Healthcare Resource Utilization and Direct Medical Costs Associated with Post COVID-19 Condition in Colombia, 2020-2021

Objectives: This study aimed to estimate the direct medical costs of patients with post COVID-19 condition in a Colombian insurance company with more than 2.5 million affiliates. Method(s): We conducted a bottom-up cost-of-illness study of adults with persistent symptoms after at least three months of hospital discharge due to COVID-19. We surveyed patients that were hospitalized between March 2020 and August 2021. We asked about healthcare resource utilization (HCRU), which included laboratories and images, medications, consults, rehospitalizations, and others, associated with post COVID-19 condition. The answers were verified using the company's outpatient and inpatient service authorization records. Costs were estimated from the third payer perspective and expressed in American dollars using an exchange rate of 1USD$=3,743COP. Result(s): We included 202 participants, 51.5% were male, mean age of 55.6 years old, 49% had a comorbidity (41.9% hypertension), and 46 patients (22.8%) required an intensive care unit. A total of 159 (78.7%) patients reported at least one symptom after discharge. Of these, 132 (65.3%) persisted with at least one symptom during the telephone survey. Seventy-five (47.2%) of the 159 patients with persistent symptoms reported HCRU. Of these, 93.3% consulted a physician (mean consultations: 2.1 SD 1.1;mean consultations with specialists: 2.4 SD 2.0), and 9.3% were re-hospitalized. The average direct medical costs of post COVID-19 condition were US$824 (95%CI 195-1,454). Costs in outpatient were US$373 (95%CI 158-588), and in inpatient, US$3,285 (95%CI -167-6,738). Conclusion(s): It is crucial to follow up and identify patients discharged from the hospital who persist with symptoms after three months since we observed a greater HCRU, including prolonged recovery therapiesCopyright © 2023

Neurocognitive Outcomes in Congenital Heart Defects Ethics, Evidence, and Vaccination in Pregnancy: Lessons from COVID-19

Among the longstanding problems made vivid by the COVID-19 pandemic are challenges in gathering data to inform the use of vaccines in pregnancy. Although it was known early on that pregnant persons and their offspring faced greater risks of morbidity and mortality from COVID-19 infection, they were excluded from all trials that led to authorization of vaccines. And while reassuring evidence has since been gathered, delays, as well as mixed public health messaging, have led to low uptake of vaccines among pregnant populations, as well as disproportionate burdens for pregnant persons. Dr. Lyerly will consider key ethical issues foregrounded by the COVID-19 response in pregnancy, including the distortions of risk, misaligned incentives, and regulatory challenges. Drawing on results of the NIH-funded PHASES Project, she will describe key conceptual shifts and ethical frameworks that have recently been advanced to better serve the interests of pregnant persons and their offspring facing illness in pandemic and other contexts, as well as specific recommendations for responsible and timely research with this population.

THE RED FLAG OF EMERGENCY USE AUTHORIZATION (EUA)

