Enabling mRNA medicine for brain tumors

mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.

Evaluation of COVID-19 Vaccines in Primary Prevention Against Infections and Reduction in Severity of Illness Following the Outbreak of Sars-Cov-2 Omicron Variant in Shanghai

Objectives: To evaluate COVID-19 vaccines in primary prevention against infections and lessening the severity of illness following the most recent outbreak of the SARS-CoV-2 Omicron variant in Shanghai. Method(s): To investigate whether inactivated vaccines were effective in protecting against COVID-19 infections, we estimated the odds ratio (OR) of the vaccination in COVID-19 cases vs. matched community-based healthy controls. To evaluate the potential benefits of vaccination in lowering the risk of symptomatic infection (vs. asymptomatic), we estimated the relative risk (RR) of symptomatic infections among diagnosed patients. We also applied the multivariate stepwise Logistic regression analyses to measure the risk of disease severity (symptomatic vs. asymptomatic and moderate/severe vs. mild) in COVID-19 patient cohort with vaccination status as an independent variable while controlling for potential confounding factors. Result(s): Out of the 153,544 COVID-19 patients included in the analysis, 118,124 (76.9%) patients had been vaccinated and 143,225(93.3%) were asymptomatic patients. Of the 10,319 symptomatic patients, 10,031(97.2%), 281(2.7%) and 7(0.1%) experienced mild, moderate, and severe infections, respectively. There is no evidence that the vaccination helped protect from infections (OR=0.82, p=0.613). The vaccination, however, offered a small but significant protection against symptomatic infections (RR=0.92, p < 0.001) and halved the risk of moderate/severe infections (OR=0.48, 95% CI: 0.37 - 0.61). Older age (> 60 years) and malignant tumors were significantly associated with moderate/severe infections. Gender also appeared to be a risk factor for symptomatic infections, with females being associated with a lower risk for moderate/severe illness. Conclusion(s): Inactivated COVID-19 vaccines helped provide a small but significant protection against symptomatic infections and halved risk of moderate/severe illness among symptomatic patients. The vaccination was not effective in blocking COVID-19 Omicron variant community spread.Copyright © 2023

Characterization of Adaptive Immune Responses to SARS-CoV-2 Updated Bivalent Booster

Bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and Omicron BA.4/5 spike proteins are successful in preventing infection from the original strain and Omicron variants, but the quality of adaptive immune responses is still not well documented. This study aims at characterizing adaptive immune responses to the bivalent booster vaccination in 46 healthy participants. Plasma and PBMC were collected prior and three weeks after bivalent booster. We measured anti-N, anti-S, and RBD IgM, IgA, IgG plasma titers against original, Omicron BA.1, and BA.5 variants (pending) as well as total anti-S IgG titers and surrogate Virus Neutralization capacity against the Alpha, Delta, and BA.1 variant. With spectral flow-cytometry we identified peripheral blood B-cells specific for the RBD of the S-protein of the original and BA.1 variants. T-cell-specific responses were assessed by cytokine release assay after stimulation with SARS-CoV-2 peptides from the original, BA.1, BA.4, and BA.5 variants (pending). Finally, we performed TRB and IGH repertoire studies on sorted CD4+, CD8+, CD19+ lymphocytes, to study breadth of SARS-CoV-2 specific clonotypes (pending). 27/46 participants were analyzed;9 had SARS-CoV-2 infection (COVID+), while 18 are infection naive (COVID-). In both groups, median time since last dose of SARS-CoV-2 vaccine (3rd or 4th) was 11 months. All subjects were positive for anti-S IgG prior to bivalent booster. The COVID + group displayed anti-S IgG pre-booster levels and neutralization against BA.1 higher than the COVID- group. Significant increase post-boost of total anti-S IgG and BA.1 neutralizing activity was detected in the COVID- but not in the COVID+ group;however, no difference in neutralization activity post-boost was detected between the two groups. Furthermore, the COVIDgroup showed significant increase in the frequency of CD19+ and CD27+ switched memory B-cells specific for BA.1 RBD in post-boost compared to pre-boost samples. However, post-boost frequencies of the same B-cells were higher in the COVID+ compared to the COVID- group. These preliminary findings confirm that among individual immunized with the original COVID-19 mRNAvaccine, prior COVID infection provides increased protection against SARS-CoV-2 variants. They also demonstrate that booster immunization with the bivalent vaccine induces robust adaptive immune responses against Omicron variant.[Formula presented][Formula presented]Copyright © 2023 Elsevier Inc.

