Post-authorization safety surveillance of Ad.26.COV2.S vaccine: Reports to the Vaccine Adverse Event Reporting System and v-safe, February 2021-February 2022.

BACKGROUND: On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system. METHODS: VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated. RESULTS: During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care. CONCLUSION: Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis.

Vaccination against COVID-19.

Vaccination is essential to manage the COVID-19 pandemic. Vaccination significantly protects against severe COVID-19, hospitalization and death;it also protects against symptomatic infection and reduces the risk of transmission to other people. Protection against the new SARS-CoV-2 variants may be lower, but protection against severe course and death remains high. Two mRNA vaccines (BNT162b2 and mRNA-1273) and two vector vaccines (AZD1222 and Ad26.COV2.S) are currently available in the Czech Republic. Vaccination of persons over 60 years of age and immunocompromised persons, who are demonstrably at the highest risk of a serious course of the disease, is of the utmost importance. In order to achieve adequate vaccination coverage, it is necessary to motivate other groups of people to be vaccinated, including children over 12 years of age and young adults. Vaccination is also recommended in preg-nant women in the 2nd and 3rd trimesters and in breastfeeding women. For selected groups of vaccines, a third dose of vaccination is recommended (additional third dose 4 weeks after the second dose or a booster dose 8 to 12 months after the second dose). The side effects are usually mild, with serious complications (including anaphylaxis, thrombocytopenia with thrombosis syndrome, myocardi-tis, Guillain-Barre syndrome and capillary leak syndrome) being rare.Copyright © 2021, Trios spol. s.r.o.. All rights reserved.

Potential mechanisms of vaccine-induced thrombosis.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome characterized by high-titer anti-platelet factor 4 (PF4) antibodies, thrombocytopenia and arterial and venous thrombosis in unusual sites, as cerebral venous sinuses and splanchnic veins. VITT has been described to occur almost exclusively after administration of ChAdOx1 nCoV-19 and Ad26.COV2.S adenovirus vector- based COVID-19 vaccines. Clinical and laboratory features of VITT resemble those of heparin-induced thrombocytopenia (HIT). It has been hypothesized that negatively charged polyadenylated hexone proteins of the AdV vectors could act as heparin to induce the conformational changes of PF4 molecule that lead to the formation of anti-PF4/polyanion antibodies. The anti-PF4 immune response in VITT is fostered by the presence of a proinflammatory milieu, elicited by some impurities found in ChAdOx1 nCoV-19 vaccine, as well as by soluble spike protein resulting from alternative splice events. Anti-PF4 antibodies bind PF4, forming immune complexes which activate platelets, monocytes and granulocytes, resulting in the VITT's immunothrombosis. The reason why only a tiny minority of patents receiving AdV-based COVID-19 vaccines develop VITT is still unknown. It has been hypothesized that individual intrinsic factors, either acquired (i.e., pre-priming of B cells to produce anti-PF4 antibodies by previous contacts with bacteria or viruses) or inherited (i.e., differences in platelet T-cell ubiquitin ligand-2 [TULA-2] expression) can predispose a few subjects to develop VITT. A better knowledge of the mechanistic basis of VITT is essential to improve the safety and the effectiveness of future vaccines and gene therapies using adenovirus vectors.

