COVID-19

Posted on Diabetes

Newly diagnosed diabetes in patients with COVID-19 may simply be a transitory form of the blood sugar disorder


Many COVID-19 patients newly diagnosed with diabetes during hospital admission may in fact have a temporary form of the disease related to the acute stress of the viral infection and may return to normal blood sugar levels soon after discharge, a study by Massachusetts General Hospital (MGH) has found. These patients are more likely to be younger, non-white, and on Medicaid or uninsured compared to individuals with previously diagnosed diabetes, suggesting many of these “new-onset” cases may simply be pre-existing but undiagnosed diabetes in individuals with limited access to healthcare services, according to the study published in Journal of Diabetes and Its Complications.

High rates of newly diagnosed diabetes mellitus (NDDM) have been reported in COVID-19 hospital admissions around the world. It is still unclear, however, if this phenomenon represents truly new diabetes or previously undiagnosed cases, what the cause of these elevated blood sugars may be, and whether patients’ blood sugars improve after resolution of COVID-19 infection. Pre-existing diabetes in people with COVID-19 has been associated with higher rates of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death.

“We believe that the inflammatory stress caused by COVID-19 may be a leading contributor to ‘new-onset’ or newly diagnosed diabetes,” says lead author Sara Cromer, MD, an investigator with the Department of Medicine-Endocrinology, Diabetes and Metabolism at MGH. “Instead of directly causing diabetes, COVID-19 may push patients with pre-existing but undiagnosed diabetes to see a physician for the first time, where their blood sugar disorder can be clinically diagnosed. Our study showed these individuals had higher inflammatory markers and more frequently required admission to hospital ICUs than COVID-19 patients with pre-existing diabetes.”

For its study, the MGH team looked at 594 individuals who exhibited signs of diabetes mellitus when admitted to MGH at the height of the pandemic in the spring of 2020. Of that group, 78 had no known diagnosis of diabetes prior to admission. Researchers learned that many of these newly diagnosed patients — versus those with pre-existing diabetes — had less severe blood sugar levels but more severe COVID-19. Follow-up with this cohort after hospital discharge revealed that roughly half its members reverted to normal blood sugar levels and that only eight percent required insulin after one year.

“This suggests to us that newly diagnosed diabetes may be a transitory condition related to the acute stress of COVID-19 infection,” explains Cromer. Indeed, this key finding supports the clinical argument that newly diagnosed diabetes is likely caused by insulin resistance — the inability of cells to properly absorb blood sugar in response to insulin, resulting in higher-than- normal build-up of glucose in the blood – rather than by insulin deficiency, caused by direct and permanent injury to the beta cells which manufacture insulin.

“Our results suggest that acute insulin resistance is the major mechanism underlying newly diagnosed diabetes in most patients with COVID-19, and that insulin deficiency, if it occurs at all, is generally not permanent,” says Cromer.  “These patients may only need insulin or other medications for a short time, and it’s therefore critical that physicians closely follow them to see if and when their conditions improve.”

Posted on Autism

Survey heightens concern about pandemic’s impact on education of autistic students

Helen M. Genova, PhD


Dr. Genova is associate director of the Center for Autism Research at Kessler Foundation. CREDIT Kessler Foundation

Kessler Foundation scientists conducted an online survey of parents of school-aged children to compare the effects of pandemic-related school closures on autistic vs neurotypical students. Their findings indicate that children on the autism spectrum are at greater risk for negative educational outcomes.

The article, “Effects of school closures resulting from COVID-19 in autistic and neurotypical children,” (doi: 10.3389/feduc.2021761485) was published open access on November 23, 2021, by Frontiers in Education. This open access article is available at:https://www.frontiersin.org/articles/10.3389/feduc.2021.761485/full The authors are Helen Genova, PhD, Aditi Arora, PhD, and Amanda Botticello, PhD, MPH, of Kessler Foundation.

