An Old Acquaintance: Could Adenoviruses Be Our Next Pandemic Threat?

Human adenoviruses (HAdV) are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 110 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, are stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. This review aimed to highlight the HAdV variability and the pandemic potential that a HAdV3 and 7 recombinant could have considering the aggressive outbreaks produced in health facilities. Herein, we described the characteristics of HAdV, from the infection to treatment, vaccine development, and the evaluation of the social determinants of health associated with HAdV, suggesting the necessary measures for future sanitary control to prevent disasters such as the SARS-CoV-2 pandemic, with an emphasis on the use of recombinant AdV vaccines to control other potential pandemics.

Allergological study in patients referred for adverse reactions to the SARS CoV2 vaccine: Our experience

Background: Adverse reaction's reported after COVID 19 vaccination had a negative impact on public opinion. These adverse reactions may be or may be not be mediated by hypersensibility reactions. The proper assesment and the manegament of adverse reactions are crucial in order to offer a safer inmunitation and also to reduce the misinformation and the growing rejection to COVID 19 vaccination. Objective(s): To describe clinical characteristics and the allergological study done in different patients who had an adverse event right after COVID 19 vaccine administration Method: Descriptive study in patients who have experienced an adverse event after one single dose of the SARS CoV2's vaccine. Sex, age, atopy, drug allergies, anaphylaxis reaction (according to EEACI), syntoms, timing, vaccine and dose are described on this study. Skin test were done in every patient (Prick-Test and intradermo reaction) with ARN vaccine samples (Pfizer and Moderna), Adenovirus vaccine extract (Astrazeneca) and a battery of excipients (Polietilenglicol, Polisorbato80 and Trometamol). Result(s): The study included 44 patients with an average of 48,76 +/- 12,23 years, (93% women-29% atopic). 29% of the patients reported to be allergic to other drugs (AINES especially). The most frequent reaction according to EEACI anaphilaxy's classification was Grade 1 with a 61%. Grade 2: 18%, Grade 3: 21%. Urticaria and/or angioedema were the most frequent syntoms (60%) followed by disnea (20%) and being late syntoms (50%) the most usual ones. Pfizer was the most implicated vaccine (64%) with the first dose (84%). Skin tests with Polietilenglicol, Trometamol and Polisorbato80 at different concentrations were negative in all patients but two, one positive to Polisorbato80 0.004mg/ml with a previous sensitization to Prontosan (contains Polisorbato) and another one positive to Trometamol 0.1mg/ml. Conclusion(s): Allergists play a main role to offer the maximum befenits to their patients and to improve the vaccine's safety. Skin tests were the most efective tool to diagnose hypersensibility reactions. The 93,17% of the patients with a negative test result tolerated the second dose. The others did not get the second dose due to their own will. Avoiding the COVID 19 vaccine was recommended in those patients with a hypersensibility to the vaccine components diagnose.

An experience of scaling and intensifying the industrial production of the Gam-COVID-Vac vector adenovirus vaccine in the limiting conditions of the pandemic.

The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vac, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

COVID-19 vaccine-induced neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 are diminished in patients with inflammatory bowel disease on anti-TNF or JAK-inhibitor therapy

Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .

An experience of scaling and intensifying the industrial production of the Gam-COVID-Vac vector adenovirus vaccine in the limiting conditions of the pandemic

The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vaс, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries.

The type of SARS-CoV-2 vaccine does not affect ovarian function in assisted reproduction cycle.

OBJECTIVE: To assess whether vaccination or the type of vaccine against SARS-CoV-2 affects ovarian function in an assisted reproduction treatment. DESIGN: A retrospective and observational study. SETTING: University-affiliated private in vitro fertilization (IVF) center. PATIENT(S): Five hundred one patients who had received the complete vaccination schedule. INTERVENTION(S): Treatment before and after vaccination. MAIN OUTCOME MEASURE(S): Parameters for both reproductive outcomes and IVF results in patients vaccinated RESULT(S): We included 510 patients, distributed as follows: 13.5% (n = 69) received a viral vector vaccine, either the adenovirus serotype 26 vector vaccine (Ad26.CoV2.S; Janssen; n = 31) or the chimpanzee adenovirus vector vaccine (ChAdOx; AstraZeneca; n = 38). The remaining 86.5% (n = 441) received an messenger RNA vaccine from either Pfizer-BioNTech (n = 336) or Moderna (n = 105). Sample size for the unexposed women was n = 1190. No differences were found in any of the evaluated parameters for both reproductive outcomes and IVF results in patients vaccinated with any adenovirus or messenger RNA vaccine. When we compared the results after vaccination with different types of vaccines between the exposed and unexposed groups, and similar results were obtained in the days of stimulation or the doses of administered follicle stimulating hormone. Finally, the numbers of oocytes were as follows: Johnson & Johnson (9.2 ± 2.6), AstraZeneca (7.7 ± 1.2), Moderna (11.3 ± 1.8), Pfizer (12.6 ± 1.0), and the unvaccinated group (10.2 ± 1.5), P=0.057. CONCLUSION(S): These early results suggest no measurable detrimental effect on reproductive outcomes, regardless of the type of vaccine received.