The Emergency Use Authorization (EUA) policy, a representative biodefense policy, was legislated in the United States in 2001 based on lessons learned from Amerithrax, whereas Korea's EUA policy was based on lessons learned from the Middle East Respiratory Syndrome outbreak in 2015. Due to these divergent origins, the U.S. EUA's homeland security objectives were specialized to deal with highly pathogenic biological agents that could be exploited for bioterrorism, whereas the Korean EUA pursues disease containment purposes to strengthen mass-testing practices. During the early phase of the COVID-19 pandemic, the U.S. EUA revealed limitations in its integration with public health surveillance, laboratory partnerships, and insurance systems, which hampered the rapid expansion of testing capacities. Thereafter, once the limitations of the EUA were circumvented, the testing capacity of the United States began to catch up with that of South Korea, and later skyrocketed after solving these issues. (English) [ FROM AUTHOR] La política de autorización de uso de emergencia (EUA), una política representativa de biodefensa, se legisló en los Estados Unidos en 2001 en base a las lecciones aprendidas de Amerithrax, mientras que la política de EUA de Corea se basó en las lecciones aprendidas del brote del síndrome respiratorio de Oriente Medio (MERS) en 2015 Debido a estos orígenes divergentes, los objetivos de seguridad nacional de la EUA EUA se especializaron para tratar con agentes biológicos altamente patógenos que podrían explotarse para el bioterrorismo, mientras que la EUA coreana persigue propósitos de contención de enfermedades para fortalecer las prácticas de pruebas masivas. Durante la fase inicial de la pandemia de COVID-19, la EUA EUA reveló limitaciones en su integración con la vigilancia de la salud pública, las asociaciones de laboratorios y los sistemas de seguros, lo que obstaculizó la rápida expansión de las capacidades de prueba. A partir de entonces, una vez que se eludieron las limitaciones de la EUA, la capacidad de prueba de los Estados Unidos comenzó a alcanzar a la de Corea del Sur y luego se disparó después de resolver estos problemas. (Spanish) [ FROM AUTHOR] 美国在2001年根据炭疽攻击事件(Amerithrax)的经验教训制定了一项具有代表性的生物防卫政策，即紧急使用授权(EUA)政策，而韩国的EUA政策则基于2015年爆发的中东呼吸综合征(MERS)的经验教训。鉴于这些不同的起源，美国EUA的国土安全目标专门应对可能被用于生物恐怖主义的高致病性生物制剂，而韩国EUA则追求疾病遏制目的，以加强大规模检测实践。在2019冠状病毒病(COVID-19)大流行的早期阶段，美国EUA在与公共卫生监测、实验室合作伙伴关系和保险系统的整合方面存在局限性，这阻碍了检测能力的快速扩展。此后，当绕过EUA的限制后，美国的检测能力开始赶上韩国，并在解决这些问题后，检测能力直线上升。 (Chinese) [ FROM AUTHOR] Copyright of World Affairs is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 vaccines in patients with solid tumor cancers receiving immune checkpoint inhibitors

Background: The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. It is unknown whether concurrent CPI and Sars-COV-2 vaccine administration increases the risk of irAEs. This retrospective study examined the incidence of severe irAEs in cancer patients receiving CPI therapy at the time of vaccination against Sars CoV-2. Method(s): Following IRB approval, pts with solid tumors who received any approved CPI since FDA authorization of the COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received one or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation of CPI due to irAE. Data was analyzed using descriptive statistics. Result(s): 290 pts with bladder, head/neck, liver, skin (melanoma, SCC), renal, and gynecologic cancer were included in analysis. The median age was 67 years (IQR: 59.0-74.0) and 66% pts were male. At the time of vaccination, 201 pts (69.3%) received CPI monotherapy, 53 pts (18.3%) received combination (combo) CPI therapy, and 36 pts (12.4%) received other therapies (chemo, TKIs, etc.) with CPI. The vaccine manufacturer was Pfizer Bio-N-Tech in 162 pts (55.9%), Moderna in 122 pts (42.1%), and Johnson and Johnson in 6 pts (2.1%). The number of vaccinations received was >/= 3 in 214 pts, 2 in 64 pts, and 1 in 11 pts. 30 pts (11.5%) experienced severe irAEs following vaccination. The rate of severe irAEs was 10.3% (30/290) in the total population [6% (12/201) with CPI monotherapy, 19% (10/53) with combo CPI, and 22% (8/36) in the combo CPI-other group]. Severe irAEs occurred after the first vaccine dose in 5 pts (16.7%), second dose in 16 pts (53.3%), and third dose in 9 pts (30%) pts. The median time between CPI treatment and vaccination in pts who experienced irAE was15.5 days (IQR: 10.2-23.0). Hospitalization was required for 19 patients (63.3%). 24 pts (80.0%) required immunosuppressive therapy with a median therapy duration of 98.5 days (IQR 40.2-173.0). 16 pts (53.5%) discontinued CPI therapy following severe irAEs Conclusion(s): In this retrospective study, we observed a 10.3% rate of severe irAE in cancer pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI.

