COVID-19

Posted on Infectious Diseases

Antibodies mimicking the virus may explain long haul COVID-19, rare vaccine side effects

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

With around 256 million cases and more than 5 million deaths worldwide, the COVID-19 pandemic has challenged scientists and those in the medical field. Researchers are working to find effective vaccines and therapies, as well as understand the long-term effects of the infection.

While the vaccines have been critical in pandemic control, researchers are still learning how and how well they work. This is especially true with the emergence of new viral variants and the rare vaccine side effects like allergic reactions, heart inflammation (myocarditis) and blood-clotting (thrombosis).

Critical questions about the infection itself also remain. Approximately one in four COVID-19 patients have lingering symptoms, even after recovering from the virus. These symptoms, known as “long COVID,” and the vaccines’ off-target side effects are thought to be due to a patient’s immune response.

In an article published today in The New England Journal of Medicine, the UC Davis Vice Chair of Research and Distinguished Professor of Dermatology and Internal Medicine William Murphy and Professor of Medicine at Harvard Medical School Dan Longo present a possible explanation to the diverse immune responses to the virus and the vaccines.

Antibodies mimicking the virus

Drawing upon classic immunological concepts, Murphy and Longo suggest that the Network Hypothesis by Nobel Laureate Niels Jerne might offer insights.

Jerne’s hypothesis details a means for the immune system to regulate antibodies. It describes a cascade in which the immune system initially launches protective antibody responses to an antigen (like a virus). These same protective antibodies later can trigger a new antibody response toward themselves, leading to their disappearance over time.

These secondary antibodies, called anti-idiotype antibodies, can bind to and deplete the initial protective antibody responses. They have the potential to mirror or act like the original antigen itself. This may result in adverse effects.

Coronavirus and the immune system

When SARS-CoV-2, the virus causing COVID-19, enters the body, its spike protein binds with the ACE2 receptor, gaining entry to the cell. The immune system responds by producing protective antibodies that bind to the invading virus, blocking or neutralizing its effects.

As a form of down-regulation, these protective antibodies can also cause immune responses with anti-idiotype antibodies. Over time, these anti-idiotype responses can clear the initial protective antibodies and potentially result in limited efficacy of antibody-based therapies.

“A fascinating aspect of the newly formed anti-idiotype antibodies is that some of their structures can be a mirror image of the original antigen and act like it in binding to the same receptors that the viral antigen binds. This binding can potentially lead to unwanted actions and pathology, particularly in the long term,” Murphy said.

The authors suggest that the anti-idiotype antibodies can potentially target the same ACE2 receptors. In blocking or triggering these receptors, they could affect various normal ACE2 functions.

“Given the critical functions and wide distribution of ACE2 receptors on numerous cell types, it would be important to determine if these regulatory immune responses could be responsible for some of the off-target or long-lasting effects being reported,” Murphy commented. “These responses may also explain why such long-term effects can occur long after the viral infection has passed.”

As for COVID-19 vaccines, the primary antigen used is the SARS-CoV-2 spike protein. According to Murphy and Longo, current research studies on antibody responses to these vaccines mainly focus on the initial protective responses and virus-neutralizing efficacy, rather than other long-term aspects.

“With the incredible impact of the pandemic and our reliance on vaccines as our primary weapon, there is an immense need for more basic science research to understand the complex immunological pathways at play. This need follows to what it takes to keep the protective responses going, as well as to the potential unwanted side effects of both the infection and the different SARS-CoV-2 vaccine types, especially as boosting is now applied,” Murphy said. “The good news is that these are testable questions that can be partially addressed in the laboratory, and in fact, have been used with other viral models.”

Posted on Diabetes

Long-term blood sugar history predicts risk of severe COVID-19 among diabetics

T2D and COVID-19


A long-term history of glycemic control better predicts risk of severe COVID-19 among type 2 diabetics than shorter-term measurements. CREDIT Rensselaer Polytechnic Institute

People with type 2 diabetes who contract COVID-19 are nearly 50% more likely to wind up in intensive care if they have poorly managed their blood sugar levels over the long-term than those with better long-term glycemic control, according to a study using anonymized health care data. The study, which looked at several potential impacts to COVID-19 severity among diabetics, also calculated a lower risk for patients using the common diabetes-control medication metformin, or a combination of metformin and insulin, or corticosteroids.

“We find that two- to three-year longitudinal glycemic levels better indicate the risk of COVID-19 severity than measurements which look at a shorter period of time,” said Deepak Vashishth, corresponding author, professor of biomedical engineering, and director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute. “We hope these insights aid physicians in better treating and managing high-risk patients.”

“Evaluation and management of COVID-19-related severity in people with type 2 diabetes” looked at records for more than 16,000 people with type 2 diabetes and COVID-19 between 2017 and 2020, and was published in BMJ Open Diabetes Research & Care.

Type 2 diabetes patients are unable to regulate the amount of the sugar glucose in their bloodstream without medication and managing their diet. Chronic high blood-sugar levels, typically tracked as the percentage of hemoglobin A1c (HbA1c) found in the blood, can damage a variety of functions, including the circulatory, nervous, and immune systems.