VACCINE-INDUCED THROMBOCYTOPENIA AND THROMBOSIS: SAILING CLOSE TO THE WIND IN A PANDEMIC

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Ever since the global introduction of adenovirus-vector COVID-19 vaccines, cases of cerebral venous sinus thrombosis and thrombocytopenia after immunization has been reported, posing a challenge to global effects on vaccine implementation. CASE PRESENTATION: A previously healthy 33 year old male presented to emergency room with altered mental status after a left sided seizure episode at home. Patient had a 1week history of occipital headache after receiving Ad26.COV2·S Johnson and Johnson vaccine 2 weeks prior. MRI showed superior sagittal sinus thrombosis and right high frontal hemorrhage 8.6x4.7x4.9 cm. CT angiography confirmed nearly occlusive thrombosis of superior sagittal sinus with extension to right transverse sinus. Noted to have a hemoglobin of 15, platelet count of 74000, PT/INR 16/1.2 and PTT of 28. Started on intravenous heparin and intubated for GCS of 4. Heparin was stopped due to supra therapeutic PTT of 200 overnight, drop in platelet count to 55 and hemoglobin to 13. Repeat ct head done for change in neurological exam of dilated right pupil, showed frontoparietal hemorrhage 9.3 cmx4.1 cm and 7 mm midline shift. Heparin was reversed with protamine and transfused 1 unit platelets prior to emergent decompressive craniectomy and thrombectomy. Heparin induced platelet antibody and SRA came back positive confirming vaccine induced thrombocytopenia and thrombosis. Treatment was initiated with argatroban and IVIG. Platelet count improved with no further propagation of thrombus. Patient underwent feeding tube and tracheostomy placement after 10 days due to prolonged ventilator weaning period and poor mental status. Patient's neurological status continued to improve significantly over subsequent months in acute rehabilitation facility with only residual left sided hemiparesis. Patient was successfully decannulated and anticoagulation switched to apixaban DISCUSSION: Possible pathophysiology is thought to be due to a trigger in spike protein production after biodistribution of adenovirus vaccine and a subsequent autoimmune response resulting in thrombosis. Similar to HIT, platelet consumption leads to thrombocytopenia and the continued platelet and monocyte activation increases thrombin generation, resulting in thrombosis. CDC advices to maintain a high suspicion of cases with symptoms that may indicate an underlying thrombotic event along with simultaneous thrombocytopenia. Heparin use is discouraged, unless HIT testing is negative. The International Society on Thrombosis and Hemostasis (ISTH), recommend considering non-heparin anticoagulants and high-dose intravenous immunoglobulin (IVIG). While platelet transfusions are avoided, rapid progression with rising ICP may necessitate transfusion to enable neurosurgical intervention CONCLUSIONS: Management of complications including seizures and elevated intracranial pressure (ICP) is essential to reduce morbidity and mortality risk. Reference #1: Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021;384:2092–101. Reference #2: Muir KL, Kallam A, Koepsell SA, Gundabolu K. Thrombotic thrombocytopenia after Ad26.COV2.S vaccination. N Engl J Med 2021;384:1964–5 Reference #3: Pavord S, Scully M, Hunt BJ, et al. Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. N Engl J Med 2021;385:1680–9 DISCLOSURES: No relevant relationships by Axel Duval No relevant relationships by Nadish Garg No relevant relationships by ARCHANA SREEKANTAN NAIR

A global epidemiological analysis of COVID-19 vaccine types and clinical outcomes.

