Researchers develop a tool for studying inflammatory diseases related to COVID-19

Gwangju Institute of Science and Technology Researchers Develop a Tool for Studying Inflammatory Diseases Related to COVID-19

A new bioinformatics pipeline helps investigate the mechanism underlying the development of autoimmune diseases following SARS-CoV-2 infection CREDIT
Gwangju Institute of Science and Technology (GIST)

The SARS-CoV-2, or the novel coronavirus, has affected more than 500 million people worldwide. Apart from the symptoms associated with COVID-19 infection, it has recently been reported that the virus also leads to the subsequent development of autoimmune diseases in patients.

Autoimmune diseases like rheumatoid arthritis, lupus, or multi-inflammatory syndromes arise when the immune system confuses healthy cells with pathogens and starts attacking them. But, the precise mechanism underlying this “breach of self-tolerance” is unknown. One of the possible mechanisms suggested to be involved is what is called “molecular mimicry,”
in which an autoimmune reaction is triggered when a T-cell receptor or an antibody produced from a B-cell directed against a specific antigen (foreign body) binds with an autoantigen, which is an antigen produced from our own body. This occurs due to a molecular or structural resemblance between the “epitopes” (the part of antigen attached to the antibody) of the antigens. However, a comprehensive investigation of the role of molecular mimicry in the development of such autoimmune diseases has not yet been performed due to the complexity of the epitope search and the lack of standardized tools.

To this end, a team of researchers from the Gwangju Institute of Science and Technology (GIST) led by Prof. Jihwan Park developed a new bioinformatics pipeline. Their new tool, called cross-reactive-epitope-search-using-structural-properties-of-proteins (CRESSP), was recently reported in the journal Briefings in BioinformaticsPrevious studies on molecular mimicry used bioinformatics pipelines different from one another that often involved complex algorithms and were not scalable to proteome scales. In light of this, we developed a pipeline that is easily accessible and scalable,” explains Prof. Park. “It uses the structural properties of proteins to identify epitope similarities between two proteins of interest, such as human and SARS-CoV-2 proteins.”

Using CRESSP, the team screened 4,911,245 proteins from 196,352 SARS-CoV-2 genomes obtained from an open-access database. The pipeline narrowed down 133 cross-reactive B-cell and 648 CD8+ T-cell epitopes that could be responsible for COVID-related autoimmune diseases. It further identified a protein target, PARP14, to be a potential initiator of epitope spreading between COVID-19 virus and human lung proteins.

The pipeline also predicted the cross-reactive epitopes of different coronavirus spike proteins. Moreover, the team developed an interactive web application to enable an interactive visualization of the molecular mimicry map of SARS-CoV-2. The pipeline is also available as an open-source package.

The team hopes their new tool will facilitate comparison between studies, providing a robust framework for further investigation on molecular mimicry and autoimmune diseases. “Although autoimmune diseases affect less than 10% of the population, studying them is important since it severely impacts the quality of lifeOur new tool can be used to study the possible involvement of molecular mimicry in the development of other autoimmune conditions in a systemic and scalable manner,” concludes Prof Park.

Hopefully, the new invention will help us deal with SARS-CoV-2 and other viral infections better.

Multiple Sclerosis patients with higher B cell counts have a better vaccine response

Andreas Tolf

Andreas Tolf, PhD student at Department of Medical Sciences, Uppsala University, and Resident Physician at Uppsala University Hospital, Sweden. CREDIT Ann Westermark, Uppsala University

MS patients treated with Rituximab have better responses to the COVID-19 vaccine if they have higher B cell counts. This is the finding of a study from Uppsala University published in the journal JAMA Network Open. In patients with B cell counts of 40/µL (microlitres) or more, 9 of 10 patients developed protective levels of antibodies, while significantly fewer with lower counts had similar responses.

“In our study, the B cell level in patients given Rituximab was the only factor that influenced the ability to form antibodies after vaccination. Previously, it was assumed that it was enough to wait a certain period after administering Rituximab for the vaccine to have a good effect. But to increase the chance of the vaccine causing the body to form antibodies, you first need to measure the level of B cells and ensure there are enough,” says Andreas Tolf, a doctoral student in experimental neurology at Uppsala University and physician at Uppsala University Hospital.

In Sweden, Rituximab is the most common medicine for multiple sclerosis (MS), but it is also used for many other diseases. The medicine is given as a drip, normally once or twice a year, and has a documented good effect on slowing the progression of MS. The treatment knocks out the body’s B cells, which are an important part of our immune system though they also contribute to the MS disease process. As a result, the treatment increases the risk of patients suffering from serious infections, such as COVID-19. Having low levels of B cells also makes it more difficult for the body to form protective antibodies against viruses and bacteria, which is the primary purpose of vaccinations. In this case, this concerns the S protein in the SARS-CoV-19 virus.

Researchers at Uppsala University and Uppsala University Hospital have studied how MS patients treated with Rituximab react to vaccination against COVID-19. The purpose was to determine the optimal level of B cells for the patient to form sufficient numbers of antibodies after vaccination.

