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Saturday, April 30, 2022

New tool to assess Long COVID symptoms

 A comprehensive tool that can assess the symptoms of Long COVID has been developed at the University of Birmingham for use in research and clinical care.

Developed with patients that have lived experience of Long COVID, the tool can capture symptoms and their impact on everyday life.

Currently more than 200 symptoms are associated with Long COVID which can affect people for months after the original coronavirus infection has gone. These can affect many organs in the body and include breathlessness, fatigue, or brain fog and are estimated to affect around 1.3 million people in the UK and more than 100 million people worldwide.

Healthcare providers and researchers need reliable ways of measuring these symptoms as they are experienced by patients to help them develop new treatments and provide the best possible care.

A team from the University of Birmingham’s Centre for Patient-Reported Outcomes Research  designed the Symptom Burden Questionnaire™ for Long COVID to address this challenge. Patients can use it to report symptoms and the data can be used to help identify treatments, and test whether these are safe and effective. The approach is published today (27 April 2022) in the BMJ.

“People living with Long COVID say they experience a huge range of symptoms but getting these recognised by healthcare practitioners and policy-makers has been a struggle,” said senior author, Dr Sarah Hughes. “We designed and tested this tool with our patient partners to ensure it is as comprehensive as possible, while also not being burdensome for patients to complete.”

Public partner Karen Matthews from LongCOVID SOS noted “I participated in a study quite early on in my condition and the questionnaire used didn’t capture the breadth of what I was feeling. Being able to shape something that could record that experience more effectively is worthwhile and I hope it gives researchers and people like me taking part in future studies some valuable evidence.”

The resulting questionnaire measures different symptoms of Long COVID and the impact of these symptoms on daily life.  It was developed with extensive patient input following regulatory guidance, meaning its scores may be used to support regulatory decisions around the approval of new therapies for Long COVID and by policymakers.

The study was carried out in partnership with patient data technology specialist, Aparito Ltd, and funded by the National Institute for Health Research and UK Research and Innovation. The team plans to carry out more development and testing to explore how the tool can be used in routine clinical practice, including translating it for use in other countries and minority ethnic communities.

Further details regarding the measure and access for use can be found at www.birmingham.ac.uk/sbq

 

Assessing power of T-cell immune response to Omicron BA.1 and BA.2

 Scholars from HSE University and the RAS Institute of Bioorganic Chemistry have demonstrated the efficiency of T-cell immune response against the Omicron variant of SARS-CoV-2. In approximately 90% of vaccinated Europeans, T-cell immunity was as effective against Omicron as with other variants. The results of the study were published in PeerJ.

The Omicron variant of SARS-CoV-2 caused a new wave of the global pandemic. The new mutations help the virus spread more effectively and avoid antibodies, which is why those who have already had the disease or who have been vaccinated are getting infected more often. At the same time, recent data shows that the severity of the disease in vaccinated patients is significantly lower than in people who have not contacted the virus.

The researchers assume that this can be explained by several factors. First, the Omicron variant is slower at infecting the human cells; second, there is a hypothesis that a lighter course of the disease is related to effective action of T-cell immunity.

To confirm this assumption, a team of researchers from the HSE Faculty of Biology and Biotechnology and the RAS Institute of Bioorganic Chemistry (Stepan NersisyanAnton ZhiyanovAlexey GalatenkoMaxim Shkurnikov, Maria Zakharova, Irina Ishina, Inna Kurbatskaia, Azad Mamedov, Alexander Gabibov, and Alexander Tonevitsky) studied the Omicron variant for mutations that help it avoid the T-cell immune response.

The development of T-cell response starts from the recognition of virus peptides (short fragments of proteins) with the molecules of the human major histocompatibility complex (HLA). The more peptides that are recognised, the faster and more efficient T-cell immunity is. Virus mutations can change such peptides, which is why they can stop being recognised by HLA molecules, and the T-cell response will be less effective.

T-CoV, a bioinformatics algorithm, demonstrated that the Omicron variant avoided none of the HLA molecule variants. But it detected several HLA molecule variants that started to become less effective at recognizing the Omicron’s S-protein. An outstanding discovery was the HLA-DRB1*03:01 variant of the molecule. The most important peptide of the virus managed to avoid it. Interestingly, both types of Omicron, BA.1 and BA.2 (also known as ‘Stealth’), evaded immune response recognition, though this was achieved by completely different mutations.

