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Home My WebLink About2022_11_16 RRennebohm_COVID NeuropathologyFrom:Rob Rennebohm To:Tom Locke; Allison Berry; Board of Health Subject:Neuropathology associated with COVID vaccination Date:Wednesday, November 16, 2022 9:25:59 PM Attachments:COVID ANALYSIS #139 Dr. Mörz Original Article.pdf COVID ANALYSIS #140 Dr. Mörz Article-- Summary-Commentary by RR.docx ALERT:BE CAUTIOUS This email originated outside the organization. Do not open attachments or click on links if you are not expecting them. Dear Dr. Berry, Dr. Locke, and members of the BOH, As a pediatrician/pediatric rheumatologist (formerly at Cleveland Clinic) and as a resident of Port Townsend during the first year the pandemic, I have been deeply concerned about thewisdom and safety of the COVID mass vaccination campaign, both nationally and in Jefferson County---especially the campaign to vaccinate infants and toddlers with the mRNA vaccines. Policies regarding the COVID pandemic should be based on a deep scientific understanding ofthe immunology, virology, vaccinology, evolutionary biology, and the glycosylation biology of the COVID situation. This includes a deep understanding of the immunopathology that isemerging among the COVID-vaccinated---particularly the neuro-immunopathology (which was my specialty at Cleveland Clinic). I have attached an extremely important article, recently published (in the peer-reviewedjournal Vaccines) by an excellent pathologist in Germany (Dr. Michael Morz). It provides compelling and sobering evidence that spike protein produced by the mRNA vaccines can endup in the endothelial cell lining of capillaries in the brain and heart; that this is closely associated with CNS vasculitis, necrotizing encephalitis, and myocarditis; and that thesevaccine-associated phenomena can be fatal. . I have attached the Morz article for your review. I have also attached a Summary (for the General Public) and Commentary on the Morz Article that I have written to help non-physicians to more easily understand the Morz article and its significance. I have some questions for all of you: What is your reaction to the Morz article?Do you think the COVID vaccine is responsible for the neuropathology and heart pathology documented by Dr. Morz?How worried are you about the possibility of vaccine-related neuro-immunopathology occurring in some who receive the COVID mRNA vaccine?To what extent do you, as the COVID health experts in Jefferson County, feel obligated to call this article to the attention of the public in Jefferson County?Should discussion of this article be part of the informed consent process? Do you think the Morz article should cause hesitancy about continuing the COVIDvaccination campaign? Is the Jefferson County Board of Health encouraging COVID vaccination of infants andchildren? I would appreciate hearing back from you within 2 weeks (i.e. by Nov 30), if possible. Finally, would you be interested in organizing a Town Hall meeting in PT to discuss thisarticle---so that the public could learn about the article and its significance? I would be happy to be a guest speaker at such a meeting. With Warm Regards,Rob Rennebohm, MD Citation:Mörz, M. 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 Academic Editor: Sung Ryul Shim Received: 31 August 2022 Accepted: 27 September 2022 Published: 1 October 2022 Publisher’s Note:MDPI stays neutral with regard to jurisdictional claims in published maps and institutional afﬁl- iations. Copyright:© 2022 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Case Report ACaseReport: MultifocalNecrotizingEncephalitisandMyocarditis after BNT162b2 mRNA Vaccination against COVID-19 Michael Mörz Institute of Pathology ’Georg Schmorl’, The Municipal Hospital Dresden-Friedrichstadt, Friedrichstrasse 41, 01067 Dresden, Germany; michael.moerz@klinikum-dresden.de Abstract:The current report presents the case of a 76-year-old man with Parkinson’s disease (PD) who died three weeks after receiving his third COVID-19 vaccination. The patient was ﬁrst vaccinated in May 2021 with the ChAdOx1 nCov-19 vector vaccine, followed by two doses of the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to ambiguous clinical signs before death. PD was conﬁrmed by post-mortem examinations. Furthermore, signs of aspiration pneumonia and systemic arteriosclerosis were evident. However, histopathological analyses of the brain 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 rather than to viral infection. The ﬁndings corroborate previous reports of encephalitis and myocarditis caused by gene-based COVID-19 vaccines. Keywords:COVID-19 vaccination; necrotizing encephalitis; myocarditis; detection of spike protein; detection of nucleocapsid protein; autopsy 1. Introduction The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 with the subsequent worldwide spread of COVID-19 gave rise to a perceived need for halting the progress of the COVID-19 pandemic through the rapid development and deployment of vaccines. Recent advances in genomics facilitated gene-based strategies for creating these novel vaccines, including DNA-based nonreplicating viral vectors, and mRNA-based vaccines, which were furthermore developed on an aggressively shortened timeline [1–4]. The WHO Emergency Use Listing Procedure (EUL), which determines the acceptabil- ity of medicinal products based on evidence of quality, safety, efﬁcacy, and performance [5], permitted these vaccines to be marketed as soon as 1–2 years after development had begun. Published results of the phase 3 clinical trials described only a few severe side effects [2,6–8]. However, it has since become clear that severe and even fatal adverse events may occur; these include in particular cardiovascular and neurological manifestations [9–13]. Clini- cians should take note of such case reports for the sake of early detection and management of such adverse events among their patients. In addition, a thorough post-mortem ex- amination of deaths in connection with COVID-19 vaccination should be considered in ambiguouscircumstances, includinghistology. Thisreportpresentsthecaseofasenioraged 76 years old, who had received three doses overall of two different COVID-19 vaccines, Vaccines 2022,10, 1651.https://doi.org/10.3390/vaccines10101651 https://www.mdpi.com/journal/vaccines Vaccines 2022,10, 1651 2 of 17 and who died three weeks after the second dose of the mRNA-BNT162b-vaccine. Autopsy and histology revealed unexpected necrotizing encephalitis and mild myocarditis with pathological changes in small blood vessels. A causal connection of these ﬁndings to the preceding COVID-19 vaccination was established by immunohistochemical demon- stration of SARS-CoV-2 spike protein. The methodology introduced in this study should be useful for distinguishing between causation by COVID-19 vaccination or infection in ambiguous cases. 2. Materials and Methods 2.1. Routine Histology Formalin-ﬁxed tissues were routinely processsed and parafﬁn-embedded tissues were cut into 5 m sections and stained with hematoxylin and eosin (H&E) for histopathologi- cal examination. 2.2. Immunohistochemistry Immunohistochemical staining was performed on the heart and brain, using a fully automated immunostaining system (Ventana Benchmark, Roche). An antigen retrieval (Ultra CC1, Roche Ventana) was used for every antibody. The target antigens and dilution factors for the antibodies used are summarized in Table 1. Incubation with the primary antibody was carried out for 30 min in each case. Tissues from SARS-CoV-2-positive COVID-19 patients were used as a control for the antibodies against SARS-CoV-2-spike and nucleocapsid (Figure 1). Cultured cells that had been transfected in vitro (see hereafter) served as a positive control for the detection of vaccine-induced spike protein expression and as a negative control for the detection of nucleocapsid protein. The slides were examined with a light microscope (Nikon ECLIPSE 80i) and representative images were captured by the camera system Motic®Europe Motic MP3. Table 1.Primary antibodies used for immunohistochemistry. Tissue sections were incubated 30 min with the antibody in question, diluted as stated in the table. Target Antigen Manufacturer Clone Dilution Incubation Time CD3 (expressed by T-Lymphocytes) cytomed ZM-45 1:200 30 min CD68 (expressed by monocytic cells) DAKO PG-M1 1:100 30 min SARS-CoV-2-Spike subunit 1 ProSci 9083 1:500 30 min SARS-CoV-2-Nucleocapsid ProSci 35–720 1:500 30 min Vaccines 2022, 10, 1651 2 of 17 tion, a thorough post-mortem examination of deaths in connection with COVID-19 vac- cination should be considered in ambiguous circumstances, including histology. This report presents the case of a senior aged 76 years old, who had received three doses overall of two different COVID-19 vaccines, and who died three weeks after the second dose of the mRNA-BNT162b-vaccine. Autopsy and histology revealed unexpected ne- crotizing encephalitis and mild myocarditis with pathological changes in small blood vessels. A causal connection of these findings to the preceding COVID-19 vaccination was established by immunohistochemical demonstration of SARS-CoV-2 spike protein. The methodology introduced in this study should be useful for distinguishing between causation by COVID-19 vaccination or infection in ambiguous cases. 2. Materials and Methods 2.1. Routine Histology Formalin-fixed tissues were routinely processsed and paraffin-embedded tissues were cut into 5 μm sections and stained with hematoxylin and eosin (H&E) for histo- pathological examination. 