SARS-CoV-2 vaccination induced cerebral venous sinus thrombosis: Do megakaryocytes, platelets and lipid mediators make up the orchestra?

The COVID-19 vaccines comprised of adenoviral vectors encoding the Spike (S) glycoprotein of SARS-CoV-2 are highly effective but associated with rare thrombotic complications. The adenovirus vector infects epithelial cells expressing the coxsackievirus and adenovirus receptor (CAR). The S glycoprotein expressed locally stimulates neutralizing antibody and cellular immune responses. These vaccines have been associated with thromboembolic events including cerebral venous sinus thrombosis (CVST). S glycoprotein stimulates the expression of cyclooxygenase-2 (COX-2) and leads to massive generation of thromboxane A2 in COVID-19. Megakaryocytes express CAR and we postulate that S glycoprotein stimulated generation of thromboxane A2 leads to megakaryocyte activation, biogenesis of activated platelets and thereby increased thrombogenicity. Cerebral vein sinuses express podoplanin, a natural ligand for CLEC2 receptors on platelets. Platelets traversing through the cerebral vein sinuses could be further activated by thromboxane A2-dependent podoplanin-CLEC2 signaling, leading to CVST. A prothrombotic hormonal milieu, and increased generation of thromboxane A2 and platelet activation in healthy females compared to males is consistent with increased risk for CVST observed in women. We propose that antiplatelet agents targeting thromboxane A2 receptor signaling such as low-dose aspirin merit consideration for chemoprophylaxis when administering the adenovirus based COVID-19 vaccines to young adults at risk of thrombosis provided there are no contraindications.

An unusual occurrence of autoimmune pancreatitis after gam-Covid-Vac (Sputnik V): A case report and literature review.

The safety profile of the Sputnik V vaccine is generally reassuring. Nevertheless, an enhanced risk of new-onset of immune-mediated diseases has been increasingly reported following the adenoviral-based Covid-19 vaccine, including inflammatory arthritis, Guillain-Barré syndrome, optical neuromyelitis, acute disseminated encephalomyelitis, subacute thyroiditis and acute liver injury as well as glomerulopathy. However, no case of autoimmune pancreatitis has been reported yet. Herein, we describe a case of type I autoimmune pancreatitis that may be due to the Sputnik V Covid-19 vaccine.

GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models.

The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains. We found that a single intranasal (i.n.) dose of serotype-5 adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and BAL, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of mice from a challenge with the SARS-CoV-2 beta variant. Intramuscular (i.m.) Ad5-RBD or Ad5-S administration did not induce serum or BAL IgA, and resulted in lower neutralizing titers in the serum. Moreover, prior immunity induced by an intramuscular mRNA vaccine could be potently enhanced and modulated towards a mucosal IgA response by an i.n. Ad5-S booster. Notably, Ad5 DNA was found in the liver or spleen after i.m. but not i.n. administration, indicating a lack of systemic spread of the vaccine vector, which has been associated with a risk of thrombotic thrombocytopenia. Unlike in otherwise genetically identical HLA-DQ6 mice, in HLA-DQ8 mice Ad5-RBD vaccine was inferior to Ad5-S, suggesting that the RBD fragment does not contain a sufficient collection of helper-T cell epitopes to constitute an optimal vaccine antigen. Our data add to previous promising preclinical results on intranasal SARS-CoV-2 vaccination and support the potential of this approach to elicit mucosal immunity for preventing transmission of SARS-CoV-2.

Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines.

Q fever is a highly infectious zoonosis caused by the Gram-negative bacterium Coxiella burnetii. The worldwide distribution of Q fever suggests a need for vaccines that are more efficacious, affordable, and does not induce severe adverse reactions in vaccine recipients with pre-existing immunity against Q fever. Potential Q fever vaccine antigens include lipopolysaccharide (LPS) and several C. burnetii surface proteins. Antibodies elicited by purified C. burnetii lipopolysaccharide (LPS) correlate with protection against Q fever, while antigens encoded by adenoviral vectored vaccines can induce cellular immune responses which aid clearing of intracellular pathogens. In the present study, the immunogenicity and the protection induced by adenoviral vectored constructs formulated with the addition of LPS were assessed. Multiple vaccine constructs encoding single or fusion antigens from C. burnetii were synthesised. The adenoviral vectored vaccine constructs alone elicited strong cellular immunity, but this response was not correlative with protection in mice. However, vaccination with LPS was significantly associated with lower weight loss post-bacterial challenge independent of co-administration with adenoviral vaccine constructs, supporting further vaccine development based on LPS.

