Emergency Use Authorization Research Articles

Improving Immunization Health Care Data Quality using Two-Dimensional Barcoding and Barcode Scanning Practices.

Manual data entry is time-consuming, inefficient, and error prone. In contrast, leveraging two-dimensional (2D) barcodes and barcode scanning tools is a rapid and effective practice for automatically entering vaccine data accurately and completely. CDC pilots documented clinical and public health impacts of 2D barcode scanning practices on data quality and completeness, time savings, workflow efficiencies, and staff experience. Data entry practices and entered records from routine and mass vaccination settings were analyzed. Data quality improvement opportunities were identified. A sample of 50 million emergency use authorization (EUA) coronavirus disease 2019 (COVID-19) vaccine records were analyzed for accuracy and completeness across three data fields: lot number, expiration date, and National Drug Code (NDC). The EUA COVID-19 vaccines lacked a 2D barcode containing these data fields, which necessitated manual data entry at administration. A CDC pilot at clinic compared scanned and manually entered data for routine vaccines across these same data fields. Analysis of 50 million manually entered EUA COVID-19 vaccine administration records indicated significant gaps in data accuracy and completeness across three data fields. Over half of the analyzed EUA vaccine NDCs (53%) and one-third of the expiration dates (35%) had missing or inaccurate data recorded. Pilot data also showed many errors when manually entered. However, when the pilot's routine vaccines were scanned (out of 71,969 records), nearly all entries were complete and accurate across all three data fields (ranging from 99.7% to 99.999% accurate). Vaccine 2D barcode scanning practices increased data accuracy and completeness (up to 99.999% accurate) across data fields assessed. When used consistently, vaccine 2D barcode scanning can resolve issues demonstrated in manually entered data. To realize these benefits, the immunization community should widely use scanning practices. To increase use, CDC developed a Vaccine 2D Barcode National Adoption Strategy and implementation resources.

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

The coronavirus disease 2019 (COVID-19) pandemic has been an unprecedented healthcare crisis, one that threatened to overwhelm health systems and prompted an urgent need for early treatment options for patients with mild-to-moderate COVID-19 at high risk for progression to severe disease. Randomised clinical trials established the safety and efficacy of monoclonal antibodies (mAbs) early in the pandemic; in vitro data subsequently led to use of the mAbs being discontinued, without clear evidence on how these data were linked to outcomes. In this study, we 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 patients. Electronic health records from the National COVID Cohort Collaborative (N3C) were used to identify US patients (aged ≥ 12 years) diagnosed with COVID-19 (positive test or ICD-10: U07.1) in an ambulatory setting (27 September 2021-30 April 2022) who met Emergency Use Authorization (EUA) high-risk criteria. Patients receiving the mAb sotrovimab within 10 days of diagnosis were assigned to the sotrovimab cohort, with the day of infusion as the index date. Untreated patients (no evidence of early mAb treatment, prophylactic 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 in the sotrovimab cohort. The primary endpoint was hospitalisation or death (both all-cause) within 29 days of index, reported as descriptive rate and adjusted [via inverse probability of treatment weighting (IPTW)] odds ratio (OR) and 95% confidence interval (CI). Of nearly 2.9 million patients diagnosed with COVID-19 during the analysis period, 4992 met the criteria for the sotrovimab cohort, and 541,325 were included in the untreated cohort. Before weighting, significant differences were noted between the cohorts; for example, patients in the sotrovimab cohort were older (60 years versus 54 years), were more likely to be white (85% versus 75%) and met more EUA criteria (mean 3.1 versus 2.2) versus the untreated cohort. The proportions of patients with 29-day hospitalisation or death were 3.5% (176/4992) and 4.5% (24,163/541,325) in the sotrovimab and untreated cohorts, respectively (unadjusted OR: 0.78; 95% CI: 0.67, 0.91; p = 0.001). In adjusted analysis, sotrovimab was associated with a 25% reduction in the odds of hospitalisation or death compared with the untreated cohort (IPTW-adjusted OR: 0.75; 95% CI: 0.61, 0.92; p = 0.005). Sotrovimab demonstrated clinical effectiveness in preventing severe outcomes (hospitalisation, mortality) in the period 27 September 2021-30 April 2022, which included Delta and Omicron BA.1 variants and an early surge of Omicron BA.2 variant.

