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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.)
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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.
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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
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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
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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.
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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.
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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.
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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.
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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.
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Objectives: To describe the implementation of an ED-based program to offer monoclonal antibody therapy to patients with mild-moderate COVID-19 disease. Background(s): Monoclonal antibody therapy (MOAB) has recently emerged as a treatment for mild to moderate COVID-19, potentially preventing those with underlying conditions from progressing to severe illness and hospitalization. Further, as EDs are the primary point of health care access for many at-risk individuals, offering MOAB in the ED may increase availability of treatment options for patients from traditionally underserved communities. Method(s): A retrospective chart review was conducted of patients 12 years and above who received treatment in our urban, academic, community hospital. Patients 12 years and older were screened for eligibility during ED visits or during follow-up calls providing positive test results. Staff was trained on specific consent, infusion, monitoring, and documentation procedures adherent to MOAB administration under the Emergency Use Authorization. Patients were contacted following MOAB and queried regarding symptom resolution and healthcare utilization. Data regarding patient demographics, ED course, and 7-day unscheduled visits were collected. Result(s): In this ongoing quality improvement initiative, from December 2020 to March 2021, there were 26,229 patient encounters at the pilot ED site. 84 patients were provided MOAB, 87% Bamlanivimab and 13% Bamlanivimab/Etesevimab. Patients had a mean age of 52.3 years (SD 24.4);21% were 12-17 years of age and 37% were >65 years old. 52% were male. 33% self-reported as Caucasian, 19% Black, 18% Asian/Pacific Islander, 21% as other, and 9% were unknown. 17% identified as Latinx. 19% of patients were insured by Medicaid, 36% Medicare, 39% commercially insured, and 6% were uninsured. Patients had symptoms a median of 3 days prior to MOAB. After age (46%), the most commonly reported eligibility criteria was obesity (20%), followed by hypertension (11%) and immunocompromised state (11%). 74% of infusions were administered during nights and weekends. No infusion reactions occurred. 8% returned to an ED within 7 days of MOAB, 5% were hospitalized. No patients required ICU admission or died. Conclusion(s): ED-based MOAB has been safely implemented and may be an effective treatment for patients with mild to moderate COVID-19. Health-system wide expansion of this program may provide opportunities to offer this life-saving therapy to underserved populations with poor access to care.Copyright © 2023
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This paper describes the creation of outpatient monoclonal antibody (mAb) infusion centers for COVID-19 patients in a large academic medical center. It shows how the early and consistent partnership between infection prevention and the clinical and operational teams to establish and implement policies and procedures led to efficient and safe workflows.
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COVID-19 , Humans , Academic Medical Centers , Antibodies, Monoclonal , Outpatients , PolicyABSTRACT
COVID-19 pandemic shook the country and the world. It was evident from the beginning that effective vaccines would perhaps be the most potent counter-measure required to defeat this hitherto unknown virus. Hon'ble Prime Minister gave a call to our Scientists to create an effective vaccine against COVID-19 on 141h March, 2020. Indian R & D and industry enterprises joined hands to work relentlessly to develop multiple vaccine candidates and multiple platforms. The Government of India provided support through 'Mission COVID Suraksha', facilitated research and trials, rationalized regulatory processes and, above all, encouraged and motivated the players. Hon'ble Prime Minister personally visited major vaccine-producing hubs. On rd January 2021, India issued Emergency Use Authorization to COVAXIN and COVISHIELD vaccines. Eventually a total of 11 India- made vaccines have been given Emergency Use Authorization. Today, India has the capacity to manufacture 5 billion doses per annum should the need arise. India has administered more than 219 crore doses to its people, which is the largest vaccination programme in the world. It is estimated that over a period of one year the program. has saved 34lakh lives.
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The COVID-19 pandemic has presented huge challenges to health care systems, the research community, and regulatory authorities worldwide. In recognition of the urgent need for safe and effective vaccines against this new coronavirus, the National Institutes of Health (NIH) worked with 5 manufacturers of promising vaccine candidates to mount the studies required to evaluate these vaccines and potentially support their deployment. The outcomes of the studies reported thus far have been far more successful than anyone would have imagined. In this session, perspectives on the issues raised in the COVID-19 vaccine development process under Operation Warp Speed will be shared by individuals playing a major role in the design, conduct, and analysis of these studies. We will hear from the lead company investigator of the Moderna trial, the first Operation Warp Speed trial to receive Emergency Use Authorization from the US Food and Drug Administration (FDA);from the NIH coordinator of the Data and Safety Monitoring Board (DSMB) convened to oversee all 5 trials;and from a member of that DSMB. SPEAKERS: Dr. Jacqueline Miller, Moderna, Inc., Lead company investigator for Moderna COVID-19 vaccine trial. Working title: Managing the evaluation of the data of a COVID-19 clinical trial: the manufacturer's perspective Dr. Sally Hunsberger, National Institute of Allergy & Infectious Diseases, NIH Coordinator of Data and Safety Monitoring Board for NIAO-sponsored trials of COVID-19 vaccines. Working title: Managing the evaluation of the data of a COVID-19 clinical trial: the NIH perspective Dr. Steven Joffe Department of Medical Ethics and Health Policy Perelman School of Medicine, University of Pennsylvania Member, NIAID COVID-19 vaccine trials Data and Safety Monitoring Board. Working title: Managing the evaluation of the data of a COVID- 19 clinical trial: a DSMB member's perspective.