Budget Impact Analysis of COVID-19 Vaccines on U.S. Medicare and Commercial Health Plans after Depletion of the Federally-Purchased Supply

Objectives: To analyze the budget impact (BI) of Covid-19 vaccines from a mixed U.S commercial and Medicare payer perspective after depletion of the Federally-Purchased Supply (FPS). Method(s): BI analyses were conducted in a hypothetical one-million member health plan with a mixed commercial (55%) and Medicare (45%) population over a one-year time horizon based on the current (January 2023) Covid-19 vaccine recommendations from the Centers for Disease Control and Prevention (CDC). The two scenarios in the model include 1) the health plan does not pay for Covid-19 vaccines, and 2) after the depletion of FPS, the health plan must cover all costs for Covid-19 vaccines. Model inputs include the market shares of available Covid-19 vaccines in the US as of December 2022, Covid-19 vaccine utilization trends stratified into age groups (<12, 12-17, 18-24, 25-49, 50-64, >=65 years old) between commercial and Medicare populations, and predicted Covid-19 vaccine costs. Model inputs were based on the CDC publicly available data, real world evidence, published literature, and expert opinions. Sensitivity analyses (SA) were conducted to test uncertainties arising from the input values in the model. Result(s): The number of members receiving one primary dose, completed Covid-19 vaccine series, one booster dose and two booster doses was estimated at 9,253, 49,720, 594,933 and 29,387, respectively. The incremental Covid-19 vaccine cost per member per month over one year after depletion of the FPS was $5.92 for the commercial population, $8.93 for the Medicare population, and $7.27 for the total population in the health plan. In the SA, the largest effect was observed for the scenario which varied the percentage of population >=65 years old receiving one booster dose. Conclusion(s): The model results indicate that there will be a high budget impact from a mixed U.S commercial and Medicare perspective after depletion of the FPS of Covid-19 vaccines.Copyright © 2023

Fulminant myocarditis following SARS-CoV-2 mRNA vaccination rescued with venoarterial ECMO: A report of two cases

Objectives: Cases of fulminant myocarditis after mRNA COVID-19 vaccination have been reported. The most severe may need venoarterial extracorporeal membrane oxygenation (V-A ECMO) support. Here we report two cases successfully rescued with V-A ECMO. Method(s): We included all the cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-COV2 vaccine in the high-volume adult ECMO Program in Vall Hebron University Hospital since January 2020. Result(s): We identified two cases (table). One of them was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Definite microscopic diagnosis could be reached in one case (Image, 3). Treatment was the same, using 1000mg of methylprednisolone/day for 3 days. A cardiac magnetic resonance 10 days after admission showed a significant improvement in systolic function and diffuse oedema and subepicardial contrast intake in different segments (Image, 1-2). Both patients were discharged fully recovered. Conclusion(s): V-A ECMO should be established in cases of COVID-19 vaccine-associated myocarditis with refractory cardiogenic shock during the acute phase. (Table Presented).