An Overview of Adenovirus Vector-based Vaccines against SARS-CoV-2

Adenovirus vectors have been employed to develop a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for curtailing the Covid-19 pandemic spreading. Many different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as an antigen. Spike (S) protein is comprised of S1 and S2 subunits, in which the receptor-binding domain (RBD) of S1 is responsible for recognizing and engaging with its host cellular receptor protein angiotensin-converting enzyme 2 (ACE2), S2 accounts for membrane fusion of virus and host cell. Chimpanzee adenovirus was also used as a vector vaccine for SARS-CoV-2 (ChAdSARS-CoV-2-S) by intramuscular injection, and intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced, with several vaccines receiving Emergency Use Authorization (EUA). It was shown that rhesus macaques were protected from SARS-CoV-2 challenge after a month of being vaccinated with ChAd-SARS-CoV-2-S. A single intranasal or two intramuscular ChAd-SARSCoV-2-S vaccines could induce humoral antibodies and T cell responses to protect the upper and lower respiratory tract against SARS-CoV-2. As the effectiveness was demonstrated in non-human primates, ChAd-SARS-CoV-2-Sa potential option for preventing SARS-CoV-2 infection in humans. However, detecting novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs monitoring. Moreover, the cause of recently documented rare cases of vaccine indicated immune thrombotic thrombocytopenia. This review article provided details for the adenovirus vector vaccine for SARS-CoV-2 in humans and tried to provide solutions to the adenovirus vector hemagglutinin issueCopyright © 2023, World's Veterinary Journal.All Rights Reserved.

Coagulopathies after vaccination against SARS-CoV-2: The sole solution might lead to another problem

The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.

Detection of pre-existing neutralizing antibodies against Ad26 in HIV-1-infected individuals not responding to the Ad26.COV2.S vaccine.

PURPOSE: The Ad26.COV2.S vaccine is a replication-incompetent human adenovirus type 26 vector encoding the SARS-CoV-2 spike protein. In a phase 1-2a trial, a single dose of Ad26.COV2.S induced SARS-CoV-2 spike-specific antibodies in ≥ 96% of healthy adults. To investigate vaccine immunogenicity in HIV-1-infection, we measured SARS-CoV-2 spike-specific antibodies in Ad26.COV2.S vaccinated HIV-1-infected patients and analyzed the presence of pre-existing Ad26 neutralizing antibodies. METHODS: We included all Ad26.COV2.S vaccinated HIV-1-infected patients of Erlangen HIV cohort fulfilling all inclusion criteria. The study cohort consisted of 15 HIV-1-infected patients and three HIV-1-uninfected subjects who received the Ad26.COV2.S vaccine between April and November 2021. Pre-vaccination sera were collected between October 2014 and June 2021, post-vaccination sera between June and December 2021. Neutralizing antibodies towards Ad26 were determined by a FACS-based inhibition assay measuring the expression of SARS-CoV-2 spike and adenoviral proteins in HEK293T cells after in-vitro transduction with Ad26.COV2.S or the control ChAdOx1-S. RESULTS: Six out of 15 HIV-1-infected patients failed to develop SARS-CoV-2-specific antibodies and four patients developed weak antibody responses after vaccination with Ad26.COV2.S. Pre-vaccination sera of four of the six vaccine non-responders showed neutralizing activity towards Ad26.COV2.S but not toward the ChAdOx1-S vaccine at 1:50 dilution. After Ad26.COV2.S vaccination, 17 of the 18 subjects developed strong Ad26-neutralizing activity and only one of the 18 subjects showed neutralizing activity towards the ChAdOx1-S vaccine. CONCLUSION: Ad26.COV2.S vaccination showed a high failure rate in HIV-1-infected patients. Pre-existing immunity against Ad26 could be an important contributor to poor vaccine efficacy in a subgroup of patients.

A plain language summary of the Janssen COVID-19 vaccine effectiveness and safety as a single dose and with a booster