OBJECTIVES: To compare messenger RNA (mRNA)-based and adenovirus-vectored vaccines (ADVVs) with inactivated virus vaccines (IVVs) using real-world aggregate data. METHODS: We performed longitudinal analyses of publicly accessible epidemiological, clinical, virological, vaccine-related, and other public health data from 41 eligible countries during the first half of 2021. The relationships between vaccination coverage and clinical outcomes were analyzed using repeated measures correlation analyses and mixed-effects modeling to adjust for potential mediating and confounding factors. RESULTS: Countries that used mRNA and/or ADVV (n = 31) vs IVV, among other vaccine types (n = 10), had different distributions of age (42.4 vs 33.9 years, respectively; P-value = 0.0006), gross domestic product per capita ($ 38,606 vs $ 20,422, respectively; P <0.0001), and population sizes (8,655,541 vs 5,139,162, respectively; P-value = 0.36). After adjustment for country differences, the stringency of nonpharmaceutical interventions, and dominant SARS-CoV-2 variant types, populations that received mRNA and/or ADVV had significantly lower rates of cases and deaths over time (P <0.001 for each analysis). Populations vaccinated with IVV, among others, had significantly higher rates of cases and deaths over time (P <0.05 for each analysis). CONCLUSION: The real-world effectiveness of IVV may be inferior to mRNA and/or ADVV, and prospective comparative studies are needed to critically evaluate the role of IVV in the context of contemporary SARS-CoV-2 variants.

Demographic and laboratory determinants of humoral immune responses and impact of different anti-SARS-CoV-2 vaccine platforms in patients with cancer: A systematic review and meta-analysis

Background: Patients (pts) with cancer have increased mortality from COVID-19 and their vaccination is crucial to prevent severe infection. We aimed to identify demographic and laboratory determinants of humoral immune responses to COVID-19 vaccination in pts with cancer and investigate differences in responses based on the vaccine platform. Methods: We searched for records in PubMed, Embase, and CENTRAL up to 28/09/21, as well as conference proceedings from ASCO and ESMO 2021. We included studies of pts ≥16 yr with a cancer diagnosis, who were vaccinated against SARS-CoV-2. Studies were excluded if ≥10% of the participants had other causes of immunosuppression or baseline anti- SARS-CoV-2 spike protein antibodies (Ab)/previous COVID-19 (PROSPERO ID: CRD42021282338). For this subgroup analysis of studies that reported a proportion of pts with cancer and positive Ab titers at any timepoint following complete vaccination, a random-effects model was used to estimate the humoral response rate (HRR) with 95% confidence intervals (CI). Results: We included 64 records, reporting data from 10,511 cancer pts. The HRR in the overall population and by subgroup are shown in Table. Elder patients with hematologic cancers (59%, CI 47-70%,N= 667) and patients with lymphopenia (50%, CI 25-75%, N = 111) or hypogammaglobulinemia (36%, CI 19-57%, N=226) were the subgroups with lower HRR. Male (77%, CI 69-84%, N = 2,659) and Asian (84%, CI 54-96%, N = 37) pts showed a trend to lower HRR when compared with females and other races, respectively. Pts vaccinated with mRNA vaccine platforms (79%, CI 74-83%, N = 9,404) had numerically higher HRR than those receiving the adenovirus vaccines (28%, CI 19-40%, N = 74). Conclusions: This study highlights demographic and laboratory determinants of weaker immune responses to SARS-CoV-2 vaccination, permitting better identification of more vulnerable pts. Despite the small number of pts included receiving adenovirus vaccines, these data also suggest prioritizing mRNA platform vaccination in pts with cancer.

