory tract cells, thus influencing the sensitivity of cells to infection and viral spread. Once the route of viral entry into cells is known, it should also be possible to fight infection more effectively by developing targeted therapies and assess the risk of virulence posed by any future emerging coronaviruses.
In parallel with this work, Institut Pasteur teams led by Pierre Lafaye and Felix Rey have developed and characterised nano-antibodies (very small antibodies) that inhibit HKU1 infection by binding to the TMPRSS2 receptor. These reagents have been patented for potential therapeutic activities.
A study published in the Journal of Internal Medicine indicates that SARS-CoV-2 infection may worsen lower urinary tract symptoms (LUTS) in men. The study researchers found that a enlarged prostate as a result of COVID was involved.
The study included 17 986 men receiving medication for LUTS within the public healthcare system of Hong Kong in 2021–2022, half of whom had SARS-CoV-2 infection. The group with SARS-CoV-2 had significantly higher rates of retention of urine (4.55% versus 0.86%); blood in the urine (1.36% versus 0.41%); clinical urinary tract infection (4.31% versus 1.49%); bacteria in the urine (9.02% versus 1.97%); and addition of 5-alpha reductase inhibitors, which are drugs prescribed for enlarged prostate. (0.50% versus 0.02%). These urological manifestations occurred regardless of COVID severity.
The findings might relate to the presence of certain proteins targeted by SARS-CoV-2 that are known to be expressed in the prostate.
“We are excited to be the first to report the effects of COVID on complications of benign prostatic hyperplasia – or enlarged prostate – and also demonstrate the alarming extent of its urological effects,” said corresponding author Alex Qinyang Liu, MD, of Prince of Wales Hospital, in Hong Kong.
A new study from Queen Mary University of London, published in The Lancet’s EClinicalMedicine, has found that people may experience long-term symptoms, termed ‘long colds’, after non-COVID acute respiratory infections.
The ‘long cold’s’ most common symptoms included coughing, stomach pain, and diarrhoea more than four weeks after the initial infection. While the severity of an illness appears to be a key driver of risk of long-term symptoms, just why some people suffer extended symptoms while others do not is a focus of further research.
The findings suggest that there may be long-lasting health impacts following non-COVID acute respiratory infections such as colds, influenza, or pneumonia, that are currently going unrecognised. However, the researchers do not yet have evidence suggesting that the symptoms have the same severity or duration as long COVID.
The research compared the prevalence and severity of long-term symptoms after an episode of COVID versus an episode of another acute respiratory infection that tested negative for COVID. Those recovering from COVID were more likely to experience light-headedness or dizziness and problems with taste and smell compared to those who had a non-COVID respiratory infection.
While long COVID is now a recognised condition, there have been few studies comparing long-term symptoms following SARS-CoV-2 coronavirus infection versus other respiratory infections.
The study is the latest output from COVIDENCE UK, Queen Mary University of London’s national study of COVID, launched back in 2020 and still in follow-up, with over 19 000 participants enrolled. This study analysed data from 10 171 UK adults, with responses collected via questionnaires and statistical analysis carried out to identify symptom clusters.
Giulia Vivaldi, researcher on COVIDENCE UK from Queen Mary University of London and the lead author of the study, said: “Our findings shine a light not only on the impact of long COVID on people’s lives, but also other respiratory infections. A lack of awareness – or even the lack of a common term – prevents both reporting and diagnosis of these conditions.
“As research into long COVID continues, we need to take the opportunity to investigate and consider the lasting effects of other acute respiratory infections.
“These ‘long’ infections are so difficult to diagnose and treat primarily because of a lack of diagnostic tests and there being so many possible symptoms. There have been more than 200 investigated for long COVID alone.”
Headaches are a frequent complaint of those with a COVID infection, or have received a COVID vaccination, and it is thought that it may subsequently increase the frequency of migraines. To put this to the test, an observational study published in the European Journal of Neurology investigated the effects on migraine frequency of having had either been infected with COVID or having received a COVID vaccination.