COVID-19 Vaccine: Knowledge and Acceptance among Obstetric Population in Garhwal Region of Uttarakhand

Background: Coronavirus disease-2019 (COVID-19) poses expectant mothers to a higher risk of serious complications and mortality. Following a risk-benefit review, a number of governmental and professional bodies from across the globe recently approved the COVID-19 vaccination during pregnancy. Aim(s): This study aimed to investigate knowledge, actual acceptance, and concerns about the COVID-19 vaccine among the obstetric population. Material(s) and Method(s): Participants were selected from among the expecting women who came for antenatal checkup during the study period (October 1, 2021-November 30, 2021). About 150 pregnant women who met the inclusion criteria and consented were recruited into the study. Data related to socio-demographic and clinical characteristics as well as knowledge, actual acceptance, and concerns about COVID-19 vaccine were collected through in-person interviews using a prestructured questionnaire. The SPSS version 23 was used to analyze data. The association between the attitude (acceptance and hesitance) of participants toward the COVID-19 vaccine and their sociodemographic and clinical profile was found by Fisher's exact test. Result(s): The actual acceptance of the COVID-19 vaccine among expecting women was 52.0%. The primary motive for accepting COVID-19 immunization was to protect the fetus, followed by the protection of one's own health. A significant association was found between COVID-19 vaccine acceptance and the level of education, socio-economic status, and presence of comorbidities. The leading causes for vaccine reluctance were concerns about the efficacy and safety of the vaccines and lack of awareness about their usage during pregnancy. Conclusion(s): Multifaceted activities are required to promote the effectiveness and safety profile of the COVID-19 vaccine as well as disseminate knowledge about its usage during pregnancy. Clinical significance: Unlike numerous other studies that have investigated the accepting attitude only, the present one has investigated the actual COVID-19 vaccine uptake among the obstetric population.Copyright © The Author(s).

Assessment of the knowledge, attitudes, and behaviors of individuals presenting to family medicine polyclinics for COVID-19 and influenza vaccines: a study in a Turkish population

BACKGROUND: Vaccines are one of the most important weapons in protection against diseases, especially pandemics lacking available treatment. The objective of this study was to investigate the knowledge, attitudes, and behaviors of individuals presenting to family medicine polyclinics for COVID-19 and influenza vaccines. METHOD(S): The cross-sectional descriptive study comprised healthy individuals who presented to family medicine polyclinics in Ankara Training and Research Hospital, Ankara, Turkiye between 10 December 2020 and 31 January 2021. Data on participants' knowledge and attitudes for COVID-19 and influenza vaccines were collected through questionnaire surveys. In total, 521 individuals aged older than 18 years were included in the study. RESULT(S): If a COVID-19 vaccine were available, 34.4% (N.=179) of respondents would be vaccinated, and 35.3% (N.=184) of respondents would not consider vaccination. Of those considering COVID-19 vaccination, 55.3% (N.=99) of respondents deemed the vaccine an effective way of providing protection against the virus. Increased willingness to have the COVID-19 vaccine was associated with the following factors: considering the influenza vaccine an effective protection method (P<0.001), a history of influenza vaccination (P=0.003), and concern about COVID-19 related death rates (P=0.008). CONCLUSION(S): The most common reasons for COVID-19 vaccine hesitancy and refusal were fear of vaccine-related side effects and a lack of perceived research evidence on the vaccine. Having a positive view of the influenza vaccine had a positive impact on attitudes toward the COVID-19 vaccine.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Re-vaccination against SARS-COV2 in allogeneic HSCT patients: Repeated primary vaccines doses increases seroconversion rates