Blood from a total of 67 individuals with MS was analysed, of whom 60 were undergoing treatment with Rituximab and 7 were going to begin treatment after their COVID-19 vaccinations. Blood samples were taken before and after vaccination to study the levels of B cells and antibodies for SARS-CoV-2. The patients received two doses of Pfizer’s Covid-19 vaccine Comirnaty, with the active substance tozinameran.

The results show that the levels of B cells varied greatly among the subjects. The longer a patient had been treated with Rituximab, the longer it took their B cells to recover. For some patients, it took over a year before the B cells began to come back.

The patients who responded best to the vaccine and formed sufficiently high levels of antibodies had on average 51 B cells per microlitre (µL) before the vaccination. For the group that did not reach sufficient levels, the average was 22 B cells/µL.

“There was a threshold with a level of B cells at 40/µL or more where 90 per cent formed protective levels of antibodies. Of the patients who were undergoing MS treatment with Rituximab, 72 per cent formed sufficiently high levels of antibodies. The best effect with the highest percentage of antibodies was found in subjects who had never been treated with Rituximab,” says Anna Wiberg, a researcher in clinical immunology at the Department of Immunology, Genetics and Pathology at Uppsala University.

The researchers have also studied the ability of T cells to react to the virus. No differences were found between subjects who had been treated with Rituximab and those who had never been treated.

The ability of the T cells to react to the virus was just as strong in those who had received treatment. The levels of B cells before vaccination also did not impact the T-cell response, which suggests that all patients have a certain benefit from the vaccination, even if antibodies are not formed.

Autistic adults report high rates of COVID-19 vaccination

Infographic for Autistic Individuals and COVID-19 Vaccine


Researchers from the A.J. Drexel Autism Institute found more autistic adults had received the first dose of the COVID-19 vaccine compared to the general population in Pennsylvania, as of April 21, 2021. CREDIT Policy Impact Project at the A.J. Drexel Autism Institute

As reported in 2021, autistic adults, adults with intellectual disability and adults with mental health diagnoses have multiple risk factors for COVID-19 infection, and more severe disease if contracted. Public health messaging has strongly urged everyone eligible to get vaccinated for COVID-19, as it reduces the risk of contracting, decreases the severity and limits the spread of the virus. Researchers from Drexel University’s A.J. Drexel Autism Institute recently published a study identifying the differences between autistic adults who reported COVID-19 vaccination acceptance and those who were vaccination hesitant.

Identifying health promotion strategies based on self-reported, lived experiences with COVID-19 among vulnerable groups, including autistic individuals, is important for public health, as it can inform strategies to increase vaccination rates — which, in turn, supports public health by decreasing the potential for disease transmission.

The report, published in Vaccine, described COVID-19 vaccination status, self-reported preferences among autistic adults and additional to related factors.

“Vaccine accepters were more likely to report increased loneliness during COVID-19, live in more populated counties and in counties won by President Biden in the 2020 U.S. presidential election,” said Kaitlin Koffer Miller, director of Policy Impact at the Policy and Analytics Center (PAC) at the Autism Institute and co-author of the report. “Positive relationships were found between wanting to protect others from COVID-19, concern about getting COVID-19 and trusting the safety of the vaccines.”

The report also found concern about vaccine safety was common among the vaccine hesitant, but a lack of concern of COVID-19 overall was not commonly reported among this group.

Autistic adults, who had previously participated in the 2018 Pennsylvania Autism Needs Assessment and agreed to be contacted for future research, were asked to respond to a survey which aimed to learn about community participation experiences of autistic adults in Pennsylvania. The survey included 17 questions specifically related to COVID-19 experiences, including vaccination acceptance, hesitancy and status of vaccination. It was distributed to 431 autistic adults via an online survey platform, with data being collected between March-August 2021.

Researchers found 78.3% of survey respondents reported that they had received or intended to get a COVID-19 vaccine, with 55.4% reporting that they had received at least one dose. In comparison, 42% of overall adults in Pennsylvania received at least one dose of a COVID-19 vaccine as of April 2, 2021, which was the median response date for the survey sample.

“Reaching this group effectively in public health messaging about vaccination is critical,” said Koffer Miller. “By understanding reasons for vaccine hesitancy — for example, concerns about vaccine safety — or vaccine acceptance, such as feelings of increased loneliness, amongst autistic adult respondents can help drive more effective public health messaging and vaccine outreach to this population.”

The report provides concrete suggestions and examples for how public health professionals can most effectively reach autistic adults in their outreach, such as using visual tools like social stories, which are a powerful tool for conveying information and have been shown to be an effective means of communicating with autistic individuals.

The authors noted the importance of using this tailored and accessible messaging will become increasingly paramount as fourth doses become more widely available and recommended, and regular vaccination against COVID-19 becomes part of the public health dialogue.