Poor glycemic control creates a reaction that causes molecules known as advanced glycation end-products (AGEs) to accumulate, deteriorating the quality of bone over time, and Vashishth, an expert in bone, researches the impact of diabetes on bone. At the time the SARS-CoV-2 pandemic began, his research team was investigating whether measurements of longitudinal glycemic control – measures of blood-sugar levels averaged over two to three years – could provide a more accurate predictor of bone fracture risk among diabetics than the current standard predictor, which relies on measurements of bone mineral density.

AGEs are known to contribute to increased oxidant stress and inflammation, which are risk factors in COVID-19 and other respiratory illnesses. The team reasoned that the same longitudinal glycemic control measurement they were testing as a predictor of bone fracture risk might be useful in predicting the severity of COVID-19, said Bowen Wang, first author and a doctoral student in Vashishth’s lab.

Wang divided the records of type 2 diabetic patients in the study into two groups, those with “adequate” longitudinal glycemic control ranging from 6 to 9%, and those with “poor” glycemic control of 9% or above over two to three years. His analysis of the two groups revealed that those with poor glycemic control were 48% more likely to require treatment in an intensive care unit. By another measure, a 1% increase in longitudinal HbA1c is directly associated with a 12% increase in the risk of landing in the ICU.

Other statistically significant findings showed that diabetics who were taking metformin when they contract COVID-19 face a 12% lower risk of visiting the ICU, those on metformin and insulin have an 18% lower risk, and those prescribed corticosteroids have a 29% lower risk.

“People knew that diabetes was a risk factor for COVID-19-related outcomes, but not all diabetic patients are the same. Some people have a longer history of diabetes, some have more severe diabetes, and that has to be accounted for,” said Wang. “What this study does is to better stratify the level of diabetes within the population, so diabetic patients aren’t treated as a single population without any differences among them.”

Vashishth and Wang were joined on the research by Benjamin S. Glicksberg and Girish N. Nadkarni at the Icahn School of Medicine at Mount Sinai. Their work was supported by a grant from the National Institutes of Health.

Posted on Diet

COVID-19 vaccines should be shored up with a plant-based diet

Studies suggest vegan diet boosts vaccine efficacy and reduces COVID-related morbidity and mortality

Corticosteroid injection


“A solid vaccination program is lifesaving, essential, and insufficient,” begins the commentary “Shoring Up Vaccine Efficacy,” which appears today in the American Journal of Medicine. The authors say that in addition to vaccinations, health care workers should recommend plant-based diets to help patients improve their health and decrease vulnerability to COVID-19.

The authors point to a new study of health care workers whose immune response to the Pfizer vaccine was inversely associated with waist circumference. A 2021 study of health care workers in six countries revealed that those following largely plant-based diets had 73% lower odds of developing moderate-to-severe COVID-19, compared with those following other diets.

“This benefit may come from the fact that plant-based diets are associated with significantly lower body weight, lower risk of hypertension, lower plasma lipid levels, and lower risk of diabetes,” says Saray Stancic, MD, director of medical education of the nonprofit Physicians Committee for Responsible Medicine and faculty member of Rutgers New Jersey Medical School. “A healthy vegan diet can benefit a large group of individuals who fail to respond adequately to vaccination yet do not have a classic immunosuppression condition.”

Dr. Stancic authored the commentary with Josh Cullimore, MBChB, MPH, of Brighton and Hove Clinical Commissioning Group in the UK, and Neal Barnard, MD, of the Physicians Committee.

“As of November 18, 2020, more than 60% of COVID-19 hospitalizations were attributable to obesity, hypertension, diabetes, or heart failure,” Dr. Stancic says. “We are suggesting, perhaps surprisingly, that a key, but neglected, part of our immunization strategy should be shoring up the cardiometabolic health of the patient to the extent possible.”

To improve health and decrease vulnerability to COVID-19 and other illness, the authors suggest three key strategies:

  1. Doctors should encourage patients to improve underlying health conditions, including adopting healthful dietary habits, particularly a renewed emphasis on vegetables, fruits, whole grains, and legumes, and plant-based diets. This recommendation aligns with the June 2021 American Medical Association policy urging governmental leaders to encourage individuals with underlying health conditions associated with COVID-19 morbidity and mortality to see their doctors to institute (or resume) appropriate treatment for those underlying conditions.
  2. Medical practitioners should refer appropriate patients to registered dietitians as a matter of medical urgency. They should provide nutrition information and code nutrition messaging into their electronic medical records to be automatically given to patients at check out.
  3. Hospitals should provide information about good nutrition to patients, families, visitors, and staff, and should model it with the foods they serve.

“To make an immunization program work, convincing people to roll up their sleeves for initial immunization and boosters as necessary is one key step,” Dr. Stancic says. “Improving their ability to respond to the vaccine is another. Evidence strongly suggests that urgently addressing underlying health conditions with, for starters, a healthier diet would not only reduce the likelihood of severe infection and death; over time it may also help vaccines to work better.”

Posted on Multiple Sclerosis

COVID-19 Vaccines and Multiple Sclerosis


In this video, our co-founder and chief science communicator, Brett Drummond, answers one of the recent questions submitted by a member of the MStranslate community. In this instance, it looks at the latest published data on the COVID-19 vaccines in people living with multiple sclerosis.