A preliminary study on the effectiveness of maternal to neonatal transfer of antibodies against SARS-CoV-2 in the women vaccinated with heterologous CoronaVac-ChAdOx1.

The objective is to evaluate the effectiveness of placental transfer of maternally derived SARS-CoV-2 IgG antibodies after the vaccination of pregnant women with heterologous CoronaVac-ChAdOx1. Thirty pregnant women were vaccinated with CoronaVac as the first dose, followed by ChAdOx1 3 weeks later. The antibody levels in the maternal blood and in the umbilical cord blood at the time of delivery were determined. The results showed that the vaccination effectively increased antibody levels in both mothers and newborns. The antibody levels in the mothers were strongly correlated with those in the newborns (P < .001). The high levels of passive immunity in the newborns were achieved when the first and second doses of vaccination were given more than 40 and 20 d before delivery, respectively. After 1 month of the second dose, the immune levels seemed to decline in the mothers but increase in the newborns. The antibody levels in the newborns appear to be higher than those in the mothers in cases of delivery after 20 d of the second dose (1419 ± 699 vs 1222 ± 593 BAU/L; p < .05). In conclusion, heterologous CoronaVac-ChAdOx1-S schedule can increase antibody levels in a short time during pregnancy. Also, the regimen effectively increases immunity in the newborns. The antibody levels in the newborns appear to be higher than that in the mothers in most cases, if receiving the second dose more than 3 weeks before delivery. Therefore, the regimen should be considered as an effective regimen for pregnant women, especially in settings where mRNA vaccine is not available.

Reported COVID-19 vaccines side effects among Algerian athletes: a comparison between inactivated virus, adenoviral vector, and mRNA COVID-19 vaccines.

OBJECTIVES: Many types of COVID19 vaccines are administered globally, yet there is not much evidence regarding their side effects among athletes. This study evaluated the selfreported postvaccination side effects of inactivated virus, adenoviral vector, and mRNA COVID19 vaccines among Algerian athletes. METHODS: A cross-sectional survey-based study was carried out in Algeria between March 01 and 4 April 2022. The study used a validated questionnaire with twenty-five multiple-choice items covering the participants' anamnestic characteristics, post-vaccination side effects (their onset and duration), post-vaccination medical care, and risk factors. RESULTS: A total of 273 athletes completed the survey. Overall, (54.6%) of the athletes reported at least one local side effect, while (46.9%) reported at least one systemic side effect. These side effects were more prevalent among the adenoviral vector group compared to the inactivated virus and mRNA groups. The most common local side effect was injection site pain (29.9%), while Fever (30.8%) was the most prevalent systemic side effect. The age group of 31-40 years, allergy, previous infection with COVID-19, and the first dose of vaccines were associated with an increased risk of side effects for all groups of COVID-19 vaccines. Logistic regression analysis further revealed that compared to males, the incidence of reported side effects was significantly higher in females (odd ratio (OR) = 1.16; P = 0.015*) only for the adenoviral vector vaccine group. In addition, a significantly higher percentage of athletes group of high dynamic/moderate static or high dynamic /high static components suffered from post-vaccination side effects compared to the group of athletes with high dynamic/low static components (OR = 14.68 and 14.71; P < 0.001, respectively). CONCLUSIONS: The adenoviral vector vaccines have the highest rate of side effects, followed by the inactivated virus and mRNA COVID-19 vaccines. COVID­19 vaccines were well-tolerated among Algerian athletes and there were no reports of serious side effects. Nevertheless, further long-term follow-up study with a larger sample size of athletes (from different types and sports categories) is warranted to establish the long-term safety of the COVID-19 vaccine.