“It was very important to be able to highlight practical, usable resources from organizations like the Autism, Services, Education, Resources, and Training Collaborative (ASERT) alongside the research findings to provide a direct translation and link to actionable ways to address what was identified as needed action in the study,” said Koffer Miller, who is also regional manager of the ASERT Collaborative Eastern Region.

New study examines COVID-19 vaccine hesitancy and uptake in autism community

Table 1. Participant Characteristics & COVID-19 Vaccine Hesitancy at Time 1 (pre-approval of vaccines)


Table 1. Participant Characteristics & COVID-19 Vaccine Hesitancy at Time 1 (pre-approval of vaccines) CREDIT Kennedy Krieger Institute

A new study examines factors associated with COVID-19 vaccine hesitancy and uptake in the autism community. Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2022 Meeting, taking place April 21-25 in Denver.

Individuals with autism spectrum disorder are at increased risk of hospitalization from COVID-19. Vaccines reduce the likelihood of COVID-19 infection and severity of disease. Historically, parents of children with autism spectrum disorder are more likely to be vaccine hesitant, thus delaying or declining childhood vaccinations.

The study found early COVID-19 vaccine hesitancy waned over time and a majority of caregivers and dependents received the vaccine following FDA approval. Firmly held vaccine-hesitant beliefs, not specific to COVID-19, influenced vaccine uptake in a minority of autism spectrum disorder caregivers.

“We conducted this study to better understand how baseline vaccine hesitancy in the autism community, which is higher than the general population, was impacting parent decision-making about COVID-19 vaccines,” said J. Kiely Law, MD, MPH, director of research operations at SPARK, a Simons Foundation autism research initiative. “This was especially important to understand since other studies were finding that children with developmental disabilities, like autism, were at increased risk of hospitalization due to COVID-19. Getting children vaccinated was critical to reducing this risk.”

Dr. Law added: “Early on, 60% of parents were hesitant about their child receiving the COVID-19 vaccine. Ten months later, it was reassuring to see that the majority of parents in our study made the decision for their child with autism to get vaccinated.”

Black people with diabetes disproportionately affected by diabetic ketoacidosis during COVID

Does COVID-19 vaccination affect rheumatic and musculoskeletal disease flares?

Black people with diabetes were more likely to develop cases of a life-threatening complication called diabetic ketoacidosis during the pandemic, even in people without COVID-19, according to a new study from the TID Exchange published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.

People with diabetes are more likely to get extremely sick from COVID-19, and the virus has been linked to new cases of diabetes. The pandemic has also exposed inequities in our health care system. Past research shows minorities with diabetes and COVID-19 are more likely to be hospitalized with diabetic ketoacidosis, a life-threatening yet generally preventable diabetes complication that results from insulin deficiency and is characterized by high levels of blood acids.

“Our work shows racial inequities in diabetes care were present before the pandemic, starkly visible during the pandemic, and will continue to persist after the pandemic—unless we systemically root out and target racial inequities in diabetes care,” said Andrew R. Lavik, M.D., Ph.D., of the Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio.

“Minorities continue to be affected by life-threatening yet preventable complications of diabetes more than other groups. We must redouble our efforts to relieve this burden, both during the COVID-19 pandemic and beyond,” added senior author Nana-Hawa Yayah Jones, M.D., also of Cincinnati Children’s.

The researchers, all members of the T1D Exchange Quality Improvement Collaborative, examined trends in diabetic ketoacidosis among individuals with type 1 diabetes during the COVID-19 pandemic at seven large United States medical centers. The researchers found that when COVID-19 cases surged, diabetic ketoacidosis surged as well, especially in Black people with diabetes. They determined that 45% of Black people had diabetic ketoacidosis in 2019 compared to 16% of White people, and this disparity persisted in 2020 (49% vs 19%).

“Alarmingly, we found that this disparity in diabetes complications was present even before the COVID-19 pandemic but has not been adequately addressed. T1D Exchange is actively working with partners to collaboratively address these inequities,” said co-author Osagie Ebekozien, M.D., Chief Medical Officer of the T1D Exchange in Boston, Mass.

People with diabetes using continuous glucose monitors or insulin pumps were less likely to have diabetic ketoacidosis. However, studies have found health disparities in the use of diabetes technologies.

Other authors of this study include: Sarah D. Corathers of the Cincinnati Children’s Hospital Medical Center; Nudrat Noor and Saketh Rompicherla of the T1D Exchange; G. Todd Alonso and Sarit Polsky of the University of Colorado in Aurora Colo.; Scott M. Blackman of the Johns Hopkins University School of Medicine in Baltimore, Md.; Justin Chen and Margaret Greenfield of SUNY Upstate Medical University in Syracuse, N.Y.; Carla Demeterco-Berggren of the University of California San Diego in La Jolla, Calif.; Mary Pat Gallagher of Hassenfeld Children’s Hospital at NYU Langone in New York, N.Y.; and Ashley Garrity of the University of Michigan in Ann Arbor, Mich.; and Robert Rapaport of Mount Sinai Hospital in New York, N.Y.

The study received funding from the Leona M. and Harry B. Helmsley Charitable Trust.