Patients undergoing treatment for haematological malignancies have been shown to have reduced antibody responses to vaccination against SARS-COV2. This is particularly important in patients who have undergone allogeneic haemopoietic stem cell transplantation (HSCT), in whom there is limited data about vaccine efficacy. In this retrospective single-centre analysis, we present data on serologic responses following one, two, three or four doses of either Pfizer-BioNTech (PB), AstraZeneca (AZ) or Moderna (MU) SARS-CoV- 2 vaccines from a series of 75 patients who have undergone allogeneic HSCT within 2 years from the time they were revaccinated. The seroconversion rates following post-HSCT vaccination were found to be 50.7%, 78%, 79% and 83% following the first, second, third and fourth primary post -HSCT vaccine doses, respectively. The median time from allograft to first revaccination was 145 days (range 79-700). Our findings suggest that failure to respond to the first SARS-CoV- 2 vaccine post-HSCT was associated with the presence of acute GVHD (p = 0.042) and treatment with rituximab within 12 months of vaccination (p = 0.019). A statistical trend was observed with the presence of chronic GVHD and failure to seroconvert following the second (p = 0.07) and third (p = 0.09) post-HSCT vaccine doses. Patients who had received one or more SARS-CoV- 2 vaccines prior to having an allogeneic stem cell transplant were more likely to demonstrate a positive antibody response following the first dose of revaccination against Sars-CoV- 2 (p = 0.019) and retained this seropositivity following subsequent doses. The incidence of confirmed COVID-19 diagnosis among this cohort at the time of analysis was 16%. 17% of these were hospitalised and there was one recorded death (8%) secondary to COVID-19 in a patient who was 15.7 months post allogeneic transplant. In summary, this study suggests that despite the initial low seroconversion rates observed postallogeneic transplant, increasing levels of antibody response are seen post the second primary vaccine dose. In addition, there seems to be lower risk of mortality secondary to COVID-19 in this vaccinated population, compared to what was reported in the earlier phases of the pandemic prior to use of SARS-COV2 vaccination. This adds support to the widely adopted policy of early full revaccination with repeat of primary vaccine doses and boosters post-HSCT to reduce mortality in this population. Finally, we have identified rituximab use and active GVHD as potential risk factors influencing serological responses to SARS-COV2 vaccination and further work should focus on further characterising this risk and optimum dosing schedule both pre-and post-transplant.

Adverse Effects of Covid-19 Vaccine, an Observational Studymainly Focusing on the Cutaneous Reactions in Both Genders

Objective: COVID-19 caused a deleterious impact on the health care system globally.The roll out of vaccines seems to be the only effective way to curtail the spread of disease.The purpose of this study is to assess the dermatological adverse effect of post COVID-19vaccination on a gender basis. Methodology: This was an observational,cross-sectional,questionnaire-based survey conducted in Pakistan.The sample comprises 518 participants. The questionnaire was self-designed. The trial lasted six months, from August 1, 2022, until January 31, 2023. We used a non-probability sampling technique.Dermatological adverse effects like burning pain, redness, rashes, and lymphadenopathy at the injection site were recorded.Fever was also noted. All the participants have received booster shots or double doses of any one of CCOVID-19 vaccines, such as AstraZeneca, Pfizer, Sinovac, Sinopharm,Pakvac, etc. A p-value of less than 0.05 was considered statistically significant.Qualitative data was reported as frequency and percentage, and quantitativedata was reported as standard deviation and mean. Result(s): The study included 518 subjects, of whom 262 were males and 256 were females. The mean age of male is 42.70+/-14.05 years and female is 39.04+/-14.6years with a significant difference observed between them (p=0.004). The most common complaint among dermatological adverse effects after first was pain. 106(40.5%) male and 132(51.6%) female reported painwith a significant difference observed between them (p=0.011) followed by swelling which was reported by 92(35.1%) males and 120(46.9%) females with a significant difference observed between them (p=0.006).Burning was reported in 92(35.1%) male and 148(57.8%) female with a significant difference observed between them(p<0.001). Fever was also quite commonly reported in both male 116(44.3%) and female 178(69.5%) with significantdifference observed between them (p<0.001),Likewise post 2nd dose of vaccination, pain was most commonly noted in 90(34.4%) male and female 124(48.4%) female with significant difference observed between them (p=0.001). Moreover, burning was reported by 80(30.5%) malesand 132(51.6%) females with a significant difference observed between them (p<0.001). rashes were reported by76(29.0%) males and 100(39.1%) females with a significant difference observed between them (p=0.016), lymphadenopathy was also significantly associated with genders, (p<0.001). Conclusion(s): This study concluded that the burning pain,redness,rashes,and lymphadenopathywere the most prevalent side effects in male and female post 1st and 2ndCOVID-19 vaccination.Furthermore fever was also reported in majority of subjects.In addition to this higher percentage of side effects were recorded in females as comparedto males.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Antibody levels of COVID-19 vaccine: A comparison between healthy subjects and psychiatric patients on antidepressants

