Thursday, October 19, 2023

Rome-Based IRCCS Team Find Distinct Markers Linked to mRNA COVID-19 Vax-Induced Myocarditis

A large team of Italian specialist physician-investigators represented by corresponding author Paolo Palma, affiliated with Rome Italy’s prestigious Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), the Research Unit of Clinical Immunology and Vaccinology at Bambino Gesu Children’s Hospital, and colleagues conducted a prospective observational study including 15 pediatric patients referred to the hospital’s emergency department for cardiac events (namely suspected acute myocarditis/pericarditis) after receiving a COVID-19 mRNA vaccine.

In this study, all patients were hospitalized and had samples taken on admission or within 48 hours for baseline evaluation, as well as within six months for follow-up evaluation. The study team performed cardiological evaluation with electrocardiogram (ECG) as well as echocardiogram. In this study, the physician-scientists examined the inflammatory features of the Rome children’s hospital pediatric patients developing myocarditis post the mRNA COVID-19 jab. The team combined clinical and routine laboratory data along with high-dimensional proteomic analysis.

Patients meeting the clinical case definition of the CDC (probable myocarditis, confirmed myocarditis, or acute pericarditis) were deemed “c-AEFI patients,” and compared to children with MIS-c and cardiac involvement, SARS-CoV-2 infected children and healthy controls. The Rome-based team was able to confirm a “distinct inflammatory and androgenic profile in patients developing c-AEFI following mRNA vaccination which persists months after the acute event, whereas excluding a pathogenic role of autoantibodies.”

Dr. Palma heads up the pediatric department at the tertiary care academic children’s hospital in Rome that is under extraterritorial jurisdiction of the Holy See—the jurisdiction of the Pope in his role as the bishop of Rome and sovereign of Vatican City.

The study team reports that the subjects represent the clinical and demographic characteristics in line with previously published case series, including class of vaccine product, dose linked to the injury, and the gender ratio.

All the patients in this study developed symptoms following the second or third dose except those who already experienced SARS-CoV-2 infection, who developed symptoms after the first dose. Could this point observed indicate that previous exposure to spike protein may play a role in the pathogenesis of this condition? The study authors believe so.

Study Methods

During this study, the study team investigated the inflammatory features of pediatric patients developing myocarditis following mRNA COVID-19 vaccination, by combining clinical and routine laboratory data along with high-dimensional proteomic analysis.

During the study period the team enrolled 17 patients who met the criteria for the study—CDC work case definitions for myocarditis. These patients all went into observation due to chest pain after COVID-19 mRNA vaccine (BNT162b2 mRNA-Pfizer-BioNTech and the mRNA-1273-Moderna), from August 2021 to February 2022.

The study authors report the exclusion of two patients due to not meeting the study inclusion criteria. The study team used CDC work case definitions to categorize case definitions, fitting as probable myocarditis, confirmed myocarditis or cute pericarditis. All are referred to as c-AEFI.

The Rome-based team was able to use other cohorts for comparison participant data from the CACTUS study—these children were affected by SARS-CoV-2 infection; or had MIS-C with cardiac involvement all before any treatment, as well as healthy children collected in the pre-pandemic period.

Addressing the possibility of confounding factors of age, the team age matched patients, using for comparison of proteomic analysis 21 children with acute COVID-19 infection, 14 children with MISC-C and 31 healthy children. Also, the study team compared androgen levels in children with myopericarditis.

So, what did the Italian researchers find under Dr. Palma and colleagues? TrialSite breakdowns down the outcomes.

Why conduct this study?

Because the risk of acute myocarditis linked to the mRNA vaccines developed in response to COVID-19 attracts lots of attention, and is hotly debated, particularly in the pediatric population. This is a cohort where the risk-benefit of the vaccine must be carefully evaluated. Moreover, the pathogenesis of COVID-19 mRNA vaccine-linked myocarditis remains poorly understood. Several mechanisms are possible.

What are the possible mechanisms involved with COVID-19 mRNA vaccine-induced myocarditis?

The authors suspect one or more of the following:

Immune reactivity

Cross-reacting antibodies to SARS-CoV-2 spike glycoproteins with myocardial contractile proteins

Hormonal differences

So, what were the team’s finding?
Cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported, are a real-world phenomenon, although rare, and were distinctly identified in this study.

Such events not to mention the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. The team here investigates the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Interestingly the study team reports when comparing MIS-C patients to vaccine injured myocarditis patients (c-AEFI), the former possess higher levels of proteins related to systemic inflammation than compared to the latter c-AEFI. But higher levels in proteins related to myocardial injury were found in c-AEFI.

In addition, higher levels of hormones such as DHEAS, DHEA, and cortisone were found in c-AEFI which continued months later during ongoing follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results in being well restricted on heart and to persist months after the acute event.