INCIDENT CASES of COVID-19 and VACCINATION ADHERENCE in A MULTICENTRIC COHORT of INFLAMMATORY ARTHRITIS in BRAZIL

Background: The SARS-CoV-2 virus has caused a worldwide health crisis. Patients with infammatory arthritis are at higher risk of hospitalization and death by COVID-19 due to comorbidities or immunosuppressive treatments. Vaccination is one the most important strategies to control the pandemic. Objectives: To evaluate the incident cases of SARS-CoV-2 infection in a multi-centric cohort of infammatory arthritis in Brazil. Methods: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their frst bDMARD or tsDMARD (1). The present analysis is a retrospective evaluation of adult patients with infam-matory arthritis (rheumatoid arthritis-RA, spondylarthritis-SpA and psoriatic arthritis-PsA) that were alive since the beginning of the COVID-19 pandemics in Brazil in February 2020. We evaluated the incidence and severity of COVID-19 infection and the adherence to anti-SARS-CoV-2 vaccines schedules, up to January 2022. Results: A total of 300 patients were interviewed and 69 (23.0%) reported con-frmed anti-SARS-CoV infection and 5 (1.7%) had a second infection. Among known infected patients, 18.8% need hospitalization and oxygen support, 7.2% were admitted at ICU, and 5.8% died. After COVID-19 infection, 31.8% reported worsening of disease activity but only 6.1% had modifcation in medication due to disease activity. Distribution of cases followed the pattern of waves observed in Brazil (Figure 1). Regarding vaccination, 285 (95%) reported to have received at least one dose of any anti-SARS-CoV-2 vaccine: 43% received the frst with the adenovirus ChAdOx1 nCoV-19 (AstraZeneca) adenovirus vaccine, 32% received the Sinovac-CoronaVac inactivated vaccine, 22% received the BNT162b2 (Pfzer-BioNtech) mRNA vaccine and 3% received the BNT162b2 (Pfzer-BioNtech) adenovirus vaccine. Almost all (98.1%) of these patients had already received the second dose of vaccine and after the frst and second vaccine doses, 6% and 4% of patients, respectively, reported worsening of articular disease activity, while, after the third dose, no patient reported disease activity worsening. Conclusion: During the pandemics, patients with infammatory arthritis had a pattern of distribution of cases very similar to general population. Adherence to vaccination is high and well tolerated.

Advantages of Positron Emission Tomography/Computed Tomography Over Conventional Computed Tomography in Evaluation of Lymphoma

Background: Lymphoma is one of the most common primary malignancies of the hematopoietic system. Lymphoid neoplasms are classified into Hodgkin’s and Non-Hodgkin’s lymphoma. Non-Hodgkin lymphoma accounts for about 5% of all cases of malignancies, It is less predictable than Hodgkin lymphoma and more liable for extra-nodal spread. Males are slightly more affected than females with higher incidence in white population. B-cell lymphomas have higher incidence in adults while T-cell lymphomas have higher incidence in children. With many imaging modalities that can describe the morphological changes in lymph nodes, it’s almost exclusive for the PET/CT to describe the biological changes in those lymph nodes through their uptake of FDG which has a great value in determining whether those lymph nodes are affected or not, which in turn will play an important role in treatment & management plan. What gives PET/CT scan the upper hand is that it acts on the biological level of the cells which permit early discovering of the affected lymph nodes, much earlier than standard C.T or MRI scan.

Microarray patch-based adenovirus vaccines enable effective skin immunization

Recombinant live adenovirus (Ad) vectors represent a readily modular vaccine construct that can be engineered to include any antigen of interest, thereby enabling rapid vaccine development against a myriad of infectious pathogens, including coronaviruses. However, current approaches used for delivery, storage, and distribution of Ad vaccines hinder their full potential for effective global immunization campaigns. Here, we developed simple, effective, practical, and needle-free Ad vaccines based on microarray patches (MAPs) to enable sustainable mass vaccination against SARS-CoV-2. Rational formulation of live Ads with nonreducing sugars and mechanically strong carbohydrates into dissolvable MAPs enabled effective skin-targeted delivery of Ads and efficient cutaneous transduction as determined by in vivo live imaging of mice following skin application of MAPs integrating Ad vectors with a reporter gene. Immunogenicity assessment of dissolving MAP-based Ad vectors encoding SARS-CoV-2 proteins in mice demonstrated that skin immunization via MAP delivery of Ad-vectored COVID-19 vaccines elicited robust antigen-specific antibody responses, and these antibodies led to virus-specific neutralization activities, which were enhanced compared to those obtained with traditional intramuscular immunization. Furthermore, MAP delivery of Ad-vectored vaccines elicited potent cell-mediated immune responses, including polyfunctional virus-specific CD8+ and CD4+ T-cell responses in spleens and lungs of immunized mice, as determined by intracellular cytokine staining and flow cytometry, as well as antigen-specific cytotoxic T-cell responses in spleens of mice, as determined by lytic assay. Collectively, our results suggest that dissolvable MAPs could enable the development of skin-targeted Ad-based vaccines that may increase the effectiveness of global immunization programs for SARS-CoV-2 and other existing or future pathogens.