This study compares the serological antibody level post-COVID-19 vaccine among healthy subjects and psychiatric patients on antidepressant therapy. It also examines the difference in antidepressants' side effects experienced by psychiatric patients following the completion of two vaccine doses. A comparative posttest quasi-experimental study was conducted among healthy subjects and psychiatric patients on antidepressant medication in a teaching hospital in Malaysia. Elecsys Anti-SARS-CoV-2 assay was used to detect the antibody titre between weeks 4 and 12 post vaccination. The antidepressant side-effect checklist (ASEC) was used to monitor the occurrence of antidepressant-related side effects pre-and post-vaccination. 24 psychiatric patients and 26 healthy subjects were included. There was no significant difference in the antibody level between the patients (median = 1509 u/ml) and the healthy subjects (median = 995 u/ml). There was no significant worsening in the antidepressant-related side effects. The antibody level post-COVID-19 vaccine did not differ significantly between patients on antidepressant therapy and healthy subjects. Additionally, there was no change in the antidepressant side effects experienced by the patients following the completion of the vaccine.Copyright © 2022, Research Trends (P) LTD.. All rights reserved.

Cutaneous Adverse Drug Reactions of COVID-19 Vaccines: A Cross-Sectional Study of the Largest Healthcare System in Taiwan

Objectives: Potential cutaneous adverse drug reactions (cADRs) associated with COVID-19 vaccinations are well-known. However, comprehensive evaluation including detailed patient characteristics, vaccine types, signs and symptoms, treatments and outcomes from such cADRs are still lacking in Taiwan. Method(s): A cross-sectional study was conducted from December 2019 to October 2022 to analyze spontaneous ADR reporting data from Taiwan's largest multi-institutional healthcare system. Physicians and pharmacists initially ensured the data quality and completeness of the reported ADR records. Subsequently, we applied descriptive statistics to analyze the patient cohort based on demographic characteristics, administered COVID-19 vaccines, clinical manifestations, and patient management. Result(s): We identified 242 cADRs from 759 reported COVID-19 vaccine-related ADRs, 88.3% of which were judged as "possible" using the Naranjo Scale. The mean age of patients with cADRs was 48.1+/-17.5 years, with the majority (44.2%) of cADRs reported in the 40-64yr old age group. cADRs were more common in women (68.2%) and most of the patients had no history of allergy to vaccines (99.6%). Oxford/AstraZeneca (58.6%) accounted for the most reported brand of COVID-19 vaccines. Patients developed cADRs within 1 to 198 days (median = 5.5 days), and mostly after first-dose vaccination (77.8%). The most frequently reported cADR was rash/eruption (18.7%), followed by itchiness/pruritus (11.7%) and urticaria (9.2%), mainly affecting the lower limbs (23.8%) and upper limbs (22.6%). Medications were prescribed for 65.1% of the cADRs, and signs and symptoms were resolved within 1 to 167 days (median = 7 days) after treatment with oral antihistamines (23.0%), topical corticosteroids (14.6%) or oral corticosteroids (14.4%). Conclusion(s): Our findings provide comprehensive details regarding COVID-19 vaccine-related cADRs in Taiwan. Certain groups, especially women and the middle-aged, who reported a relatively higher rate of cADRs, may benefit from pre-vaccination counseling about the risks of cADRs and the use of appropriate medications.Copyright © 2023

Chemical synthesis of super messenger RNA medicine.

Messenger RNAmRNAmedicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.

Analysis of approaches to sterility testing of COVID-19 prevention vaccines.