2.2. Immunohistochemistry Immunohistochemical staining was performed on the heart and brain, using a fully automated immunostaining system (Ventana Benchmark, Roche). An antigen retrieval (Ultra CC1, Roche Ventana) was used for every antibody. The target antigens and dilu- tion factors for the antibodies used are summarized in Table 1. Incubation with the pri- mary antibody was carried out for 30 min in each case. Tissues from SARS-CoV-2-positive COVID-19 patients were used as a control for the antibodies against SARS-CoV-2-spike and nucleocapsid (Figure 1). Cultured cells that had been transfected in vitro (see hereafter) served as a positive control for the detection of vac- cine-induced spike protein expression and as a negative control for the detection of nu- cleocapsid protein. The slides were examined with a light microscope (Nikon ECLIPSE 80i) and representative images were captured by the camera system Motic® Europe Motic MP3. Table 1. Primary antibodies used for immunohistochemistry. Tissue sections were incubated 30 min with the antibody in question, diluted as stated in the table. Target Antigen Manufacturer Clone Dilution Incubation Time CD3 (expressed by T-Lymphocytes) cytomed ZM-45 1:200 30 min CD68 (expressed by monocytic cells) DAKO PG-M1 1:100 30 min SARS-CoV-2-Spike subunit 1 ProSci 9083 1:500 30 min SARS-CoV-2-Nucleocapsid ProSci 35–720 1:500 30 min Figure 1.Nasal smear from a person with acute symptomatic SARS-CoV-2-infection (conﬁrmed by PCR). Note the presence of ciliated epithelium. Immunohistochemistry for two SARS-CoV-2 antigens (spike and nucleocapsid protein) revealed a positive reaction for both as to be expected after infection. (a) Detection of the spike protein. Positive control for spike subunit 1 SARS-CoV-2 protein detection. Several Vaccines 2022,10, 1651 3 of 17 ciliated epithelia of the nasal mucosa show brownish granular deposits of DAB (red arrow). Com- pared to nucleocapsid, the DAB-granules are fewer and less densely packed granular deposits of DAB. (b) Detection of nucleocapsid protein. Positive control for nucleocapsid SARS-CoV-2 protein detection. Several ciliated epithelia of the nasal mucosa show dense brownish granular deposits of DAB in immunohistochemistry (examples red arrows). Compared to spike detection, the granules of DAB are ﬁner and more densely packed. Magniﬁcation: 400x. 2.3. Preparation of Positive Control Samples for the Immunohistochemical Detection of the Vaccine-Induced Spike Protein Cell culture and transfection: Ovarian cancer cell lines (OVCAR-3 and SK-OV3, CSL cell Lines Service, Heidelberg, Germany) were grown to 70% conﬂuence in ﬂat bottom 75 cm 2 cell culture ﬂasks (Cell star) in DMEM/HAMS-F12 medium supplemented with Glutamax (Sigma-Aldrich, St. Louis, MO, USA), 10% FCS (Gibco, Shanghai, China) and Gentamycin (ﬁnal concentration 20 g/mL, Gibco), at 37 C, 5% CO2 in a humidiﬁed cell incubator. For transfection, the medium was completely removed, and cells were incubated for 1 h with 2 mL of fresh medium containing the injection solutions directly from the original bottles, diluted 1:500 in the case of BNT162b2 (Pﬁzer/Biotech), and 1:100 in cases of mRNA-1273 (Moderna), Vaxzevria (AstraZeneca), and Jansen (COVID-19 vaccine Jansen). Then, another 15 mL of fresh medium was added to the cell cultures and cells were grown to conﬂuence for another 3 days. Preparation of tissue blocks from transfected cells: The cell culture medium was removed from transfected cells, and the monolayer was washed twice with PBS, then trypsinized by adding 1 mL of 0.25% Trypsin-EDTA (Gibco), harvested with 10 mL of PBS/10% FCS, and washed 2 with PBS and centrifugation at 280 g for 10 min each. Cell pellets were ﬁxed overnight in 2 mL in PBS/4% Formalin at 8 C and then washed in PBS once. The cell pellets remaining after centrifugation were suspended in 200 L PBS each, mixed with 400 L 2% agarose in PBS solution (precooled to around 40 C), and immediately transferred to small (1 cm) dishes for ﬁxation. The ﬁxed and agarose- embedded cell pellets were stored in 4% Formalin/PBS till subjection to routine parafﬁn embedding in parallel to tissue samples. 2.4. Case Presentation and Description 2.4.1. Clinical History This report presents the case of a 76-year-old male with a history of Parkinson’s disease (PD) who passed away three weeks after his third COVID-19 vaccination. On the day of his ﬁrst vaccination in May 2021 (ChAdOx1 nCov-19 vector vaccine), he experienced pronounced cardiovascular side effects, for which he repeatedly had to consult his doctor. AfterthesecondvaccinationinJuly2021(BNT162b2mRNAvaccine/Comirnaty), thefamily noted obvious behavioral and psychological changes (e.g., he did not want to be touched anymore and experienced increased anxiety, lethargy, and social withdrawal even from close family members). Furthermore, there was a striking worsening of his PD symptoms, which led to severe motor impairment and a recurrent need for wheelchair support. He never fully recovered from these side effects after the ﬁrst two vaccinations but still got another vaccination in December 2021. Two weeks after the third vaccination (second vaccination with BNT162b2), he suddenly collapsed while taking his dinner. Remarkably, he did not show coughing or any signs of food aspiration but just fell down silently. He recovered from this more or less, but one week later, he again suddenly collapsed silently while taking his meal. The emergency unit was called, and after successful, but prolonged resuscitation attempts (over one hour), he was transferred to the hospital and directly put into an artiﬁcial coma but died shortly thereafter. The clinical diagnosis was death due to aspiration pneumonia. According to his family, there was no history of a clinical or laboratory diagnosis of COVID-19 in the past. Vaccines 2022,10, 1651 4 of 17 2.4.2. Autopsy The autopsy was requested and consented to by the family of the patient because of the ambiguityofsymptomsbeforehisdeath. Theautopsywasperformedaccordingtostandard procedures including macroscopic and microscopic investigation. Gross brain tissue was prepared for histological examination including the brain (frontal cortex, Substantia nigra, and Nucleus ruber) as well as the heart (left and right ventricular cardiac tissue). 3. Results 3.1. Autopsy Findings Anatomical Speciﬁcations: Body weight, height, and speciﬁcations of body organs were summarized in Table 2. Table 2.Anatomical Speciﬁcations. Item Measure Body weight 60 kg Hight 175 cm Heart weight 410 g Brain weight 1560 g Liver weight 1500 g Brain: A macroscopic examination of brain tissue revealed a circumscribed segmen- tal cerebral parenchymal necrosis at the site of the right hippocampus. Substantia nigra showed a loss of pigmented neurons. Microscopically, several areas with lacunar necrosis were detected with inﬂammatory debris reaction on the left frontal side (Figure 2). Stain- ing of Nucleus ruber with H&E showed neuronal cell death, microglia, and lymphocyte inﬁltration (Figure 3). Furthermore, there were microglial and lymphocytic reactions as well as predominantly lymphocytic vasculitis, sometimes with mixed inﬁltrates includ- ing neutrophilic granulocytes (Figure 4) in the frontal cortex, paraventricular, Substantia nigra, and Nucleus ruber on both sides. In some places with inﬂammatory changes in brain capillaries, there were also signs of apoptotic cell death within the endothelium (Figure 4). Meninges’ ﬁndings were unremarkable. The collective ﬁndings were sugges- tive of multifocal necrotizing encephalitis. Furthermore, chronic arteriosclerotic lesions of varying degrees were noted in large brain vessels, which are described in detail in section “Vascular system”. Parkinson’s disease (PD): Macroscopic and histological examination of brain tis- sue revealed bilateral pallor of the substantia nigra with loss of pigmented neurons. In addition, pigment-storing macrophages as well as scattered neuronal necrosis with glial debris reaction were noted. These ﬁndings were suggestive of PD, conﬁrming the clinical diagnosis. Thoracic cavity: An examination of the chest showed a funnel-shaped chest with serial rib fractures (extending from the second to ﬁfth ribs on the right, and from the second to sixth ribs on the left); which is a common picture of a patient who underwent cardiopulmonary resuscitation. An endotracheal tube was properly inserted. There was evidence of regular placement of a central venous catheter in the left femoral vein. There was evidence of regular placement of an arterial catheter in the left radial artery. The urinary catheter was inserted as well. There was a 9 cm long skin scar on the front of the right shoulder. Vaccines 2022,10, 1651 5 of 17Vaccines 2022, 10, 1651 6 of 17 Figure 2. Frontal brain. Already in the overview image (a), prominent vacuolations with increased parenchymal cellularity are evident, indicative of degenerative and inflammatory processes. At higher magnification (b), acute brain damage is visible with diffuse and zonal neuronal and glial cell death, activation of microglia, and inflammatory infiltration by granulocytes and lymphocytes. 1: neuronal deaths (cells with red cytoplasm); 2: microglial proliferation; 3: lymphocytes. H&E stain. Magnification 40× (a) and 200× (b). Figure 3. Brain, Nucleus ruber. In the overview image (a), note pronounced focal necrosis with increased cellularity, indicative of ongoing inflammation and glial reaction. At higher magnification (b), death of neuronal cells is evident and associated with an increased number of glial cells. Note activation of microglia and presence of inflammatory cell infiltrates, predominantly lymphocytic. 1: neuronal death with hypereosinophilia and destruction of cell nucleus with signs of karyolysis (nuclear content being distributed into the cytoplasm); 2: microglia (example); 3: lymphocyte (example). H&E stain. Magnification 40× (a) and 400× (b). Figure 2.Frontal brain. Already in the overview image (a), prominent vacuolations with in- creased parenchymal cellularity are evident, indicative of degenerative and inﬂammatory processes. At higher magniﬁcation (b), acute brain damage is visible with diffuse and zonal neuronal and glial cell death, activation of microglia, and inﬂammatory inﬁltration by granulocytes and lymphocytes. 1: neuronal deaths (cells with red cytoplasm); 2: microglial proliferation; 3: lymphocytes. H&E stain. Magniﬁcation 40 (a) and 200 (b). Vaccines 2022, 10, 1651 6 of 17 Figure 2. Frontal brain. Already in the overview image (a), prominent vacuolations with increased parenchymal cellularity are evident, indicative of degenerative and inflammatory processes. At higher magnification (b), acute brain damage is visible with diffuse and zonal neuronal and glial cell death, activation of microglia, and inflammatory infiltration by granulocytes and lymphocytes. 1: neuronal deaths (cells with red cytoplasm); 2: microglial proliferation; 3: lymphocytes. H&E stain. Magnification 40× (a) and 200× (b). Figure 3. Brain, Nucleus ruber. In the overview image (a), note pronounced focal necrosis with increased cellularity, indicative of ongoing inflammation and glial reaction. At higher magnification (b), death of neuronal cells is evident and associated with an increased number of glial cells. Note activation of microglia and presence of inflammatory cell infiltrates, predominantly lymphocytic. 1: neuronal death with hypereosinophilia and destruction of cell nucleus with signs of karyolysis (nuclear content being distributed into the cytoplasm); 2: microglia (example); 3: lymphocyte (example). H&E stain. Magnification 40× (a) and 400× (b). Figure 3.Brain, Nucleus ruber. In the overview image (a), note pronounced focal necrosis with increased cellularity, indicative of ongoing inﬂammation and glial reaction. At higher magniﬁcation (b), death of neuronal cells is evident and associated with an increased number of glial cells. Note activation of microglia and presence of inﬂammatory cell inﬁltrates, predominantly lymphocytic. 