Microsurgical complication associated with vaccine-induced immune thrombotic thrombocytopenia (VITT): A case report.

RATIONALE: The use of ChAdOx1 nCoV-19 (Astra Zeneca) vaccine has proven beneficial, but in a limited number of the general population, it was found to be associated with vaccine-induced immune thrombotic thrombocytopenia (VITT). However, there have been no reports of this complication occurring in a microsurgical free tissue transfer. PATIENT CONCERNS: A 49-year-old man developed an acute myocardial infarction 3 weeks after receiving his first dose of ChAdOx1 nCoV-19 in June 2021. Three months later, he presented with right third toe wet gangrene with extension into the plantar foot nine days after receiving his second dose of ChAdOx1 nCoV-19 vaccine. DIAGNOSIS: Based on recent exposure to vaccination, the timing of inoculation before the development of his symptoms, and serology tests (platelet, D-dimer, and anti-PF4 antibodies), the patient was diagnosed with VITT. INTERVENTIONS: Fasciectomy and sequestrectomy were performed for wound bed preparation. Limb salvage was done using free vastus lateralis muscle flap and skin graft for reconstruction. OUTCOME: The flap was complicated by persistent microthrombi leading to superficial necrosis without vascular pedicle compromise. Repeated debridement of the superficial necrosis was done. Three months after the development of VITT, no further new superficial necrosis was seen. A well-contoured flap was seen 5 months after the initial surgery. LESSONS: We believe this is the first case describing microthrombi in the free flap due to VITT after microsurgical reconstruction. Patients and surgeons should be advised of this possible risk when contemplating microsurgery once VITT has developed after ChAdOx1 nCoV-19 administration.

Anaphylaxis to SARS-CoV-2 Vaccines in the Setting of a Nationwide Passive Epidemiological Surveillance Program.

BACKGROUND: Information on anaphylaxis among recipients of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains scarce. OBJECTIVE: To identify the observed incidence of anaphylaxis in recipients of different anti-SARS-CoV-2 vaccines. METHODS: A nationwide observational study among recipients of 61,414,803 doses of seven different anti-SARS-CoV-2 vaccines, describing the incidence and characteristics of adult patients (age ≥ 18 years) who developed anaphylaxis as an adverse event following immunization (AEFI) against SARS-CoV-2 vaccines between December 24, 2020, and October 15, 2021, in Mexico. RESULTS: Sixty-six patients developed anaphylaxis as an AEFI, for an overall observed incidence of 1.07 cases per 1,000,000 (95% CI 0.84-1.37) administered doses. Eighty-six percent of the patients were female, consistent with previous reports of AEFI to COVID-19 vaccines. mRNA-based vaccine recipients had the highest frequency of anaphylaxis, followed by adenovirus-vectored vaccines and inactivated virus recipients, with an observed incidence of 2.5, 0.7, and 0.2 cases per 1,000,000 doses administered, respectively. Only 46% of the patients received correct treatment with epinephrine as the first-line treatment through the appropriate route and dose. We detected one case of anaphylactic reaction-related death occurring 5 min following immunization with ChAdOx1 nCov-19 for a mortality rate of 1.5% among those who developed this AEFI. CONCLUSIONS: In our population, anaphylactic reactions were infrequent. Our study provides further evidence supporting the security of these newly developed vaccines.

Acute Kidney Injury after First Dose of AstraZeneca COVID-19 Vaccine Managed in a Nigerian Hospital.

INTRODUCTION: The association of kidney disease and COVID-19 vaccination has been reported with minimal change disease being a common presentation. CASE REPORT: Index patient is a 54-year-old female who presented with a history of reduction in urine output within 3 weeks of receiving the Oxford-AztraZeneca COVID-19 vaccine. Her serum creatinine on admission was 1,057 µmol/L with a premorbid serum creatinine of 78 µmol/L. Her vital signs were stable. She was on antihypertensive and antidiabetic medications for hypertension and diabetes mellitus, respectively. Renal biopsy was precluded by her morbid obesity and she was commenced on oral prednisolone. She had 5 sessions of hemodialysis and her serum creatinine gradually reduced to 106 µmol/L, and she is being followed up on an outpatient basis. CONCLUSION: We report a case of a female patient with acute kidney injury following COVID-19 Oxford-AztraZeneca vaccination. Further studies are required to better understand the pathogenesis of the renal affectation post-vaccination.

