There are more than 1,300 scientific articles published in peer reviewed scientific journals disclosing adverse effects to COVID-19 vaccination, just to name a few:
We estimated an extra two, one and six myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40, according to Martina Patone et al., “Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection,” Nature Medicine, vol. 28, February 2022, 410-422, https://doi.org/10.1038/s41591-021-01630-0, JIF 87.244 (top 0.4% journals in Biochemistry & Molecular Biology, top 0.7% journals in Medicine, Research & Experimental and top 1% journals in Cell Biology).
We found progressively waning vaccine effectiveness against SARS-CoV-2 infection of any severity across all subgroups, but the rate of waning differed according to vaccine type. With respect to severe COVID-19, vaccine effectiveness seemed to be better maintained, although some waning became evident after 4 months, according to Peter Nordström et al., “Risk of infection, hospitalisation, and death up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden,” Lancet 2022; 399:814–23 February 4, 2022, https://doi.org/10.1016/S0140-6736(22)00089-7, 202.731 (top 0.6% journals in Medicine, General & Internal).
Between Dec 8, 2020, and Feb 28, 2022, 16,208,600 individuals completed their primary vaccine schedule and 13,836,390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59,510 (0.4%) of the primary vaccine group and 26,100 (0.2%) of those who received their booster had severe COVID-19 outcomes, according to Utkarsh Agrawal et al., “Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales,” Lancet 2022; 400:1305-1320, October 15, 2022, https://doi.org/10.1016/S0140-6736(22)01656-7, JIF 202.731 (top 0.6% journals in Medicine, General & Internal).
Vaccine efficacy is generally reported as a relative risk reduction (RRR). It uses the relative risk (RR)-i.e., the ratio of attack rates with and without a vaccine-which is expressed as 1-RR. Ranking by reported efficacy gives relative risk reductions of 95% for the Pfizer-BioNTech, 94% for the Moderna-NIH, 91% for the Gamaleya, 67% for the J&J, and 67% for the AstraZeneca-Oxford vaccines. However, RRR should be seen against the background risk of being infected and becoming ill with COVID-19, which varies between populations and over time. Although the RRR considers only participants who could benefit from the vaccine, the absolute risk reduction (ARR), which is the difference between attack rates with and without a vaccine, considers the whole population. ARRs tend to be ignored because they give a much less impressive effect size than RRRs: 1.3% for the AstraZeneca-Oxford, 1.2% for the Moderna-NIH, 1.2% for the J&J, 0.93% for the Gamaleya, and 0.84% for the Pfizer-BioNTech vaccines, according to Piero Olliaro et al., “COVID-19 vaccine efficacy and effectiveness-the elephant (not) in the room,” Lancet Microbe 2021, April 20, 2021, https://doi.org/10.1016/S2666-5247(21)00069-0, JIF 86.208 (top 0.7% journals in Microbiology and top 1% journals in Infectious Diseases).
In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons in the largest health care organization in Israel. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection, according to Noam Barda et al., “Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting,” The New England Journal of Medicine 2021;385:1078-90, 25 August 2021, https://doi.org/10.1056/NEJMoa2110475, JIF 176.082 (top 1.2% journals in Medicine, General & Internal).
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. From our data, we observed something called the birth cohort effect. This effect shows that each successive group of people born at a later time — e.g., a decade later — have a higher risk of developing cancer later in life, likely due to risk factors they were exposed to at a young age. We found that this risk is increasing with each generation. For instance, people born in 1960 experienced higher cancer risk before they turn 50 than people born in 1950, and we predict that this risk level will continue to climb in successive generations. Risk factors such as highly processed foods, sugary beverages, obesity, Type 2 diabetes, sedentary lifestyle, and alcohol consumption have all significantly increased since the 1950s. Among the 14 cancer types on the rise that we studied, eight were related to the digestive system. The food we eat feeds the microorganisms in our gut,” said Ugai. “Diet directly affects microbiome composition and eventually these changes can influence disease risk and outcomes, according to Tomotaka Ugai et al., “Is early-onset cancer an emerging global epidemic? Current evidence and future implications,” Nature Review Clinical Oncology 19, 656–673 (2022), 6 September 2022, https://doi.org/10.1038/s41571-022-00672-8, Complimentary shared article is available at: https://www.nature.com/articles/s41571-022-00672-8.epdf?sharing_token=1umLnn8X8BYzX5QTMHyArtRgN0jAjWel9jnR3ZoTv0Mbf4RPi-ocNFWHJz8DUBZsAPhKJF2UqgYLHsA0Cpbtq9pHyF5VY4_JUzOCW23Ny67AuPivP2QGjseGKUadh2IPLERt0L07AH5dSEBqCheSrvp_NMPuByyxFdBZ3yftAdU%3D, JIF 65.111 (top 1.2% journals in Oncology).
Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels. ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients. There was no evidence of acute COVID-19 or other viral infections, according to Biykem Bozkurt et al., “Myocarditis With COVID-19 mRNA Vaccines,” Circulation, 2021;144:471–484, https://doi.org/10.1161/CIRCULATIONAHA.121.056135, JIF 39.922 (top 1.4% journals in Cardiac & Cardiovascular Systems and top 1.5% journals in Peripheral Vascular Disease).
Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine, according to Martina Patone et al., “Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex,” Circulation, Volume 146, Issue 10, 6 September 2022; Pages 743-754, https://doi.org/10.1161/CIRCULATIONAHA.122.059970, JIF 39.922 (top 1.4% journals in Cardiac & Cardiovascular Systems and top 1.5% journals in Peripheral Vascular Disease).
Among 23,122,522 Nordic residents (81% vaccinated by study end), 1,077 incident myocarditis events and 1,149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis. Estimates for pericarditis were similar, according to Øystein Karlstad et al., “SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents,” JAMA Cardiology 2022;7(6):600-612, https://doi.org/10.1001/jamacardio.2022.0583, JIF 30.157 (top 2.8% journals in Cardiac & Cardiovascular Systems).
The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis, according to Manuela De Michele et al., “Cerebrovascular Complications of COVID-19 and COVID-19 Vaccination,” Circulation Research 2022;130:1187–1203, https://doi.org/10.1161/CIRCRESAHA.122.319954, JIF 23.218 (top 3% journals in Peripheral Vascular Disease, top 4% journals in Cardiac & Cardiovascular Systems and top 4% journals in Hematology).
In summary, autoimmune hepatitis developed in a healthy 35-year-old female in her third month postpartum. Whether there exists a causal relationship between COVID-19 vaccination and the development of autoimmune hepatitis remains to be determined. We are hopeful that this manuscript will not discourage healthcare providers from getting and prescribing COVID-19 vaccines, but that it will raise awareness about potential side effects that will likely emerge as we continue to vaccinate more people. Only long-term follow-up of large cohorts of patients receiving the vaccine will answer the question as to whether it increases the risk of autoimmune conditions. Until then, healthcare providers are encouraged to remain vigilant, according to Fernando Bril et al., “Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?” Journal of Hepatology, Volume 5, Issue 1, 222-224, July 01, 2021, https://doi.org/10.1016/j.jhep.2021.04.003, JIF 30.083 (top 5.4% journals in Gastroenterology & Hepatology).
It is speculated that SARS-CoV-2 can disturb self tolerance and trigger autoimmune responses through crossreactivity with host cells and that the COVID-19 mRNA vaccines may trigger the same response. We report a further case of autoimmune hepatitis (AIH) following COVID-19 mRNA vaccination. Cathy McShane et al., “The mRNA COVID-19 vaccine – A rare trigger of autoimmune hepatitis?” Journal of Hepatology 2021, volume 75, issue 5, 1239–1260, https://doi.org/10.1016/j.jhep.2021.06.044, JIF 30.083 (top 5.4% journals in Gastroenterology & Hepatology).
The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females, according to Stéphane Le Vu et al., “Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines,” Nature Communications (2022) 13:3633, https://doi.org/10.1038/s41467-022-31401-5, JIF 17.694 (top 8% journals in Multidisciplinary Sciences).
Cases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females, according to Stéphane Le Vu et al., “Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines,” Nature Communications (2022) 13:3633, https://doi.org/10.1038/s41467-022-31401-5, JIF 17.694 (top 8% journals in Multidisciplinary Sciences).
Some recent reports have been suggested that COVID-19 vaccination can lead to the development of autoimmune diseases. It is speculated that the vaccine can disturb self-tolerance and trigger autoimmune responses through cross-reactivity with host cells. We report a case of a 65-year-old woman who experienced acute severe autoimmune hepatitis two weeks after receiving the first dose of Moderna-COVID-19 vaccine. Liver histology showed a marked expansion of the portal tracts, severe interface hepatitis and multiple confluent foci of lobular necrosis, according to Isabel Garrido et al., “Autoimmune hepatitis after COVID-19 vaccine – more than a coincidence,” Journal of Autoimmunity 125 (2021) 102741, https://doi.org/10.1016/j.jaut.2021.102741, JIF 14.511 (top 10% journals in Immunology).
The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and nonresponsiveness, it was determined the effects of pre-exposure to the mRNA-LNP or LNP alone led to long-term inhibition of the adaptive immune responses and innate immune fitness, according to Zhen Qin et al., “Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion,” PLoS Pathogens, 18(9): e1010830, https://doi.org/10.1371/journal.ppat.1010830, JIF 7.464 (top 11% journals in Parasitology, top 18% journals in Microbiology and top 22% journals in Virology).