Summary What is this summary about? This is a summary of the results of 2 global clinical studies of the Janssen Ad26.COV2.S vaccine against COVID-19. The ENSEMBLE study looked at the effectiveness of a single injection of the vaccine. The separate ENSEMBLE2 study looked at the effectiveness of a booster dose of the vaccine given 2 months after the first dose. In both studies, people received either the vaccine or a placebo. Vaccine effectiveness was evaluated 14 and 28 days after vaccination to allow sufficient time for generation of an immune response. What were the results? In ENSEMBLE, compared to the placebo, a single dose of the vaccine prevented: 56% of moderate to severe-critical COVID-19 cases occurring at least 14 days after vaccination 53% of moderate to severe-critical COVID-19 cases occurring at least 28 days after vaccination 75% of severe-critical COVID-19 cases occurring at least 28 days after vaccination 76% of people with COVID-19 from needing to be hospitalized for treatment 83% of COVID-19-related deaths The vaccine continued to work well for at least 6 months after a single vaccine injection. In ENSEMBLE2, compared to the placebo, a single dose of the vaccine followed by a booster dose 2 months later prevented: 75% of moderate to severe-critical COVID-19 cases occurring at least 14 days after booster vaccination 100% of severe-critical COVID-19 cases occurring at least 14 days after booster vaccination In ENSEMBLE2, there were too few cases of COVID-19 to estimate vaccine effectiveness for preventing COVID-19-related deaths or hospitalization. ENSEMBLE2 was done during early 2021, when several COVID-19 vaccines became available by emergency use authorization. For ethical reasons, people could check whether they had received vaccine or placebo and decide whether they could be vaccinated outside of the study. This meant that the researchers could not look at the long-term effectiveness of the vaccine. In both studies, after receiving the vaccine, some people experienced pain at the injection site, headache, tiredness, muscle pain, and nausea. In most cases, these were mild and went away within a few days. Serious side effects were very rare. In ENSEMBLE, blood clots, seizures, hives, and ringing in the ears were more common in the people who got the vaccine than in those who got the placebo. These side effects were very rare. In ENSEMBLE2, bleeding, hives, and ringing in the ears were slightly more common in people who got the vaccine than those who got the placebo. In ENSEMBLE2, blood clots were more common in people who got the placebo. At the time of the study, it was not clear if these side effects were caused by the vaccine. What do the results of the study mean? The vaccine was effective at protecting against moderate to severe-critical COVID-19 at 14 days after a single injection. Effectiveness was increased by a booster injection given 2 months after the first injection. You can find more detailed information and references in the original articles. Links to these articles can be found at the end of this summary. Clinical Trial Registration: NCT04505722 and NCT04614948 (ClinicalTrials.gov) </sec.Copyright © 2022 The Authors.

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)

An observational study of adverse drug reactions to COVID-19 vaccines reported to the New Mexico poison center hotline.

INTRODUCTION: Post-marketing data on coronavirus vaccines are limited. This study evaluated adverse reactions reported to a statewide hotline after the administration of a coronavirus disease-2019 (COVID-19) vaccine. METHODS: We collected reports between 1 December 2020 through 30 August 2021 of any individual 12 years of age and older who received an FDA EUA-approved vaccine and experienced an adverse reaction. For each case, we collected vaccine brand, demographics, adverse reaction type, severity, onset of reaction, duration, and outcome. Relative risk analyses were conducted to investigate factors associated with vaccine adverse reactions. RESULTS: 638 adverse drug reaction cases were recorded. The majority identified as female (70.8%) and the median age was 56. Implicated brands were Pfizer BNT162b2 (46.6%), Moderna mRNA-1273 (43.41%), and Janssen Ad26.COV2.S (8.78%). Although the lowest number of cases was with Janssen, this vaccine had the highest incident rate based on reactions per 100,000 doses. Adverse reactions with the highest incidence were systemic reactions (92.7%), injection-site reactions (8.5%), and local non-injection-site reactions (10.4%), with most judged as minor severity. Relative risk was higher for Moderna compared to Pfizer for injection-site non-severe (RR 2.01) and injection-site severe (RR 1.94) reactions. Janssen had a higher risk of headache, dyspnea, and vision changes compared to Pfizer, and a higher risk of headache compared to Moderna. The relative risk for fever, chills, and lymphadenopathy was higher for the second dose than the first dose for all patients. CONCLUSION: This observational study analyzing adverse drug reactions of the COVID-19 vaccine found that most complaints concerned systemic reactions. We found reaction differences among vaccine brands, between first and second doses for some effects, and selected recurrent events. Poison control centers are uniquely positioned to conduct post-marketing surveillance for the new vaccines as they are available 24/7 to the public and are healthcare providers. Further post-marketing studies are essential to provide a holistic safety profile of COVID-19 vaccines.