The bioinformatics calculations were verified experimentally in a laboratory. The researchers proved that there is no binding between Omicron peptides and HLA-DRB1*03:01 molecule, which was expressed in vitro.

The researchers emphasise that the initial peptide from the Wuhan basic variant, as well as Delta peptide, are recognised effectively by this molecule.

The authors emphasise that the detected HLA-DRB1*03:01 variant is present in a big share of the global population: for example, in 8.9% of Europeans.

‘The population diversity of HLA molecules, as well as the specificity of their work do not let the virus avoid the T-cell immune response. But the virus has managed to hide its S-protein from one of the HLA molecules. Importantly, most of COVID-19 vaccines (Sputnik V, Pfizer, Moderna, AstraZeneca and some others) carry specifically this virus protein. This means that people with the variant HLA-DRB1*03:01 (who make up 9% of Europe’s population, for example) vaccinated by S-protein may suffer from a more severe course of the disease caused by the Omicron variant,’ said Alexander Tonevitsky, Dean of the HSE Faculty of Biology and Biotechnology.

 

Tackling the consequences of Long Covid

 As the pandemic progresses, the number of people living with Long Covid will grow. But it remains unclear how and why Long Covid develops, whether it can be prevented, and how it is best treated. To better understand Long Covid, it is essential to comprehend the needs and priorities of those affected. A team of scientists at UZH’s Epidemiology, Biostatistics and Prevention Institute (EBPI) has now joined forces with representatives of Long Covid Switzerland and the Long Covid Network Altea to amplify the voices of those living with Long Covid.

The Long COVID citizen science board: First-of-its-kind

“Collaborative projects that bring together different stakeholders allow us to grasp the impact of such a new disease and hopefully effectively tackle the challenges for people living with Long Covid,” says Milo Puhan, professor of epidemiology and public health at UZH. For this purpose, a citizen science project was developed and supported by the Participatory Science Academy of the University of Zurich and ETH with seed financing in 2021.

The research team recruited a first-of-its-kind Long Covid citizen science board, including 21 people affected by Long Covid and seven with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Board members met online to discuss their needs and identify the most relevant research areas. They acted as citizen scientists in co-shaping the study’s direction, analysis and findings.

From patients’ needs to research priorities

The study found that people affected by Long Covid and their families need answers to a long list of 68 questions, which fall into four areas: Medical (e.g. risk factors, diagnosis, treatment), healthcare services, socio-economic (e.g. impact on work and finances), and disease burden. Through an online survey, the research team asked the citizen scientists and 241 other people affected by Long Covid to rate and prioritize the 68 identified questions.

“The scientists empowered us to define those research topics which have the largest impact on our health and lives – not surprisingly the results reflect our top concern, which is that we still lack effective therapies,” says Chantal Britt, founder and president of Long Covid Switzerland.

Treatment, rehabilitation, disease management, healthcare services, ensuring care is not interrupted, awareness of Long Covid among doctors and nurses, and how often Long Covid occurs in children were the research areas of most importance to Long Covid patients. “Our findings suggest that in addition to adequate treatment options, people affected by Long Covid are currently mostly lacking a clear diagnosis and access to adequate care that meets their multidimensional needs,” says Sarah Ziegler, epidemiologist at the EBPI.

Future research agendas

The research team hopes that this study will guide the funding of future Long Covid research. Resources are limited and it is important to prioritize the areas of most relevance to those affected by Long Covid. “Our methodology can be adapted to other settings and health conditions and may pave the way towards future co-created and person-centered research agendas,” says Milo Puhan.

Contacts

Dr. Sarah Ziegler

Epidemiology, Biostatistics and Prevention Institute (EBPI)

University of Zurich

Phone +41 44 634 46 49

E-mail: sarah.ziegler@uzh.ch

 

Prof. Dr. Milo Puhan

Epidemiology, Biostatistics and Prevention Institute (EBPI)

University of Zurich

Phone: +41 44 634 46 10

E-mail: miloalan.puhan@uzh.ch

Vaccination campaign messages often prove ineffective

 Conventional vaccination campaign messages often miss their targets. A study in eight European countries shows that information on the benefits of vaccines can even reduce the willingness to get immunized. The researchers also looked into the factors that influenced the impact of messages, including low health literacy.

