LIVE BLOG: R&D response to COVID-19 pandemic (archived)

Researchers at Imperial College London found that symptoms of COVID-19, including the initial triad of cough, fever and loss of smell, varied by both country and presence of underlying health conditions like asthma and diabetes.

They say this is the first study to explore symptoms among those who test positive for COVID-19 by location and underlying chronic disease, but are not so seriously ill they are admitted to hospital.

It involved analysis of data on symptoms self-reported by 78,299 individuals in 190 countries between April and September 2020. Of these, 64,699 were symptomatic and untested, 7,980 tested positive, and 5,620 tested negative.

The researchers say the study creates a framework for using global self-reported data to identify parallels between health conditions, world region, and symptom profile of infectious diseases.

Joint senior author Aldo Faisal, professor in the departments of Computing and Bioengineering at Imperial, said understanding symptom variation by location and health is crucial for clinical practice. “It could help speed up diagnosis, predict outcomes more precisely and target treatment, particularly with the emergence of new variants."

Global snapshots can help to inform treatment of patients, whose age and underlying health conditions like asthma or diabetes are likely to affect COVID-19 symptoms and outcomes. The approach could also help to inform public health messaging and practice by monitoring in real-time the effects of new outbreaks or variants.

The symptom mapper was advertised primarily on social media and surveyed both tested and untested individuals, so that countries with poor testing infrastructure could still be included. The data represent a snapshot of symptoms from the early stage of the pandemic and relate only to the initial SARS-CoV-2 strains circulating between April and September 2020 and not the subsequent Delta and Omicron variants.

Most responses were from India (22.5%), Mexico (16.8%), Pakistan (9.5%), Philippines (9%), UK (5.7%), and Brazil (5.5%). The researchers used the machine learning technique of clustering to identify similarities between the symptom profile of different countries and underlying health conditions.

Respondents who tested positive for COVID-19 were more likely to report joint pain, loss of appetite and loss of smell and taste, than responders who had tested negative, or had symptoms but had not been tested. Fewer respondents who had tested positive for COVID-19 reported sore throat and nasal congestion than those who had tested negative or had symptoms but were untested.

Respondents with underlying lung conditions and/or type 2 diabetes were more likely to report several symptoms than those with no underlying conditions. However, loss of smell and taste was more likely to be reported as a symptom amongst COVID-19 positive responders with no underlying disease.

Respondents in Brazil were five times more likely to report chest pain and joint pain than other countries. Respondents in Pakistan were four times more likely to report chest pain and five times more likely to report joint pain. Respondents in India were three times more likely to report chest pain and four times more likely to report joint pain.

The UK symptom profile differed from the majority of countries, which the researchers say could be because its respondents were overall older than those of other countries.

The research provides a global snapshot of symptoms, an approach that could help to track variation in symptoms and identify changes linked to future variants or vaccination status.

First author Balasundaram Kadirvelu, of the Department of Computing, said, “Although many around the world have been hospitalised, most people who contract COVID-19 treat it at home with no clinical contact. These self-reported data allow us to capture the symptom profiles of patients not in contact with health services. In doing so, they offer a new perspective on the pandemic.”

A new study from Karolinska Institutet, the Helmholtz Center Munich and the Technical University of Munich has demonstrated that immune system macrophages show altered inflammatory and metabolic expression several months after mild COVID-19.

“We can show that the macrophages from people with mild COVID-19 exhibit an altered inflammatory and metabolic expression for three to five months post-infection,” said Craig Wheelock, of the Department of Medical Biochemistry and Biophysics at the Karolinska. “Even though the majority of these people did not have any persistent symptoms, their immune system was more sensitive than that of their healthy counterparts,” he said.

Long-term symptoms are relatively common after severe COVID-19 infection but may also affect people who had mild disease. More research is needed to understand the long-term immune aberrations in patients who have recovered from the infection, the researchers say.

They analysed blood samples from 68 people who had mild COVID-19 infection and a control group of 36 people who had not had COVID-19, isolating and sequencing macrophages to measure active genes. The researchers also measured eicosanoid signalling molecules, which are a fundamental feature of inflammation.

“It is not surprising to find a large number of eicosanoid molecules in people with COVID-19 as the disease causes inflammation, but it was surprising that they were still being produced in high quantities several months after the infection,” Wheelock said.

A new study published in The Lancet Public Health indicates serious COVID-19 illness is linked to an increase in the risk of long-term adverse mental health effects.

