Thursday, July 13, 2023

University of Zurich COVID-19 Vax Adverse Effect Study

A team at the University of Zurich, Epidemiology, Biostatistics and Prevention Institute (EBPI) led a population-based cohort study involving 575 individuals who received a SARS-CoV-2 vaccine, and as part of the study, were monitored and followed up over 12 weeks, with participants sharing commonly reported adverse effects, mostly local pain, fatigue, headache and fever. Not surprisingly, a majority of adverse effects were mild to moderate and resolved within three days. The findings here are comparable to other reported prevalence and severity of adverse effects in randomized controlled trials. Hospitalizations out of the cohort totaled 0.7%.


The results of this Swiss study concerning the prevalence and severity of adverse effects are overall similar to previously reported data from randomized controlled trials and other observational studies as cited by the Swiss-based study authors.

The team provides an overview of other important safety surveillance studies for some perspective. For example, in one online survey among persons who received either the Pfizer (BNT162b2), Moderna (mRNA-1273) or J&J (JNJ-78436735), study team of Beatty et al. reported that 80.3% of participants experienced adverse effects, with comparable estimates for each vaccine type.

The proportion of adverse effects that were self-reported as severe or required hospitalization in the current study (14.7%) was well below that of Swiss and European governmental surveillance systems (37.9% in Swiss ElViS). These are actually high rates.

Furthermore, safety surveillance systems in America reveal higher estimates of serious adverse events based on hospitalization rates, serious illness and deaths (9.2% vs. our 0.7%). The Swiss authors propose: “These higher estimates from governmental reporting systems are likely related to the underreporting of mild symptoms and underscore the importance of real-world data.”

Reports on prevalence of anaphylaxis and severe allergic reactions vary from 0.03% to 3% based on differing definitions. In the current University of Zurich study, two (0.4%) participants reported allergic reactions, without the need to consult a medical professional.

The study

Data is derived from participants at a University of Zurich vaccination center. Individuals receiving BNT162b2 or mRNA-1273 vaccines were recruited between March 10, 2021, and July 21, 2021, while participants receiving JNJ-78436735 were recruited between October 20, 2021, and January 27, 2022.

The findings

Out of the entire study population, 454 participants reported experiencing at least one adverse event up to three months post-vaccination equaling 79.0% of the total. The study showed a total of 2233 adverse events meaning on average there were 3.88 adverse events reported per study participant.


Canadian Investigators Discovery Unique Blood Plasma Protein Patterns in Long COVID Patients

A Canadian research unit may come up with a way to treat at least some long COVID patients more effectively. The condition has emerged since the pandemic as a real problem. With anywhere from 10-20% of people that have been infected with SARS-CoV-2 susceptible to long COVID, some estimate north of 14 million people in America alone struggling with the condition, which can last for many months. Often impacting the quality of life, symptoms from brain fog and fatigue to breathing difficulties can be outright debilitating. Led by Dr. Douglas Faser, a professor in pediatrics at Schulich School of Medicine & Dentist, and physician at London Health Sciences Centre (LHSC) a team of Canadians designed a study using artificial intelligence (AI) as part of advanced research to discover unique patterns of blood plasma proteins in patients with suspected long COVID, with an aim on improving patient outcomes. Enter the “plasma proteome,” as the research centers on proteins identified in blood plasma, released by cells often playing a vital role in pathogen immune response.

With study results recently published in the Journal of Translational Medicine this study team sought out to better understand how these plasma cells impact patients with long COVID, and why some patients struggle more than others.

Corresponding authors Dr. Douglas Faser and Cristiana Losef, both with Children’s Health Research Institute, Victoria Research Laboratories, and colleagues investigated possible mechanisms, and to inform the prognosis and treatment of long COVID.

This technology allowed researchers to determine unique patterns in the blood proteins. The team discovered that people with suspected long COVID have prolonged inflammation associated with changes in their immune cells and blood vessels. These changes may lead to problems in specific organs, like the brain and the heart, as reported by Western University.