The patient is the corresponding author of this case report. The vaccination with the BNT162b2 mRNA vaccine might induce rapid progression of Angioimmunoblastic T Cell Lymphoma, according to Serge Goldman et al., “Rapid Progression of Angioimmunoblastic T Cell Lymphoma Following BNT162b2 mRNA Vaccine Booster Shot: A Case Report,” Frontiers in Medicine, 8:798095, 25 November 2021, https://doi.org/10.3389/fmed.2021.798095, JIF 9.927 (top 13% journals in Medicine, Research & Experimental and top 13% journals in Oncology).
COVID-19 vaccine safety and efficacy has not been established in individuals with chronic autoimmune diseases such as multiple sclerosis (MS). Anecdotal reports suggest that the vaccines may be associated with brain, spinal cord, peripheral nervous system, and cardiac inflammation. Based on the high morbidity and unpredictable course of COVID-19, and the need to achieve herd immunity, vaccination has been recommended for patients with MS. We report clinical and MRI features of seven individuals who received the Moderna (n = 3) or Pfizer (n = 4) SARS-CoV-2 mRNA vaccines. Within one to 21 days of either the first (n = 2) or second (n = 5) vaccine dose, these patients developed neurologic symptoms and MRI findings consistent with active CNS demyelination of the optic nerve, brain, and/or spinal cord. Symptoms included visual loss, dysmetria, gait instability, paresthesias, sphincter disturbance, and limb weakness, according to Mahsa Khayat‑Khoei et al., “COVID‑19 mRNA vaccination leading to CNS inflammation: a case series,” Journal of Neurology (2022) 269:1093–1106, https://doi.org/10.1007/s00415-021-10780-7, JIF 6.682 (top 14% journals in Clinical Neurology).
The many alterations in the vaccine mRNA hide the mRNA from cellular defenses and promote a longer biological half-life and high production of spike protein. However, the immune response to the vaccine is very different from that to a SARS-CoV-2 infection. In this paper, we present evidence that vaccination induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. Immune cells that have taken up the vaccine nanoparticles release into circulation large numbers of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances potentially have a causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell’s palsy, liver disease, impaired adaptive immunity, impaired DNA damage response and tumorigenesis, according to Stephanie Seneff et al., “Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs,” Food and Chemical Toxicology 164 (2022) 113008, https://doi.org/10.1016/j.fct.2022.113008, JIF 5.572 (top 16% journals in Toxicology and top 24% journals in Food Science & Technology).
The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls. However, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient, according to Bruce K. Patterson, “Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection,” Frontiers in Immunology, Volume 12, Arrticle 746021, 10 January 2022, https://doi.org/10.3389/fimmu.2021.746021, JIF 8.787 (top 22% journals in Immunology).
As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge about adverse events of SARS-CoV-2 vaccines during post-marketing surveillance. Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation has already been reported in COVID-19 patients. In addition, adverse events after SARS-CoV-2 mRNA vaccination have also been in the context of varicella zoster virus (VZV) reactivation and directly associated with the mRNA vaccine. We present the first case of CMV reactivation and pericarditis in temporal association with SARS-CoV-2 vaccination, particularly adenovirus-based DNA vector vaccine ChAdOx1 nCoV-19 against SARS-CoV-2. After initiation of antiviral therapy with oral valganciclovir, CMV viremia disappeared and clinical symptoms rapidly improved. Since huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must be in place to assess vaccine safety that is important for the detection of any events. In the context of the hundreds of millions of individuals to be vaccinated against SARS-CoV-2, a potential causal association with CMV reactivation may result in a considerable number of cases with potentially severe complications, according to Marlene Plüß et al., “Case Report: Cytomegalovirus Reactivation and Pericarditis Following ChAdOx1 nCoV-19 Vaccination Against SARS-CoV-2,” Frontiers in Immunology, January 2022, Volume 12, Article 784145, https://doi.org/10.3389/fimmu.2021.784145, JIF 8.787 (top 22% journals in Immunology).
Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. The present study summarizes EMB-based diagnostics of 15 patients with clinical suspicion of myocarditis following vaccination against SARS-CoV-2. It identifies 14 of 15 patients with myocardial inflammation, ranging from inflammatory cardiomyopathy to active myocarditis and severe giant cell myocarditis. Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination, according to Christian Baumeier et al., “Intramyocardial inflammation after COVID-19 vaccination: An endomyocardial biopsy-proven case series,” International Journal of Molecular Sciences, 2022, 23, 6940, https://doi.org/10.3390/ijms23136940, JIF 6.208 (top 23% journals in Biochemistry & Molecular Biology and top 28% journals in Chemistry, Multidisciplinary).
Repetitive measurements revealed -15.4% and -15.9% sperm concentration decrease at 2 and 3 months after the vaccination, respectively, as well as total motile count -22.1% and -19.4% decrease at 2 and 3 months, after the vaccination, respectively, according to Itai Gat et al., “Covid-19 vaccination BNT162b2 temporarily impairs semen concentration and total motile count among semen donors,” Andrology, Volume 10, Issue 6, Pages 1016-1022, September 2022, https://doi.org/10.1111/andr.13209, JIF 4.456 (top 25% journals in Andrology).
Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16–39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of over 25% was detected in both call types during January–May 2021, compared with the years 2019–2020, according to Christopher L. F. Sun et al., “Increased emergency cardiovascular events among under‑40 population in Israel during vaccine rollout and third COVID‑19 wave,” Scientific Reports (2022) 12:6978, https://doi.org/10.1038/s41598-022-10928-z, JIF 4.997 (top 26% journals in Multidisciplinary Sciences).
We report a 40-year-old, previously healthy man who was admitted to our emergency unit by his family doctor because of fever (till 39 °C), headache, chest pain and shortness of breath. Six days ago, he got the first dose of the mRNA COVID-19 vaccine Comirnaty® (BioNTech/Pfizer). Two days after vaccination, he developed fever and headache and another 2 days later, he suffered from resting dyspnea and angina pectoris, according to Peter Ehrlich et al., “Biopsy‑proven lymphocytic myocarditis following first mRNA COVID‑19 vaccination in a 40‑year‑old male: case report,” Clinical Research in Cardiology (2021) 110:1855–1859, 6 September 2021, https://doi.org/10.1007/s00392-021-01936-6, JIF 6.138 (top 28% journals in Cardiac & Cardiovascular Systems).
Cases of myocarditis, diagnosed clinically by laboratory tests and imaging have been described in the context of mRNA-based anti-SARS-CoV-2 vaccination. Autopsy-based description of detailed histological features of vaccine-induced myocarditis is lacking. We describe the autopsy findings and common characteristics of myocarditis in untreated persons who received anti-SARS-CoV-2 vaccination. Standardized autopsies were performed on 25 persons who had died unexpectedly and within 20 days after anti-SARS-CoV-2 vaccination. In our patients who received a mRNA vaccination, we identified acute (epi-) myocarditis without detection of another significant disease or health constellation that may have caused an unexpected death. Histology showed patchy interstitial myocardial T-lymphocytic infiltration, predominantly of the CD4 positive subset, associated with mild myocyte damage. Overall, autopsy findings indicated death due to acute arrhythmogenic cardiac failure. Thus, myocarditis can be a potentially lethal complication following mRNA-based anti-SARS-CoV-2 vaccination. Our findings may aid in adequately diagnosing unclear cases after vaccination and in establishing a timely diagnosis in vivo, thus, providing the framework for adequate monitoring and early treatment of severe clinical cases, according to Constantin Schwab et al., “Autopsy‑based histopathological characterization of myocarditis after anti‑SARS‑CoV‑2‑vaccination,” Clinical Research in Cardiology, 27 November 2022, https://doi.org/10.1007/s00392-022-02129-5, JIF 6.138 (top 28% journals in Cardiac & Cardiovascular Systems).
There has been a surge in COVID-19 vaccine–associated lymphadenopathy (LAD), including after the booster dose of vaccine. This can create diagnostic dilemmas in oncology patients as the relatively sudden LAD can mimic metastasis or cancer recurrence, at a risk of leading to additional but unnecessary anti-neoplastic therapy. Here we report the histopathologic features in a case of persistent LAD occurring in a patient with history of breast invasive ductal carcinoma which followed a COVID-19 vaccine booster. A needle core and then excisional biopsy showed atypical follicular hyperplasia with features that histologically and phenotypically could mimic follicular lymphoma, but the findings were ultimately interpreted to be reactive in nature and related temporally to COVID-19 vaccine. To our knowledge, this is the first case of an atypical lymphoproliferative lesion with features potentially mimicking lymphoma associated with COVID-19 vaccine, according to Ashish Patil et al., “Atypical follicular hyperplasia with light chain–restricted germinal centers after COVID‑19 booster: a diagnostic pitfall,” Virchows Archiv, 13 September 2022, https://doi.org/10.1007/s00428-022-03400-w, JIF 4.548 (top 28% journals in Pathology).
A novel cardiac disease identified as ”myocarditis after COVID-19 vaccination,” elsewhere as ”postvaccine myocarditis,” and perhaps in the future along the lines of ”vaccine-triggered, self-limiting, acute autoimmune myocarditis.” This potentially serious complication has been associated with serious harm, arguably most prominently through promotion of vaccine hesitancy, another complex mechanism underlying COVID19-mediated harm, as defined in Saidi A. Mohiddin et al., “Vaccine-Triggered Acute Autoimmune Myocarditis: Defining, Detecting, and Managing an Apparently Novel Condition,” Journal of the American Heart Association, 2022;11:e026873, https://doi.org/10.1161/JAHA.122.026873, JIF 6.107 (top 30% journals in Cardiac & Cardiovascular Systems).