Not many Covid-19 vaccination campaigns in Europe lived up to the hopes of the public health authorities. However, the results of past studies in various countries have yielded a mixed picture as to which communication strategies can increase vaccine uptake and which factors undermine certain messages. A team of the Technical University of Munich (TUM), the University of Trento and the London School of Economics and Political Science explored these questions in Bulgaria, France, Germany, Italy, Poland, Spain, Sweden and the UK.

During the intensive phase of the vaccination campaigns, in June 2021 (in April in Germany), more than 10,000 unvaccinated adults were initially provided online with general information on the available vaccines. Then they received one of three messages combining text and images or were assigned to a control group. Message 1 highlighted the efficacy of the available vaccines in reducing the risk of serious illness and death through Covid-19. Message 2 stressed the advantages of having a vaccination certificate, especially for travel. Message 3 presented the prospect of leisure-time activities without restrictions, for example restaurant and cinema visits, access to fitness studios and attendance at concerts. The participants were then asked whether they intended to be vaccinated against Covid-19 if given the opportunity during the following week.

Three messages effective only in Germany

The study, published in Science Advances, shows that the tested messages would be effective in boosting vaccination quotas only in Germany and, to a lesser extent, in the UK. In Germany the vaccination willingness was significantly higher in the three groups than in the control group. In the UK, the readiness was higher only when the message stressed the benefits of a vaccination certificate. In all other countries the messages were ineffective – or even produced results opposite to those intended: people in Spain and Italy, when informed of the reduced risk of illness through vaccines, were less likely to seek vaccination than the corresponding control groups.

Decisive factor: health literacy

Using data mining methods, the research team was able to carry out detailed analysis of various associations between the message effectiveness and sociodemographic characteristics as well as the following factors: citizens’ trust in their government, their literacy with regard to healthcare issues and the share of the population who believe in certain conspiracy theories. The scientists used existing surveys to obtain data on these factors (which are not to be seen as monocausal) for the various countries.

For all messages, the likelihood of achieving the desired effect was reduced in a country when the health literacy of the population was low. “This result surprised us,” says Matteo M. Galizzi, a professor of behavioural science at the London School of Economics and Political Science. “We had thought that understandable and clearly visualized information on Covid-19 would lead to an improved understanding of the disease among people with little prior knowledge and thus to a greater vaccination willingness.” In contrast, the study confirmed conjectures that citizens’ trust in their own government would have a positive effect on vaccination intention.

Older people less receptive

Where there was relatively high prevalence of conspiracy theories, neither the message on health benefits nor that on the prospect of future leisure-time options produced significant successes. “The analysis shows that this strong disinformation can also explain the negative impact of health information in Spain and Italy,” says Giuseppe A. Veltri, a professor in computational social science at the University of Trento.

The researchers saw differences between socio-economic groups. For example, men with low levels of educational attainment were more often convinced by the two messages highlighting advantages in everyday life and leisure time than men with the same profile in the control group. Among these men there was also a very pronounced effect in countries with a high level of trust in the government and low prevalence of conspiracy theories. Older people tended to be less receptive on the whole to all of the messages.

“Clearer differentiation in campaigns”

“During the pandemic, people often looked at other countries to see what was working better or worse. Our study showed that such comparisons have limited usefulness,” says Prof. Tim Büthe, Chair of International Relations at TUM. “A more promising approach is to investigate the existing conditions in every country and then adapt the policy measures and communication strategies accordingly. Policy makers can use our findings to inform messaging for upcoming Covid-19 booster campaigns.”

Janina Steinert, a professor of global health at TUM, who headed the study, says: “Messages encouraging people to get vaccinated should target the various groups more closely, both in terms of content and how they are communicated, for example via certain social media channels or with gender-based or age group-specific advertising. Where the public lacks trust in the government, individuals seen as role models by certain socio-economic groups can be chosen as communicators.”