Called “the plasma proteome,” the proteins are found in blood plasma and are released by cells that often play an important role in the body’s immune response to viruses. The research team is studying how those proteins adapt and change in long COVID.

The study

With a green light from the local Ethics Committee (Western University), the study team enrolled patients from London Health Sciences Center in London, Ontario, Canada and St. Joseph's including patients diagnosed with long COVID as well as acutely ill COVID-19 patients.

Upon diagnosis of long COVID, study patients were referred to a specialist clinic based on prolonged, diffuse symptoms according to the author's account in the Journal of Translational Medicine.

Conducting a series of tests including venous blood work, the study team analyzed patient plasma. COVID-19 patients were approached when they were admitted to the hospital or medical ward or intensive care unit. Healthy subjects were included—persons without disease, acute illness or any prescription medicine, but previously banked by the Translational Research Center in London, Ontario.

All samples in the study were matched by age and gender (e.g., long COVID patients to acutely ill patients to healthy controls).


Unlike acutely ill COVID-19 patients as well as healthy subjects---both matched by age and sex—the long COVID outpatients evidenced natural killer cell redistribution with a dominant resting phenotype, opposite to active and neutrophils formed in extracellular traps.

The study team reports a possible “resetting of cell phenotypes” likely resulting from “prospective vascular events mediated by both angiopoietin (ANGPT1) and vascular endothelial growth factor-A (VEGFA).

Validating several biomarkers (ANGPT1, VEGFA, CCR7, CD56, citrullinated histone 3, elastase) the authors report also that “Signaling of transforming growth factor-β1 with probable connections to elevated EP/p300” pointed to both vascular inflammation as well as tumor necrosis factor- α driven pathways. The authors suggested that the progression from acute COVID-19 to long COVID was “a vascular proliferative state associated with hypoxia-inducible factor 1 pathway.”

Fraser and Losef write that this “vascular-proliferative process predicted in Long-COVID might contribute to changes in the organ-specific proteome reflective of neurologic and cardiometabolic dysfunction.”

PI Point of View

Cristiana Losef, a research analyst at Children’s Health Research Institute (CHRI), a program of Lawson went on the record, “We used novel technologies for this study, allowing us to analyze more than 3,000 proteins in blood plasma at the same time with multiple patients.”

Losef continued:

“We used a novel bioinformatic pipeline, a form of artificial intelligence (AI), to analyze the proteins to determine the specific changes that occur in long COVID.”

Dr. Michael Nicholson, associate scientist at Lawson, and respirologist at St. Joseph’s Health Care London reports on the influence of this study, “Trying to understand this mechanism is quite important because it provides further insight into how patients are affected,” says Dr. Michael Nicholson. He continued, “This paper sheds further light on a possible mechanism that may provide insight into why some patients have certain symptoms.”

Michael Knauer, an associate scientist at Lawson shared for Western University, “The saved blood plasma samples we are using helped us determine the long-term responses to COVID-19; serial blood plasma samples from individuals that had a COVID-19 infection and now presumed long COVID will help us determine how proteins are changing over time.”

What’s the potential value from a therapeutic perspective?

Dr. Faser, a professor at Schulich Medicine, said the proteins discovered could act as a potential drug target. The team is now examining potential new drug therapies with the hopes of improving outcomes for these patients.

Fraser emphasized:

“When we identify these signaling patterns within the blood plasma, we can then take the information and screen drug databases to better understand which drugs would be best to target the changes we identified in long COVID patients.” Pointing to the potential of these findings, “With this understanding, the identified drugs may be used in future long COVID clinical trials.”

Key Point: This research, which used multiple state-of-the-art technologies, was enabled by existing expertise and infrastructure through Children’s Health Research Institute (CHRI). It reveals that the findings point to a “vascular-proliferative process in Long-COVID that is likely initiated either prior hypoxia (localized or systemic) and/or stimulatory factors (i.e., cytokines, chemokines, growth factors, angiotensin, etc.). Analyses of the plasma proteome, used as a surrogate for cellular signaling, unveiled potential organ-specific prognostic biomarkers and therapeutic targets.”




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