INTRODUCTION: L'association de la maladie rénale et de la vaccination COVID-19 a été signalée, la maladie à changement minimal est une présentation courante. RAPPORT DE CAS: La patiente à l'étude est une femme de 54 ans qui a présenté des antécédents de réduction du débit urinaire dans les 3 semaines après avoir reçu le vaccin COVID-19 d'Oxford-AztraZeneca. Sa créatinine sérique à l'admission était de 1 057 µmol/L avec une créatinine sérique prémorbide de 78 µmol/L. Ses signes vitaux étaient stables. Elle prenait des médicaments antihypertenseurs et antidiabétiques pour l'hypertension et le diabète sucré, respectivement. Une biopsie rénale était impossible à cause de son obésité morbide et elle a été mise sous prednisolone par voie orale. Elle a subi 5 sessions d'hémodialyse et son taux de créatinine sérique a progressivement à 106 µmol/L, et elle est suivie en ambulatoire. CONCLUSION: Nous rapportons le cas d'une patiente souffrant d'une lésion rénale aiguë après la vaccination par le COVID-19 Oxford-AztraZeneca. D'autres études sont nécessaires pour mieux comprendre la pathogenèse de l'affectation rénale post-vaccination. Mots-clés: Vaccin COVID-19, Événement Indésirable, Lésion Rénale Aiguë.

Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines.

BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.

A case of adenoviral covid-19 vector vaccine possibly linked to severe but reversible interstitial lung injury post-vaccination.

BACKGROUND: Several safe and effective vaccines against nCoV-19 have been developed to contain the pandemic with very few severe adverse-reactions reported. Vaccine-induced interstitial lung disease (ILD) is a very rare and difficult to recognise and diagnose adverse-reaction and is mostly associated with Influenza vaccines. METHODS: We report a 55-yr old male who presented with severe respiratory failure that required for several days oxygen supplementation with high flow nasal cannula, and myocardial infarction. Symptoms onset was eighteen days after the first shot of adenoviral AZD1222 vector vaccine. Possible SARS-CoV-2 natural infection post-vaccination was excluded with rigorous laboratory work-up including multiple nasopharengeal rt-qPCR tests for SARS-CoV-2 detection and close monitoring of his serum SARS-CoV-2 antibodies. Other potential infectious agents and alternate diagnoses were thoroughly investigated. RESULTS: Patient responded impressively to high dose steroids. A repeat chest CT nine days after the first one showed a remarkable resolution of the bilateral ground glass opacities. Except for his cardiology medication, no supplemental oxygen neither steroids were prescribed upon his discharge. On one month follow-up, no residual pulmonary dysfunction was noticed with patient preserving a SatO2 of 97-98% on ambient air. CONCLUSION: Vaccine-induced ILD might constitute a rare nCoV-19 post-vaccination adverse-event. According to current restricted data, when post-vaccination ILD is early suspected and recognised, then prompt implementation of steroid treatment reverses significantly the lung lesions without progression to fibrosis.

Facial Angioedema after the first dose of Covishield (adenovirus-vectored severe acute respiratory syndrome coronavirus 2 vaccine): follow-up after the second and third booster doses.

Mass vaccination campaigns are essential to control the ongoing novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic. The Covishield vaccine consists of the replication-deficient simian adenovirus vector ChAdOx1, which contains the full-length structural spike protein of SARS-CoV-2. Occasionally, it can lead to cutaneous reactions that contribute to fear of vaccination, hesitancy, and incomplete vaccination schedules. We report a case of facial angioedema following the first dose of Covishield in a 63-year-old woman with no previous history of allergies or hypersensitivity to drugs or vaccines. No rebound of angioedema was recorded after the second homologous and third heterologous doses.

Longitudinal Aspects of VITT.