The findings suggest that, on the whole, non-hospitalised patients with a SARS-CoV-2 infection were more likely to experience depressive symptoms up to 16 months after diagnosis, compared to those never infected.

Patients who were bedridden for seven days or more had higher rates of depression and anxiety, compared to people who were diagnosed with COVID-19, but never bedridden.

The analysis finds that symptoms of depression and anxiety mostly subsided within two months for non-hospitalised patients with COVID-19. However, patients who were bedridden for seven days or more remained at increased risk of depression and anxiety over the 16-month study period.

Most studies to date have only examined adverse mental health impacts for up to six months after a COVID-19 diagnosis, and little is known about the long-term mental health impacts beyond that period, particularly for non-hospitalised patients with varying degrees of illness severity.

The analysis drew upon data from seven cohorts across Denmark, Estonia, Iceland, Norway, Sweden, and the UK and included 247,249 people.

Overall, participants diagnosed with COVID-19 had a higher prevalence of depression and poorer sleep quality compared to individuals who were never diagnosed (20.2% vs 11.3% experienced symptoms of depression; and 29.4% vs 23.8% experienced poor sleep quality; equivalent to an 18% and 13% increase in prevalence respectively after adjusting for other factors including but not limited to age, gender, education, body mass index, and previous psychiatric diagnosis.

Study author Unnur Anna Valdimarsdóttir, professor at the University of Iceland, said, “Our research is among the first to explore mental health symptoms after a serious COVID-19 illness in the general population up to 16 months after diagnosis. It suggests that mental health effects aren’t equal for all COVID-19 patients and that time spent bedridden is a key factor in determining the severity of the impacts on mental health.”

Researchers at Birmingham University have developed a new antimicrobial technology for air filters which can kill bacteria, fungi and viruses, including SARS-CoV-2, in seconds, providing a potential means of preventing the spread of airborne infections.

A paper published in Scientific Reports reports on the testing of air filters coated with the chemical biocide chlorhexidine digluconate and how its antimicrobial action compares to standard filters commonly used in industrial air condensing units, and on passenger trains.

In the laboratory, cells of the Wuhan strain of SARS-CoV-2 were added to the surface of both the treated and control filters and measured at intervals over a period of more than an hour. While much of the virus remained on the surface of the control filter for an hour, all SARS-CoV-2 cells were killed within 60 seconds on the treated filter.

To determine how effective the filters are in a real-world setting, both the control and treated filters were installed in heating, ventilation and air conditioning systems on train carriages. The filters were installed for three months in matched pairs across carriages on the same train line, before being removed and shipped for researchers to analyse colonies of bacteria trapped on them. 

The trial found no pathogens survived on the treated filter, even after three months on the train. Further tests also found the treated filters are durable, and are able to maintain their structure and filtration function over the lifetime of their use.

Felicity de Cogan of the Institute of Biology and Infection at Birmingham University, who is a co-author of the paper, said most ventilation systems recycle air through the system, and the filters currently being used in these systems are not normally designed to prevent the spread of pathogens, only to block air particles. “This means filters can actually act as a potential reservoir for harmful pathogens,” she said. “We have been able to develop a filter treatment which can kill bacteria, fungi and viruses, including SARS-CoV-2, in seconds.”

Other novel filters, ranging from high efficiency particulate air filters used in aerospace cabins, to UV light and silver nanoparticles added to filter mesh, have been developed to purify air. However, they have shortcomings, including not being energy efficient, or being slow to be exert their effect, meaning they are not suitable for the majority of existing heating, ventilation and air conditioning systems, which would require significant infrastructure upgrades to use them.

“In comparison, the technology we have developed can be applied to existing filters and can be used in existing heating, ventilation and air conditioning systems with no need for the cost or hassle of any modifications,” de Cogan said.

Long-lasting immune activity in the airways could be the cause of persistent breathlessness following COVID-19, according to a new study of 38 people who had been hospitalised with severe COVID-19.

The results, published in the journal Immunity, indicate these patients have an altered landscape of immune cells in their airways and signs of ongoing lung damage. However, the preliminary results suggest that this might improve over time.

The researchers say that their findings need to be confirmed by a larger study, but that anti-inflammatory drugs could possibly speed recovery

Co-author James Harker, senior lecturer in respiratory science at Imperial College London said, “Our study found that many months after SARS-CoV-2 infection, there were still abnormal immune cells in the airways of patients with persistent breathlessness. We also identified a protein signature in the lungs indicating ongoing injury to the airways.”