Durability of immune responses after boosting in Ad26.COV2.S-primed healthcare workers.

The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous booster vaccination after Ad26.COV2.S priming. We found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies and T-cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed.

Challenges of Storage and Transport of Covid-19 Vaccines - A Review

A vaccine is a material administered to an individual to boost their immune system's resistance against infection. Diseases that can be prevented by vaccination can be controlled and eradicated with proper vaccine handling and storage. It is crucial to formulate and deliver stable, effective and safe vaccines. Since vaccines are intricate biological products so any kind of temperature fluctuation can result in reduction of their effectiveness. To prevent this, cold storage facility is set up;refrigerators, thermometers and storage protocols are in place. The main vaccines distributed for COVID in India are Covishield and Covaxin. In order to maintain a cold chain supply for these vaccines, they must be transported and stored at a regulated temperature in accordance with the manufacturer's guidelines. The end-to-end supply chain for COVID-19 vaccines must adhere to specific cold chain standards from manufacturing to distribution in warehouses and healthcare facilities. Audits for cold chains and temperature monitoring should be performed regularly on the vaccine lots to ensure proper distribution practices are adhered. The present study focuses on the good distribution practice and storage of vaccines. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2.

SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, previously prescribed vaccines were based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity. We validate it with available clinical data and use it to simulate the effectiveness of vaccines against viral variants with lower antigenicity, increased virulence, or enhanced cell binding for various vaccine platforms. The analysis includes the omicron variant as well as hypothetical future variants with even greater immune evasion of vaccine-induced antibodies and addresses the potential benefits of the new bivalent vaccines. We further account for concurrent cancer or underlying immunosuppression. The model confirms enhanced immunogenicity following booster vaccination in immunosuppressed patients but predicts ongoing booster requirements for these individuals to maintain protection. We further studied the impact of variants on immunosuppressed individuals as a function of the interval between multiple booster doses. Our model suggests possible strategies for future vaccinations and suggests tailored strategies for high-risk groups.

Acute disseminated encephalomyelitis following the COVID-19 vaccine Ad26.COV2.S, a case report.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has been leading to dramatic health, social and economic problems around the world. It was necessary to introduce worldwide vaccination program against SARS-CoV-2 virus. Vaccination of billions of people around the world leads to many questions about risk of vaccines and possible side effects. It is well known that acute disseminated encephalomyelitis (ADEM) is a rare, but possible complication of vaccines. Previously, cases of ADEM following various COVID-19 vaccines, including the vaccines from AstraZenica, Pfizer, Sputnik V, SinoVac, Moderna, Sinopharm, have been described. In this case report, we present the first documented case of ADEM following the COVID-19 vaccine Ad26.COV2.S from Johnson & Johnson. Case presentation: We present the case of a 31-year-old female with gradually progression of right-sided weakness and numbness during a three-week period. Four weeks prior to symptom onset, the patient received the single-dose SARS-CoV-2 vaccine Ad26.COV2.S. Neuroimaging revealed five large juxtacortical T2 FLAIR hyperintense lesions with incomplete contrast enhancement on post-contrast T1 images located supratentorial: one in the right cerebral hemisphere and four in left cerebral hemisphere. The patient was followed up for four months. Symptom debut, clinical picture and MRI were typical for ADEM and the patient completely recovered after high dose intravenous methylprednisolone treatment. Conclusions: This is, to the best of our knowledge, the first case report of ADEM following the COVID-19 vaccine Ad26.COV2.S. This case illustrates, although ADEM is a rare complication following SARS-CoV-2 vaccines, the necessity of maintaining a vaccine safety monitoring system to identify patients at high risk from developing severe complications from the vaccines.