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Introduction: Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease, as of writing this article there are over 6.3million people are affected. The virus can result in a dysregulated immune response and cytokine storm which is associated with disease severity, leading to capillary leak syndrome, progressive lung injury, respiratory failure, and acute respiratory distress syndrome (ARDS). CytoSorb is a European Union-approved extracorporeal cytokine adsorber, designed to broadly reduce cytokine storm and other inflammatory mediators in the blood. On 10 April 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for emergency use of CytoSorb to treat patients 18 years of age or older with confirmed COVID-19 admitted to the ICU. In this case report, we discuss two COVID-19 positive patients who were admitted to the ICU with severe ARDS and were treated with VV ECMO and Cytosorb. Cytosorb has been extensively studied in patients with sepsis however the reports of treating patients with COVID-19 in cytokine storm are scanty hence this descriptive article will benefit the institutions who are planning on adopting this mode of therapy to treat COVID-19 patients Methods: We discuss COVID-19 positive patients who were admitted to the ICU with severe ARDS, AKI and were treated with VV ECMO, Cytosorb and CRRT. Cytosorb has been extensively studied in patients with sepsis however the reports of treating patients with COVID-19 in cytokine storm are scanty hence this descriptive article will benefit the institutions who are planning on adopting this mode of therapy to treat COVID-19 patients Results: In this case series we have described an improvement clinically in terms of reducing pressor and fio2 requirements which co-related well with the reduction of IL-6 levels however there were other confounding factors like administration of Tocilizumab and VV ECMO which could have contributed to the improvement of the patients. The patients are now dialysis dependent and became hemodynamically stable 3-4 weeks into their admission and were eventually extubated Conclusion(s): Cytokine adsorbing column in severe COVID-19 patients with Acute kidney injury does help in improvement of pressor and fio2 requirements which co-related well with the reduction of IL-6 levels in a short period of time. With other centers adapting Cytosorb we will eventually have better information about the overall outcome of these patients No conflict of interestCopyright © 2023
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Since late 2019, the pandemic of COVID-19, caused by SARS-CoV-2, has resulted in high morbidity and mortality worldwide. During 2020, safety monitoring of medicinal treatments for this novel disease was performed by Uppsala Monitoring Centre (UMC) in VigiBase, WHO's global database of suspected adverse drug reactions, which is the largest international repository of reported ADRs. Initially, COVID-19 treatments included numerous repurposed medicines previously approved for other indications, such as chloroquine and hydroxychloroquine. Although chloroquine is a widely used drug which has been on the market for a very long time, the efficacy and safety profile have not been thoroughly studied in COVID-19 patients. In early 2020, chloroquine and hydroxychloroquine were authorized by major regulatory agencies for emergency use, or only for use within clinical trials. Given the interest over the use of these drugs in COVID-19, the ADR reports in VigiBase for them were summarized and communicated to reiterate their toxicities, in particular the cardiac reactions which may result in fatal outcomes.1 Remdesivir, the first novel antiviral drug authorized for use in treatment for COVID-19, was the most commonly reported COVID-19 medicine within VigiBase during 2020. Employing indication- focused descriptive statistics (disproportionality analysis), together with the use of a comparator tocilizumab with a known safety profile, it was possible to identify known safety information for both remdesivir and tocilizumab and suggest potential safety concerns for remdesivir. The most reported adverse events were liver dysfunction, kidney injury, death and bradycardia.2 In late 2020, several new vaccines for COVID-19 were developed, received emergency authorization and rolled out on a large scale. The vaccines used novel technology and a rapid and vast deployment was anticipated. For this scale of activity, a well-functioning international postmarketing safety surveillance system is essential. The unprecedented volume of reports of suspected adverse events following immunization has led to the development of new routines and the use of new tools at UMC, for example, a digital reporting form designed for mobile devices was implemented;more frequent updates of VigiBase data allowed timely data analyses;a COVID-19 vaccine-specific standardized drug grouping (SDG) was created enabling the data analysis on a vaccine platform level;and a monthly descriptive report regarding COVID-19 vaccine reporting in VigiBase was made available for member countries of the WHO Programme for International Drug Monitoring (PIDM).3 UMC regularly screened VigiBase for previously unknown or incompletely documented COVID- 19 vaccines adverse reactions. These signals were shared with all WHO PIDM members to complement their signal detection and support local action to protect patients from harm. Some signals were also published outside the WHO PIDM to raise awareness or encourage data collection.4,5 In summary, successful adaptations were made at UMC in a short period to handle the COVID- 19 pandemic situation. However, the pandemic has not ended yet and further challenges are anticipated. The safety monitoring of COVID- 19 therapies and vaccines still needs to continue.
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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.