However, if a communication campaign has poor prospects of success due to several known barriers, the research team recommends shifting the focus to other measures. These might include concrete incentives or individually assigned vaccination appointments, which can only be actively objected to. “In the long term, all countries should develop their citizens’ health literacy to improve the effectiveness of future vaccination campaigns,” says Steinert.

More information:
The study published in Science Advances is part of the project “PERISCOPE – Pan-European Response to the ImpactS of COVID-19 and future Pandemics and Epidemics”, which has received 10 million euros in EU funding. 32 partner institutions from 15 European countries are investigating the social, political and economic impacts of the pandemic.

Analysis of Firearm Violence During the COVID-19 Pandemic in the US

 Shengzhi Sun, PhD1,2Wangnan Cao, PhD3Yang Ge, MSc4,5et al

doi:10.1001/jamanetworkopen.2022.9393

Key Points

Question  How did interpersonal firearm violence change temporally and spatially in the first year of the COVID-19 pandemic period in the US?

Findings  In this nationwide cross-sectional study of the US, the pandemic period was associated with a 15.0% increase in firearm-related incidents, a 34.3% increase in firearm-related nonfatal injuries, and a 28.4% increase in firearm-related deaths. The excess burden was more pronounced from June to October 2020 and in Minnesota and New York State.

Meaning  These findings suggest that the COVID-19 pandemic was associated with an excess burden of firearm violence, with substantial temporal and spatial variations.

Abstract

Importance  In the US, the COVID-19 pandemic intensified some conditions that may contribute to firearm violence, and a recent surge in firearm sales during the pandemic has been reported. However, patterns of change in firearm violence in the first year of the COVID-19 pandemic in the US remain unclear.

Objective  To quantify the changes in interpersonal firearm violence associated with the pandemic across all 50 US states and the District of Columbia.

Design, Setting, and Participants  This population-based cross-sectional study examined 50 US states and the District of Columbia from January 1, 2016, to February 28, 2021. The COVID-19 pandemic period was defined as between March 1, 2020, and February 28, 2021. Statistical analysis was performed from April to December 2021.

Main Outcomes and Measures  A 2-stage interrupted time-series design was used to examine the excess burden of firearm-related incidents, nonfatal injuries, and deaths associated with the pandemic while accounting for long-term trends and seasonality. In the first stage, separate quasi-Poisson regression models were fit to the daily number of firearm events in each state. In the second stage, estimates were pooled using a multivariate meta-analysis.

Results  In the US (all 50 states and the District of Columbia) during the pandemic period of March 1, 2020, to February 28, 2021, there were 62 485 identified firearm-related incidents, 40 021 firearm-related nonfatal injuries, and 19 818 firearm-related deaths. The pandemic period was associated with 8138 (95% empirical confidence interval [eCI], 2769-12 948) excess incidents (increase of 15.0% [95% eCI, 4.6%-26.1%]), 10 222 (95% eCI, 8284-11 650) excess nonfatal injuries (increase of 34.3% [95% eCI, 26.1%-41.1%]), and 4381 (95% eCI, 2262-6264) excess deaths (increase of 28.4% [95% eCI, 12.9%-46.2%]). The increase in firearm-related violence was more pronounced from June to October 2020 and in Minnesota and New York State.

Conclusions and Relevance  In the US, the first year of the COVID-19 pandemic was associated with an excess burden of firearm-related incidents, nonfatal injuries, and deaths, with substantial temporal and spatial variations.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791600

Genetic links revealed between severe COVID-19 and other diseases

 A new analysis of data from the Veterans Affairs Million Veteran Program has uncovered genetic links between COVID-19 severity and certain medical conditions that are known risk factors for severe COVID-19. Anurag Verma of the Corporal Michael Crescenz VA Medical Center in Philadelphia, Pennsylvania, US, and colleagues present these findings on April 28th in the open-access journal PLOS Genetics.

Some people with COVID-19 experience the disease more severely than others. Previous research has identified certain variants in specific human genes that are associated with a person experiencing more severe COVID-19. Some of these variants may also be associated with other medical conditions that may already be well understood; identifying these shared variants could improve understanding of COVID-19 and illuminate potential new paths for treatment.

To identify shared variants, Verma and colleagues used an unprecedented dataset of genotypic information linked to electronic health record data (EHR) for more than 650,000 U.S. veterans. They conducted a type of analysis known as a phenome-wide association study (PheWAS) to examine links between variants often found in Veterans who experienced severe COVID-19 and variants associated with a broad selection of medical conditions.