In hundreds of patients worldwide, vaccination against COVID-19 with adenovirus vector vaccines (ChAdOx1 nCoV-19; Ad26.COV2.S) triggered platelet-activating anti-platelet factor 4 (PF4) antibodies inducing vaccine-induced immune thrombotic thrombocytopenia (VITT). In most VITT patients, platelet-activating anti-PF4-antibodies are transient and the disorder is discrete and non-recurring. However, in some patients platelet-activating antibodies persist, associated with recurrent thrombocytopenia and sometimes with relapse of thrombosis despite therapeutic-dose anticoagulation. Anti-PF4 IgG antibodies measured by enzyme-immunoassay (EIA) are usually detectable for longer than platelet-activating antibodies in functional assays, but duration of detectability is highly assay-dependent. As more than 1 vaccination dose against COVID-19 is required to achieve sufficient protection, at least 69 VITT patients have undergone subsequent vaccination with an mRNA vaccine, with no relevant subsequent increase in anti-PF4 antibody titers, thrombocytopenia, or thrombotic complications. Also, re-exposure to adenoviral vector-based vaccines in 5 VITT patients was not associated with adverse reactions. Although data are limited, vaccination against influenza also appears to be safe. SARS-CoV-2 infection reported in 1 patient with preceding VITT did not influence anti-PF4 antibody levels. We discuss how these temporal characteristics of VITT provide insights into pathogenesis.

Epidemiology of VITT.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a life-threatening syndrome of aggressive thrombosis, often profound thrombocytopenia, and frequently overt disseminated intravascular coagulation. It has been associated with 2 adenovirus vector COVID-19 vaccines: ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen). Unlike the myriad of other conditions that cause thrombosis and thrombocytopenia, VITT has an important distinguishing feature: affected individuals have platelet activating anti-PF4 antibodies that appear in a predictable time frame following vaccination. The reported incidence of VITT differs between jurisdictions; it is dependent on accurate ascertainment of cases and accurate estimates of the size of the vaccinated population. The incidence ranges from 1 case per 26,500 to 127,3000 first doses of ChAdOx1 nCoV-19 administered. It is estimated at 1 case per 518,181 second doses of ChAdOx1 nCoV-19 administered, and 1 case per 263,000 Ad26.COV2.S doses administered. There are no clear risk factors for VITT, including sex, age, or comorbidities. VITT is a rare event, but its considerable morbidity and mortality merit ongoing pharmacovigilance, and accurate case ascertainment.

Concomitant myocarditis and painless thyroiditis after AstraZeneca coronavirus disease 2019 vaccination: a case report.

BACKGROUND: Incidence of myocarditis following messenger RNA coronavirus disease 2019 vaccination has been widely described, but this clinical scenario after adenoviral vector coronavirus disease 2019 vaccination has only been rarely reported. In addition, a few case reports of thyroiditis after adenoviral vector coronavirus disease 2019 vaccination have been published. CASE PRESENTATION: A 55-year-old Thai woman presented with palpitation without neck pain 14 days after receiving AstraZeneca coronavirus disease 2019 vaccination. Electrocardiography revealed sinus tachycardia. Her blood tests showed elevation of cardiac troponin and free triiodothyronine with suppressed serum thyroid stimulating hormone, reflecting a hyperthyroid status. Evidence of myocardial inflammation and necrosis from cardiac magnetic resonance imaging supported the diagnosis of recent myocarditis. Laboratory results and imaging findings were consistent with thyroiditis. After 3 weeks of symptomatic treatment, her symptom and blood tests had returned to normal. CONCLUSIONS: This case demonstrates that the adenoviral vector coronavirus disease 2019 vaccine could possibly cause myocarditis and painless thyroiditis. Clinicians should have a high index of suspicion and promptly evaluate these conditions, despite minimal symptoms.

Explaining COVID-19 postvaccination-related immune thrombotic thrombocytopenia: a hypothesis-generating in-silico approach.

Cases that experienced COVID-19 postvaccination-related thrombosis have been reported after the first dose of ChAdOx1 nCov-19 (Vaxzevria, AstraZeneca) or Ad26.COV2.S (Johnson & Johnson/Janssen) vaccine. These rare thrombotic events were observed within the expected vaccine-induced seroconversion period and could be attributed to platelet-activating (auto)antibodies against platelet factor 4 (PF4). Newly, vaccine-induced, cross-reactive anti-PF4 antibodies could explain this observation. An in-silico analysis using the Basic Local Alignment Search Tool was used to identify sequence similarity between PF4 and antigens contained in or encoded by ChAdOx1 nCov-19 or Ad26.COV2.S vaccines. Only one sequence within the signaling peptide of the SARS-CoV-2 spike protein exhibited a high percent identity (85.71%) with PF4. This sequence overlaps with a proven immunogenic peptide recognized from convalescent COVID-19 sera and could be responsible for the formation of platelet-activating immunocomplexes in susceptible patients. Manipulation of the immunogenicity of this particular sequence within the encoded SARS-CoV-2 spike protein signaling peptide may eliminate this iatrogenic severe adverse effect.