Preventive vaccination against SARS-CoV-2 infection is currently receiving close attention in the Russian Federation. Improving public confidence in immunisation with new vaccines largely depends on a guarantee of the absence of side effects caused by contamination. A high risk of contamination is inherent to biological products, including coronavirus prevention vaccines, due to their properties and the nature of raw materials used. This risk adds to the need for using effective contaminant detection approaches. The aim of the study was to evaluate the possibility to improve sterility testing of preventive vaccines against SARS-CoV-2 infection. This article presents an analysis of the procedures proposed by pharmaceutical developers for sterility testing of ten Russian vaccines approved in the country for COVID-19 prevention. The authors considered specific characteristics of these vaccines, including their physical and chemical properties, the presence of antimicrobial components, and other critical factors affecting the correctness of the experimental setup. The results suggest that it is possible to improve sterility testing. According to the authors, the main directions for its improvement are the proposal to develop an alternative procedure based on compendial method 2 (OFS.1.2.4.0003.15, Ph. Rus. XIV), as well as the use of a universal culture medium. If used for refining the established procedures and developing new ones, the authors' recommendations will improve the reliability and applicability of sterility testing during both manufacturing and pre-approval regulatory assessment of updated coronavirus vaccines for subsequent release to the market. The proposed approaches can be applied to testing other medicinal products for sterility.Copyright © 2023 National Electronic-Information Consortium (NEICON). All rights reserved.

Mild COVID-19 clinical course among paediatric patients with primary immunodeficiency

Background: The clinical course of coronavirus disease-2019 (COVID-19) varies from those who are asymptomatic, experience mild symptoms such as fever, cough, and dyspnea, to more severe outcomes including acute respiratory distress, pneumonia, renal failure, and death. Early reports suggested severe outcomes in patients with primary immunodeficiency (PID), particularly those with type 1 interferon signalling defects. This prompted a rigid approach to social distancing to protect this patient population, particularly children. To date, real-world data describing the course and outcome of COVID-19 in paediatric PID patients remains scarce. Method(s): In this retrospective case series, we describe the clinical course of 36 paediatric patients with underlying primary immunodeficiency (PID) followed by SickKids Hospital (Toronto, Canada) who were symptomatic and tested positive for SARS-CoV-2 infection between October 2020 to November 2022. Result(s): Our cohort consisted of patients with combined immunodeficiency (66.7%), antibody deficiency (22.2%), neutrophil dysfunction (8.3%), and immune dysregulation (2.8%). The median age was 7.5 years (range: 8 months - 17 years), with 21 male and 15 female patients. Three (8.3%) patients were post-hematopoietic stem cell transplant (HSCT) and 12 (33%) patients were on immunoglobulin replacement. Nine (25%) patients had underlying lung problems including bronchiectasis (1), interstitial lung disease on home oxygen therapy (1), and underlying asthma (7). Most patients had mild clinical course and were managed at home. The most common symptoms were fever (80%), cough (75%) and other upper respiratory tract symptoms (72%). Nineteen (52.7%) patients experienced other symptoms which included headache, lethargy, or gastrointestinal upset. At the time of the infection, 13 patients (36.1%) had received 2 doses of a SARS-CoV-2 vaccine, 5 patients (13.9%) had received 1 dose, and 18 (50%) were not vaccinated. None of the patients received antiviral or monoclonal antibody as prophylaxis or treatment. Only 1 patient required hospital admission out of precaution given the close proximity to HSCT. All patients recovered without complications. Conclusion(s): The paediatric patients with PID followed by our centre experienced mild to moderate COVID-19 symptoms and recovered fully without complications. These findings support the return of much needed social interactions among children, which were impacted severely during the COVID-19 pandemic.Copyright © 2023 Elsevier Inc.