Epidemiology and Management of Cerebral Venous Thrombosis during the COVID-19 Pandemic.

Cerebral venous thrombosis (CVT) is a rare type of stroke that may cause an intracranial hypertension syndrome as well as focal neurological deficits due to venous infarcts. MRI with venography is the method of choice for diagnosis, and treatment with anticoagulants should be promptly started. CVT incidence has increased in COVID-19-infected patients due to a hypercoagulability state and endothelial inflammation. CVT following COVID-19 vaccination could be related to vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare but severe complication that should be promptly identified because of its high mortality rate. Platelet count, D-dimer and PF4 antibodies should be dosed. Treatment with non-heparin anticoagulants and immunoglobulin could improve recuperation. Development of headache associated with seizures, impaired consciousness or focal signs should raise immediate suspicion of CVT. In patients who received a COVID-19 adenovirus-vector vaccine presenting thromboembolic events, VITT should be suspected and rapidly treated. Nevertheless, vaccination benefits clearly outweigh risks and should be continued.

ACUTE MYOCARDITIS FOLLOWING COVID-19 VACCINATION: A PECULIAR CASE SERIES

Objective: Although acute myocarditis has not been observed as an adverse event in landmark trials of COVID-19 vaccines, it has been reported as a rare complication in real-world. The study aims to report a single-center experience on this issue. Design and method: We identified five cases of acute myocarditis with consistent temporal association to administration of COVID-19 vaccine and described clinical, serological, echocardiographic and cardiac magnetic resonance findings both in the acute phase and after a median follow up of 6 months. Results: All five patients received a COVID-19 vaccination dose within 24 to 96 hours before the onset of symptoms. Four patients received an mRNA vaccine (Comirnaty or Spikevax) and one received the adenovirus vaccine (Janssen). Only one patient had a known prior COVID-19 infection. All patients presented with chest pain and troponin I elevation occurring after the first vaccine dose in four cases. All patients tested negative for acute COVID-19 infection by polymerase chain reaction at admission. Blood tests revealed no or only mild inflammatory serological changes. Only one patient developed an increase in white blood cell count. None had specific changes on electrocardiography and echocardiography demonstrated preserved left ventricular systolic function and no regional wall motion abnormalities in all patients. Three patients underwent coronary angiography since risk factors and troponin trends raised clinical suspicion of acute coronary syndrome, none showed evidence of obstructive coronary artery disease. All patients had a mild to moderate disease not complicated by acute heart failure or arrhythmias. Cardiac Magnetic Resonance was performed in four cases and showed myocardial oedema and late gadolinium enhancement during the acute phase with persistence of areas of late gadolinium enhancement after a median follow-up of 6 months. None had further symptoms or hospitalizations since discharge. Conclusions: Acute myocarditis following COVID-19 vaccination is a well-defined clinical entity. Our findings suggest an immune rather than inflammatory pathogenesis and a benign course without clinical complication after a median follow-up of 6 months, but further studies are needed to define the prognostic significance of persistent findings on cardiac magnetic resonance.

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

APPROACHING COVID-19 VACCINATION AND ANAPHYLAXIS FROM TWO DIRECTIONS

The SARS-COV-2 infection has already claimed the lives of more than 150 000 South Africans. In order to combat ongoing infections and fatalities, South Africa has commenced its largest adult mass vaccination roll-out ever. Roll-out commences against a backdrop of emerging science, increased anti-vaccine sentiments and much public anxiety about vaccine safety. Vaccine anaphylaxis is a serious adverse event known to occur in ~1 in a million doses with current registered vaccines. We discuss briefly the known epidemiology, diagnosis and common offending parts of vaccines that cause hypersensitivity. Similar to registered vaccines, anaphylaxis has been attributed to several COVID-19 vaccines, including a possible higher incidence up to ~8 in a million doses with the use of the novel mRNA COVID-19 vaccines. It is important that allergists approach both the risks and the management of COVID-19 vaccine-related anaphylaxis soundly. We present two recent cases to highlight our approach (i) to safe COVID-19 vaccination for patients with prior vaccine-related anaphylaxis, multiple-drug hypersensitivity syndrome or clonal mast-cell disorders;and (ii) to allergy work-up and the management of patients with COVID-19 vaccine-related allergy or anaphylaxis. In particular, we discuss administering a safe second dose if required for vaccine efficacy. © 2021, Allergy Society of South Africa. All rights reserved.