1: neuronal death with hypereosinophilia and destruction of cell nucleus with signs of karyolysis (nuclear content being distributed into the cytoplasm); 2: microglia (example); 3: lymphocyte (example). H&E stain. Magniﬁcation 40 (a) and 400 (b). Vaccines 2022,10, 1651 6 of 17Vaccines 2022, 10, 1651 7 of 17 Figure 4. Brain, periventricular vasculitis. Cross section through a capillary vessel showing prominent signs of vasculitis. The endothelial cells (5) show swelling and vacuolation and are increased in number with enlargement of nuclei, indicative for activation. Furthermore, presence of mixed inflammatory cell infiltrates within the endothelial layer, consisting of lymphocytes (1), granulocytes (2), and histiocytes (4). The adjacent brain tissue also shows signs of inflammation (encephalitis) with presence of lymphocytes as well and activated microglia (3). H&E. Magnification: 200× (a) and 400× (b). Figure4.Brain, periventricular vasculitis. Crosssection through acapillaryvessel showingprominent signs of vasculitis. The endothelial cells (5) show swelling and vacuolation and are increased in number with enlargement of nuclei, indicative for activation. Furthermore, presence of mixed inﬂammatory cell inﬁltrates within the endothelial layer, consisting of lymphocytes (1), granulocytes (2), and histiocytes (4). The adjacent brain tissue also shows signs of inﬂammation (encephalitis) with presence of lymphocytes as well and activated microglia (3). H&E. Magniﬁcation: 200 (a) and 400 (b). Lungs: Macroscopical lung examination revealed cloudy secretion and purulent spots with notably brittle parenchyma. The pleura showed bilateral serous effusion, amounting to 450 mL of ﬂuid on the right side and 400 mL on the left side. Bilateral mucopurulent tracheobronchitis was evident with copious purulent secretion in the trachea and bronchi. Bilateral chronic destructive pulmonary emphysema was detected. Bilateral bronchopneu- monia was noted in the lower lung lobes at multiple stages of development and lobe-ﬁlling with secretions and fragile parenchyma. Furthermore, chronic arteriosclerotic lesions of varying degrees were noted, which are described in detail in the section “Vascular system”. Heart: Macroscopic cardiac examination revealed manifestations of acute and chronic cardiovascular insufﬁciency, including ectasia of the atria and ventricles. Furthermore, left ventricular hypertrophy was noted (wall thickness: 18 mm, heart weight: 410 g, body weight: 60 kg, height: 1.75 m). There was evidence of tissue congestion (presumably due to cardiac insufﬁciency) in the form of pulmonary edema, cerebral edema, brain congestion, chronic hepatic congestion, renal tissue edema, and pituitary tissue edema. Moreover, there was evidence of shock kidney disorder. Histological examination of the heart revealed mild myocarditis with ﬁne-spotted ﬁbrosis and lympho-histiocytic inﬁltration (Figure 5). Furthermore, there were chronic arteriosclerotic lesions of varying degrees, which are described in detail under “Vascular system”. In addition to these, there were more acute myocardial and vascular changes in the heart. They consisted of mild signs of myocarditis, characterized by inﬁltrations with foamy histiocytes and lymphocytes as well as hypereosinophilia and some hypercontraction of cardiomyocytes. Furthermore, mild acute vascular changes were observed in the capillaries and other small blood vessels of the heart. They consisted of mild lympho-histiocytic inﬁltrates, prominent endothelial swelling and vacuolation, multifocal myocytic degeneration and coagulation necrosis as well as karyopyknosis of single endothelial cells and vascular muscle cells (Figure 5). Occasionally, adhering plasma coagulates/ﬁbrin clots were present on the endothelial surface, indicative of endothelial damage (Figure 5). Vaccines 2022,10, 1651 7 of 17 Vaccines 2022, 10, 1651 7 of 17 Figure 4. Brain, periventricular vasculitis. Cross section through a capillary vessel showing prominent signs of vasculitis. The endothelial cells (5) show swelling and vacuolation and are increased in number with enlargement of nuclei, indicative for activation. Furthermore, presence of mixed inflammatory cell infiltrates within the endothelial layer, consisting of lymphocytes (1), granulocytes (2), and histiocytes (4). The adjacent brain tissue also shows signs of inflammation (encephalitis) with presence of lymphocytes as well and activated microglia (3). H&E. Magnification: 200× (a) and 400× (b). Figure 5.Heart left ventricle. (a): Mild lympho-histiocytic myocarditis.Pronounced interstitial edema (7) and mild lympho-histiocytic inﬁltrates (2 + 4). Signs of cardiomyocytic degeneration (5) with cytoplasmic hypereosinophilia and single contraction bands. (d): Arteriole with signs of acute degeneration and associated inﬂammation, associated by lymphocytic inﬁltrates (2) within the vascular wall, endothelial swelling and vacuolation (3), and vacuolation of vascular myocytes with signs of karyopyknosis (1). Within the vascular lumen (d), note plasma coagulation/ﬁbrin clots adhering to the endothelial surface, indicative of endothelial damage. 1: pyknotic vascular myocytes, 2: lymphocytes, 3: swollen endothelial cells, 4: macrophages, 5: necrotic cardiomyocytes, 6: eosinophilic granulocytes, 7 (blue line): interstitial edema. H&E stain. Magniﬁcation: 200 (a) and (c), 40 (b), and detailed enlargement (d). Vascular system (large blood vessels): The pulmonary arteries showed ectasia and lipidosis. The kidney showed slight diffuse glomerulosclerosis and arteriosclerosis with renal cortical scars (up to 10 mm in diameter). The ﬁndings are suggestive of generalized atherosclerosis and systemic hypertension. Major arteries including the aorta and its branches as well as the coronary arteries showed variable degrees of arteriosclerosis and mild to moderate stenosis. Furthermore, examination revealed mild nodular arteriosclerosis of cervical arteries. Ascending aorta, aortic arch, and thoracic aorta showed moderate, nodular, and partially calciﬁed arteriosclerosis. The cerebral basilar artery showed mild arteriosclerosis. Nodular and calciﬁed arteriosclerosis were of high grade in the abdominal aorta and iliac arteries and moderate grade with moderate stenosis in the right coronary arteries. Coronary artery examination showed variable degrees of arteriosclerosis and stenosis more on the left coronary arteries. The left anterior descending coronary artery (the anterior interventricular branch of the left coronary artery; LAD) showed high-grade and moderately stenosed arteriosclerosis. The arteriosclerosis and stenosis of the left circumﬂex artery (the circumﬂex branch of the left coronary artery) were mild. Mild cerebral basal artery sclerosis. High-grade nodular and calciﬁed arteriosclerosis of the abdominal aorta and the iliac arteries. Moderate stenosed arteriosclerosis of the right coronary artery. Lymphocytic periarteritis was detected as well. Vaccines 2022,10, 1651 8 of 17 3.2. Other Findings -Oral cavity: tongue bite was detected with bleeding under the tongue muscle (tongue bite is common with epileptic seizures). -Adrenal glands: bilateral mild cortical hyperplasia. -Colon: the elongated sigmoid colon was elongated with fecal impaction. -Kidneys: slight diffuse glomerulosclerosis and arterio-sclerosis, renal cortical scars (up to 10 mm in diameter), bilateral mild active nephritis and urocystitis as well as evidence of shock kidney disorder. -Liver: slight lipofuscinosis. -Spleen: mild acute splenitis. -Stomach: mild diffuse gastric mucosal bleeding. -Thyroid gland: bilateral nodular goiter with chocolate cysts (up to 0.5 cm in diameter). -Prostate gland: benign nodular prostatic hyperplasia and chronic persistent prostatitis. 3.3. Immunohistochemical Analyses Immunohistochemical staining for the presence of SARS-CoV-2 antigens (spike protein and nucleocapsid) was studied in the brain and heart. In the brain, SARS-CoV-2 spike protein subunit 1 was detected in the endothelia, microglia, and astrocytes in the necrotic areas (Figures 6 and 7). Furthermore, spike protein could be demonstrated in the areas of lymphocytic periarteritis, present in the thoracic and abdominal aorta and iliac branches, as well as a cerebral basal artery (Figure 8). The SARS-CoV-2 subunit 1 was found in macrophages and in the cells of the vessel wall, in particular the endothelium (Figure 9), as well as in the Nucleus ruber (Figure 10). In contrast, the nucleocapsid protein of SARS- CoV-2 could not be detected in any of the corresponding tissue sections (Figures 11 and 12). In addition, SARS-CoV-2 spike protein subunit 1 was detected in the cardiac endothelial cells that showed lymphocytic myocarditis (Figure 13). Immunohistochemical staining did not detect the SARS-CoV-2 nucleocapsid protein (Figure 14). Vaccines 2022, 10, 1651 9 of 17 Figure 6. Frontal brain. Immunohistochemistry for CD68 (expressed by monocytic cells). Note map-like tissue destruction with the presence of CD68-positive microglial cells. Furthermore zonal activation of microglia (brown granules). Activation of the microglia means that tissue destruction has taken place in the brain, which is cleared/removed by macrophages (called microglia in the brain). Brown granules: macrophages/microglia. Magnification: 40×. Figure 7. Brain. Nucleus ruber. Immunohistochemistry for CD68 (expressed by monocytic cells) shows abundant positive cells, indicative of zonal activation of microglia (brown granules). Mag- nification: 40×. Figure 6.Frontal brain. Immunohistochemistry for CD68 (expressed by monocytic cells). Note map-like tissue destruction with the presence of CD68-positive microglial cells. Furthermore zonal activation of microglia (brown granules). Activation of the microglia means that tissue destruction has taken place in the brain, which is cleared/removed by macrophages (called microglia in the brain). Brown granules: macrophages/microglia. Magniﬁcation: 40 . Vaccines 2022,10, 1651 9 of 17 Vaccines 2022, 10, 1651 9 of 17 Figure 6. Frontal brain. Immunohistochemistry for CD68 (expressed by monocytic cells). Note map-like tissue destruction with the presence of CD68-positive microglial cells. Furthermore zonal activation of microglia (brown granules). Activation of the microglia means that tissue destruction has taken place in the brain, which is cleared/removed by macrophages (called microglia in the brain). Brown granules: macrophages/microglia. Magnification: 40×. Figure 7. Brain. Nucleus ruber. Immunohistochemistry for CD68 (expressed by monocytic cells) shows abundant positive cells, indicative of zonal activation of microglia (brown granules). Mag- nification: 40×. Figure 7.Brain. Nucleus