Evaluation of the Updated French Autorisation D'Acces Precoce (AAP) Early Access Authorization Pathway

Objectives: To evaluate products reviewed by the Transparency Committee (TC) of the Haute Authorite de Sante (HAS) under the Autorisation d'Acces Precoce (AAP) Early Access Authorization (EAA) pathway and investigate any trends. Method(s): All 97 AAP submissions are publicly available from HAS and were evaluated on or before January 4th, 2023. The TC's opinion was reviewed to obtain the outcome, decision date, therapeutic area, and reasons for rejection. Results were tabulated and descriptive statistics were compiled. Result(s): In total, 79 of the 97 (81%) submissions evaluated were approved for EAA, including renewals of previously granted authorization (6 of 79);18 were rejected. Of the 97 submissions, 35% were indicated for the treatment of solid cancers, 14% for haematological cancers, 10% for ultra-rare diseases, 10% for infectious diseases, 4% for rare diseases, 4% for autoimmune diseases, 4% for skin diseases, and 2% for weight management. Notable approved submissions including those indicated for rare diseases, cancer, autoimmune diseases, and COVID-19, with 93%, 90%, 75%, and 63% of these submissions being granted EAA, respectively. Across the 18 unsuccessful submissions, the main reasons cited for rejection were insufficient efficacy and safety data (78%), lack of innovation compared to existing treatment options (61%), the availability of existing treatment options (56%), and the treatment not being rare enough to qualify for special consideration (28%). Conclusion(s): Since its inception in July 2021, the AAP has proven to be a popular program. As awareness of the program grows and more information becomes available about its benefits and eligibility criteria, it is likely that the number of submissions will continue to increase. However, given the link between submission success and the quality of available data (including a data collection plan), it is recommended manufacturers provide robust evidence to bolster their submissions.Copyright © 2023

Updated Real-World Safety of the Pfizer-BioNTech COVID-19 Vaccine in Pregnancy: Data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry

Purpose: Preliminary data indicate that pregnant women infected with COVID-19 are at increased risk of pregnancy complications (US Centers for Disease Control and Prevention, October 2022). Information on the real-world safety of COVID-19 vaccination in pregnancy is essential. We sought to describe preliminary results for pregnancy status among pregnancy registry participants enrolled in an ongoing safety study of the Pfizer-BioNTech COVID-19 vaccine to date. Method(s): This study uses data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry as part of the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) which enrolls pregnant women residing in the US or Canada. Data are captured through maternal interviews and the ion of medical records. The study population for this descriptive analysis includes Registry participants who met eligibility criteria on or after December 11, 2020, the date the US Food and Drug Administration granted emergency-use authorization for the Pfizer-BioNTech vaccine. The target sample size is 1,100 pregnant women who received any dose of the Pfizer-BioNTech vaccine from 30 days prior to the last menstrual period through the end of pregnancy, and 900 comparison women who received no COVID-19 vaccine in pregnancy. Result(s): Among pregnant women participating in the Registry between 11 December 2020 and 22 July 2022, 1,100/1,100 participants (100.0% of the target sample) were enrolled as part of the Pfizer-BioNTech COVID-19 vaccine exposure cohort, and 635/900 participants (70.6% of the target sample) were enrolled in the comparator cohort. As of 22 July 2022, 858 (78.0%) in the vaccine exposure cohort and 313 (34.8%) in the comparator cohort had completed pregnancies. Descriptive data indicated numerically similar percentages of pregnancies ending in at least one liveborn infant, spontaneous abortions, stillbirths, and elective terminations across the exposed cohort stratified by trimester of the earliest dose of the Pfizer-BioNTech COVID-19 vaccine received in pregnancy, and overall in the unexposed comparator cohort. Conclusion(s): Preliminary data have not identified any new safety concerns thus far for pregnant women who receive the Pfizer-BioNTech COVID-19 vaccine during pregnancy. Funding(s): This study was conducted as a collaboration between the University of California San Diego and Pfizer. Pfizer is the study sponsor.

Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19: Evidence from the National COVID Cohort Collaborative (N3C)

Objectives: To describe and compare real-world outcomes for patients with mild-to-moderate COVID-19 at high risk for progression to severe COVID-19, treated with sotrovimab versus untreated. Method(s): Electronic health records from the National COVID Cohort Collaborative were used to identify US patients (aged >=12 years) diagnosed with COVID-19 (positive test or ICD-10: U07.1) in an ambulatory setting (26 May 2021-30 April 2022) who met Emergency Use Authorization high-risk criteria. Patients receiving the monoclonal antibody (mAb) sotrovimab within 10 days of diagnosis were assigned to the sotrovimab cohort with an index date on the day of infusion. Untreated patients (no evidence of early mAb treatment or prophylaxis mAb or oral antiviral treatment) were assigned to the untreated cohort with an imputed index date based on the time distribution between diagnosis and sotrovimab infusion for the sotrovimab cohort. The primary endpoint was hospitalization or death (both all-cause) within 29 days of index, reported as descriptive rates and adjusted (via inverse-probability-of-treatment weighting [IPTW]) odds ratios (OR) and 95% confidence intervals (CI). Result(s): Of nearly 2.9 million patients diagnosed with COVID-19 during the analysis time period, 4,992 met the criteria for the sotrovimab cohort and 541,325 were included in the untreated cohort. Patients in the sotrovimab cohort were older (60 versus 54 years), more likely to be male (40% versus 38%) and White (85% versus 75%), and met more EUA criteria (3 versus 2) versus the untreated cohort. The 29-day hospitalization or mortality rates were 3.5% (176/4,992) and 4.5% (24,163/541,325) in the sotrovimab and untreated cohorts respectively (unadjusted OR [95% CI]: 0.77 [0.67,0.90];p=0.001;IPTW-adjusted OR [95% CI]: 0.74 [0.61,0.91];p=0.004). Conclusion(s): Sotrovimab demonstrated clinical effectiveness in preventing severe outcomes (hospitalization, mortality) between 26 May 2021-30 April 2022, which included the Delta variant and early surge of Omicron BA.1/BA.2. Funding(s): GSK (Study 219020)Copyright © 2023

Effects of Homologous and Heterologous Booster Vaccinations of the Inactivated Dual-Adjuvanted Vaccine Vla2001 against Covid-19 Including Variants of Concern: A Phase 3 Randomized Clinical Trial

Intro: VLA2001 is a highly-purified, inactivated whole-virus SARS-CoV-2 vaccine based on a dual-adjuvant system of Alum and CpG1018 for induction of a robust immune response. The vaccine was designed using a well-established technology platform and has received full marketing authorization in Europe. In a pivotal Phase 3 trial, VLA2001 demonstrated superior neutralizing antibody geometric mean titers (GMT) to the comparator, AstraZeneca's AZD1222, as well as non-inferior seroconversion rates two weeks after priming. The extension of the Phase 3 trial evaluated safety and immunogenicity of homologous and heterologous booster vaccinations of VLA2001. Method(s): This is a randomized observer-blind controlled, pivotal trial conducted in the UK in participants aged >=18 years who were randomly assigned 2:1 to receive two doses of VLA2001 or AZD1222, 28 days apart. A booster with VLA2001 was administered to eligible participants at 7 to 8 months after priming. The primary safety outcome was the frequency and severity of any adverse event following the booster vaccination. The primary immunogenicity outcomes were the GMT and fold increase of neutralizing antibodies against SARS-CoV-2 two weeks after the booster vaccination. The study is registered under NCT04864561. Finding(s): A booster dose of VLA2001 is well-tolerated in both AZD1222 and VLA2001 primed participants. High neutralizing antibody titers and fold- increases were generated two weeks following a booster of VLA2001. Cross- neutralizing serological responses against Delta and the Omicron BA.4/BA.5 variants of concern are elicited following a homologous or heterologous booster dose in VLA2001 or AZD1222 primed participants, respectively. Additionally, VLA2001 induced broad T-cell responses with antigen-specific IFN-gamma producing T-cells against the Spike, the Nucleocapsid and the Membrane protein. Conclusion(s): Homologous and heterologous booster doses of VLA2001 demonstrated a favorable tolerability profile irrespective of priming and induced broadly reactive neutralizing antibodies against the ancestral virus and variants of concern, including the currently circulating BA.4/BA.5.Copyright © 2023

Rheumatologistadherence to Vaccine Recommendation in Patients with Immune-Mediated Inflammatory Diseases