Using the COVID-19 Adolescent Symptom and Psychological Questionnaire, survey data were collected from May 2020 to August 2020 from parents/guardians of school-aged children – autistic and neurotypical – aged 4 to 15 years. Final sample was N=250, including respondents with neurotypical children (65%), and those with autistic children (35%).

The survey revealed differences in the psychological impact of the pandemic on neurotypical and autistic children, as reported by their parents. Overall, parents of autistic children were more likely to report negative effects of the pandemic. For neurotypical children, being isolated from friends was the most negative experience; for autistic children, disruption of their routine schedule was the most negative.

While neurotypical children turned to virtual experiences to connect socially, autistic children were less likely to participate in virtual experiences. This finding has implications for the shift to online delivery of education, medical treatment, and therapy precipitated by the pandemic. “Children on the autism spectrum may benefit less from virtual services,” noted Dr. Genova. “While remote delivery of educational and therapy services may be a convenient way for schools and facilities to remain open when in-person attendance carries risks, the long-term negative effects for children on the autism spectrum may be significant. To help them continue to achieve their educational goals, autistic children may need alternative ways to keep pace with their peers.”

The study also revealed that parents of children on the autism spectrum had specific concerns related to their children’s diagnosis. “Addressing these concerns is important for the mental health of parents and children,” added Dr. Genova, “since stress levels of caregivers can influence stress levels of autistic children.”

Funding: None

Posted on Infectious Diseases

Discovery could enable broad coronavirus vaccine

Scripps Research discovery could enable broad coronavirus vaccine


Scripps Research scientists identified a site on SARS-CoV-2, the virus that causes COVID-19, that could be useful in developing a vaccine against a broad set of coronaviruses. CREDIT Scripps Research

The COVID-causing virus SARS-CoV-2 harbors a vulnerable site at the base of its spike protein that is found also on closely related coronaviruses, according to a new study from Scripps Research. The discovery, published Feb 8 in Science Translational Medicine, could inform the design of broad-acting vaccines and antibody therapies capable of stopping future coronavirus pandemics.

The scientists had previously isolated an antibody from a COVID-19 survivor that can neutralize not only SARS-CoV-2 but also several other members of the family of coronaviruses known as beta-coronaviruses. In the new work, they mapped at atomic scale the site, or “epitope,” to which the antibody binds on the SARS-Cov-2 spike protein. They showed that the same epitope exists on other beta coronaviruses, and demonstrated with animal models that the antibody is protective against the effects of SARS-CoV-2 infection.

“We’re hopeful that the identification of this epitope will help us develop vaccines and antibody therapies that work against all beta-coronaviruses, including coronaviruses that may jump from animals to humans in the future,” says study co-senior author Raiees Andrabi, PhD, an institute investigator in the Department of Immunology and Microbiology at Scripps Research.

Beta-coronaviruses have emerged recently as major, ongoing threats to public health. These coronaviruses include SARS-CoV-1, which killed about 800 people, mostly in Asia, in a series of outbreaks in 2002-04; MERS-CoV, which has killed about 900 people, mostly in the Middle East, since 2012; and, of course, SARS-CoV-2, which by now has killed over 5 million people worldwide in the COVID-19 pandemic. Two other beta coronaviruses, HCoV-HKU1 and HCoV-OC43, cause only common colds, but are suspected of having caused deadly pandemics centuries ago, when they first jumped from animals to humans. Researchers widely believe that future coronavirus pandemics initiated by animal-to-human spread are inevitable.

That prospect has spurred efforts towards the development of a pan-beta-coronaviral vaccine or antibody therapy. Scripps researchers took an initial step in that direction in 2020 when they identified an antibody, in a blood sample from a COVID-19 survivor, that could neutralize both SARS-CoV-2 and SARS-CoV-1. Although neutralizing tests weren’t available for all other beta-coronaviruses, they found that the antibody at least bound to most of these viruses.