ruber. Immunohistochemistry for CD68 (expressed by monocytic cells) shows abundant positive cells, indicative of zonal activation of microglia (brown granules). Magniﬁ- cation: 40 . Vaccines 2022, 10, 1651 10 of 17 Figure 8. Frontal brain. Immunohistochemistry for CD3 (expressed by T-Lymphocytes) shows numerous CD3-positive lymphocytes (brown granules, red arrow highlights an example), partic- ularly within the endothelium, but also in the brain tissue, indicative of lymphocytic vasculitis and encephalitis. Blue dotted lines: blood vessels. Magnification: 200×. Figure 9. Frontal brain. Positive reaction for SARS-CoV-2 spike protein. Cross section through a capillary vessel (same vessel as shown in Figure 11, serial sections of 5 to 20 µm). Immunohisto- chemical reaction for SARS-CoV-2 spike subunit 1 detectable as brown granules in capillary en- dothelial cells (red arrow) and individual glial cells (blue arrow). Magnification: 200×. Figure 8.Frontal brain. Immunohistochemistry for CD3 (expressed by T-Lymphocytes) shows numerous CD3-positive lymphocytes (brown granules, red arrow highlights an example), particu- larly within the endothelium, but also in the brain tissue, indicative of lymphocytic vasculitis and encephalitis. Blue dotted lines: blood vessels. Magniﬁcation: 200 . Vaccines 2022,10, 1651 10 of 17 Vaccines 2022, 10, 1651 10 of 17 Figure 8. Frontal brain. Immunohistochemistry for CD3 (expressed by T-Lymphocytes) shows numerous CD3-positive lymphocytes (brown granules, red arrow highlights an example), partic- ularly within the endothelium, but also in the brain tissue, indicative of lymphocytic vasculitis and encephalitis. Blue dotted lines: blood vessels. Magnification: 200×. Figure 9. Frontal brain. Positive reaction for SARS-CoV-2 spike protein. Cross section through a capillary vessel (same vessel as shown in Figure 11, serial sections of 5 to 20 µm). Immunohisto- chemical reaction for SARS-CoV-2 spike subunit 1 detectable as brown granules in capillary en- dothelial cells (red arrow) and individual glial cells (blue arrow). Magnification: 200×. Figure 9.Frontal brain. Positive reaction for SARS-CoV-2 spike protein. Cross section through a cap- illary vessel (same vessel as shown in Figure 11, serial sections of 5 to 20 m). Immunohistochemical reaction for SARS-CoV-2 spike subunit 1 detectable as brown granules in capillary endothelial cells (red arrow) and individual glial cells (blue arrow). Magniﬁcation: 200 . Vaccines 2022, 10, 1651 11 of 17 Figure 10. Brain, Nucleus ruber. The abundant presence of SARS-CoV-2 spike protein in swollen endothelium of a capillary vessel shows acute signs of inflammation with sparse mononuclear in- flammatory cell infiltrates (same vessel as shown in Figure 12, serial sections of 5 to 20 µm). Im- munohistochemical demonstration for SARS-CoV-2 spike protein subunit 1 visible as brown granules in capillary endothelial cells (red arrow) and individual glial cells (blue arrow). Magnifi- cation: 200×. Figure 11. Frontal brain. Negative immunohistochemical reaction for SARS-CoV-2 nucleocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 9, serial sections of 5 to 20 µm). Magnification: 200×. Figure 10.Brain, Nucleus ruber. The abundant presence of SARS-CoV-2 spike protein in swollen endothelium of a capillary vessel shows acute signs of inﬂammation with sparse mononuclear inﬂammatory cell inﬁltrates (same vessel as shown in Figure 12, serial sections of 5 to 20 m). Im- munohistochemical demonstration for SARS-CoV-2 spike protein subunit 1 visible as brown granules in capillary endothelial cells (red arrow) and individual glial cells (blue arrow). Magniﬁcation: 200 . Vaccines 2022,10, 1651 11 of 17 Vaccines 2022, 10, 1651 11 of 17 Figure 10. Brain, Nucleus ruber. The abundant presence of SARS-CoV-2 spike protein in swollen endothelium of a capillary vessel shows acute signs of inflammation with sparse mononuclear in- flammatory cell infiltrates (same vessel as shown in Figure 12, serial sections of 5 to 20 µm). Im- munohistochemical demonstration for SARS-CoV-2 spike protein subunit 1 visible as brown granules in capillary endothelial cells (red arrow) and individual glial cells (blue arrow). Magnifi- cation: 200×. Figure 11. Frontal brain. Negative immunohistochemical reaction for SARS-CoV-2 nucleocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 9, serial sections of 5 to 20 µm). Magnification: 200×. Figure 11.Frontal brain. Negative immunohistochemical reaction for SARS-CoV-2 nucleocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 9, serial sections of 5 to 20 m). Magniﬁcation: 200 . Vaccines 2022, 10, 1651 12 of 17 Figure 12. Brain, Nucleus ruber. Negative immunohistochemical reaction for SARS-CoV-2 nucle- ocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 11, serial sections of 5 to 20 µm). Magnification: 200×. Figure 13. Heart left ventricle. Positive reaction for SARS-CoV-2 spike protein. Cross section through a capillary vessel (same vessel as shown in Figure 14, serial sections of 5 to 20 µm). Im- munohistochemical demonstration of SARS-CoV-2 spike subunit 1 as brown granules. Note the abundant presence of spike protein in capillary endothelial cells (red arrow) associated with prominent endothelial swelling and the presence of a few mononuclear inflammatory cells. Mag- nification: 400×. Figure 12.Brain, Nucleus ruber. Negative immunohistochemical reaction for SARS-CoV-2 nucleo- capsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 11, serial sections of 5 to 20 m). Magniﬁcation: 200 . Vaccines 2022,10, 1651 12 of 17 Vaccines 2022, 10, 1651 12 of 17 Figure 12. Brain, Nucleus ruber. Negative immunohistochemical reaction for SARS-CoV-2 nucle- ocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 11, serial sections of 5 to 20 µm). Magnification: 200×. Figure 13. Heart left ventricle. Positive reaction for SARS-CoV-2 spike protein. Cross section through a capillary vessel (same vessel as shown in Figure 14, serial sections of 5 to 20 µm). Im- munohistochemical demonstration of SARS-CoV-2 spike subunit 1 as brown granules. Note the abundant presence of spike protein in capillary endothelial cells (red arrow) associated with prominent endothelial swelling and the presence of a few mononuclear inflammatory cells. Mag- nification: 400×. Figure 13.Heart left ventricle. Positive reaction for SARS-CoV-2 spike protein. Cross section through a capillary vessel (same vessel as shown in Figure 14, serial sections of 5 to 20 m). Immunohistochem- ical demonstration of SARS-CoV-2 spike subunit 1 as brown granules. Note the abundant presence of spike protein in capillary endothelial cells (red arrow) associated with prominent endothelial swelling and the presence of a few mononuclear inﬂammatory cells. Magniﬁcation: 400 . Vaccines 2022, 10, 1651 13 of 17 Figure 14. Heart left ventricle. Negative immunohistochemical reaction for SARS-CoV-2 nucle- ocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 13, serial sections of 5 to 20 µm). Magnification: 400×. 3.4. Autopsy-Based Diagnosis The 76-year-old deceased male patient had PD, which corresponded to typical post-mortem findings. The main cause of death was recurrent aspiration pneumonia. In addition, necrotizing encephalitis and vasculitis were considered to be major contribu- tors to death. Furthermore, there was mild lympho-histiocytic myocarditis with fi- ne-spotted myocardial fibrosis as well as systemic arteriosclerosis, which will have also contributed to the deterioration of the physical condition of the senior. The final diagnosis was abscedating bilateral bronchopneumonia (J18.9), Parkin- son’s disease (G20.9), necrotic encephalitis (G04.9), and myocarditis (I40.9). Immunohistochemistry for SARS-CoV-2 antigens (spike protein and nucleocapsid) revealed that the lesions with necrotizing encephalitis as well as the acute inflammatory changes in the small blood vessels (brain and heart) were associated with abundant de- posits of the spike protein SARS-CoV-2 subunit 1. Since the nucleocapsid protein of SARS-CoV-2 was consistently absent, it must be assumed that the presence of spike pro- tein in affected tissues was not due to an infection with SARS-CoV-2 but rather to the transfection of the tissues by the gene-based COVID-19-vaccines. Importantly, spike protein could be only demonstrated in the areas with acute inflammatory reactions (brain, heart, and small blood vessels), in particular in endothelial cells, microglia, and astrocytes. This is strongly suggestive that the spike protein may have played at least a contributing role to the development of the lesions and the course of the disease in this patient. 4. Discussion This is a case report of a 76-year-old patient with Parkinson’s disease (PD) who died three weeks after his third COVID-19 vaccination. The stated cause of death appeared to be a recurrent attack of aspiration pneumonia, which is indeed common in PD [14,15]. However, the detailed autopsy study revealed additional pathology, in particular ne- crotizing encephalitis and myocarditis. While the histopathological signs of myocarditis were comparatively mild, the encephalitis had resulted in significant multifocal necrosis and may well have contributed to the fatal outcome. Encephalitis often causes epileptic seizures, and the tongue bite found at the autopsy suggests that it had done so in this Figure 14.Heart left ventricle. Negative immunohistochemical reaction for SARS-CoV-2 nucleocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 13, serial sections of 5 to 20 m). Magniﬁcation: 400 . 3.4. Autopsy-Based Diagnosis The 76-year-old deceased male patient had PD, which corresponded to typical post- mortem ﬁndings. The main cause of death was recurrent aspiration pneumonia. In addition, necrotizing encephalitis and vasculitis were considered to be major contributors to death. Furthermore, there was mild lympho-histiocytic myocarditis with ﬁne-spotted myocardial ﬁbrosis as well as systemic arteriosclerosis, which will have also contributed to the deterioration of the physical condition of the senior. Vaccines 2022,10, 1651 13 of 17 The ﬁnal diagnosis was abscedating bilateral bronchopneumonia (J18.9), Parkinson’s disease (G20.9), necrotic encephalitis (G04.9), and myocarditis (I40.9). Immunohistochemistry for SARS-CoV-2 antigens (spike protein and nucleocapsid) revealed that the lesions with necrotizing encephalitis as well as the acute inﬂammatory changes in the small blood vessels (brain and heart) were associated with abundant deposits of the spike protein SARS-CoV-2 subunit 1. Since the nucleocapsid protein of SARS-CoV-2 was consistently absent, it must be assumed that the presence of spike protein in affected tissues was not due to an infection with SARS-CoV-2 but rather to the transfection of the tissues by the gene-based COVID-19-vaccines. Importantly, spike protein could be only demonstrated in the areas with acute inﬂammatory reactions (brain, heart, and small blood vessels), in particular in endothelial cells, microglia, and astrocytes. This is strongly suggestive that the spike protein may have played at least a contributing role to the development of the lesions and the course of the disease in this patient. 