Among 550 adults who had received migraine-related care at a Spanish headache clinic, 44.9% (247) reported COVID at least once and 83.3% (458) had been vaccinated; 61 patients (24.7%) reported migraine worsening since COVID and 52 (11.4%) since vaccination.
In participants who perceived that their migraines worsened, those who had been infected were 2.5-times more likely to be concerned about migraine worsening and patients who had been vaccinated were 17.3-times more likely to have this concern.
When investigators examined patients’ e-diary information, they observed no significant difference in headache frequency one month before and after infection or vaccination, even when comparing patients with and without self-reported migraine worsening.
“In the case of COVID-19, we reported previously that indeed headache is a frequent and disabling symptom of the infection; yet, it may not necessarily be linked to an increase in migraine frequency,” the authors wrote. “In light of our results, we believe that clinicians should deliver to patients a more reassuring message that COVID-19 and COVID-19 vaccines may marginally affect migraine course and that probably the impact of the infection and vaccines is less than the individual rhythmicity to have attacks. This information may help minimise their worry.”
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.
‘Long COVID’ is a mysterious constellation of symptoms associated with having recovered from COVID infection – but how many cases represent a true condition, and how many fall under a poorly-defined umbrella of currently known ones? Overly broad definitions, a lack of appropriate, or any, comparison groups, among other things, in studies looking at the epidemiology of the condition have distorted the risks, say the authors of a review published in BMJ Evidence-based Medicine.
This is further compounded by inclusion of poorly conducted studies into systematic reviews and pooled data analyses that end up overstating the risk yet again, they add.
Likely consequences include increased public anxiety and healthcare spend; misdiagnoses; and diversion of funds from those who really do have other long term conditions secondary to COVID infection, suggest the researchers.
Many after-effects of COVID infection include post-ICU syndrome, which is a constellation of health issues that are present when the patient is in intensive care and which persist after discharge home, and shortness of breath following pneumonia. The trouble is that these are common to many upper respiratory viruses, the researchers point out.
None of the working definitions of ‘long COVID’ used by influential health bodies, such as the US Centers for Disease Control and Prevention, the World Health Organization, the UK National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), and the Royal College of General Practitioners requires a causal link between SARS-CoV2 and a range of symptoms.
Not only should comparator (control) groups be included in ‘long COVID’ studies, when they often aren’t, but they should also be properly matched to cases, ideally by age, sex, geography, socioeconomic status and, if possible, underlying health and health behaviours, which they rarely are, say the researchers.
During the early stages of the pandemic, when SARS-CoV-2 testing wasn’t widely available, studies were more likely to include a non-representative sample of SARS-CoV-2-positive patients by including fewer patients with mild or no symptoms.
This is known as sampling bias, which occurs when certain members of a population have a higher probability of being included in a study sample than others, potentially limiting the generalisability of a study’s findings, explain the researchers.
“Our analysis indicates that, in addition to including appropriately matched controls, there is a need for better case definitions and more stringent [‘long COVID’] criteria, which should include continuous symptoms after confirmed SARS-CoV-2 infection and take into consideration baseline characteristics, including physical and mental health, which may contribute to an individual’s post COVID experience, “ they write, adding that the umbrella term ‘long COVID’ should be jettisoned in favour of different terms for specific after effects.
While the results of high quality population studies on ‘long COVID’ in adults and children have been reassuring, they point out, the body of research “is replete with studies with critical biases” they add, setting out common pitfalls.
“Ultimately, biomedicine must seek to aid all people who are suffering. In order to do so, the best scientific methods and analysis must be applied. Inappropriate definitions and flawed methods do not serve those whom medicine seeks to help,” they insist.
“Improving standards of evidence generation is the ideal method to take long COVID seriously, improve outcomes, and avoid the risks of misdiagnosis and inappropriate treatment,” they include.