The findings suggest that persistent breathlessness in the cohort of COVID-19 patients was caused by the immune system failing to switch off once the COVID-19 infection wanes, leading to airway inflammation and injury.

While previous studies have examined the causes of post-COVID-19 breathlessness by looking at blood biomarkers, this latest study looked directly at which immune cells are active in the lungs.

The researchers studied scans of the lungs and how well they were functioning, as well as analysing fluid from within the lungs and blood samples, to assess the presence of nearly 500 proteins.

The study included 38 post-COVID-19 patients three to six months after they left hospital and 29 healthy volunteers, who had no underlying diseases and had not had COVID-19.

At three to six months, there were more immune cells in the lungs of the post-COVID-19 participants than in the healthy controls, but there was no difference in the immune cells seen in the blood of the post-COVID-19 patients and the healthy participants.

The finding that the immune response in the blood does not seem to match that of the lungs emphasises the importance of assessing airway immunity in order to better understand persistent respiratory symptoms post COVID-19, the researchers say.

The participants in the study contracted COVID-19 before vaccines were available.

There was a substantial decrease in the number of cancer research projects getting off the ground in the UK between 2019 and 2020, with the lifetime value of the projects funded in 2020 falling 57%, to £1.29 billion, compared to pre-pandemic 2019 when £3.03 billion was committed.

The new figures are from the UK National Cancer Research Institute, which has been collecting data on cancer research funding since 2002.

NCRI is concerned that as a result, the amount spent on cancer research will continue to decline over the next five years.

In the financial year 2020/21, funding agencies that are members of NCRI spent a total of £634 million on cancer research, a decrease of 9% compared to 2019/20. For the five years before the COVID-19 pandemic, there was an upward trend in cancer research spending.

In particular, the pandemic has hit charities like Cancer Research UK, which rely on High Street shops and events such as coffee mornings and sponsored runs to raise much of their revenue. Charity funding bodies have done everything possible to ensure that funding commitments made before the pandemic were honoured, but this has meant less money for new research.

While a 9% decrease in the amount spent on cancer research is alarming, there is concern this does not reflect the full impact of the COVID-19 pandemic, said Iain Frame, CEO of NCRI. “This is because several NCRI partners made tough decisions during the COVID-19 pandemic to maintain their research funding commitments, including moving priorities away from other areas and making redundancies,” he said.

There has been a substantial decrease in the number and lifetime value of new cancer research projects funded, and as current projects come to an end, there could be a continued decrease in spending on cancer research over the coming years.

More than 20 human genetic variants that predispose patients who are infected with SARS-CoV-2 to become critically ill have been uncovered by the UK Genomicc (Genetics Of Mortality In Critical Care) project.

The findings may have direct implications for the development of new treatments and the future prioritisation of therapy. 

Critical illness in COVID-19 is caused by inflammatory lung injury, which is mediated by the host’s immune system. Genetic factors are known to have a role.

In the study, the researchers compared whole genome sequences of more than 7,000 patients who became critically ill with COVID-19, with those of more than 48,000 matched control individuals.

They found 23 variants that predispose to life-threatening disease, 16 of which were previously unknown. They include variants within genes involved in interferon signalling, leukocyte differentiation and the production of mucin proteins, all of which are important factors in the regulation of the immune system and functioning of the lungs.

Some of the variants identified are potential drug targets, raising the possibility of new therapies aimed at genetic mechanisms that predispose to life-threatening disease.

The results, published in Nature, are also broadly consistent with the multicomponent model of COVID-19, which holds at least two distinct components can predispose to life-threatening illness: a failure to control viral replication and an enhanced tendency towards lung inflammation and blood clotting.

New research has found there are changes to the human brain, including in areas associated with smell and memory, following SARS-CoV-2 infection.

The findings reveal damaging effects of COVID-19 and also increase understanding of how the disease spreads through the central nervous system.

Whether these effects persist in the long term, or can be partially reversed, requires further investigation.

Although there was some evidence to suggest COVID-19 may cause brain-related abnormalities, most studies have focused on hospitalised patients with severe disease, and have been limited to imaging patients after they had the infection.

The effects of SARS-CoV-2 on the brain in milder and far more common cases remain unknown,

To investigate this, the researchers looked for changes in the brains of 785 UK Biobank participants, aged 51–81. They had had two brain scans, on average 38 months apart, and had completed cognitive tests.

A total of 401 participants tested positive for infection with SARS-CoV-2 between their two scans, of whom 15 were hospitalised; the remaining 384 individuals were age- and sex-matched controls.