A large sample size of 58 million individuals was studied. Myocarditis can be self-limiting, but some cases can advance to life-threatening conditions with associated heart failure, arrhythmias, or myocardial infarction. The pathophysiology of myocarditis in COVID-19 infection is thought to be related to direct viral injury to the cardiacmyocytes, but it is also proposed that there may be a component of cytokine storm syndrome. Similarly, mechanisms of myocarditis associated with COVID-19 vaccines include but are not limited to molecular mimicry, autoantibody formation, mRNA immune reactivity, trigger of preexisting dysregulated immune processes, and genetic predisposition, according to Navya Voleti et al., “Myocarditis in SARS-CoV-2 infection vs. COVID-19 vaccination: A systematic review and meta-analysis,” Frontiers in Cardiovascular Medicine, 9:951314, 29 August 2022, https://doi.org/10.3389/fcvm.2022.951314, JIF 5.848 (top 30% journals in Cardiac & Cardiovascular Systems).
Recently, an article by Seneff et al. entitled “Innate immunosuppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs” was published in Food and Chemical Toxicology (FCT). Here, we describe why this article, which contains unsubstantiated claims and misunderstandings such as “billions of lives are potentially at risk” with COVID-19 mRNA vaccines, is problematic and should be retracted. We report here our request to the editor of FCT to have our rebuttal published, unfortunately rejected after three rounds of reviewing, according to Jérôme Barrière et al., “Scientific Integrity Requires Publishing Rebuttals and Retracting Problematic Papers,” Stem Cell Reviews and Reports, 26 October 2022, https://doi.org/10.1007/s12015-022-10465-2, JIF 6.692 (top 25% journals in Medicine, Research & Experimental, top 31% journals in Cell & Tissue Engineering and top 32% journals in Cell Biology).
The interval between COVID-19 vaccination and transplanted corneal graft rejection ranged from 1 day to 6 weeks, according to Kenta Fujio et al., “Characteristics and Clinical Ocular Manifestations in Patients with Acute Corneal Graft Rejection after Receiving the COVID-19 Vaccine: A Systematic Review,” Journal of Clinical Medicine, 2022, 11, 4500, https://doi.org/10.3390/jcm11154500, JIF 4.964 (top 32% journals in Medicine, General & Internal).
Recently, The Lancet published a study on the effectiveness of COVID-19 vaccines and the waning of immunity with time. The study showed that immune function among vaccinated individuals 8 months after the administration of two doses of COVID-19 vaccine was lower than that among the unvaccinated individuals. According to European Medicines Agency recommendations, frequent COVID-19 booster shots could adversely affect the immune response and may not be feasible. The decrease in immunity can be caused by several factors such as N1-methylpseudouridine, the spike protein, lipid nanoparticles, antibody-dependent enhancement, and the original antigenic stimulus. These clinical alterations may explain the association reported between COVID-19 vaccination and shingles. As a safety measure, further booster vaccinations should be discontinued. In addition, the date of vaccination should be recorded in the medical record of patients. Several practical measures to prevent a decrease in immunity have been reported. These include limiting the use of non-steroidal anti-inflammatory drugs, including acetaminophen to maintain deep body temperature, appropriate use of antibiotics, smoking cessation, stress control, and limiting the use of lipid emulsions, including propofol, which may cause perioperative immunosuppression. In conclusion, COVID-19 vaccination is a major risk factor for infections in critically ill patients.Kenji Yamamoto et al., “Adverse effects of COVID‑19 vaccines and measures to prevent them,” Virology Journal (2022) 19:100, https://doi.org/10.1186/s12985-022-01831-0, JIF 5.916 (top 35% journals in Virology).
Myocarditis is consistently associated with BNT162b2, according to Shin-Jie Yong et al., “Rare Adverse Events Associated with BNT162b2 mRNA Vaccine (Pfizer-BioNTech): A Review of Large-Scale, Controlled Surveillance Studies,” Vaccines 2022, 10, 1067, 2 July 2022, https://doi.org/10.3390/vaccines10071067, JIF 4.961 (top 42% journals in Medicine, Research & Experimental and top 48% journals in Immunology).
Post-authorization, a wide spectrum of neurological complications is continuously being reported following COVID-19 vaccination. Neurological adverse events following vaccination are generally mild and transient, like fever and chills, headache, fatigue, myalgia and arthralgia, or local injection site effects like swelling, redness, or pain. The most devastating neurological post-vaccination complication is cerebral venous sinus thrombosis. Cerebral venous sinus is frequently reported in females of childbearing age, generally following adenovector-based vaccination. Another major neurological complication of concern is Bell’s palsy that was reported dominantly following mRNA vaccine administration. Acute transverse myelitis, acute disseminated encephalomyelitis, and acute demyelinating polyneuropathy are other unexpected neurological adverse events that occur as result of phenomenon of molecular mimicry. Reactivation of herpes zoster in many persons, following administration of mRNA vaccines, has been also recorded, according to Ravindra Kumar Garg et al., “Spectrum of neurological complications following COVID‑19 vaccination,” Neurological Sciences (2022) 43:3–40, https://doi.org/10.1007/s10072-021-05662-9, JIF 3.830 (top 47% journals in Clinical Neurology and 50% journals in Neurosciences).