4. Discussion This is a case report of a 76-year-old patient with Parkinson’s disease (PD) who died three weeks after his third COVID-19 vaccination. The stated cause of death appeared to be a recurrent attack of aspiration pneumonia, which is indeed common in PD [14,15]. However, the detailed autopsy study revealed additional pathology, in particular necrotiz- ing encephalitis and myocarditis. While the histopathological signs of myocarditis were comparatively mild, the encephalitis had resulted in signiﬁcant multifocal necrosis and may well have contributed to the fatal outcome. Encephalitis often causes epileptic seizures, and the tongue bite found at the autopsy suggests that it had done so in this case. Several other cases of COVID-19 vaccine-associated encephalitis with status epilepticus have appeared previously [16–18]. The clinical history of the current case showed some remarkable events in correlation to his COVID-19 vaccinations. Already on the day of his ﬁrst vaccination in May 2021 (ChAdOx1 nCov-19 vector vaccine), he experienced cardiovascular symptoms, which needed medical care and from which he recovered only slowly. After the second vaccination in July 2021 (BNT162b2 mRNA vaccine), the family recognized remarkable behavioral and psychological changes and a sudden onset of marked progression of his PD symptoms, which led to severe motor impairment and recurrent need for wheelchair support. He never fully recovered from this but still was again vaccinated in December 2021. Two weeks after this third vaccination (second vaccination with BNT162b2), he suddenly collapsed while taking his dinner. Remarkably, he did not show any coughing or other signs of food aspiration but just fell from his chair. This raises the question of whether this sudden collapse was really due to aspiration pneumonia. After intense resuscitation, he recovered from this more or less, but one week later, he again suddenly collapsed silently while taking his meal. After successful but prolonged resuscitation attempts, he was transferred to the hospital and directly set into an artiﬁcial coma but died shortly thereafter. The clinical diagnosis was death due to aspiration pneumonia. Due to his ambiguous symptoms after the COVID-vaccinations the family asked for an autopsy. Based on the alteration pattern in the brain and heart, it appeared that the small blood vessels were especially affected, in particular, the endothelium. Endothelial dysfunction is known to be highly involved in organ dysfunction during viral infections, as it induces a pro-coagulant state, microvascular leak, and organ ischemia [19,20]. This is also the case for severe SARS-CoV-2 infections, where a systemic exposure to the virus and its spike protein elicits a strong immunological reaction in which the endothelial cells play a crucial role, leading to vascular dysfunction, immune-thrombosis, and inﬂammation [21]. Although there was no history of COVID-19 for this patient, immunohistochemistry for SARS-CoV-2 antigens (spike and nucleocapsid proteins) was performed. Spike protein could be indeed demonstrated in the areas of acute inﬂammation in the brain (particularly within the capillary endothelium) and the small blood vessels of the heart. Remarkably, however, the nucleocapsid was uniformly absent. During an infection with the virus, both Vaccines 2022,10, 1651 14 of 17 proteins should be expressed and detected together. On the other hand, the gene-based COVID-19 vaccines encode only the spike protein and therefore, the presence of spike protein only (but no nucleocapsid protein) in the heart and brain of the current case can be attributed to vaccination rather than to infection. This agrees with the patient’s history, which includes three vaccine injections, the third one just 3 weeks before his death, but no positive laboratory or clinical diagnosis of the infection. Discrimination of vaccination response from natural infection is an important question and had been addressed already in clinical immunology, where the combined application of anti-spike and anti-nucleocapsid protein-based serology was proven as a useful tool [22]. In histology, however, this immunohistochemical approach has not yet been described, but it is straightforward and appears to be very useful for identifying the potential origin of SARS-CoV-2 spike protein in autopsy or biopsy samples. Where additional conﬁrmation is required, for instance in a forensic context, rt-PCR methods might be used to ascertain the presence of the vaccine mRNA in the affected tissues [23,24]. Assuming that, in the current case, the presence of spike protein was indeed driven by the gene-based vaccine, then the question arises whether this was also the cause the accompanying acute tissue alterations and inﬂammation. The stated purpose of the gene- based vaccines is to induce an immune response against the spike protein. Such an immune response will, however, not only results in antibody formation against the spike protein but also lead to direct cell- and antibody-mediated cytotoxicity against the cells expressing this foreign antigen. In addition, there are indications that the spike protein on its own can elicit distinct toxicity, in particular, on pericytes and endothelial cells of blood vessels [25,26]. While it is widely held that spike protein expression, and the ensuing cell and tissue damage will be limited to the injection site, several studies have found the vaccine mRNA and/or the spike protein encoded by it at a considerable distance from the injection site for up to three months after the injection [23,24,27–29]. Biodistribution studies in rats with the mRNA-COVID-19 vaccine BNT162b2 also showed that the vaccine does not stay at the injection site but is distributed to all tissues and organs, including the brain [30]. After the worldwide roll-out of COVID-19 vaccinations in humans, spike protein has been detected in humans as well in several tissues distant from the injection site (deltoid muscle): for instance in heart muscle biopsies from myocarditis patients [28], within the skeletal muscle of a patient with myositis [23] and within the skin, where it was associated with a sudden onset of Herpes zoster lesions after mRNA-COVID-19 vaccination [29]. The underlying diagnosis in this patient was Parkinson’s disease, and one may ask what role, if any, this condition had played in the causation of the encephalitis, and the myocarditis detected at post-mortem examination. PD had been long-standing in the cur- rent case, whereas the encephalitis was acute. Conversely, there is no plausible mechanism and no case report of PD causing secondary necrotizing encephalitis. On the other hand, numerous cases have been reported of autoimmune encephalitis and encephalomyelitis after COVID-19 vaccination [12,31]. Autoimmune diseases in organs other than the CNS have been reported as well, for example, a striking case of a patient who after mRNA vaccination suffered multiple autoimmune disorders all at once—acute disseminated en- cephalomyelitis, myasthenia gravis, and thyroiditis [32]. In the case reported here, it may be noted that the spike protein was primarily detected in the vascular endothelium and sparsely in the glial cells but not in the neurons. Nevertheless, neuronal cell death was widespread in the encephalitic foci, which suggests some contribution of immunological bystander activation, i.e., autoimmunity, to the observed cell and tissue damage. A contributory role of PD in the development of cardiomyopathy is indeed docu- mented and cannot be ruled out with absolute certainty. However, inﬂammatory myocar- dial changes with pathological alterations in small blood vessels as seen in the current case are uncommon. Instead, the most prominent cause of cardiac failure in PD patients is rather due to cardiac autonomic dysfunction [33,34]. PD seems well to be signiﬁcantly associated with increased left ventricular hypertrophy and diastolic dysfunction [34]. In the current case, ventricular dilatation and hypertrophy were present but seem rather related to mani- Vaccines 2022,10, 1651 15 of 17 fest signs of chronic hypertension. In contrast, myocardial inﬂammatory reactions had been well-linked to gene-based COVID-19 vaccinations in numerous cases [9,35–37]. In one case, the spike protein of SARS-CoV-2 could also be demonstrated by immunohistochemistry in the heart of vaccinated individuals [28]. 5. Conclusions Numerous cases of encephalitis and encephalomyelitis have been reported in connec- tion with the gene-based COVID-19 vaccines, with many being considered causally related to vaccination [31,38,39]. However, this is the ﬁrst report to demonstrate the presence of the spike protein within the encephalitic lesions and to attribute it to vaccination rather than infection. These ﬁndings corroborate a causative role of the gene-based COVID-19 vaccines, and this diagnostic approach is relevant to potentially vaccine-induced damage to other organs as well. Funding:This research received no speciﬁc funding. Institutional Review Board Statement:According to the Saxonian State Chamber of Medicine (Ethikkommission Landesärztekammer Sachsen), no explicit ethical approval is required for autopsy case reports as long as informed consent was obtained from the entitled person and all data has been anonymized. Informed Consent Statement:The informed consent was obtained from the entitled person for the subject involved in this case report. Data Availability Statement:Data are available upon request. Acknowledgments:The author wishes to thank Hany A. Salem and David O. Fischer for supporting the preparation of this paper with valuable comments and suggestions. Conﬂicts of Interest:The author declares he has no conﬂict of interest. 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[CrossRef] [PubMed] 1 A Summary (for the General Public) and Commentary Regarding the Case Report Published by Dr. Michael Mörz: Multifocal Necrotizing Encephalitis and Myocarditis After BNT162b2 mRNA Vaccination against COVID-19 By Rob Rennebohm, MD November 10, 2022 Take Home Visual images; Take Home Message: The above image (from the Mörz article*) shows a cross section of a capillary in the heart. It demonstrates the presence of an abundant amount of spike protein (the brown material to which the red arrow points) within endothelial cells, which are the cells that line the inner wall of the capillary. There is endothelial cell swelling, and there are a few mononuclear inflammatory cells within the wall of the capillary. The spike protein was demonstrated to be of vaccinal origin, not from SARS-CoV-2 infection. 