Perceptions of COVID-19 Vaccines Side Effects

BACKGROUND: Vaccines are one of the best interventions developed for eradicating COVID-19. In Albania, COVID-19 vaccination uses different types of vaccines: Pfizer, AstraZeneca, CoronaVac, and Sputnik V. Like any other vaccine, these have side effects too. AIM: This study was carried out to identify the perception of the side effects of vaccines. METHOD(S): A quantitative study using a cross-sectional survey was conducted between April and September 2021 to collect data on the effects of the COVID-19 vaccine among individuals in Shkodra region. Data were collected online through a self-administered survey created on Google Forms which had been randomly delivered to individuals (aged >=18 years) using social media sites (Email and WhatsApp). All data collected were analyzed with Microsoft Office Excel 2010, using the exact Fisher's test and x2 test. RESULT(S): This study included 292 citizens, out of which 200 were female and 92 were male;62% were from urban areas and 38% from rural areas of Shkodra region. The random sample of the citizens who took part in this study is 44.5% (18-30 years old). A massive percentage of the participants, 66.4%, had received the second dose of the vaccine. Our study shows that 55.8% of these citizens have had side effects after the first vaccination dose, and only 43.8% have had side effects after the second dose. About 80.6% of the participants were well informed about the type of vaccine they got. CONCLUSION(S): Side effects from vaccines were reported. Injection site pain and fatigue were the most common first dose side effects (55.8%). The same side effects were reported for the second dose. The side effects were presented during the first 12 h after the vaccination in most cases. Side effects were more prevalent in people >50 years old. Older people have a higher probability to have more side effects from the COVID vaccine. There is no statistically significant relationship between gender and the presence of the side effect from the COVID vaccine. People living in urban areas have a higher probability to have side effect from COVID vaccine comparing with people living in rural areas. People being vaccinated with Pfizer vaccine have a higher probability to admit the presence of side effects.Copyright: © 2022 Zamira Shabani, Arketa Guli, Julian Kraja, Arlinda Ramaj, Nertila Podgorica.

Knowledge and Attitude towards COVID-19 Vaccine among Medical Students in a Tertiary Care Hospital, Visakhapatnam

Aim and Objectives: 1. Knowledge of the COVID 19 vaccine among medical students in a tertiary care hospital. 2. Attitude towards the COVID 19 vaccine among medical students in a tertiary care hospital. Methodology: Study Location: Tertiary care hospital facility in Visakhapatnam. Study Period: From August to September 2022 will be the study period. Study Sample Size: 316. Statistics: Data are gathered using google forms, and the spread document is error-checked. Calculations are made for descriptive numbers like frequency and percentage. Result(s): Sociodemographic details about the participants-There were 316 competitors in total. Men make up about 34.5% (n=109) of the members. Approximately 65.5% of the members (n=207) are female. About 40.5% (n=128) of the participants are first-year students, 39.25% (n=124) are second-year students, 14.5% (n=46) are third-year students, and 5.7% (n=18) are fourth-year students. Conclusion(s): The majority of medical students' responses to this research show moderate knowledge of and a favorable outlook towards the COVID 19 vaccine. It also demonstrates that medical students are more knowledgeable and have more optimistic dispositions. Our findings can be applied to interventions that promote public health, particularly for medical students. To dispel the medical students' fears and misunderstandings regarding the COVID 19 vaccine, there should be seminars, lectures, and instructional videos that are specifically aimed at them.Copyright © 2023, Dr. Yashwant Research Labs Pvt. Ltd. All rights reserved.

Uptake of vaccination in older Indian patients with cancer: A cross-sectional observational study