In the new study, the team used X-ray crystallography and other techniques to precisely map the antibody’s binding site on the SARS-CoV-2 spike protein. They showed that the same site is found on most other beta coronaviruses—which helps explain the antibody’s broad effect on these viruses.

“The site is on the stem of the viral spike protein and is part of the ‘machinery’ the virus uses to fuse with cell membranes in its human or animal hosts after the virus has initially bound to a cell-surface receptor,” says study co-senior author Dennis Burton, PhD, Chair of the Department of Immunology and Microbiology at Scripps Research. “Fusion allows the viral genetic material to enter and take over host cells, and the crucial role of this machinery explains why the site is consistently present across beta-coronaviruses.”

By contrast, the receptor binding site at the top of the viral spike protein mutates relatively rapidly and thus tends to vary greatly from one beta-coronavirus to the next—making it a poor target for broad beta-coronavirus vaccines or antibody therapies.

The researchers now are following up with efforts to find other, perhaps even more broadly effective antibodies, in their search for optimal antibodies and vaccines against coronaviruses.

Posted on Rheumatoid arthritis

Rheumatoid Arthritis – COVID-19 booster vaccination is safe and effective in immunosuppressed patients


Patients under immunosuppressive therapy, who do not respond to primary COVID-19 vaccination, have an increased risk for severe COVID-19 disease courses. Until now, it was not clear whether those patients at risk can benefit from an additional booster vaccination. Recent research findings from MedUni Vienna show that a third vaccination is safe and effective in those patients who were initially unable to produce antibodies after vaccination. The study was recently published in the acclaimed journal Annals of the Rheumatic Diseases.

Even after two vaccinations, patients receiving immunosuppressive treatment for autoimmune diseases often fail to develop an adequate immune response after vaccination to protect them against COVID-19. In particular patients treated with the B-cell depleting drug rituximab, e.g. for rheumatoid arthritis, are considered to be particularly at risk for severe disease courses. Up until now, it had not been established whether these patients can benefit from a third vaccination and whether they should be vaccinated with the same vaccine or a different vaccination strategy.

Booster vaccination essential
This question has now been answered by a recently published study conducted by an interdisciplinary research group from MedUni Vienna, coordinated by the Division of Rheumatology of the Department of Medicine III. First author Michael Bonelli and his study team were able to show that even patients under rituximab treatment who did not respond to primary vaccination are able to develop an immune response following a booster vaccination. “Since patients under certain immunosuppressive therapy are at high risk for an insufficient vaccination response and therefore a severe COVID-19 disease, an early booster vaccination should be considered” explains Michael Bonelli.

Included in vaccination recommendations
“Our study is the first randomised, blinded trial to show the efficacy and safety of a booster vaccination in patients without an immune response after two vaccinations because of an rituximab treatment. In addition, ongoing studies investigate the efficacy of a forth vaccination in our patients at risk.” points out Daniel Aletaha, Head of the Division of Rheumatology at MedUni Vienna. The results obtained with the chosen study design are considered particularly reliable within the scientific community. Daniel Aletaha says: “Accordingly, our study, which also compared the efficacy and safety of different vaccination strategies, has already been included in the World Health Organization (WHO) and Australian Technical Advisory Group on Immunization (ATAGI) Covid-19 vaccination recommendations for immunosuppressed patients.”

Posted on Multiple Sclerosis

New insights into impact of multiple sclerosis treatments on Covid-19 vaccine effectiveness

Treatments used to help people with multiple sclerosis (MS) manage their condition can reduce the effectiveness of Covid-19 vaccines, according to research from Cardiff University and Queen Mary University of London.

Disease-modifying therapies (DMTs) are a group of treatments for people with MS and affect the immune system. As vaccines work by triggering the body to produce an immune response, it was suspected that some DMTs could reduce the effectiveness of Covid-19 vaccines. The study, published in the journal Annals of Neurology, provides the largest peer-reviewed, published evidence of the effect of DMTs on immune responses to Covid-19 vaccines.

It is hoped this new information will better equip clinicians to provide guidance to people with MS on treatment options.  