Objectives: Backgroud: Patients with immune-mediated inflammatory diseases (IMID), have an increased risk of presenting infections, this arises from immunosuppression related to the disease and its treatments. Vaccination in patients with autoimmune diseases is highly recommended by various clinical practice guidelines(1). Studies in Latin America show low rates of adherence, both in patients vaccine application and doctor's recommendations. One study shows that the lack of vaccination in 43% of their patients was due to their rheumatologist not recommending it (2). This is an eye opener on the key role physicians play in the overall outcome. Objective(s): To determine the adherence rate rheumatologists have, when it comes to recommending their patients vaccinations, suggested by clinical practice guidelines. Method(s): A descriptive study was performed, with previous authorization by the research department of the Colombian rheumatology association (ASOREUMA). A survey was sent via email to all its members asking about general knowledge about the subject and percentages on recommendations in their daily practice. Result(s): The survey was sent to 214 rheumatologist members of ASOREUMA, 34 (16%) of whom responded. In clinical practice there is a universal knowledge on the vaccination requirements for patients with IMID, nevertheless just 38.2% of clinicians tell patients to vaccinate against influenza of the 80%-100% of patients they see. For pneumococcus its 26.5%, hepatitis B 20.6%, human papilloma virus 8.8%, herpes zoster 2.9%. When it comes to SARS CoV2 vaccines it's by far the most recommended with 79.4%, and most physicians consider its mechanism of action before prescribing it. In table 1 we are summarizing the primary results. Conclusion(s): Despite the fact that rheumatologists are widely aware of the indications for vaccination in patients with IMID, these recommendations are not transmitted to all patients, due to the limited care time for each patient;in addition to the fact that the vast majority consider that the health system does not allow quick and timely access to these services.

Immunogenicity of Sars-Cov-2 Vaccines by Vaccine Type in Randomised Clinical Trials

Background: Currently five SARS-CoV-2 vaccines are approved in North America (FDA) and Europe (EMA). Across the world other vaccines have been developed but not approved in high-income countries. Of the approved vaccines, 2 are mRNA vaccines, 2 are viral vectored vaccines, and 1 is a protein subunit vaccine. As immunogenicity markers are increasingly being used by regulatory agencies as surrogate markers for vaccine efficacy to inform authorization decisions, this meta-analysis compared the size of immunogenicity responses response elicited by the different COVID-19 vaccine types (mRNA, protein subunit, inactivated virus, viral vectors) and approved and unapproved COVID-19 vaccines. Method(s): Systematic review of trial registers and databases identified RCTs for SARS-CoV-2 vaccines. Risk of bias analysis was conducted using the Cochrane Risk of Bias tool. High risk of bias studies were excluded from analysis. Meta-analysis of seroconversion rates and geometric antibody titers (GMT) for neutralising (NAb) and anti-spike antibodies was conducted, each compared with a placebo using random effects model Cochrane-Mantel Haenszel Tests. Result(s): All studies assessed immunogenicity of COVID-19 vaccines on healthy non-immunocompromised adults between the age of 18 and 59. Statistically significant difference was identified between the different vaccine types for NAb GMT, anti-spike GMT, NAb seroconversion, and anti-spike seroconversion (P< 0.00001 for all). Conversely, no statistical significant difference was identified between approved and unapproved vaccines for NAb seroconversion (P=0.39), Nab GMT (P=0.36), anti-spike seroconversion (P=0.07), and antispike GMT (P=0.54). mRNA vaccines had the best immunogenicity results for NAb seroconversion, GMT, and anti-spike seroconversion. Viral vector vaccines had the lowest results for NAb seroconversion and GMT, while inactivated viruses had the lowest result for anti-spike seroconversion and mRNA vaccines for anti-spike GMT. High heterogeneity was observed across the different studies. Conclusion(s): This metanalysis of 35 randomised trials in 33,813 participants showed approved and unapproved vaccines to be comparable in postvaccination GMT values and seroconversion for both NAb and anti-spike. However, while comparing COVID-19 vaccines by vaccine types, statistically significant differences are observed. Variations in study designs, populations enrolled, and infection prevalence during trial duration could have influenced results.