Adenovirus Vaccine Containing Truncated SARS-CoV-2 Spike Protein S1 Subunit Leads to a Specific Immune Response in Mice.

The development of an efficient and safe coronavirus disease 2019 (COVID-19) vaccine is a crucial approach for managing the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) pandemic in light of current conditions. In this study, we produced a shortened segment of the optimized SARS-CoV-2 spike gene (2043 bp, termed S1) that was able to encode a truncated S1 protein. The protein was tested to determine if it could elicit efficient immunization in mice against SARS-CoV-2. The presence of the S1 protein was confirmed with immunofluorescence and Western blotting. An adenovirus vaccine bearing the S1 gene fragment (Ad-S1) was administered intramuscularly to mice four times over 4 weeks. SARS-CoV-2 S1 protein humoral immunity was demonstrated in all immunized mice. The serum from immunized mice demonstrated excellent anti-infection activity in vitro. A robust humoral immune response against SARS-CoV-2 was observed in the mice after vaccination with Ad-S1, suggesting that the adenovirus vaccine may aid the development of vaccines against SARS-CoV-2 and other genetically distinct viruses.

Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies.

BACKGROUND: There are multiple reviews on cardiovascular aspects of COVID-19 disease on cardiovascular system in different population but there is lack of evidence about cardiovascular adverse effects of COVID vaccines. OBJECTIVES: The purpose of this study was to compare the cardiac complications of COVID19 vaccines, based on vaccine type (mRNA, vector-based, and inactivated vaccines). METHODS: A systematic search was performed covering PubMed for English case-reports and case-series studies, and finally 100 studies were included. RESULTS: Myocarditis (with overall rate around 1.62%) was shown to be the most common post-COVID19 immunization cardiac event. More than 90% of post-COVID19 vaccination myocarditis occurred after receiving mRNA vaccines (Moderna & Pfizer-BioNTech), but the report of this event was less in the case of vector-based vaccinations and/or inactivated vaccines. Myocarditis was reported more commonly in men and following the second dose of the immunization. Takotsubo cardiomyopathy (TTC) was reported after mRNA (more commonly) and vector-based vaccinations, with no case report after inactivated vaccines. When mRNA and vector-based vaccinations were used instead of inactivated vaccines, a greater frequency of vaccine-induced thrombotic thrombocytopenia (VITT) and pulmonary emboli (PE) was reported. Myocardial infarction/cardiac arrest was recorded in those beyond the age of 75 years. CONCLUSION: The personal and public health benefits of COVID-19 vaccination much outweigh the minor cardiac risks. Reporting bias, regarding more available mRNA vaccines in developed countries, may conflict these results.

Frequently Asked Questions on Coronavirus Disease 2019 Vaccination for Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Recipients From the American Society for Transplantation and Cellular Therapy and the American Society of Hematology.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects immunocompromised and elderly patients. Not only are hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell recipients at greater risk for severe COVID-19 and COVID-19-related complications, but they also may experience suboptimal immune responses to currently available COVID-19 vaccines. Optimizing the use, timing, and number of doses of the COVID-19 vaccines in these patients may provide better protection against SARS-CoV-2 infection and better outcomes after infection. To this end, current guidelines for COVID-19 vaccination in HCT and CAR T-cell recipients from the American Society of Transplantation and Cellular Therapy Transplant Infectious Disease Special Interest Group and the American Society of Hematology are provided in a frequently asked questions format.

The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine.

The adenovirus vector platform remains one of the most efficient toolboxes for generation of transfer vehicles used in gene therapy and virotherapy to treat tumors, as well as vaccines to protect from infectious diseases. The adenovirus genome and capsids can be modified using highly efficient techniques, and vectors can be produced at high titers, which facilitates their rapid adaptation to current needs and disease applications. Over recent years, the adenovirus vector platform has been in the center of attention for vaccine development against the ongoing coronavirus SARS-CoV-2/COVID-19 pandemic. The worldwide deployment of these vaccines has greatly deepened the knowledge on virus-host interactions and highlighted the need to further improve the effectiveness and safety not only of adenovirus-based vaccines but also of gene therapy and oncolytic virotherapy vectors. Based on the current evidence, we discuss here how adenoviral vectors can be further improved by intelligent molecular design. This review covers the full spectrum of state-of-the-art strategies to avoid vector-induced side effects ranging from the vectorization of non-canonical adenovirus types to novel genome engineering techniques.