Using Machine Learning to Determine a Suitable Patient Population for Anakinra for the Treatment of COVID-19 Under the Emergency Use Authorization.

A randomized, double-blind, placebo-controlled study (SAVEMORE trial) provided data to support an Emergency Use Authorization (EUA) of anakinra in hospitalized adults with positive results of direct severe acute respiratory syndrome-coronavirus 2 viral testing with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR). Currently, the suPAR assay is not commercially available in the United States. An alternative method was needed to identify patients that best reflect the population in the clinical trial selected based on suPAR level ≥ 6 ng/mL at baseline. A machine learning approach based on data from the SAVEMORE trial was used to develop a scoring rule to identify patients who are likely to have a suPAR level ≥ 6 ng/mL at baseline. External validation of the scoring rule was conducted with data from a different trial (SAVE). This clinical scoring rule with high positive predictive value, high specificity, reasonable sensitivity, and biological relevance is expected to identify patients who are likely to have an elevated suPAR level ≥ 6 ng/mL at baseline. As such, it is included in the EUA to identify patients that fall within the authorized population for whom the known and potential benefits outweigh the known and potential risks of anakinra.

Food and Drug Administration Oversight: Origins and Contribution to the National Covid Response

The Food and Drug Administration (FDA) has been a key actor in the USA’s response to the Covid-19 pandemic. The extensive use of Emergency Use Authorizations (EUAs) during the pandemic as part of its broader strategy to protect the health of the country has raised this federal agency to the public psyche. The FDA’s response has been guided by its position within the national governing framework as well as its own unique history. A review of this framework and the FDA’s history can be illuminating in understanding this agency’s response during a national crisis.

Monoclonal Antibody Infusions for Outpatient Management of Mild-Moderate COVID-19.

The COVID-19 pandemic has led to a rapid, exponential increase in hospitalizations and morbidity/mortality. In November 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) permitting administration of the first monoclonal antibodies (mAb) for outpatient treatment of COVID-19. Early data showed a reduction in COVID-19-related hospitalizations with few adverse events. However, since these treatments are only authorized under an EUA, real-world data are minimal. To assess efficacy and safety of mAbs in a veteran population. This retrospective study analyzed veterans at the Ralph H. Johnson Veterans Affairs Health Care System with mild-moderate COVID-19 and screened for mAb eligibility between December 1, 2020, and October 31, 2021. The primary outcome was hospitalizations and/or emergency department (ED) visits within 30 days. Secondary outcomes included 30-day mortality and post-COVID-19 conditions. Adverse events were also evaluated. Outcomes were compared between mAb-treated patients and eligible veterans who were not treated. There were 296 and 275 veterans in the mAb and control groups, respectively. No statistically significant difference was found for the primary outcome overall (25.7% vs 25.1%; P = 0.87), nor for COVID-19-related return visits or hospitalizations (13.9% v. 16%; P = 0.4). However, the mAb group had more return ED visits (P = 0.35), and the control group had significantly more hospitalizations (P = 0.02). Vaccinated veterans who received an mAb had fewer return visits and hospitalizations (P = 0.01). More mAb-treated veterans experienced post-COVID-19 conditions. No difference in mortality was found. Four nonsevere adverse events occurred after the mAb therapy. Overall, the mAbs appeared safe and effective. Sicker, higher-risk mAb-treated veterans faired similarly to less-sick, high-risk veterans not treated. Those who were vaccinated seemed to benefit the most from mAb therapy. Future prospective studies with more matched groups are needed to assess full benefits and risks of mAbs shown to neutralize the predominant variants.