Cerebral venous thrombosis (CVT), a rare thrombotic event that can cause serious neurologic deficits, has been reported after some ChAdOx1 nCoV-19 vaccinations against coronavirus disease 2019 (COVID-19). However, there are few reports of associations between COVID-19 mRNA vaccination and CVT, according to Jin Park et al., “Association of Cerebral Venous Thrombosis with mRNA COVID-19 Vaccines: A Disproportionality Analysis of the World Health Organization Pharmacovigilance Database,” Vaccines 2022, 10, 799, https://doi.org/10.3390/vaccines10050799, JIF 4.961 (top 42% journals in Medicine, Research & Experimental and top 48% journals in Immunology).
Histopathological analyses of the brain of the deceased man uncovered previously unsuspected findings, including acute vasculitis (predominantly lymphocytic) as well as multifocal necrotizing encephalitis of unknown etiology with pronounced inflammation including glial and lymphocytic reaction. In the heart, signs of chronic cardiomyopathy as well as mild acute lympho-histiocytic myocarditis and vasculitis were present. Although there was no history of COVID-19 for this patient, immunohistochemistry for SARS-CoV-2 antigens (spike and nucleocapsid proteins) was performed. Surprisingly, only spike protein but no nucleocapsid protein could be detected within the foci of inflammation in both the brain and the heart, particularly in the endothelial cells of small blood vessels. Since no nucleocapsid protein could be detected, the presence of spike protein must be ascribed to vaccination (three COVID-19 vaccinations) rather than to viral infection, according to Michael Mörz et al., “A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against COVID-19,” Vaccines 2022, 10, 1651, https://doi.org/10.3390/vaccines10101651, JIF 4.961 (top 42% journals in Medicine, Research & Experimental and top 48% journals in Immunology).
For Doses 1 and 2 of ChAdOx1 and Dose 1 of BNT162b2, VE/rVE reached zero by approximately Days 60–80 and then went negative. By Day 70, VE/rVE was –25% (95% CI: –80 to 14) and 10% (95% CI: –32 to 39) for Doses 1 and 2 of ChAdOx1, respectively, and 42% (95% CI: 9 to 64) and 53% (95% CI: 26 to 70) for Doses 1 and 2 of BNT162b2, respectively. rVE for Dose 2 of BNT162b2 remained above zero throughout and reached 46% (95% CI: 13 to 67) after 98 days of follow-up, according to Steven Kerr et al., “Waning of first- and second-dose ChAdOx1 and BNT162b2 COVID-19 vaccinations: a pooled target trial study of 12.9 million individuals in England, Northern Ireland, Scotland and Wales,” International Journal of Epidemiology, 2022, 1–10, https://doi.org/10.1093/ije/dyac199, JIF 9.685 (top 57% journals in Public, Environmental & Occupational Health).
Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2, respectively. Combined, the mRNA vaccines were associated with an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated; risk ratio 1.43. The Pfizer trial exhibited a 36% higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated; risk ratio 1.36. The Moderna trial exhibited a 6% higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000; risk ratio 1.06. Combined, there was a 16% higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2; risk ratio 1.16, according to Joseph Fraiman et al., “Serious adverse events of special interest following mRNA vaccination in randomized trials,” Vaccine 40 (2022) 5798–5805, https://doi.org/10.1016/j.vaccine.2022.08.036, JIF 4.169 (top 58% journals in Immunology and top 52% journals in Medicine, Research & Experimental).
Encephalopathy related to the Moderna COVID-19 vaccine should be acknowledged as an adverse effect of the Moderna COVID-19 vaccine, according to Rizaldy Taslim Pinzon et al., “Acute dizziness and mental alteration associated with Moderna COVID‑19 vaccine: a case report,” BMC Neurology (2022) 22:322, https://doi.org/10.1186/s12883-022-02834-8, JIF 2.903 (top 65% journals in Clinical Neurology).