Resposta Sorologica Apos Duas Doses Da Vacina Contra Sars-Cov-2 Em Pacientes Com Leucemia Mieloide Cronica

Objetivos: Avaliar as taxas de seroconversao apos duas doses da vacina contra SARS-CoV-2 em pacientes com Leucemia Mieloide Cronica (LMC). Material e Metodos: Foram coletadas amostras para teste sorologico de triagem para avaliacao da presenca de anticorpos IgG (CMIA, SARS-CoV-2 IgM, IgG - Alinity System, Abbott Laboratories, Ireland) no periodo de 1-3 meses apos duas doses de vacina para COVID-19. Nas amostras positivas, foi realizada analise quantitativa de IgG (anti-S1 - SARS-CoV-2 IgG II Quant, Alinity System, Abbott Laboratories, Ireland) e os Titulos de Anticorpos Neutralizantes (TAN), que detectam o efeito citopatico do virus em cultura celular induzidos pelas vacinas (Vero CCL-81 cells). Resultados: Entre agosto e novembro de 2021, foram avaliados 102 pacientes com LMC com media de idade de 56,2 anos (33-85), sendo 58,8% do sexo masculino, 98,5% em Fase Cronica (FC), 80% apresentavam ao menos Resposta Molecular Maior (RMM). 87% dos pacientes estavam em uso de ITQ e 13% estavam em descontinuacao da medicacao. 66,7% receberam a vacina ChAdOx1 nCoV-19 (AZD1222)-Covishield (Oxford/AstraZeneca/Fiocruz), 29,41% CoronaVac (Sinovac/Butatan), 1,96% BNT162b2 (Pfeizer/BioNTech/Fosun Pharma) e 1,96% Ad26.COV2.S (Janssen-Cilag). 15% dos pacientes apresentaram COVID-19 antes da vacinacao. O teste sorologico de triagem (CMIA) foi positivo em 25% dos pacientes. COVID-19 previa foi associada a presenca de anticorpos IgG (p<=0,001). Os TAN foram maiores que 1:320 em 13/26 casos, dentre os quais 5 haviam apresentado COVID-19 antes de completar o esquema vacinal. Neste grupo, 76% receberam a vacina ChAdOx1 nCoV-19, 19% Coronavac e 1% BNT162b2. Dentre os casos com infeccao previa pelo SARS-CoV-2, 7 apresentaram confirmacao laboratorial e 2 tinham quadro clinico sugestivo. Oito casos ocorreram antes da vacinacao e um paciente apresentou quadro leve, apos ter recebido a primeira dose da vacina ChAdOx1 nCoV-19. Onze pacientes estavam em tratamento com Imatinibe, 6 com Dasatinibe e um com Nilotinibe (6 com RMM), 5 em terceira ou quarta linha (sem RMM) e 3 pacientes em descontinuacao de ITQ. A proporcao de pacientes com TAN >1:320 foi superior no grupo que recebia terceira ou quarta linha (p=0,022). Entretanto, neste grupo havia mais pacientes com infeccao previa por COVID-19. Nao houve diferenca estatistica entre as taxas de seroconversao (CMIA, IgM and IgG) entre pacientes que receberam Coronavac ou ChAdOx1 nCoV-19. Nao houve diferencas nas taxas de seroconversao entre pacientes que receberam ITQ e naqueles em descontinuacao (p=0,77). Discussao: Estudos observacionais demonstraram que pacientes com LMC-FC produzem anticorpos em niveis semelhantes a populacao geral, apos receberem as vacinas ChAdOx1 nCoV-19 ou BNT162b2. No estudo conduzido por Rotterdam et al., 100/101 pacientes apresentaram seroconversao apos duas doses. Outro estudo avaliou as taxas de conversao em pacientes que receberam Coronavac, demonstrando menores taxas de conversao se comparados a vacina BNT162b2. Nosso estudo demonstrou que a resposta sorologica apos duas doses de vacina contra SARS-CoV-2 foi menor do que a descrita previamente na literatura. Conclusoes: Nao foram demonstradas diferencas entre os tipos de vacina (Coronavac vs. ChAdOx1 nCoV-19) ou em relacao a fase da doenca na taxa de seroconversao. Duas doses de vacinas para COVID-19 foram insuficientes para imunizacao adequada em pacientes com LMC. Agradecimentos: Brazilian National Council for Scientific and Technological Development (CNPq), grant ndegree 401977/2020-0. Copyright © 2022

Impact of SARS-CoV-2 exposure history on the T cell and IgG response.