2 The above image (also from the Mörz article) is a cross section through a capillary in the brain. It shows prominent signs of vasculitis (inflammation of the blood vessel wall). The vessel is filled with hemolyzed blood, which is normal in autopsied cases. The many tiny blue cells that are present in the walls of the vessel (immediately surrounding the hemolyzed blood) include many lymphocytes (inflammatory cells). The presence of numerous lymphocytes in the wall of this vessel means that the vessel wall is inflamed-- --i.e., the vessel is experiencing vasculitis. Take Home Message: As we will discuss in detail below, the above two images (along with the several other images presented in the Mörz article) support the following hypothesis: When the mRNA (that is embedded in the lipid nanoparticle of the Pfizer/BioNTech COVID-19 vaccine) is injected into the arm, the mRNA finds its way (via the blood stream) into distant cells---in this case endothelial cells that line the small blood vessels in the heart and brain. (The vaccine does not simply stay in the arm.) Once in the endothelial cell(s), the mRNA instructs the ribosomes in the cell to manufacture spike protein. The spike protein then migrates to the outer surface of the endothelial cell. The immune system then recognizes the spike protein (or fragments thereof) as foreign and concludes that the endothelial cell has become infected. Accordingly, the immune system sends lymphocytes and other inflammatory cells into the walls of the vessel to attack the presumed infected endothelial cell. The vessel wall becomes inflamed (vasculitis) and, during this process, the endothelial cells become immunologically injured and may swell to varying degrees. Sometimes, abnormal intravascular coagulation (clotting within the vessel) may be triggered. In some instances spike protein may appear within the brain (or heart) tissue, where the spike protein may trigger an inflammatory reaction (encephalitis, myocarditis). Introduction: Above is the title page of the article written by Dr. Michael Mörz , a pathologist in Dresden, Germany. Here is the link to the full article: (https://www.mdpi.com/2076-393X/10/10/1651). It is a case report of autopsy findings in a 76-year-old man who had died 3 weeks after receiving his third vaccination against COVID-19. This case report was published by the peer-reviewed journal Vaccines on October 1, 2022 (Vaccines 2022, 10, 1651). Dr. Mörz’s article provides compelling and sobering evidence of potential serious side effects of the mRNA vaccines. His article may prove to be one of the most pivotal articles to be published in the formal conventional medical literature during the COVID-19 pandemic---because of its potential to change attitudes about the safety of mRNA vaccines against COVID-19. I will try to summarize the Mörz article and present its pathology images in a way that might be more understandable to non-pathologists and the general public. I will also make further comments about the significance of the Mörz article and what future studies and actions might be helpful to do. 3 Summary of the Mörz Article: The a Mörz article provides details of an autopsy performed on a 76-year-old man who had died 3 weeks after receiving his third dose of vaccine against COVID-19. He had a past history of Parkinson’s disease. Initially, he had received a single dose of the AstraZeneca vaccine (ChAdOx-1-nCoV-19, a recombinant adenoviral vector vaccine, not a mRNA vaccine), after which he experienced “pronounced cardiovascular side effects.” Subsequently, he received 2 doses of the Pfizer mRNA vaccine (BNT162b2). After the first Pfizer dose, he developed “obvious behavioral and psychological symptoms,” lethargy, and worsening of his overall neurological function. Despite continuation of these symptoms, he was given a second Pfizer dose. Three weeks after his second dose of the Pfizer vaccine, he inexplicably collapsed, was rushed to the hospital, could not be resuscitated, and died. It was thought that he might have aspirated and developed pneumonia (which commonly occurs with severe Parkinsonism). He had never been suspected of having COVID-19, nor had he ever tested positive for COVID-19. Because the cause of death was uncertain, the family requested an autopsy. After completion of the autopsy, it was concluded that the main cause of death was recurrent aspiration pneumonia. Additional findings, however, included: vasculitis (inflammation of blood vessel walls) within the brain and heart, particularly in small blood vessels (capillaries and arterioles) in his case; necrotizing encephalitis (inflammation of the brain, with associated death of brain cells); and mild myocarditis (inflammation of the heart muscle). These additional findings were thought to be major contributors to his death; they were not thought to be related to his Parkinson’s disease. The final diagnosis was bilateral bronchopneumonia, Parkinson’s disease, vasculitis (in brain and heart), necrotizing encephalitis, and myocarditis. Among the most remarkable findings were that: the vasculitis, encephalitis, and myocarditis were associated with deposits of spike protein, and the spike protein was vaccinal in origin. As the next several images will show, spike protein was documented to be present within the walls of small blood vessels and also within brain and heart tissue. Inflammatory cells (primarily lymphocytes) were found next to the deposited spike protein. Spike protein could be demonstrated only in the areas with acute inflammatory reactions (brain, heart, and small blood vessels), in particular in endothelial cells, microglia, and astrocytes. The most logical interpretation of these findings is that vaccinal spike protein provoked an inflammatory reaction (by the immune system), resulting in vasculitis, encephalitis, and myocarditis. It should be added that if vasculitis (inflammation of blood vessel walls) is sufficiently severe, blood flow through the inflamed vessel can be diminished, and this can cause death (necrosis) of the cells that normally receive oxygen and nutrients from blood flowing through those vessels---hence, death of brain cells, for example. Importantly, Mörz determined that the spike protein came from the vaccine, not from the natural virus. This was concluded because the spike protein was not accompanied by nucleocapsid protein, which is a separate protein located within the SARS-CoV-2 virus. If the spike protein had been of natural viral origin, both the spike protein and nucleocapsid protein should have been present. If the spike protein were of vaccinal origin, spike protein would be present but nucleocapsid would be absent. (The mRNA vaccine instructs the cells to manufacture only spike protein, not nucleocapsid protein.) In this autopsy study, tests for presence of spike protein were positive and tests for presence of nucleocapsid protein were negative. 4 Glossary: Before we review the pathology images provided in the Mörz article, let us define key pathological and anatomical terms. Vascular: This word refers to blood vessels, large and small. The largest blood vessel in the human body is the aorta. In descending order of size, there are large arteries, medium sized arteries, small arteries, arterioles (tiny arteries), and capillaries. In the Mörz article we are primarily talking about arterioles and capillaries. Vasculitis: When the walls of a blood vessel (large or tiny) are inflamed (meaning that the immune system has sent many inflammatory cells into the vessel walls), the vessel is said to be experiencing “vasculitis.” Many inflammatory cells accumulate on the scene, as if the vessel wall is “infiltrated” or invaded by these cells. Vasculitis can be minimal, mild, moderate, or severe. Inflammatory cells: Inflammatory cells are key components of the immune system. The immune system sends them to sites of infection, for example, to fight off the infection. Lymphocytes (e.g., T cells and B cells) are key inflammatory cells. Granulocytes, histiocytes, and macrophages are also inflammatory cells. Glial cells: A type of cell that provides physical and chemical support to neurons (brain cells). Glial cells provide and maintain a healthy, supportive environment for neurons. Microglia: Microglia is the name given to macrophages that reside in the brain. An important task of microglia is debris clearance. They engulf debris from damaged or dead cells, as well as other debris. Inflammation: Inflammation is said to be present if an abnormal number of inflammatory cells have accumulated at a site---e.g., within a blood vessel wall (vasculitis), or within brain tissue (encephalitis), or within heart muscle (myocarditis). Endothelial cells: These are thin elongated cells that line the inner walls of blood vessels. They provide many protective functions and are extremely important. Endotheliopathy: Disease of (sickness of) endothelial cells. Encephalitis: Encephalitis means “inflammation of the brain.” It refers to inflammation of brain tissue itself (not inflammation of blood vessels within the brain). Necrotizing/Necrotic: “Necrotizing” means “capable of causing something to die.” Necrotic cells or necrotic tissue means dead cells or dead tissue. Necrotizing encephalitis: A severe form of encephalitis---one that is associated with necrosis (death) of brain tissue/cells, including death of neurons (brain cells) and glial cells. Myocarditis: Inflammation of the heart muscle. Parenchyma: The functional tissue of an organ, as opposed to the connective and supporting tissue in the organ. In the brain, the parenchyma refers to the “brain tissue,” primarily, the neurons (brain cells) but also glial cells. 