The analysis revealed that certain variants associated with COVID-19 are also associated with known risk factors for COVID-19. Particularly strong links were found for variants associated with venous embolism and thrombosis, as well as type 2 diabetes and ischemic heart disease—two known COVID-19 risk factors.

The analysis also found genetic links between severe COVID-19 and neutropenia for Veterans of African and Hispanic ancestry; these links did not appear for those of European ancestry.

Among respiratory conditions, idiopathic pulmonary fibrosis and chronic alveolar lung disease shared genetic links with severe COVID-19, but other respiratory infections and chronic obstructive pulmonary disease (COPD) did not. Some variants associated with severe COVID-19 were also associated with reduced risk of autoimmune conditions, such as psoriasis and lupus. These findings highlight the need to carefully weigh various aspects of the immune system when developing new treatments.

Despite some limitations of the PheWAS method, these findings could help deepen understanding of COVID-19 and guide development of new treatments.

Verma concludes, “The study demonstrates the value and impact of large biobanks linking genetic variations with EHR data in public health response to the current and future pandemics. MVP is one of the most diverse cohorts in the US. We had a unique opportunity to scan thousands of conditions documented before the COVID-19 pandemic. We gained insights into the genetic architecture of COVID-19 risk factors and disease complication.”

“One thing that stood out to us was the high number of immune-mediated conditions that shared genetic architecture with severe manifestations of COVID-19,” coauthor Katherine Liao adds. “The nature of the associations brought to light how the SARS-CoV2 virus pushes on a pressure point in the human immune system and its constant balancing act of fighting infection while maintaining enough control so that it does not also become an autoimmune process, attacking self.”

Citation: Verma A, Tsao NL, Thomann LO, Ho Y-L, Iyengar SK, Luoh S-W, et al. (2022) A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program. PLoS Genet 18(4): e1010113. https://doi.org/10.1371/journal.pgen.1010113

Author Countries: United States, Australia

Funding: This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by award MVP035. S.M.D. is supported by US Department of Veterans Affairs (IK2-CX001780). R.C. is supported by NIH grants R01 AA026302 and P30 DK0503060. K.P.L. is supported by NIH P30 AR072577, and the Harold and Duval Bowen Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Immune system culprit in severe COVID cases found

 Yale researchers have identified a particular immune response pathway that leads to severe illness and death in people infected by the SARS-CoV-2 virus.

The study was published April 28 in the journal Nature.

Researchers have known that once the COVID-19 virus infects the lungs it can trigger what has been called a “cytokine storm,” or an overactive immune response that leads to deadly inflammation in the lungs. For the new study, a Yale team led by postdoctoral fellow Esen Sefik, who is part of the lab of senior author Richard Flavell, studied the effects of SARS-CoV-2 infection in mice engineered to have a human immune system.

To their surprise, they found that immune cells themselves, not just epithelial cells lining the lung, can harbor the virus. When the body detects the virus in these cells, inflammasomes, part of the immune system’s early warning system, produce and release cytokines which prompt these immune cells to commit suicide in an attempt to abort infection. However, the cytokines also recruit even more inflammatory cells to the lungs from the blood, which drives a vicious cycle that leads to pneumonia.

“It’s like a broadcast system, but in this case the message is lethal,” said Flavell, Sterling Professor of Immunobiology and investigator for the Howard Hughes Medical Institute.

In the mouse model of COVID-19, researchers were able to rescue infected mice from pneumonia by blocking the NLPR3 inflammasome pathway. With the inflammasome pathway blocked, immune system cells were still infected. But they were no longer inflammatory and therefore could not contribute to damaging levels of inflammation, researchers found.

One byproduct of this rescue, however, is that the cells no longer die and as a consequence release more virus. Nonetheless, blockade of the inflammasome pathway along with antiviral treatment could provide a way to treat COVID-19 pneumonia and prevent severe cases of COVID -19, researchers say.

Although there are no approved drugs that block the NLPR3 pathway, several pharmaceutical and biotech companies are developing them, Flavell said.

The research was funded by the Howard Hughes Medical Institute.