There was an average of 141 days between participants receiving a COVID diagnosis and the second imaging scan. The researchers identified various long-term effects following infection, including a greater reduction in grey matter thickness in the orbitofrontal cortex and parahippocampal gyrus, regions that are associated with smell and memory of events.

In addition, participants who had COVID-19 displayed evidence of tissue damage in regions associated with the olfactory cortex, which is an area of the brain linked to smell, and an average reduction in whole brain sizes.

On average, the participants who were infected with SARS-CoV-2 also showed greater cognitive decline between their two scans. This was associated with the atrophy of the cerebellum, which is linked to cognition.

The researchers also performed a control analysis on people who developed pneumonia that was not related to COVID-19, enabling them to show that the changes were specific to COVID-19, and not due to generic effects of contracting a respiratory illness.

A new study has analysed over 3,000 proteins to identify those which are causally linked to the development of severe COVID-19. The researchers found six proteins that could underlie an increased risk of severe COVID-19 and eight that could contribute to protection from severe COVID-19.

The findings provide insight into potential new targets for approaches to treat and prevent severe COVID-19.

One of the proteins, ABO, which was identified as having a causal connection to the risk of developing severe COVID-19, determines blood groups. The researchers say that suggests blood groups play an instrumental role in whether people develop severe forms of the disease.

Researcher Alish Palmos from Institute of Psychiatry, Psychology & Neuroscience, King’s College London said, “We have used a purely genetic approach to investigate a large number of blood proteins and established that a handful have causal links to the development of severe COVID-19. Honing in on this group of proteins is a vital first step in discovering potentially valuable targets for development of new treatments.”

The study considered two incremental levels of severity of COVID-19: hospitalisation and respiratory support or death. Using data from a number of genome-wide association studies the researchers found the six proteins that were causally linked to an increased risk of hospitalisation or respiratory support/death due to COVID-19 and the eight that were causally linked to protection against severe disease.

ABO was causally associated with both an increased risk of hospitalisation and a requirement for respiratory support. This supports previous findings around the association of blood group with higher likelihood of death. Taken together with previous research showing that the proportion of blood group A is higher in COVID-19 positive individuals, this suggests blood group A is a candidate for follow-up studies.

Gerome Breen, professor of genetics at King’s College said, “What we have done in our study is provide a shortlist for the next stage of research. Out of 1,000s of blood proteins we have whittled it down to about 14 that have some form of causal connection to the risk of severe COVID-19.”

A study analysing the spread and refutation of misinformation about facemasks on Twitter during the Covid-19 pandemic shows that rather than trying to provide the correct information, people were made fun of for their ignorance.

From a democratic debate perspective, the results are not encouraging, said Rebecca Adler-Nissen, one of the five researchers at the University of Copenhagen and Aarhus University, who carried out the research.

“We tend to believe that people eager to correct misinformation will be very fact-oriented. But our study shows that this group of people typically choose to ridicule those spreading misinformation,” Adler-Nissen said. “Instead of bridging gaps or inviting people to change their minds by updating their knowledge, their response to misinformation takes the form of know-it-all remarks intended to patronise their opponent and praise themselves.”

The researchers analysed 9,345 Danish-language tweets about facemasks and COVID-19 posted between February and November 2020.

The analysis shows that only around 5% (471 tweets) focus on misinformation. Of these, around 3% of all tweets and retweets disseminated misinformation about facemasks, for example claiming facemasks are dangerous because they raise the user’s CO2 levels, or that facemasks are irrelevant because COVID-19 is pure fabrication.

For only 2% of the 471 incorrect tweets was there any attempt to correct the misinformation. In most cases the response was rather to deride, ridicule or stigmatise the sender of the misinformation, often using humour: 33% of all tweets rejecting misinformation used satire, irony and humour.

The researchers conclude that a lot of the people who either spread or reject misinformation are really trying to do the same thing: namely defend their own social position among like-minded people.

The study is part of the interdisciplinary HOPE project, which with support from the Carlsberg Foundation is examining how democracies have coped with the COVID-19 pandemic.

The study calls into question our ability as citizens to discuss and correct misinformation in social media, when those who should know better often choose to ridicule rather than to inform, the researchers say.

“Twitter in the US has experimented with tasking volunteers with checking assertions. Our analysis suggests that this is a complex task, because people do not go online simply to exchange information, but also to consolidate their own status and identity,” Adler-Nissen said. “When people commit to fighting misinformation, it is also a way to make themselves visible to like-minded people. And we need to be aware of that dynamic.”