In Silico Therapeutic Study: The Next Frontier in the Fight against SARS-CoV-2 and Its Variants

COVID-19 has claimed around 7 million lives (from December 2019–November 2023) worldwide and continues to impact global health. SARS-CoV-2, the virus causing COVID-19 disease, is characterized by a high rate of mutations, which contributes to its rapid spread, virulence, and vaccine escape. While several vaccines have been produced to minimize the severity of the coronavirus, and diverse treatment regimens have been approved by the US FDA under Emergency Use Authorization (EUA), SARS-CoV-2 viral mutations continue to derail the efforts of scientists as the emerging variants evade the recommended therapies. Nonetheless, diverse computational models exist that offer an opportunity for the swift development of new drugs or the repurposing of old drugs. In this review, we focus on the use of various virtual screening techniques like homology modeling, molecular docking, molecular dynamics simulations, QSAR, pharmacophore modeling, etc., in repurposing SARS-CoV-2 therapeutics against major variants of SARS-CoV-2 (Alpha, Beta, Gamma, Delta, and Omicron). The results have been promising from the computer-aided drug design (CADD) studies in suggesting potential compounds for the treatment of COVID-19 variants. Hence, in silico therapeutic studies represent a transformative approach that holds great promise in advancing our fight against the ever-evolving landscape of SARS-CoV-2 and its variants.

Comparing the Efficacy and Safety of the Pfizer BNT162b2 Vaccine with Other Alternatives Under COVID-19

In an epidemic or pandemic caused by a pathogen that has never been encountered, scientists have to compete against time to develop new vaccines. Vaccination effectively prevents the spread of the disease and saves lives. Under the COVID-19 crisis, several types of vaccines were developed and authorized as Emergency Use Authorization (EUA), including the first mRNA vaccine product ever approved by FDA, the BNT162b1. The transiently expressed mRNA does not encounter the problem of genome integration with the host and it takes less time to develop, which differentiates it from alternative types such as inactivated and subunit vaccines. This paper attempts to present the difference of the BNT162b2 mRNA vaccine from the Novavax subunit vaccine, and the Sinovac inactivated vaccine, in terms of COVID-19 prevention and adverse events, therefore attempts to provide a better understanding of the behaviors of mRNA vaccines under COVID-19.

The spectrum of side effects associated with COVID-19 vaccines in patients with inborn errors of immunity

ObjectiveCOVID-19 immunization was implemented with emergency-use authorization. We had concerns/lack of information on mRNA vaccine side effects in different inborn errors of immunity (IEI) types. MethodsWe enrolled 141 patients (IEIP) and 151 healthy controls(HC) who received SARS-CoV-2 vaccine/s(Sinovac and/or Pfizer-BioNTech(mRNA vaccine), one to five doses), questioned them for side-effects, evaluated in three groups according to the vaccine/s they received; only Sinovac, only Pfizer-BioNTech, and both vaccines. ResultsArm pain, generalized weakness, myalgia, and fever were common side effects in IEI-P and HC groups. Generalized weakness/fatigue, fever, and palpitation were significantly frequent in IEI-P who experienced COVID-19 compared to those who did not (p = 0.021, p = 0.047, and p = 0.024, respectively). Severe symptoms after vaccination, new-onset splenomegaly and pancytopenia, urticaria, herpes simplex virus (HSV), and varicella zoster virus (VZV) reactivation were seen in four IEI-P (2.8%). ConclusionIEI-P mRNA vaccination is relatively safe compared to the conventional vaccine. Individuals who experience uncommon side effects should undergo immunological screening.

Real-World Efficacy of COVID-19 Pre-Exposure Prophylaxis with Tixagevimab/Cilgavimab in People with Multiple Sclerosis.

Vaccines against the SARS-CoV-2 virus were authorized for use by the Food and Drug Administration (FDA) in the United States and have proven effective for the prevention of morbidity and death from COVID-19. Certain immunosuppressant medications prevent the development of protective immunity following COVID-19 vaccination. In December 2021, the FDA issued an emergency use authorization (EUA) for a monoclonal-antibody combination of tixagevimab and cilgavimab, under the brand name Evusheld, for pre-exposure prophylaxis (PrEP) against COVID-19 for individuals with moderate-to-severe immune compromise. While a 77% reduction in symptomatic COVID-19 was observed in the PROVENT study, the trial was conducted prior to emergence of the B.1.1.529 Omicron variant. We suspected reduced efficacy of PrEP against Omicron subvariants. We conducted a retrospective cohort study comparing the prevalence of symptomatic COVID-19 infections between 1 January 2022 and 1 July 2022 in eligible patients treated with PrEP versus untreated using a questionnaire administered with the REDCap survey tool. Responses from 235 participants were included in the final analysis, with 176 untreated respondents and 59 in the PrEP cohort. Symptomatic COVID-19 infections were reported in 50 (28.4%) untreated participants and only 9 (15.3%) of those who received PrEP (p = 0.0557; OR 0.4536; 95% CI 0.2046 to 0.9599). Only two participants were hospitalized for COVID-19 infection, both in the untreated cohort. The reduction in COVID-19 infections did not achieve statistical significance, indicating diminished efficacy against Omicron variants.