5 Pathogenesis: The sequence of causative processes that lead to disease. The exact mechanisms or chain of events that lead to disease. Spike protein: Spike protein is just one of many proteins that are present within or on the surface of the SARS-CoV-2 virus. Spike protein (also called spike glycoprotein) is located on the surface of the virus and enables the virus to enter human cells. The mRNA vaccines instruct cells to make only the spike protein, not any of the other proteins of the SARS-CoV-2. The vaccine provokes the immune system to make antibodies to the spike protein (but not to other proteins of the virus). Nucleocapsid protein: Nucleocapsid protein is located inside the spherical SARS-CoV-2 virus. It is very different from the spike protein. The mRNA vaccines do not instruct cells to make nucleocapsid protein. Accordingly, the mRNA vaccines do not result in production of antibody to nucleocapsid protein. When a person is infected with the actual virus, both the spike protein and nucleocapsid protein will be present and the person will usually produce antibodies to both proteins. See image below. Review of Images from the Mörz article: Instructive images from the Mörz article are shown and discussed below: 6 Mörz Figure 4a: Vasculitis (inflammation of the blood vessel wall) in the brain. This is a cross section through a capillary vessel showing prominent signs of vasculitis. The vessel is filled with hemolyzed red blood cells, which is normal in autopsy cases (and, therefore, ignorable). The many tiny blue cells that are present in the walls of the vessel (immediately surrounding the hemolyzed red blood cells) include many lymphocytes (inflammatory cells). So, the walls of this vessel are inflamed, which means the vessel is experiencing vasculitis. The next image provides a closer, more detailed view of the right half of this vessel. 7 Mörz Figure 4b: Endothelial cells are the cells that line the inner walls of blood vessels. In this image, endothelial cells (5) are swollen and vacuolated and are increased in number with enlargement of nuclei, indicative for activation. Furthermore, within the endothelial layer there is a mixture of different types of inflammatory cells, consisting of lymphocytes (1), granulocytes (2), and histiocytes (4). The adjacent brain tissue also shows signs of inflammation (encephalitis) with presence of lymphocytes as well as activated microglia (3). Lymphocytes are inflammatory cells (such as T lymphocytes). Microglia are macrophages that reside in the brain. A major task of microglia is to engulf and incinerate dead cells. The main finding in this image is inflammation in the vessel wall---i.e. vasculitis. 8 Mörz Figure 5d: This is an arteriole (in the left ventricle of the heart) with signs of inflammation and associated acute degeneration. Lymphocytes (2) have accumulated within the vessel wall; endothelial swelling and vacuolation (3) have occurred; and there is vacuolation of vessel wall myocytes (muscle cells in the wall of the vessel) with signs of karyopyknosis (1). Within the vascular lumen (the open channel of the vessel), note plasma coagulation/fibrin clots adhering to the endothelial surface, indicative of endothelial damage. 1=pyknotic vascular myocytes, 2=lymphocytes, 3= swollen endothelial cells, 4=macrophages, 5=necrotic cardiomyocytes, 6=eosinophilic granulocytes, 7 (blue line)=interstitial edema. 9 Mörz Figure 8: Frontal brain. Immunohistochemistry for CD3 (expressed by T-Lymphocytes) shows numerous CD3-positive lymphocytes (brown granules, red arrow highlights an example), particularly within the endothelium, but also in the brain tissue, indicative of lymphocytic vasculitis and encephalitis. Blue dotted lines: blood vessels. This image conclusively documents the accumulation of lymphocytes in the vessel wall (vasculitis) and in brain tissue (encephalitis). Mörz Figure 9: Frontal brain. Positive reaction for SARS-CoV-2 spike protein. Cross section through a capillary vessel. Immunohistochemical reaction for SARS-CoV-2 spike subunit 1 detectable as brown 10 granules in capillary endothelial cells (red arrow) and individual glial cells (blue arrow). This image conclusively documents presence of spike protein within the vessel wall and in the brain tissue. Mörz Figure 10: Brain, Nucleus ruber. This image shows the abundant presence of SARS-CoV-2 spike protein in swollen endothelium of a capillary vessel. It also shows acute signs of inflammation with sparse mononuclear inflammatory cell infiltrates in the vessel wall. Immunohistochemical demonstration for SARS-CoV-2 spike protein subunit 1 is visible as brown granules in capillary endothelial cells (red arrow) and individual glial cells (blue arrow). This image conclusively documents presence of spike protein within the vessel wall and in the brain tissue. 11 Mörz Figure 11: Frontal brain. Negative immunohistochemical reaction for SARS-CoV-2 nucleocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 9, serial sections of 5 to 20 µm). This image documents that nucleocapsid protein was not present, at least in this vessel. Mörz Figure 12: Brain, Nucleus ruber. Negative immunohistochemical reaction for SARS-CoV-2 nucleocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 11, serial sections of 5 to 20 µm). Nucleocapsid protein was not present. 12 Mörz Figure 13: Heart left ventricle. Positive reaction for SARS-CoV-2 spike protein. Cross section through a capillary vessel (same vessel as shown in Figure 14, serial sections of 5 to 20 µm). Immunohistochemical demonstration of SARS-CoV-2 spike subunit 1 as brown granules. Note the abundant presence of spike protein in capillary endothelial cells (red arrow) associated with prominent endothelial swelling and the presence of a few mononuclear inflammatory cells. 13 Mörz Figure 14: Heart left ventricle. Negative immunohistochemical reaction for SARS-CoV-2 nucleocapsid protein. Cross section through a capillary vessel (same vessel as shown in Figure 13, serial sections of 5 to 20 µm). Nucleocapsid protein was not present. Mörz Figure 2b: Acute brain damage (due to necrotizing encephalitis) is visible with diffuse and zonal neuronal and glial cell death, activation of microglia, and inflammatory infiltration by granulocytes and lymphocytes. 1: neuronal deaths (cells with red cytoplasm); 2: microglial proliferation; 3: lymphocytes. 14 Mörz Figure 3b: Necrotizing encephalitis: Death of neuronal cells is evident and associated with an increased number of glial cells. Note activation of microglia and presence of inflammatory cell infiltrates, predominantly lymphocytic. 1: neuronal death with hypereosinophilia and destruction of cell nucleus with signs of karyolysis (nuclear content being distributed into the cytoplasm); 2: microglia (example); 3: lymphocyte (example). 15 Mörz Figure 5a: Heart left ventricle. Mild lympho-histiocytic myocarditis. Mild lympho-histiocytic infiltrates (2 + 4). Signs of cardiomyocytic degeneration (5) with cytoplasmic hypereosinophilia and single contraction bands. Mörz Figure 6: Frontal brain. Diffuse, multifocal necrotizing encephalitis. Immunohistochemistry for CD68 (expressed by monocytic cells). Note map-like tissue destruction with the presence of CD68- 16 positive microglial cells. Furthermore zonal activation of microglia (brown granules). Activation of the microglia means that tissue destruction has taken place in the brain, and macrophages (called microglia in the brain) are clearing/removing the cellular debris. Brown granules: macrophages/microglia. Additional observations and comments made by Dr. Mörz: “In some places with inflammatory changes in brain capillaries, there were also signs of apoptotic cell death within the endothelium (Figure 4). The collective findings were suggestive of multifocal necrotizing encephalitis. Furthermore, mild acute vascular changes were observed in the capillaries and other small blood vessels of the heart. They consisted of mild lympho-histiocytic infiltrates, prominent endothelial swelling. Occasionally, adhering plasma coagulates/fibrin clots were present on the endothelial surface, indicative of endothelial damage (Figure 5). Immunohistochemical staining for the presence of SARS-CoV-2 antigens (spike protein and nucleocapsid) was studied in the brain and heart. In the brain, SARS-CoV-2 spike protein subunit 1 was detected in the endothelia, microglia, and astrocytes in the necrotic areas (Figures 6 and 7). Furthermore, spike protein could be demonstrated in the areas of lymphocytic periarteritis, present in the thoracic and abdominal aorta and iliac branches, as well as a cerebral basal artery (Figure 8). The SARS-CoV-2 subunit 1 was found in macrophages and in the cells of the vessel wall, in particular the endothelium (Figure 9), as well as in the Nucleus ruber (Figure 10). In contrast, the nucleocapsid protein of SARSCoV-2 could not be detected in any of the corresponding tissue sections (Figures 11 and 12). In addition, SARS-CoV-2 spike protein subunit 1 was detected in the cardiac endothelial cells that showed lymphocytic myocarditis (Figure 13). Immunohistochemical staining did not detect the SARS-CoV-2 nucleocapsid protein (Figure 14). Immunohistochemistry for SARS-CoV-2 antigens (spike protein and nucleocapsid) revealed that the lesions with necrotizing encephalitis as well as the acute inflammatory changes in the small blood vessels (brain and heart) were associated with abundant deposits of the spike protein SARS-CoV-2 subunit 1. Since the nucleocapsid protein of SARS-CoV-2 was consistently absent, it must be assumed that the presence of spike protein in affected tissues was not due to an infection with SARS-CoV-2 but rather to the transfection of the tissues by the gene-based COVID-19-vaccines. Importantly, spike protein could be only demonstrated in the areas with acute inflammatory reactions (brain, heart, and small blood vessels), in particular in endothelial cells, microglia, and astrocytes. This is strongly suggestive that the spike protein may have played at least a contributing role to the development of the lesions and the course of the disease in this patient. The detailed autopsy study revealed additional pathology, in particular necrotizing encephalitis and myocarditis. While the histopathological signs of myocarditis were comparatively mild, the encephalitis had resulted in significant multifocal necrosis and may well have contributed to the fatal outcome. In the brain and heart, it appeared that the small blood vessels were especially affected, in particular, the endothelium. In severe SARS-CoV-2 infections, a systemic exposure to the virus and its spike protein 17 elicits a strong immunological reaction in which the endothelial cells play a crucial role, leading to vascular dysfunction, immune-thrombosis, and inflammation. During an infection with the virus, both proteins should be expressed and detected together. On the other hand, the gene-based COVID-19 vaccines encode only the spike protein and therefore, the presence of spike protein only (but no nucleocapsid protein) in the heart and brain of the current case can be attributed to vaccination rather than to infection. This agrees with the patient’s history, which includes three vaccine injections, the third one just 3 weeks before his death, but no positive laboratory or clinical diagnosis of the infection. The stated purpose of the gene-based vaccines is to induce an immune response against the spike protein. Such an immune response will, however, not only result in antibody formation against the spike protein but also lead to