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific T cell and immunoglobulin G (IgG) responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number of SARS-CoV-2 spike exposures significantly enhances the magnitude of IgG responses, while repeated exposures improve the number of T cell responders but have less impact on SARS-CoV-2 spike-specific T cell frequencies in the circulation. Moreover, we find that the number and nature of exposures (rather than the order of infection and vaccination) shape the spike immune response, with spike-specific CD4 T cells displaying a greater polyfunctional potential following hybrid immunity compared with vaccination only. Characterizing adaptive immunity from an evolving viral and immunological landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progress.

Safety, reactogenicity, and immunogenicity of Ad26.COV2.S: Results of a phase 1, randomized, double-blind, placebo-controlled COVID-19 vaccine trial in Japan.

BACKGROUND: This study evaluated safety, reactogenicity, and immunogenicity of a 2-month homologous booster regimen of Ad26.COV2.S in Japanese adults. METHODS: In this multicenter, placebo-controlled, Phase 1 trial, adults (Cohort 1, aged 20-55 years, N = 125; Cohort 2, aged ≥ 65 years, N = 125) were randomized 2:2:1 to receive Ad26.COV2.S 5 × 1010 viral particles (vp), Ad26.COV2.S 1 × 1011 vp, or placebo, followed by a homologous booster 56 days later. Safety, reactogenicity, and immunogenicity were assessed. RESULTS: Two hundred participants received Ad26.COV2.S and 50 received placebo. The most frequent solicited local adverse event (AE) was vaccination-site pain, and the most frequent solicited systemic AEs were fatigue, myalgia, and headache. After primary vaccination, neutralizing and binding antibody levels increased through Day 57 (post-prime) in both cohorts. Fourteen days after boosting (Day 71), neutralizing antibody geometric mean titers (GMTs) had almost reached their peak value in Cohort 1 (5 × 1010 vp: GMT = 1049; 1 × 1011 vp: GMT = 1470) and peaked in Cohort 2 (504; 651); at Day 85, GMTs had declined minimally in Cohort 2. For both cohorts, binding antibody levels peaked at Day 71 with minimal decline at Day 85. CONCLUSION: A single dose and homologous Ad26.COV2.S booster increased antibody responses with an acceptable safety profile in Japanese adults (ClinicalTrials.gov Identifier: NCT04509947).

Neutralizing Antibody Responses Elicited by Inactivated Whole Virus and Genetic Vaccines against Dominant SARS-CoV-2 Variants during the Four Epidemic Peaks of COVID-19 in Colombia.

Several SARS-CoV-2 variants of concern (VOC) and interest (VOI) co-circulate in Colombia, and determining the neutralizing antibody (nAb) responses is useful to improve the efficacy of COVID-19 vaccination programs. Thus, nAb responses against SARS-CoV-2 isolates from the lineages B.1.111, P.1 (Gamma), B.1.621 (Mu), AY.25.1 (Delta), and BA.1 (Omicron), were evaluated in serum samples from immunologically naïve individuals between 9 and 13 weeks after receiving complete regimens of CoronaVac, BNT162b2, ChAdOx1, or Ad26.COV2.S, using microneutralization assays. An overall reduction of the nAb responses against Mu, Delta, and Omicron, relative to B.1.111 and Gamma was observed in sera from vaccinated individuals with BNT162b2, ChAdOx1, and Ad26.COV2.S. The seropositivity rate elicited by all the vaccines against B.1.111 and Gamma was 100%, while for Mu, Delta, and Omicron ranged between 32 to 87%, 65 to 96%, and 41 to 96%, respectively, depending on the vaccine tested. The significant reductions in the nAb responses against the last three dominant SARS-CoV-2 lineages in Colombia indicate that booster doses should be administered following complete vaccination schemes to increase the nAb titers against emerging SARS-CoV-2 lineages.