In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates

ABSTRACT COVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.

Using a web platform for equitable distribution of COVID-19 monoclonal antibodies: a case study in resource allocation.

While medical countermeasures in COVID-19 have largely focused on vaccinations, monoclonal antibodies (mAbs) were early outpatient treatment options for COVID-positive patients. In Minnesota, a centralized access platform was developed to offer access to mAbs that linked over 31,000 patients to care during its operation. The website allowed patients, their representative, or providers to screen the patient for mAbs against Emergency Use Authorization (EUA) criteria and connect them with a treatment site if provisionally eligible. A validated clinical risk scoring system was used to prioritize patients during times of scarcity. Both an ethics and a clinical subject matter expert group advised the Minnesota Department of Health on equitable approaches to distribution across a range of situations as the pandemic evolved. This case study outlines the implementation of this online platform and clinical outcomes of its users. We assess the impact of referral for mAbs on hospitalizations and death during a period of scarcity, finding in particular that vaccination conferred a substantially larger protection against hospitalization than a referral for mAbs, but among unvaccinated users that did not get a referral, chances of hospitalization increased by 4.1 percentage points.

409. Unvaccinated Adolescents Bear the Majority of Disease Burden of Severe COVID-19 Among Those Admitted to the Intensive Care Unit (ICU)

Abstract Background COVID-19 vaccination is one of the most important public health tools to prevent severe COVID-19. Methods COVID-19 vaccine (Pfizer-BioNTech) first received the U.S. Food and Drug Administration (FDA) Emergency use authorization (EUA) for individuals 16 years of age and older on 12/11/2020 and for 12-15 years of age on 5/10/2021. We evaluated clinical and epidemiologic characteristics of critically ill adolescents with COVID-19 admitted to the intensive care unit (ICU) at our tertiary-care centers in Northwestern Iowa (encompassing Sioux City and Sergeant Bluff locations) during the 1-year post-vaccination approval period from June 1, 2021- May 31, 2022. Adolescence was defined as age-group 12-21 years per WHO definition. Results Twenty-one adolescents were admitted to the ICU with a median age of 16 years (IQR 12-20 years) and male: female ratio of 1:1.3. The majority (77%) were admitted with COVID-19 related pneumonia and 10 developed hypoxemic respiratory failure; 19 of 21 (90%) adolescent patients admitted to the ICU during this period were unvaccinated and all adolescents developing respiratory failure (10/10, 100%) were unvaccinated. Majority of patients with respiratory failure (70%) required mechanical ventilation (MV). Seventy % of patients with respiratory failure were obese (BMI of >30); 40% of patients had two or more pre-existing comorbidities; those with BMI >40 were 4.3 times more likely to develop respiratory failure (p< 0.0001). Inflammatory markers were 5-20 times higher among patients with respiratory failure (p< 0.05); 60% of those with respiratory failure developed complications including ARDS, acute renal injury and cerebral anoxic encephalopathy. All with respiratory failure required parenteral steroids. Mean duration of ICU stay was significantly longer for patients with respiratory failure [14.6 (±1.7) days versus 7.5 (± 2.6) days, p< 0.0001)]. None of the patients died. After hospital discharge, 30% patients reported post COVID-19 fatigue at 3-month follow up. Conclusion Our results showed that all of the critically ill adolescent patients with COVID-19 associated hypoxemic respiratory failure were unvaccinated and majority developed complications. These results further emphasize importance of COVID-19 vaccination efforts for adolescents. Disclosures All Authors: No reported disclosures