COVID-19 Vaccines and Reports of Deep Vein Thrombosis (DVT)

Reports of deep vein thrombosis (DVT), the formation of blood clots, as an adverse effect associated with COVID-19 vaccines, are increasing. TrialSite has reported before on the blood clot crisis linked to COVID-19 and its vaccines. A compilation of such hematological case reports has been contributed by Aaron Hertzberg. We will summarize some of them here.

Deep vein thrombosis (DVT) is a medical condition where blood clots form in a deep vein; usually in the lower leg, thigh, or pelvis. However, sometimes they can form in the arm.

Case reports of the adverse events following the COVID-19 vaccine administration are appearing after the massive vaccination campaigns to control the pandemic. Studies have been conducted to investigate the link between these vaccines and blood clot formation. Here we present a summary of case reports of DVT, post-COVID-19 vaccination.

Case 1
The first paper mentioned here entitled “Deep vein thrombosis (DVT) occurring shortly after the second dose of mRNA SARS-CoV-2 vaccine” was published in the Internal and Emergency Medicine journal in 2021.

This case involved a 66-year-old female who received two doses of the Pfizer vaccine. Before vaccination, the woman had been completely healthy and did not smoke or have any allergies. She just had a history of left leg neuropathy (damage to peripheral nerves in the leg) after a trauma. A day after receiving her second dose, she had a persistent fever with chills, fatigue, muscle pain, and discomfort. To control these symptoms, she was administered acetaminophen, a drug used for bringing down fever and easing pain. The fever had not resolved by the next day and the patient had also developed acute pain in her right calf in the absence of any trauma. On the third day post vaccine administration, she could not walk and was admitted for investigations. She had mild swelling in her right calf. A diagnosis of DVT was confirmed through a color-doppler ultrasound scan, a non-invasive method to test for deep vein thrombosis. To treat this condition, she was given 10 mg of apixaban, an anticoagulant, for a week. The dose was later reduced to 5 mg and the symptoms resolved rapidly.

Case 2
The second case study was published in the American Journal of Case Reports in 2021. It is titled “A 59-Year-Old Woman with Extensive Deep Vein Thrombosis and Pulmonary Thromboembolism 7 Days Following a First Dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 Vaccine”.

It involved a 59-year-old female who reported to a hospital in Oman after suddenly experiencing pain in her left leg. She had a medical history of type 2 diabetes mellitus (T2DM), a condition in which there is a decrease in the insulin secretion to metabolize glucose in the body, osteoarthritis, a degenerative joint disease, and COVID-19 pneumonia. She had been diagnosed with COVID pneumonia in September 2020 for which she had been hospitalized for a week, but the condition had not been complicated. Seven months later, she received the Pfizer BioNTech vaccine, and seven days after that, she developed leg pain with swelling and tenderness. Acute DVT was diagnosed by performing duplex ultrasonography, a test to visualize how blood travels through arteries and veins. The patient experienced tachycardia for which computed pulmonary tomography angiography (CTPA) was performed to look for blood clots within the arteries of the lungs. The test confirmed the presence of blood clots in her pulmonary arteries. For treatment, she was given enoxaparin, an injectable anticoagulant. This was later switched to rivaroxaban – an oral anticoagulant – due to a positive heparin-induced thrombocytopenia test (HIT).

Case 3
The third case report entitled “An unusual presentation of acute deep vein thrombosis after the Moderna COVID-19 vaccine-a case report” was published in 2021 in the Annals of Translational Medicine journal.

It involved a 27-year-old female who had been completely healthy before receiving the second dose of mRNA-1273 (Moderna) COVID-19 vaccine. She had an unremarkable medical history. On the third day after receiving the dose, she reported to the hospital with swelling, redness, and pain with bruising in her upper right arm. (The first dose of this vaccine had been well-tolerated by her with mild soreness at the injection site which had lasted for a few days.) An acute thrombosis in her subclavian and axillary veins was diagnosed using venous duplex ultrasound. For treatment, she was given a heparin infusion to clear the blood clots. After that, she was given rivaroxaban for three months. Her symptoms significantly improved two weeks after being discharged.

Case 4
The fourth case titled “Deep Vein Thrombosis and Pulmonary Thrombosis After BNT162b2 mRNA SARS-CoV2 Vaccination” was published in Circulation Journal in 2022.

This case involved a 14-year-old male who presented at the clinic with pain in his left lower leg 24 hours after receiving the second dose of the Moderna vaccine. He had no family history of juvenile thrombosis or medical history of thrombosis. A contrast-enhanced computed tomography scan revealed multi-organ thrombosis. The patient was administered heparin initially and then shifted to an oral anticoagulant.




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