The research team studied almost 500 people with MS and used a technique known as dried blood spot sampling to investigate the effects of DMTs on Covid-19 vaccine effectiveness. This approach reduced study costs as well as the need for potentially vulnerable patients to attend the clinic during the pandemic.

The findings show that people with MS taking either of two specific DMTs, fingolimod and ocrelizumab, were less likely to produce antibodies in response to AstraZeneca and Pfizer Covid-19 vaccines than people with MS not taking any DMT. If they did produce antibodies, the levels were lower than those found in people taking other DMTs, or not taking any DMT at all.  However, the researchers found that other DMTs, including some that are highly effective for MS treatment, had no detrimental effect on Covid-19 vaccine response. 

Immune cells, such as T-cells, are also an important part of our immune response to vaccines or viruses. The researchers studied T-cell responses in a small group of study participants who failed to mount an adequate antibody response to Covid-19 vaccination. They found that overall, 40 per cent of this group were able to produce a strong T-cell response, despite having a poor antibody response.

“People with MS have faced uncertainty during the Covid-19 pandemic as a direct result of their condition and the treatments they take to manage it,” says Dr Ruth Dobson, Clinical Senior Lecturer in Neurology at Queen Mary.

“Our study provides high-quality evidence that will support clinicians to advise people with MS on treatment options considering the Covid-19 pandemic. However, further trials are essential to help us understand how best to balance the risks of potentially suspending or delaying MS treatment with the need to effectively vaccinate people with MS against Covid-19.”

Dr Emma Tallantyre, Clinical Senior Lecturer in Neurology at Cardiff University, adds: “Questions about the Covid vaccine are among the most common we are currently facing from people with MS in our clinics. Highlighting groups who have mounted an inadequate Covid vaccine response has already been helpful in guiding who should receive additional doses of the vaccine, and who may need to continue to take additional infection-prevention precautions over the winter. We hope further work will allow us to individualise our management, to protect people with MS from Covid, while keeping their MS under control.”

Jo Welton, 38 was diagnosed with relapsing MS in 2009. She is a medical writer from South Wales. Day-to-day Jo mainly experiences fatigue, weakness, and pain in her left leg. She has been on disease modifying treatment (DMT) Gilenya for nearly eight years. She joined the study after being told about it by her MS team. Since, despite having two AstraZeneca vaccinations she has been told she has reduced immunity to COVID-19 and is waiting to find out if her booster vaccination has worked.

Jo says: “I have a scientific background so was interested in the study as soon as I heard about it. It was also important for me to know how much immunity I had as this impacts my day-to-day living. I’ve followed the guidelines about DMTs and MS right from the start, so this has meant I’ve been shielding for over 20 months. It’s been so difficult seeing everyone getting back to some sort of normality and not feeling like I was able to. I feel vulnerable and, although it’s not deliberate, left behind.

“Ignorance is bliss for some people, but it’s not a risk I want to take. I lost my Grandma to the virus earlier this year – this has made it even more important for me to take the necessary steps to mitigate the risk. Knowing I don’t have immunity means I can continue working remotely, socially distance, and ask friends and family to get their booster vaccine and do lateral flow tests when we meet. Having MS is hard enough without getting COVID-19 as well.”

Dr Clare Walton, Head of Research at the MS Society, says: “This is the largest published study looking at the relationship between certain high intensity disease modifying treatments (DMTs) and the AstraZeneca and Pfizer Covid-19 vaccines. It found some people with MS on these DMTs had a significantly reduced immune response to the vaccine compared to people not taking any.

“While this doesn’t mean these patients are necessarily at higher risk of severe illness if they catch COVID-19, it will be worrying for some. It’s vital that people with weakened immune systems are better supported to protect themselves from the virus, including a right to work from home and feeling assured that the general public are doing everything they can to help keep them safe. We also advise people with MS on these DMTs not to alter their treatment without speaking to someone from their MS healthcare team.”