A total of 32 cases were identified, with female predominance (68.8%) and median age of 44 years. Eleven cases were reported after Pfizer vaccine, 8 following AstraZeneca vaccine, 6 following Moderna, 5 following Sinovac/ Sinopharm vaccines, and one following each of Sputnik and Johnson&Johnson vaccines. The majority of cases (71.8%) occurred after the first dose of the vaccine, with neurological symptoms manifesting after a median of 9 days. The most common reported presentations were transverse myelitis (12/32) and MS-like pictures (first diagnosis or a relapse) in another 12/32 cases, followed by ADEM- like (5/32), and NMOSD- like (3/32) presentations. History of a previous immune-mediated disease was reported in 17/32 (53.1%) cases. The mRNA-based vaccines resulted in the greatest number of demyelinating syndromes (17/32), followed by viral vector vaccines (10/32), and inactivated vaccines (5/32). Most MS-like episodes (9/12) were triggered by mRNA-based vaccines, while TM occurred following both viral vector and mRNA-based vaccines. Management included high dose methylprednisolone, PLEX, IVIg, or a combination of those, with a favorable outcome in the majority of case; marked/complete improvement (25/32) or stabilized/ partial recovery in the remaining cases. Conclusion: This systematic review identified few cases of CNS demyelination following all types of approved COVID-19 vaccines so far. Clinical presentation was heterogenous, mainly following the first dose, however, half of the reported cases had a history of immune-mediated disease. Favorable outcome was observed in most cases. We suggest long-term post-marketing surveillance for these cases, to assess for causality, and ensure the safety of COVID-19 vaccines, according to Ismail Ibrahim Ismail et al., “A systematic review of cases of CNS demyelination following COVID-19 vaccination,” Journal of Neuroimmunology, Volume 362, 577765, 9 November 2021, https://doi.org/10.1016/j.jneuroim.2021.577765, JIF 3.221 (top 66% journals in Neurosciences and top 76% journals in Immunology).
A case of acute cervical dystonia occurring after the first dose of the BNT162b2 COVID-19 vaccine is attributed to the vaccine due to the temporal relationship. The likely mechanism is autoimmune, according to Hussein A. Algahtani et al., “Acute cervical dystonia following the BNT162b2 mRNA COVID-19 vaccine,” Clinical Neurology and Neurosurgery 218 (2022) 107304, https://doi.org/10.1016/j.clineuro.2022.107304, JIF 1.885 (top 69% journals in Surgery and top 86% journals in Clinical Neurology).
Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reversfe-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure, according to Markus Aldén et al., “Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line,” Current Issues in Molecular Biology 2022, 44, 1115–1126, https://doi.org/10.3390/cimb44030073, JIF 2.976 (top 73% journals in Biochemistry & Molecular Biology).
A 60-year-old Japanese woman was hospitalized for cardiogenic shock 24 days after receiving the second dose of the COVID-19 BNT162b2 vaccine. Impella-CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were immediately initiated along with inotropic support and steroid pulse therapy, as an endomyocardial biopsy specimen showed myocarditis. Three weeks later, her cardiac function had recovered, and she was discharged. An immune response associated with the presence of spike protein in cardiac myocytes may be related to myocarditis in the present case because of positive immunostaining for severe acute respiratory syndrome coronavirus 2 spike protein and C4d in the myocardium, according to Hiroaki Kawano et al., “Fulminant Myocarditis 24 Days after Coronavirus Disease Messenger Ribonucleic Acid Vaccination: A Case Report,” Internal Medicine, The Japanese Society of Internal Medicine, https://doi.org/10.2169/internalmedicine.9800-22, JIF 1.282 (top 82% journals in Medicine, General & Internal).
mRNA vaccines including Pfizer BioNTech and Moderna have categorically been considered safe when it comes to preventing COVID-19. However, there is still a small associated risk of thromboembolic phenomenon including venous sinus thrombosis with it and our case report highlights one. We describe a patient who developed severe progressive headache, tinnitus and visual disturbance symptoms post-Pfizer-SARS-CoV-2 vaccination. His medical history included essential tremors, hypertension, type 2 diabetes mellitus, chronic kidney disease stage 3, anxiety, depression and long-term catheterisation. Systemic examination revealed hypotonia, generalised reduced power and central diplopia along with peripheral visual field defect in the left eye. He was extensively investigated, the COVID-19 PCR test was negative and all routine blood tests were in the normal range except a marginally raised D-dimer of 779 ng/mL. CT head was unremarkable. He was also tested for myasthenia gravis; however, acetylcholine receptors antibodies were negative and nerve conduction studies were normal. Subsequent MRI of the brain with venography confirmed venous sinus thrombosis. A 24-hour Holter monitoring test did not reveal any cardiac rate or rhythm abnormality, according to Muhammad Imran Ahmad Qureshi et al., “Venous sinus thrombosis after the first dose of Pfizer BioNTech vaccine,” BMJ Case Reports 2022;15:e247493, https://doi.org/10.1136/bcr-2021-247493, JIF N/A.
Because vaccines have been fast-tracked for emergency use, the short and long-term safety profile has been an area of concern.The literature review yielded several neurological complications post vaccination, including cerebral sinus venous thrombosis, transverse myelitis, Guillain-Barré Syndrome and optic neuritis, to name a few.Shitiz Sriwastava et al., “Spectrum of Neuroimaging Findings in Post-COVID-19 Vaccination: A Case Series and Review of Literature,” Neurology International 2021, 13, 622–639, https://doi.org/10.3390/neurolint13040061, JIF N/A.