Risk factors affecting COVID-19 vaccine effectiveness identified from 290 cross-country observational studies until February 2022: a meta-analysis and meta-regression.

BACKGROUND: Observational studies made it possible to assess the impact of risk factors on the long-term effectiveness of mRNA and adenoviral vector (AdV) vaccines against COVID-19. METHODS: A computerized literature search was undertaken using the MEDLINE, EMBASE, and MedRxiv databases to identify eligible studies, with no language restrictions, published up to 28 February 2022. Eligible were observational studies assessing vaccine effectiveness (VE) by disease severity with reference groups of unvaccinated participants or participants immunized with one, two, or three vaccine doses. Our study was carried out in compliance with the PRISMA and MOOSE guidelines. The risk of study bias was identified using the Newcastle-Ottawa Quality Assessment Scale. The GRADE guidelines were applied to assess the strength of evidence for the primary outcome. The synthesis was conducted using a meta-analysis and meta-regression. RESULTS: Out of a total of 14,155 publications, 290 studies were included. Early VE of full vaccination against COVID-19 of any symptomatology and severity decreased from 96% (95% CI, 95-96%) for mRNA and from 86% (95% CI, 83-89%) for AdV vaccines to 67% for both vaccine types in the last 2 months of 2021. A similar 1-year decline from 98 to 86% was found for severe COVID-19 after full immunization with mRNA, but not with AdV vaccines providing persistent 82-87% effectiveness. Variant-reduced VE was only associated with Omicron regardless of disease severity, vaccine type, or vaccination completeness. The level of protection was reduced in participants aged >65 years, with a comorbidity or those in long-term care or residential homes independently of the number of doses received. The booster effect of the third mRNA dose was unclear because incompletely restored effectiveness, regardless of disease severity, declined within a short-term interval of 4 months. CONCLUSIONS: Full vaccination provided an early high, yet waning level of protection against COVID-19 of any severity with a strong impact on the high-risk population. Moreover, the potential risk of new antigenically distinct variants should not be underestimated, and any future immunization strategy should include variant-updated vaccines.

Short-Term Adverse Effects Following Booster Dose of Inactivated-Virus vs. Adenoviral-Vector COVID-19 Vaccines in Algeria: A Cross-Sectional Study of the General Population.

COVID-19 booster vaccines have been adopted in almost all countries to enhance the immune response and combat the emergence of new variants. Algeria adopted this strategy in November 2021. This study was conducted to consider the self-reported side effects of COVID-19 booster vaccines by Algerians who were vaccinated with a booster dose of one of the approved inactivated-virus vaccines, such as BBIBP-CorV and CoronaVac, or one of the adenoviral-vector-based vaccines, such as Gam-COVID-Vac, AZD1222 and Ad26.COV2.S, and to determine the eventual risk factors. A cross-sectional study using an online self-administered questionnaire (SAQ) was conducted in Algeria between 28 April 2022, and 20 July 2022. A descriptive analysis of the 196 individuals who were included showed a nearly equal distribution of adenoviral- (52%) and inactivated-virus vaccines (48%) and of males (49.5%) and females (50.5%). The results showed that 74.7% of the studied population reported at least one local or systemic side effect. These side effects were more frequent among adenoviral-vector vaccinees (87.3%) than inactivated-virus vaccinees (60.6%) (sig. < 0.001). Injection site pain (40.3%), heat at the injection site (21.4%), and arm pain (16.3%) were the most common local side effects. These signs generally appeared in the first 12 h (73.3%) and generally lasted less than 24 h (32.8%). More interestingly, these signs differed from those that followed the administration of primer doses (48.5%) and were generally more severe (37%). The same observation was reported for systemic side effects, where the signs were especially most severe in the adenoviral-vaccinated group (49.4% vs. 20.8%; sig. = 0.001). These signs generally appeared within the first day (63.6%) and mostly disappeared before two days (50.8%), with fatigue (41.8%), fever (41.3%), and headache (30.1%) being the most common. Adenoviral-vector vaccinees (62.7%) were more likely to use medications to manage these side effects than were inactivated-virus vaccinees (45.7%) (sig. = 0.035) and paracetamol (48.5%) was the most used medication. Adenoviral-based vaccines were the types of vaccines that were most likely to cause side effects. In addition, being female increased the risk of developing side effects; regular medication was associated with local side effects among inactivated-virus vaccinees; and previous infection with COVID-19 was associated with systemic and local side effects among adenovirus-based vaccinees. These results support the short-term safety of booster vaccines, as has been reported for primer doses.