Thrombocytopenia and splenic platelet-directed immune responses after IV ChAdOx1 nCov-19 administration.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are based on a range of novel platforms, with adenovirus-based approaches (like ChAdOx1 nCov-19) being one of them. Recently, a novel complication of SARS-CoV-2-targeted adenovirus vaccines has emerged: immune thrombocytopenia, either isolated, or accompanied by thrombosis (then termed VITT). This complication is characterized by low platelet counts, and in the case of VITT, also by platelet-activating platelet factor 4 antibodies reminiscent of heparin-induced thrombocytopenia, leading to a prothrombotic state with clot formation at unusual anatomic sites. Here, we detected antiplatelet antibodies targeting platelet glycoprotein receptors in 30% of patients with proven VITT (n = 27) and 42% of patients with isolated thrombocytopenia after ChAdOx1 nCov-19 vaccination (n = 26), indicating broad antiplatelet autoimmunity in these clinical entities. We use in vitro and in vivo models to characterize possible mechanisms of these platelet-targeted autoimmune responses leading to thrombocytopenia. We show that IV but not intramuscular injection of ChAdOx1 nCov-19 triggers platelet-adenovirus aggregate formation and platelet activation in mice. After IV injection, these aggregates are phagocytosed by macrophages in the spleen, and platelet remnants are found in the marginal zone and follicles. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelets. Our work contributes to the understanding of platelet-associated complications after ChAdOx1 nCov-19 administration and highlights accidental IV injection as a potential mechanism of platelet-targeted autoimmunity. Hence, preventing IV injection when administering adenovirus-based vaccines could be a potential measure against platelet-associated pathologies after vaccination.

Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England.

BACKGROUND: Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. METHODS AND FINDINGS: In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. CONCLUSIONS: In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.

Venous Thrombosis within 30 Days after Vaccination against SARS-CoV-2 in a Multinational Venous Thromboembolism Registry.

BACKGROUND: Venous thromboembolism (VTE)-including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)-may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. METHODS: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4-30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018-2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. RESULTS: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7-94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07-47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls. CONCLUSIONS: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes.

Coincidental Onset of Ocular Myasthenia Gravis Following ChAdOx1 n-CoV-19 Vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: The Oxford-AstraZeneca vaccine ChAdOx1 (AZD1222, Vaxzevria) is playing a crucial role in counteracting the coronavirus disease-2019 (COVID-19) pandemic [1]. Since March 2021, reports of unexpected thrombotic events associated with thrombocytopenia and vaccination have been published [2]. To the best of our knowledge there is only one report about vaccination-associated myasthenia gravis (MG) occurring after a second dose of BNT162b2 (Pfizer-BioNTech).

Vaccine-induced COVID-19 mimicry syndrome.

To fight the COVID-19 pandemic caused by the RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve the immunization of billions of people mainly with adenoviral vector- or mRNA-based vaccines, all of which encode the SARS-CoV-2 Spike protein. In some rare cases, cerebral venous sinus thromboses (CVST) have been reported as a severe side effect occurring 4-14 days after the first vaccination and were often accompanied by thrombocytopenia. Besides CVST, splanchnic vein thromboses (SVT) and other thromboembolic events have been observed. These events only occurred following vaccination with adenoviral vector-based vaccines but not following vaccination with mRNA-based vaccines. Meanwhile, scientists have proposed an immune-based pathomechanism and the condition has been coined vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe an unexpected mechanism that could explain thromboembolic events occurring with DNA-based but not with RNA-based vaccines. We show that DNA-encoded mRNA coding for Spike protein can be spliced in a way that the transmembrane anchor of Spike is lost, so that nearly full-length Spike is secreted from cells. Secreted Spike variants could potentially initiate severe side effects when binding to cells via the ACE2 receptor. Avoiding such splicing events should become part of a rational vaccine design to increase safety of prospective vaccines.

Ultrastructural findings of lung injury due to Vaccine-induced Immune Thrombotic Thrombo- cytopenia (VITT) following COVID-19 vaccination: a scanning electron microscopic study.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.