Vaccine versus infection - COVID-19-related loss of training time in elite athletes.

OBJECTIVES: To determine the number of training days lost due to COVID-19 and vaccination against COVID-19 in elite athletes. DESIGN: Retrospective cohort study. METHODS: The questionnaire on the impact of vaccination and COVID-19 on training plans was filled out by 1073 elite Polish athletes who underwent routine medical screening between September and December 2021. RESULTS: COVID-19 was diagnosed in 421 subjects (39 %), of whom 26 % were asymptomatic. On the 10-point scale, <1 % of athletes had perceived severity of the disease above 8, whereas for 64 % it was 4 or below. Vaccination against COVID-19 was administered in 820 athletes (76 %), and adverse events were observed more frequently after the first dose than the second (69 % vs. 47 %). Influence on training (modified or lost) was declared by 369 of 421 (88 %) COVID-19 athletes, and by 226 of 820 vaccinated athletes (28 %). During the observation period, the average number of lost training days was 8.1 for COVID-19 and 2.6 for vaccination (p < 0.001). The cumulative number of person-days lost due to COVID-19 was 1041 versus 295 after vaccination thus, the average loss ratio was 1041/1073 = 0.97 vs. 295/820 = 0.36, respectively, p < 0.01. CONCLUSIONS: Athletes have a considerable loss of training days due to COVID-19. Vaccination against COVID-19 causes significantly smaller and predictable loss. This supports the inclusion of vaccination into prevention policies for athletes whenever they are available.

Serious adverse reaction associated with the COVID-19 vaccines of BNT162b2, Ad26.COV2.S, and mRNA-1273: Gaining insight through the VAERS.

Background and purpose: Serious adverse events following immunization (AEFI) associated with the COVID-19 vaccines, including BNT162b2 (Pfizer-BioNTech), Ad26.COV2.S (Janssen), and mRNA-1273 (Moderna), have not yet been fully investigated. This study was designed to evaluate the serious AEFI associated with these three vaccines. Methods: A disproportionality study was performed to analyze data acquired from the Vaccine Adverse Event-Reporting System (VAERS) between 1 January 2010 and 30 April 2021. The reporting odds ratio (ROR) method was used to identify the association between the COVID-19 vaccines BNT162b2, Ad26.COV2.S, and mRNA-1273 and each adverse event reported. Moreover, the ratio of the ROR value to the 95% CI span was applied to improve the credibility of the ROR. The median values of time from vaccination to onset (TTO) for the three vaccines were analyzed. Results: Compared with BNT162b2 and mRNA-1273, Ad26.COV2.S vaccination was associated with a lower death frequency (p < 0.05). Ad26.COV2.S vaccination was associated with a lower birth defect and emergency room visit frequency than BNT162b2 (p < 0.05). There were 6,605, 830, and 2,292 vaccine recipients who suffered from COVID-19-related symptoms after vaccination with BNT162b2, Ad26.COV2.S, and mRNA-1273, respectively, including people who were infected by COVID-19, demonstrated a positive SARS-CoV-2 test, and were asymptomatic. Serious AEFI, including thromboembolism, hemorrhage, thrombocytopenia, cardiac arrhythmia, hypertension, and hepatotoxicity, were associated with all three vaccines. Cardiac failure and acute renal impairment events were associated with BNT162b2 and mRNA-1273, while seizure events were associated with BNT162b2 and Ad26.COV2.S. The median values of TTO associated with the three vaccinations were similar. Conclusion: These findings may be useful for health workers and the general public prior to inoculation, especially for patients with underlying diseases; however, the risk/benefit profile of these vaccines remains unchanged. The exact mechanism of SARS-CoV-2 vaccine-induced AEFI remains unknown, and further studies are required to explore these phenomena.