Epidemiological aspects of headache after different types of COVID-19 vaccines: An online survey.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine-related side effects are a key concern with the emergence of various types of vaccines in the market. We aimed to assess the frequency and characteristics of headache following different types of COVID-19 vaccines. METHODS: Fully vaccinated people were recruited by a convenience sample through an online survey from September 1 to December 1, 2021. Detailed analysis of headache following vaccination was investigated. Participants with a history of pre-existing headaches were telephone interviewed by a neurologist to ascertain the type of headache. RESULTS: A total of 1372 participants participated (mean age 32.9 ± 11.1). The highest frequency of headache was reported with the adenoviral vector type (302/563, 53.6%), followed by mRNA vaccines (129/269, 48%) and then the inactivated type (188/540, 34.8%). Recipients of the adenoviral vector type had a significantly longer latency between vaccination and the headache onset (median 8 h [5:12]) than recipients of the inactivated type (median 4 h [2:8], p < 0.001). Headache intensity was significantly higher with the adenoviral vector type (median 6 [5:8]) than with the inactivated type (median 5 [4:7], p < 0.001). Adenoviral vector vaccines would increase the likelihood of headache by 2.38 times more than inactivated vaccines (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.83-3.04, p < 0.001). Female sex and thyroid disease were significantly associated with headache related to COVID-19 vaccines (OR 1.52, 95% CI 1.16-1.99; OR 3.97, 95% CI 1.55-10.2, respectively). CONCLUSION: Recipients of the COVID-19 vaccine should be counseled that they may experience headaches, especially after the adenoviral vector type. However, the intensity of such headache is mild to moderate and can resolve within a few days. Based on the current study design and the potential recall bias, these results may not be generalizable and should be preliminary.

Acute vestibular neuritis: A rare complication after the adenoviral vector-based COVID-19 vaccine.

Vestibular neuritis was first reported in 1952 by Dix and Hallpike, and 30% of patients reporting a flu-like symptom before acquiring the disorder. The most common causes are viral infections, often resulting from systemic viral infections or bacterial labyrinthitis. Here we presented a rare case of acute vestibular neuritis after the adenoviral vector-based COVID-19 vaccination. A 51-year-old male pilot awoke early in the morning with severe vertigo, nausea, and vomiting after receiving the first dose of the ChAdOx1 nCoV-19 vaccine 11 days ago. Nasopharyngeal SARS-CoV-2 RT-PCR test and chest CT scan were inconclusive for COVID-19 pneumonia. Significant findings were a severe spontaneous and constant true-whirling vertigo which worsened with head movement, horizontal-torsional spontaneous nystagmus, abnormal caloric test, positive bedside head impulse tests, and inability to tolerate head-thrust test. PTA, MRI of the brain and internal auditory canal, and cerebral CT arteriography were normal. According to the clinical, imaging, and laboratory findings, he was admitted to the neurology ward and received treatment for vestibular neuritis. His vertigo increased gradually over 6-8 h, peaking on the first day, and gradually subsided over 7 days. Ten days later, the symptoms became tolerable; the patient was discharged with advice for home-based vestibular rehabilitation exercises. Despite the proper treatment and rehabilitation, signs of dynamic vestibular imbalances persisted after 1 year. Based on the Federal Aviation Administration (FAA) regulations, the Air Medical Council (AMC) suspended him from flight duties until receiving full recovery. Several cases of vestibular neuritis have been reported in the COVID-19 patients and after the COVID-19 vaccination. This is the first case report of acute vestibular neuritis after the ChAdOx1 nCoV-19 vaccination in a healthy pilot without past medical history. However, the authors believe that this is a primary clinical suspicion that must be considered and confirmed after complete investigations.