Real World Experience Using Tixagevimab/Cilgavimab (EvusheldTM) in Pre-Exposure Prophylaxis for Allogeneic Hematopoietic Cell Transplant Recipients: A Single Center Retrospective Review

Background: Tixagevimab(Txg)/cilgavimab (Cgv) was given emergency use authorization (EUA) to provide passive immunity against COVID-19(CoV) for immunocompromised (IC) pts who may not mount an adequate response to CoV vaccination [1]. Recipients of allogeneic hematopoietic cell transplant (Allo-HCT) are amongst the most IC. Due to high risk of mortality and complications of CoV in this population, Txg/ Cgv was used as pre-exposure prophylaxis (PrEP) under EUA without prior study. Our study aims to assess efficacy and adverse events (AE) of Txg/Cgv administration in this cohort of patients to help guide future practice. Method(s): We retrospectively investigated Allo-HCT recipients who received Txg/Cgv as PrEP. Data were gathered including changes in blood counts, incidence of graft-vs-host-disease (GVHD), history of prior CoV infection and vaccination status. Pts who developed CoV infection after PrEP were assessed for supplemental oxygen(O2) need and hospitalization. Data cutoff date was 9/30/2022. Result(s): A total of 18 Allo-HCT recipients received Txg/Cgv. Table 1 summarizes patient and transplant characteristics. Thirteen (72.2%) pts received 2 doses of 150mg of Txg / Cgv, while 4 pts received 1 dose of 300mg, and one patient received one dose of 150mg. Median time to first dose was 213 days [range 22-3660] post-transplant. Two pts had lab confirmed CoV, one at 24 days post dosing and the 2nd patient at 22 days post dose. Neither required supplemental O2;one was hospitalized for fever. Prior to dosing, 44.4% (8/18) of pts had GVHD. (Table Presented) (Figure Presented) (Figure Presented) Of these, 62.5% (5/8) had no changes in the severity of their GVHD. Two of 8 (25%) pts with pre-existing chronic GVHD had a flare of symptoms. Two (25%) had improvement of GVHD. Two pts developed new onset acute GVHD following Txg/Cgv administration, one requiring 1mg/kg prednisone and the other topical steroids (2/18, 11%). Figure 1 summarizes GVHD patterns observed. Hematologic parameters did not change significantly, see Figure 2. None of the pts reported any subjective AE following dosing. Summary: Txg/Cgv was found to be safe and effective for Allo-HCT pts, without significant toxicity. Two patients had new onset GVHD and 2 patients had progressive GVHD. Whether there is a true association between Txg/Cgv and development of GVHD should be investigated in a larger cohort and then investigated for possible underlying mechanisms.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Covax-19/Spikogen: The first exclusively Australian-developed human vaccine in four decades

Introduction/Aim: The development of safe and effective vaccines is crucial to conquering the COVID-19 pandemic. Recombinant proteins represent the best understood and reliable approach to pandemic vaccine delivery with well-established safety;however, they face challenges in design, structural characterisation, manufacture, potency testing and ensuring adequate immunogenicity. Method(s): Our team used in silico structural modelling to design a vaccine based on a stabilised spike protein extracellular domain (ECD). The insect cell expressed recombinant spike ECD was formulated with Vaxine's proprietary Advax-CpG55.2 adjuvant. Result(s): The vaccine known as Covax-19 or SpikoGen induced high titers of antibody and memory T-cells which translated to protection against SARS-CoV-2 infection in hamsters, ferrets, and aged monkeys. Despite numerous challenges along the journey, clinical trials in Iran during a major wave of delta variant infection confirmed SpikoGen vaccine was 78% effective in reducing risk of severe disease and with no evidence of vaccine-associated thrombosis, myocarditis, or sudden death, receiving marketing approval under emergency use authorisation in Iran on 6 October 2021. This made it the first recombinant spike-protein vaccine in the world to be approved, and the first Australian-developed human vaccine to receive marketing approval in four decades. Since approval millions of doses have been administered and additional trials in Australia and Iran have confirmed its effectiveness as a booster to prevent waning immunity, as well as its safety and effectiveness in children from the age of 5 years. The ongoing Australian and overseas clinical trial program is focussed on gaining better understanding the effect of dosing intervals on vaccine immunogenicity, gathering additional data on use as a booster, and development of new variant formulations. Conclusion(s): Covax-19/Spikogen is safe and effective adjuvanted recombinant protein vaccine.