direct cell- and antibody-mediated cytotoxicity against the cells expressing this foreign antigen. In addition, there are indications that the spike protein on its own can elicit distinct toxicity, in particular, on pericytes and endothelial cells of blood vessels. Several studies have found the vaccine mRNA and/or the spike protein encoded by it at a considerable distance from the injection site for up to three months after the injection. Biodistribution studies in rats with the mRNA-COVID-19 vaccine BNT162b2 also showed that the vaccine does not stay at the injection site but is distributed to all tissues and organs, including the brain. In the case reported here, it may be noted that the spike protein was primarily detected in the vascular endothelium and sparsely in the glial cells but not in the neurons. Nevertheless, neuronal cell death was widespread in the encephalitic foci, which suggests some contribution of immunological bystander activation, i.e., autoimmunity, to the observed cell and tissue damage. This is the first report to demonstrate the presence of the spike protein within the encephalitic lesions and to attribute it to vaccination rather than infection. These findings corroborate a causative role of the gene-based COVID-19 vaccines, and this diagnostic approach is relevant to potentially vaccine-induced damage to other organs as well.” Conclusions: Dr. Mörz has conclusively demonstrated the presence of an abundance of vaccinal spike protein in the endothelial lining of the walls of capillaries and arterioles in the brain and heart. He has also demonstrated significant inflammation within the walls of these same vessels. His interpretations of the findings are appropriate and not overstated. He has appropriately suggested that these two findings are linked---that the inflammation in the vessel walls (vasculitis) was most likely triggered by the presence of vaccinal spike protein in those walls. Dr. Mörz has also conclusively demonstrated diffuse and multifocal inflammation in the brain tissue (encephalitis) and in heart muscle (myocarditis). The encephalitis was necrotizing---i.e., associated with death (necrosis) of brain cells (neurons). It is difficult to know what was chiefly responsible for the necrosis of the brain cells. The findings do not provide good evidence for a direct immune attack on neurons. It is possible that this necrosis represented collateral damage that occurred while nearby microglia/inflammatory cells dealt with spike protein that had penetrated into the brain tissue. It is also 18 possible that the necrosis was partly due to critically impaired blood flow, due either to partial or complete occlusion of capillaries (due to endothelial cell swelling or accumulation of cellular debris and/or thrombotic material) or to severe injury/obliteration of capillaries---such that brain tissue did not receive sufficient vascular delivery of oxygen and nutrients. The latter possibility (death of brain cells due to impaired blood flow at the capillary level), may not be detectable without use of electron microscopy (EM). That is, such capillary damage may not be visible upon light microscopic examination and may be detectable only upon examination by EM. In studies of Susac syndrome (SuS), for example, EM has revealed spectacularly abnormal endothelial swelling and damage in brain capillaries (including capillary obliteration) that were not evident on light microscopy.1 (SuS is a rare immune-mediated, ischemia-producing, occlusive microvascular endotheliopathy/basement membranopathy that affects the brain, retina, and inner ear.) Experience with SuS, therefore, raises the possibility that EM studies of possible vaccine-induced brain injury might reveal extensive capillary abnormalities that are not evident on light microscopy. Dr. Mörz’s examinations included light microscopy but not EM. Taken together, Dr. Mörz findings provide strong support for the following hypothesis: When the mRNA (that is embedded in the lipid nanoparticle of the Pfizer/BioNTech COVID-19 vaccine) is injected into the arm, the mRNA finds its way (via the blood stream) into distant cells---in this case endothelial cells that line the small blood vessels in the heart and brain. (The vaccine does not simply stay in the arm.) Once in an endothelial cell(s), the mRNA instructs the ribosomes in the cell to manufacture spike protein. The spike protein then migrates to the outer surface of the endothelial cell. The immune system then recognizes the spike protein (or fragments thereof) as foreign and concludes that the endothelial cell has become infected. Accordingly, the immune system sends lymphocytes and other inflammatory cells into the walls of the vessel to attack the presumed infected endothelial cells. The vessel wall becomes inflamed (vasculitis) and, during this process, the endothelial cells become immunologically injured and may swell to varying degrees. Sometimes, abnormal intravascular coagulation (clotting within the vessel) may be triggered. In some instances spike protein appears within the brain (or heart) tissue, where the spike protein may trigger an inflammatory reaction (encephalitis, myocarditis) that harms neurons (brain cells) and glial cells. Vaccinees (and those contemplating vaccination) deserve to know whether the Mörz report of probable vaccine-induced microvascular and parenchymal (tissue) injury in the brain and heart represent extremely rare phenomena or are more common than that. Vaccinees and the public at large deserve to know the prevalence of such phenomena, and they deserve to know the full spectrum of such findings. If such phenomena are more than rare, our hope would be that the abnormalities are usually only minimal, not as dramatic as in the case reported. We would also hope that the abnormalities might be reversible, possibly amenable to treatment---particularly if patients are warned to not receive any further COVID-19 mRNA vaccination. It would be helpful if autopsies were to be more frequently considered when people have died inexplicably after COVID-19 vaccination and the possibility of vaccine-injury is deemed a plausible contributor to death. For completeness, EM examination would be helpful when such autopsies are performed. (EM has, unfortunately, nearly become a lost art, except with kidney diseases.) Brain biopsy could also be considered in carefully selected patients who are suffering from considerable new, unexplained brain dysfunction that could quite plausibly be due to injury induced by mRNA COVID-19 vaccination. 19 Our scientific understanding of potential serious complications of the mRNA vaccines---including knowledge of the prevalence, spectrum, pathogenesis, and potential treatment options---will improve if more autopsies (including EM examination when possible) are performed in situations like that of the case reported by Mörz. Our scientific understanding will also be advanced if the Mörz article is widely distributed and thoroughly discussed among as many physicians and scientists as possible---including those who, heretofore, have promoted mRNA COVID-19 vaccination, as well as those who have challenged the wisdom and safety of the COVID-19 mass vaccination campaign. For example, a simple but helpful next step would be for all academic medical centers, globally, to dedicate a Grand Rounds presentation and discussion (with respectful encouragement of multiple points of view) of the significance of the Mörz article. Such scientific dialogue is an essential fundamental principle of medicine. It would also be helpful to convene an international panel of representative experts in pathology, neuropathology, neurology, immunology, and vaccinology to carefully, respectfully, objectively, honestly, transparently, and publicly evaluate Dr. Mörz’s findings and the significance of them. If some believe that Dr. Mörz has overstated the findings or has overstated the likelihood of a link between the presence of the vaccinal spike protein and the inflammation in the vessel wall (and in brain and heart tissue), the most helpful and scientifically rigorous way to address such disagreement is to engage in respectful scientific dialogue. Physicians, nurses, hospitals, medical centers, health departments, the CDC, NIH, FDA, WHO, the pharmaceutical industry, government leaders, and media outlets that have assured the Public that the COVID-19 vaccines are “very safe” (or at least “sufficiently safe under the circumstances”) owe it to the Public to thoroughly, openly, honestly, publicly, and prominently discuss Dr. Mörz’s article and its implications. To those people who have been encouraged, pressured, even mandated to receive COVID vaccination--- physicians and scientists owe a massive top priority collaborative effort to thoroughly study the pathogenesis (the causative chain of events that lead to disease) and potential treatment of vaccine- induced endotheliopathy, vasculitis, encephalitis, and myocarditis---even if these complications prove to be rare. The death of the 76-year-old man reported by Dr. Mörz should not go in vain. We need to determine how to promptly recognize and promptly provide optimal early treatment for vaccinated people who may be developing early evidence of similar complications in their brain, heart, both, and/or elsewhere. In the meantime we should deeply thank Dr. Mörz for performing and publishing his extensive and careful study of this one patient. The scientific quality of his work is excellent. His careful article represents a major contribution to medicine and Humanity. He is to be commended for the expertise, time, effort, and courage it took to present this compelling and extremely valuable information. He has superbly honored the best traditions of science, medicine, and ethics and has performed a great service to Humanity. We should also commend and thank the journal Vaccines for demonstrating the wisdom and moral courage to publish Dr. Mörz’s article. Like Dr. Mörz, Vaccines has honored the best traditions of science, medicine, and ethics, and has honored Humanity in the process. 20 Rob Rennebohm, MD Pediatrician and Pediatric Rheumatologist Retired (formerly at Cleveland Clinic) Email: rmrennebohm@gmail.com Website: www.notesfromthesocialclinic.org 1Dimitri P. Agamanolis, Richard A. Prayson, Negar Asdaghi, Sakir H. Gultekin, Kim Bigley & Robert M. Rennebohm (2019) Brain microvascular pathology in Susac syndrome: an electron microscopic study of five cases, Ultrastructural Pathology, 43:6, 229-236, DOI: 10.1080/01913123.2019.1692117 https://www.tandfonline.com/doi/abs/10.1080/01913123.2019.1692117 *Dr. Mörz has kindly shared the images I have presented in this paper. I have modified his captions to make them more comprehensible to non-physician readers.