Retrospective review COVID-19 vaccine induced thrombotic thrombocytopenia and cerebral venous thrombosis-what can we learn from the immune response.

INTRODUCTION: Cerebral Venous Thrombosis (CVT), prior to the COVID pandemic, was rare representing 0.5 of all strokes, with the diagnosis made by MRI or CT venography.1-,3 COVID-19 patients compared to general populations have a 30-60 times greater risk of CVT compared to non-affected populations, and up to a third of severe COVID patients may have thrombotic complications.4-8 Currently, vaccines are the best way to prevent severe COVID-19. In February 2021, reports of CVT and Vaccine-induced immune thrombotic thrombocytopenia (VITT) related to adenovirus viral vector vaccines including the Oxford-AstraZeneca vaccine (AZD1222 (ChAdOx1)) and Johnson & Johnson COVID-19 vaccine (JNJ-78436735 (Ad26.COV2·S)), were noted, with a 1/583,000 incidence from Johnson and Johnson vaccine in the United States.11, 12 This study retrospectively analyzed CVT and cross-sectional venography at an Eastern Medical Center from 2018 to 2021, and presents radiographic examples of CVT and what is learned from the immune response. METHODS: After IRB approval, a retrospective review of cross-sectional CTV and MRVs from January 1st 2018 to April 30th 2021, at a single health system was performed. Indications, vaccine status, patient age, sex, and positive finding incidence were specifically assessed during March and April for each year. A multivariable-adjusted trends analysis using Poisson regression estimated venogram frequencies and multivariable logistic regression compared sex, age, indications and vaccination status. RESULTS AND DISCUSSION: From January 1, 2018 to April 30, 2021, (Fig. 1), a total of n = 2206 in patient and emergency room cross-sectional venograms were obtained, with 322 CTVs and 1884 MRVs. In 2018, 2019, 2020, respective totals of cross-sectional venograms were 568, 657, 660, compared to 321 cross-sectional venograms in the first four months of 2021. CTV in 2018, 2019, 2020, respective totals were 51, 86, 97, MRV totals were 517, 571, 563, compared to the 2021 first four month totals of 88 CTVs and 233 MRVs. March, April 2018, 2019, 2020, CTVs respectively were 6, 17, 11, compared to the 2021 first four months of 59 CTVs, comprising 63% of the total 93 CTVs, respective MRVs were 79, 97, 52, compared to 143 MRVs in the first four months of 2021 for 39% of the total 371 MRVs. In March, April 2020 during the pandemic onset, cross-sectional imaging at the East Coast Medical Center decreased, as priorities were on maintaining patient ventilation, high level of care and limiting spread of disease. In March/April 2021, reports of VITT and CVT likely contributed to increased CTVs and MRVs, of 39.65% [1.20-1.63] increase (P < 0.001) from prior. In March, April 2021 of 202 venograms obtained, 158 (78.2.%) were unvaccinated patients, 16 positive for CVT (10.1%), 44 were on vaccinated patients (21.7%), 8 specifically ordered with vaccination as a clinical indication, 2 positive for CVT (4.5%), (odds ratio = 0.52 [0.12-2.38], p = 0.200). CONCLUSION: CTV prior to the COVID pandemic, was rare, responsible for 0.5 of all strokes, at the onset of the pandemic in the East Coast, overall cross-sectional imaging volumes declined due to maintaining ventilation, high levels of care and limiting disease spread, although COVID-19 patients have a 30-60 times greater risk of CVT compared to the general population, and vaccination is currently the best option to mitigate severe disease. In early 2021, reports of adenoviral vector COVID vaccines causing CTV and VITT, led to at 39.65% increase in cross-sectional venography, however, in this study unvaccinated patients in 2021 had higher incidence of CVT (10.1%), compared to the vaccinated patients (4.5%). Clinicians should be aware that VITT CVT may present with a headache 5-30 days post-vaccination with thrombosis best diagnosed on CTV or MRV. If thrombosis is present with thrombocytopenia, platelets <150 × 109, elevated D-Dimer >4000 FEU, and positive anti-PF4 ELISA assay, the diagnosis is definitive.13 VITT CVT resembles spontaneous autoimmune heparin induced thrombocytopenia (HIT), and is postulated to occur from platelet factor 4 (PF4) binding to vaccine adenoviral vectors forming a novel antigen, anti-PF4 memory B-cells and anti-PF4 (VITT) antibodies.14-17.