Besides the common and usually mild side effects of the authorized vaccines, some rare, major adverse reactions are increasingly being reported worldwide during the post marketing surveillance phase of vaccines’ circulation, such as anaphylaxis, vaccine-induced thrombotic thrombocytopenia, myopericarditis and Guillain-Barr´e syndrome.Paraskevi C. Fragkou et al., “Serious complications of COVID-19 vaccines: A mini-review,” Metabolism Open 12 (2021) 100145, https://doi.org/10.1016/j.metop.2021.100145, JIF N/A.
The pathogenesis of mRNA-vaccine associated myocarditis has not yet been elucidated, although a number of mechanisms have been proposed, typically implicating the administered Sprotein mRNA and likely mediated through an autoimmune mechanism. Nonetheless, other mechanisms may be implicated given the fact that myocarditis cases are very rarely observed among recipients of non mRNA vaccines. The recent observation of a similar adverse event in a recipient of the non-mRNA, peptide-based NVXCoV2373 in the frame of a phase III clinical trial with 7020 participants in the active treatment arm raises the question whether the lipid nanoparticle sheath, which is a common structural component of these platforms could be implicated in the pathogenesis of vaccine-induced myocarditis, according to Dimitrios Tsilingiris et al., “Potential implications of lipid nanoparticles in the pathogenesis of myocarditis associated with the use of mRNA vaccines against SARS-CoV-2,” Metabolism Open 13 (2022) 100159, https://doi.org/10.1016/j.metop.2021.100159, JIF N/A.
Several cases of myocarditis and pericarditis have been reported after mRNA COVID-19 vaccination. Interestingly, most cases were seen in male adolescents and young adults, commonly after 3-4 days of the second dose of mRNA vaccine. The vaccine contains the viral spike glycoprotein in the nucleoside-modified mRNA of the coronavirus that activates the proinflammatory cascades and immunological pathways, which can cause myocarditis and pericarditis. Here we report a case of a middle-aged Caucasian male who presented with progressive dyspnea, fever, and chills seven days after the second dose of the COVID-19 vaccine. He was found to have pericarditis with massive hemorrhagic pericardial effusion, large bilateral pleural effusions, circulatory shock, and cardiac arrhythmia. Our case report describes a correlation between mRNA COVID-19 vaccine and pericarditis, suggesting the importance of pharmacovigilance and reporting of adverse outcomes and encourages a high index of clinical suspicion in physicians to facilitate early diagnosis and interventions, according to Krunalkumar Patel et al., “COVID-19 mRNA Vaccine Induced Pericarditis With Large Pericardial Effusion Followed by New-Onset Arrhythmia,” Cureus 14(5): e24699, https://doi.org/10.7759/cureus.24699, JIF N/A.
High COVID-19 vaccination rates were expected to reduce transmission of SARS-CoV-2 in populations by reducing the number of possible sources for transmission and thereby to reduce the burden of COVID-19 disease. Recent data, however, indicate that the epidemiological relevance of COVID-19 vaccinated individuals is increasing. In the UK it was described that secondary attack rates among household contacts exposed to fully vaccinated index cases was similar to household contacts exposed to unvaccinated index cases (25% for vaccinated vs. 23% for unvaccinated). 12 of 31 infections in fully vaccinated household contacts (39%) arose from fully vaccinated epidemiologically linked index cases. Peak viral load did not differ by vaccination status or variant type. In Germany, the rate of symptomatic COVID-19 cases among the fully vaccinated (“breakthrough infections”) is reported weekly since 21. July 2021 and was 16.9% at that time among patients of 60 years and older, according to Günter Kampf, “The epidemiological relevance of the COVID-19-vaccinated population is increasing,” The Lancet Regional Health - Europe 11 (2021) 100272, https://doi.org/10.1016/j.lanepe.2021.100272, JIF N/A.
We report a case of multiple attacks of transient monocular visual loss in a previously healthy middle-aged man two weeks after Pfizer-BioNTech COVID-19 vaccination. TVL attacks were described as sudden and painless complete visual loss, lasting about one minute, followed by a full recovery. He presented several non-simultaneous attacks in both eyes, 16 in the right eye, and 2 in the left eye on the same day, fifteen days after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine, according to Leonardo Provetti Cunha et al., “Multiple attacks of transient monocular visual loss in a previously healthy man: a possible complication after COVID‑19 vaccination?” International Journal of Retina and Vitreous (2022) 8:43, https://doi.org/10.1186/s40942-022-00393-1, JIF N/A.
Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds, according to Mie Agermose Gram et al., “Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha, Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study,” PLOS Medicine, September 1, 2022, https://doi.org/10.1371/journal.pmed.1003992, JIF N/A.
In our population of recreational endurance athletes, booster vaccination with the BNT162b2 mRNA vaccine resulted in a statistically significant decrease in VO2max 7 days after vaccination, according to Hielko Miljoen et al., “Effect of BNT162b2 mRNA booster vaccination on VO2max in recreational athletes: A prospective cohort study,” Health Science Reports 2022;5:e929, https://doi.org/10.1002/hsr2.929, JIF N/A.