Background: Older patients with cancer are at a higher risk of invasive infections. Vaccination is an effective approach to decrease the mortality and morbidity associated with infections. Objective(s): Our primary objective was to evaluate the proportion of older patients with cancer who had received routine vaccinations against pneumococcal, influenza, and coronavirus disease 2019 (COVID-19). Our secondary objective was to identify the factors associated with vaccine uptake such as age, sex, education, marital status, comorbidities, and place of residence. Material(s) and Method(s): This cross-sectional observational study was conducted in the geriatric oncology outpatient clinic of the Department of Medical Oncology at the Tata Memorial Hospital, a tertiary care cancer hospital in Mumbai, India, from February 2020 to January 2023. We included all patients aged >=60 years who were evaluated in the geriatric oncology clinic during the study period and for whom the immunization details were available. The uptake of COVID-19 vaccine was calculated from March 2021 onwards, which was when the COVID-19 vaccine became available to patients aged >=60 years in India. Result(s): We enrolled 1762 patients;1342 (76.2%) were male. The mean age was 68.4 (SD, 5.8) years;795 (45%) patients were from the west zone of India. Only 12 (0.68%) patients had received the pneumococcal vaccine, and 13 (0.7%) had received the influenza vaccine. At least one dose of the COVID-19 vaccine had been taken by 1302 of 1562 patients (83.3%). On univariate logistic regression, education, marital status, geographic zone of residence, and primary tumor site were correlated with the uptake of COVID-19 vaccine. Factors associated with a greater COVID-19 vaccine uptake included education (up to Std 10 and higher vs. less than Std 10: Odds Ratio [OR], 1.46;95% confidence interval [CI], 1.07-1.99;P = 0.018, and illiterate vs. less than Std 10: OR, 0.70;95% CI, 0.50-0.99;P = 0.041), marital status (unmarried vs. married: OR, 0.27;95% CI, 0.08-1.08;P = 0.046, and widow/widower vs. married: OR, 0.67;95% CI, 0.48-0.94;P = 0.017), lung and gastrointestinal vs. head-and-neck primary tumors (lung cancer vs. head-and-neck cancer: OR, 1.60;95% CI, 1.02-2.47;P = 0.038, and gastrointestinal vs.head-and-neck cancer: OR, 2.18;95% CI, 1.37-3.42;P < 0.001), and place of residence (west zone vs. central India: OR, 0.34;95% CI, 0.13-0.75;P = 0.015). Conclusion(s): Fewer than 1 in 100 older Indian patients with cancer receive routine immunization with influenza and pneumococcal vaccines. Hearteningly, the uptake of COVID-19 vaccination in older Indian patients with cancer is over 80%, possibly due to the global recognition of its importance during the pandemic. Similar measures as those used to increase the uptake of COVID-19 vaccines during the pandemic may be beneficial to increase the uptake of routine vaccinations.Copyright © 2023 Cancer Research, Statistics, and Treatment.

Omicron driven ECMO in a vaccinated critically ill patient

Objectives: Reporting a case of a COVID-19 vaccinated patient admitted to our intensive care unit with severe acute respiratory failure due to SARSCoV2 - Omicron variant, rapidly deteriorating requiring intubation, prone ventilation, and ECMO support. Method(s): A 62 years old Caucasian male was admitted in ICU for rapidly deranging respiratory failure and fever which occurred over the previous 24h. The patient received two doses of SARS-CoV2 vaccine (Oxford, AstraZeneca), the last one over five months before onset of symptoms. The patient was admitted to the intensive care unit (ICU) with tachypnea, low peripheral saturation (80%), elevated serum creatinine (2.4 mg/dl), and mild obesity (BMI 34,6). Pressure support ventilation trial (2 hours) failed carryng out to orotracheal intubation and protective ventilation. Worsening of respiratory exchanges (5 th day from the admission) required a rescue prone ventilation cycle, in the meantime an indication was given to the placement of veno-venous ECMO. The cannulation site was femoro-femoral and the configuration used was Vivc25- Va21, according to the current ELSO nomenclature;ECMO flow was progressively increased until a peripheral saturation of 95% was obtained. Result(s): The patient passed out after 2 month of extracorporeal support with no sign of recovery of pulmonary and renal function. Conclusion(s): Unlike evidences showing a lower symptomatic engagement of the Omicron variant SARSCoV2 positive patients, we have witnessed a rapid and massive pulmonary involvement. The short time that passed from the onset of symptoms and the rapid decay of respiratory function required rapid escalation of the intensity of care up to extracorporeal support. The patient showed previous pathologies that can lead to suspicion of a loss of immune coverage given by the vaccine, in addition to the long time elapsed since the last dose. (Figure Presented).