ChAdOx1 nCoV-19 Vaccine Side Effects among Healthcare Workers in Trinidad and Tobago.

Vaccine hesitancy due to safety concerns is a hindrance to the success of vaccination campaigns. In February 2021, Trinidad and Tobago commenced its National COVID-19 Vaccination Program. Healthcare workers were among the first group to receive the ChAdOx1 nCoV-19 (Oxford-AstraZeneca (Covishield, Serum Institute of India, Pune, India), the first COVID-19 vaccine available nationally. This study examined the safety of this vaccine in terms of the systemic and local adverse events following immunization reported by healthcare worker recipients. A cross-sectional study was conducted via a telephone questionnaire. Data concerning demographics, medical and COVID-19-related anamneses, and local and systemic side effects experienced within the first 48 h after receiving the first and second dose of this vaccine, respectively, were gathered. Among the 687 participants (male = 275; female = 412), prevalence of fever, body pain, chills, nausea, myalgia, headache, malaise, fatigue, and other systemic symptoms declined significantly 48 h after administration of the second dose compared to the first dose. Chi-square test and multiple logistic regression demonstrated the greater likelihood of younger recipients to report systemic symptoms compared to older recipients. Multiple logistic regression indicated that females were more likely to report headache, fatigue, and discomfort, and were less likely to report no symptoms, compared to males, after both doses. On average, recipients reported less local and systemic side effects 48 h after receiving the second dose compared to the first dose. The reported rate of occurrence of side effects was <50% for most adverse events, which is consistent with the manufacturer's claims that the vaccine is safe. This study adds data on the safety of this vaccine in a population that has not been previously studied. The findings can inform public health policy efforts to lower vaccine hesitancy based on safety concerns surrounding the ChAdOx1 nCoV-19 vaccine across various groups in society, including healthcare workers.

Global research and development of COVID-19 vaccine and therapeutics: status and trend

As of May 2021, 6 new vaccines against coronavirus disease 2019 (COVID-19) have been conditionally approved and urgently used in China, including products of 4 new inactivated vaccines, 1 new adenovirus vaccine and 1 new recombinant vaccine. All the six vaccine products have been under different stages of clinical trials in global scale, and the results of the clinical trials have demonstrated the safety of the vaccines and the efficacy against COVID-19. Focusing on the above products, this paper deeply summarizes the characteristics of different new vaccine products and the clinical trial results as the key evidence supporting the approval of the products. In addition, facing the current severe situation of COVID-19, the status and challenges regarding the research and development of new vaccines and therapeutics are analyzed. © 2022, Chinese Journal of New Drugs Co. Ltd. All right reserved.

Immunogenicity and safety of adenovirus-based vector vaccines for COVID-19: a systematic review and meta-analysis

BACKGROUND Despite various research on vaccine development, severe acute respiratory syndrome coronavirus 2 infection continues to spread. Thus, developing a more effective vaccine for production and clinical efficacy is still in high demand. This review aimed to assess the immunogenicity and safety of adenovirus-based vector vaccines (Ad-vaccines) including Ad5-vectored, ChAdOx1 nCoV-19, rAd26-S or rAd5-S, and Ad26.COV2.S as the promising solutions for COVID-19. METHODS We conducted a systematic review and meta-analysis of clinical trials based on the preferred reporting items for systematic reviews and meta-analyses guidelines through PubMed, Scopus, Cochrane, and EBSCOhost until August 17, 2021. We implemented inclusion and exclusion criteria and assessed the studies using the US National Toxicology Program's Office of Health Assessment and Translation risk of bias rating tool for human and animal studies. Pooled estimates of odds ratio (OR) were analyzed using fixed-effect model. RESULTS This systematic review yielded 12 clinical studies with a total of 75,105 subjects. Although the studies were heterogeneous, this meta-analysis showed that Ad-vaccine significantly increased protection and immune response against COVID-19 with a pooled efficacy of 84.68% compared to placebo (p<0.00001). Forest plot also indicated that Ad-vaccine conferred protection against moderate to severe COVID-19 with a pooled OR of 0.26 (p<0.00001). Ad-vaccine had also shown a good safety profile with local site pain and fever as the most common side effects. CONCLUSIONS Ad-vaccine had shown a good immunogenicity for COVID-19 with a good pooled efficacy and was proven safe for COVID-19 patients.