A Disproportionality Analysis for Association of Systemic Capillary Leak Syndrome with COVID-19 Vaccination Using the World Health Organization Pharmacovigilance Database.

Systemic capillary leak syndrome (SCLS) is a rare and potentially life-threatening disorder characterized by reversible plasma extravasation and vascular collapse. This study aimed to investigate the association between different types of COVID-19 vaccine and SCLS in a real-world setting. We used individual case safety reports of SCLS after COVID-19 vaccination from the WHO pharmacovigilance database, VigiBase. A disproportionality analysis of ChAdOx1 nCoV-19 and mRNA-based vaccines was performed. The information component (IC) and reporting odds ratio (ROR) were calculated from the entire database and viral vaccines data subset. A positive 95% lower end of the IC (IC025) value (>0) using Bayesian neural network analysis and lower end of the ROR 95% confidence interval (ROR025) ≥1 were defined as the ADR signal detection threshold. A total of 101 (0.004%) events of SCLS were identified. A significant potential signal of disproportionality of SCLS was noted in ChAdOx1 nCoV-19 when applied as the denominator for entire database (IC025 = 0.24, ROR025 = 1.23) and all viral vaccines (IC025 = 0.41, ROR025 = 1.59). No significant potential signal was noted for two mRNA-based vaccines as denominators for the entire database (IC025 = -0.49, ROR025 = 0.71) and all viral vaccines (IC025 = -0.32, ROR025 = 0.77). Contrary to ChAdOx1 nCoV-1, no safety signal for developing SCLS was identified for mRNA-based vaccines.

Thrombotic Complications after COVID-19 Vaccination: Diagnosis and Treatment Options.

Coronavirus disease 2019 (COVID-19) vaccines were developed a few months after the emergence of the pandemic. The first cases of vaccine-induced thrombotic complications after the use of adenoviral vector vaccines ChAdOx1 nCoV-19 by AstraZeneca, and Ad26.COV2.S by Johnson & Johnson/Janssen, were announced shortly after the initiation of a global vaccination program. In these cases, the occurrence of thrombotic events at unusual sites-predominantly located in the venous vascular system-in association with concomitant thrombocytopenia were observed. Since this new entity termed vaccine-induced thrombotic thrombocytopenia (VITT) shows similar pathophysiologic mechanisms as heparin-induced thrombocytopenia (HIT), including the presence of antibodies against heparin/platelet factor 4 (PF4), standard routine treatment for thrombotic events-arterial or venous-are not appropriate and may also cause severe harm in affected patients. Thrombotic complications were also rarely documented after vaccination with mRNA vaccines, but a typical VITT phenomenon has, to date, not been established for these vaccines. The aim of this review is to give a concise and feasible overview of diagnostic and therapeutic strategies in COVID-19 vaccine-induced thrombotic complications.

SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia.

SARS-CoV-2 vaccines have been carefully developed and significantly alleviate the global pandemic. However, a rare but severe complication after vaccination of adenoviral vector vaccines has attracted worldwide attention. It is characterized by thrombosis at unusual sites (often cerebral or abdominal), thrombocytopenia, and the presence of antibodies against platelet factor 4 (PF4), termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Its pathogenesis is similar to that of heparin-induced thrombocytopenia (HIT). VITT progresses rapidly and has a high mortality rate. Clinicians and the public should raise their vigilance to this disease so that accurate and timely treatment is provided.