Covid-19 Vaccine Associated Acute Myocarditis

Case Presentation: A 19 year old male presented with sudden onset chest pain radiating to back. He was a smoker and denied using cocaine since his last hospitalization for cocaine-induced myocardial infarction 2 years ago. UDS was negative. EKG showed normal sinus rhythm with no ST-T wave changes. Initial troponin was 0.850. Potassium levels were low at 2.9 mmol/L but other labs were normal. Chest CT angiography ruled out aortic dissection. He was started on heparin drip. Stat Echocardiogram showed LVEF of 55-60% with no wall motion abnormalities. Repeat potassium levels normalized after replacement, however, his troponins were trending up from 3.9 and 11.5. He continued to complain of severe chest pain, so underwent cardiac catheterization which showed normal coronary arteries and LVEF 55-60%. Heparin drip was discontinued and NSAIDs and colchicine were started. Cardiac MRI (see Figure) was done that showed patchy mid-wall and epicardial delayed gadolinium enhancement involving the basal inferolateral wall, with mild hyperintense signal on the triple IR sequence, suggestive of myocarditis. On further probing, he reported receiving a second dose of Moderna COVID vaccine 3 days prior to presentation. Discussion(s): In December 2019, a novel RNA virus causing COVID-19 infection was reported, which quickly reached a pandemic level. COVID-19 vaccines were granted emergency use authorization by FDA. With millions of people receiving COVID-19 vaccinations worldwide, rare adverse effects are now being reported. The benefits of vaccination undoubtedly outweigh any minor side effects. However major adverse effects like this are potentially fatal. This case report warrants further investigation into the association of myocarditis with COVID-19 vaccinations and further recommendations regarding vaccination in younger adults.

Comprehensive narrative review of real-world COVID-19 vaccines: viewpoints and opportunities.

Currently, people all over the world have been affected by coronavirus disease 2019 (COVID-19). Fighting against COVID-19 is the top priority for all the countries and nations. The development of a safe and effective COVID-19 vaccine is considered the optimal way of ending the pandemic. Three hundred and 44 vaccines were in development, with 149 undergoing clinical research and 35 authorized for emergency use as to March 15 of 2022. Many studies have shown the effective role of COVID-19 vaccines in preventing SARS-CoV-2 infections as well as serious and fatal COVID-19 cases. However, tough challenges have arisen regarding COVID-19 vaccines, including long-term immunity, emerging COVID-19 variants, and vaccine inequalities. A systematic review was performed of recent COVID-19 vaccine studies, with a focus on vaccine type, efficacy and effectiveness, and protection against SARS-CoV-2 variants, breakthrough infections, safety, deployment and vaccine strategies used in the real-world. Ultimately, there is a need to establish a unified evaluation standard of vaccine effectiveness, monitor vaccine safety and effectiveness, along with the virological characteristics of SARS-CoV-2 variants; and determine the most useful booster schedule. These aspects must be coordinated to ensure timely responses to beneficial or detrimental situations. In the future, global efforts should be directed toward effective and immediate vaccine allocations, improving vaccine coverage, SARS-CoV-2 new variants tracking, and vaccine booster development.

Towards Secure and Privacy-Preserving Data Sharing for COVID-19 Medical Records: A Blockchain-Empowered Approach

COVID-19 is currently a major global public health challenge. In the battle against the outbreak of COVID-19, how to manage and share the COVID-19 Electric Medical Records (CEMRs) safely and effectively in the world, prevent malicious users from tampering with CEMRs, and protect the privacy of patients are very worthy of attention. In particular, the semi-trusted medical cloud platform has become the primary means of hospital medical data management and information services. Security and privacy issues in the medical cloud platform are more prominent and should be addressed with priority. To address these issues, on the basis of ciphertext policy attribute-based encryption, we propose a blockchain-empowered security and privacy protection scheme with traceable and direct revocation for COVID-19 medical records. In this scheme, we perform the blockchain for uniform identity authentication and all public keys, revocation lists, etc are stored on a blockchain. The system manager server is responsible for generating the system parameters and publishes the private keys for the COVID-19 medical practitioners and users. The cloud service provider (CSP) stores the CEMRs and generates the intermediate decryption parameters using policy matching. The user can calculate the decryption key if the user has private keys and intermediate decrypt parameters. Only when attributes are satisfied access policy and the user's identity is out of the revocation list, the user can get the intermediate parameters by CSP. The malicious users may track according to the tracking list and can be directly revoked. The security analysis demonstrates that the proposed scheme is indicated to be safe under the Decision Bilinear Diffie-Hellman (DBDH) assumption and can resist many attacks. The simulation experiment demonstrates that the communication and storage overhead is less than other schemes in the public-private key generation, CEMRs encryption, and decryption stages. Besides, we also verify that the proposed scheme works well in the blockchain in terms of both throughput and delay.

Pandemic Makers: How Citizen Groups Mobilized Resources to Meet Local Needs in a Global Health Crisis: ET&P

The enormous scale of suffering, breadth of societal impact, and ongoing uncertainty wrought by the COVID-19 pandemic introduced dynamics seldom examined in the crisis entrepreneurship literature. Previous research indicates that when a crisis causes a failure of public goods, spontaneous citizen ventures often emerge to leverage unique local knowledge to rapidly customize abundant external resources to meet immediate needs. However, as outsiders, emergent citizen groups responding to the dire shortage of personal protective equipment at the onset of COVID-19 lacked local knowledge and legitimacy. In this study, we examine how entrepreneurial citizens mobilized collective resources in attempts to gain acceptance and meet local needs amid the urgency of the pandemic. Through longitudinal case studies of citizen groups connected to makerspaces in four U.S. cities, we study how they adapted to address the resource and legitimacy limitations they encountered. We identify three mechanisms—augmenting, circumventing, and attenuating—that helped transient citizen groups calibrate their resource mobilization based on what they learned over time. We highlight how extreme temporality imposes limits on resourcefulness and legitimation, making it critical for collective entrepreneurs to learn when to work within their limitations rather than try to overcome them.

A case of anaphylaxis to the BNT162b2 mRNA COVID-19 vaccine in a patient with confirmed polyethylene glycol allergy

Case report The Food and Drug Administration (FDA) provided emergency use authorization (EUA) for the Pfizer/BioNTech (BNT162b2) COVID-19 vaccine in December 2020. Implementation of COVID-19 mass vaccination efforts were implemented soon after. However, following the FDAs EUA, COVID-19 vaccine allergic reactions were reported. These findings led to concerns about vaccine hesitancy and the possible avoidance of future doses. The Texas Children's Hospital COVID-19 Vaccine Hypersensitivity Clinic was established in December 2020 to help address these concerns and to evaluate both pediatric and adult patients with immediate allergic reactions to the COVID-19 vaccines, as well as evaluating patients with polyethylene glycol (PEG) or polysorbate (PS) allergy. We present the case of an 18yo female who experienced anaphylaxis following her second Pfizer mRNA COVID-19 vaccine. The patient developed symptoms of generalized hives, chest tightness and dyspnea 17 minutes after receiving the Pfizer mRNA COVID-19 vaccine. She was treated in the emergency department with IM prednisone and PO diphenhydramine. Of note, in 2018, she had a similar response to her HPV9 vaccine (containing PS 80). Tryptase wasn't obtained at the time of her COVID-19 or HPV9 vaccine reactions, but she did have a baseline that was normal around 4ng/mL. Skin testing was performed to the following: PEG 3350, PS 20 and PS 80. Skin testing (skin prick and intradermal) were negative for PS20 and PS80. PEG 3350 skin prick was negative but methylprednisone acetate (PEG 3350) was positive at the 4mg/mL intradermal testing strength. She underwent a Miralax (PEG 3350) oral challenge. Within 20 minutes of ingesting 0.17grams PEG 3350 she developed an itchy macular rash on neck and upper chest, nausea and a globus throat sensation. She was treated with PO cetirizine and symptoms improved. Tryptase level was obtained 30 min after the start of her reaction and was 4ng/mL. Given the patient's reaction, she was advised to avoid PEG containing products and will return to undergo a graded-step challenge to the Janssen (J&J) COVID-19 vaccine. The prevalence of COVID-19 mRNA vaccine anaphylaxis and PEG allergies is rare. However, allergy referral is warranted in cases of immediate reactions to the COVID-19 vaccine or history of PEG or polysorbate allergies.