2733. Evusheld (AZD7442) Uptake and COVID-19 Outcomes in Solid Organ Transplant Recipients: A Secondary Analysis

Abstract Background Evusheld is a pre-exposure prophylaxis for COVID-19. It was recommended for high-risk populations, including solid organ transplant (SOT) recipients, due to their increased risk of severe COVID-19 and suboptimal vaccine response. Evusheld received emergency use authorization (EUA) in 12/2021, which was withdrawn on 1/27/2023 due to limited strain efficacy. This study examines Evusheld uptake among SOT recipients and evaluates the frequency and outcomes of COVID-19 infections in those receiving at least one dose. Methods We performed a secondary analysis using data from adult SOT recipients (heart, kidney, liver) enrolled in a phase II, multicenter, randomized controlled, double-blind immunogenicity and safety clinical trial for influenza vaccines. Our study included patients enrolled at Vanderbilt University Medical Center between 1/11/2021 and 2/28/2023 who had undergone transplantation before 1/27/2023. Demographic characteristics, transplant history, and COVID-19 vaccine information were obtained from the study database. We conducted chart abstractions until 4/27/2023 to collect data on COVID-19 infections, outcomes, and Evusheld receipt and dosage. Results Our study included 62 heart, 93 kidney, 14 liver, and 12 multiple-organ transplant recipients, for a total sample size of 181. Overall, 99 patients (54.7%) received Evusheld. We did not find sufficient evidence of differences in demographic characteristics or frequency of symptomatic COVID-19 infections between those who received Evusheld vs. those who did not. None of the 14 liver transplant recipients received Evusheld, and patients who received Evusheld were more likely to have been transplanted during the EUA period (Table 1). The number of posttransplant COVID-19 infections was 0.09 per person-years in those who did not receive Evusheld. Among those who received Evusheld, the number of posttransplant COVID-19 infections was 0.14 per person-years pre-Evusheld and 0.08 post-Evusheld (Table 2; Figure). Demographics, clinical characteristics, and COVID-19 outcomes of adult solid organ transplant recipients who received a transplant between 08/09/2020 and 01/22/2023, stratified by Evusheld receipt (N=181). Timing and characteristics of COVID-19 infections in 181 adult solid organ transplant recipients. Figure Timeline of COVID-19–related events in those who tested positive for COVID-19 at least once and (a) did not receive Evusheld or (b) received at least one dose of Evusheld. Conclusion Despite recommendations, Evusheld uptake among SOT recipients in our cohort was suboptimal. Additional research is needed to understand factors associated with suboptimal Evusheld uptake and to evaluate the effectiveness of monoclonal antibodies against COVID-19. Disclosures Daniel Dulek, MD, Eurofins Viracor: Research supplies Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support

511. Risk Factors for Seeking Medical Care Following Nirmatrelvir-Ritonavir (Paxlovid) Treatment For COVID-19

Abstract Background In December 2021, the FDA issued an emergency use authorization (EUA) for nirmatrelvir-ritonavir (Paxlovid). This was based on the randomized placebo-controlled trial data from the EPIC-HR study which showed that high-risk non-hospitalized patients given Paxlovid had an 88.9% reduction in the relative risk of progression to hospitalization or death by Day 28 in coronavirus disease 2019 (COVID-19). We aimed to study the risk factors for seeking medical care following Paxlovid treatment. Methods In this historical cohort study, we assessed risk factors for high-risk non-hospitalized patients treated with Paxlovid from January 1, 2022, to December 31, 2022, at outpatient facilities associated with Ascension St. John Hospital. Our outcome variable was the composite of subsequent evaluation in the Emergency Department (ED) or inpatient admission within four weeks of their Paxlovid treatment. Data were analyzed using SPSS v. 29.0. The study was approved by the IRB. Results Of 371 patients who received Paxlovid treatment, the mean (SD) age was 59.4 (±13.8) years; 63.9 % (237) were female, and 77.7% (282) white. The mean body mass index (BMI) of the cohort was 31.3 ± 7.8 kg/m2. The incidence of the composite event was 6.7% (25/371). The risk of the composite event was higher in patients with a history of myocardial infarction (MI) (28 % vs 9.3%), congestive heart failure (CHF) (12 % vs 2.3%), chronic lung diseases (CLD) (48 % vs 26.4%) and diabetes mellitus (DM) with complication (24% vs 4.1%), respectively. Alcohol users were less likely to seek medical care following Paxlovid (40 % vs 63.7%, respectively). There were no differences in BMI, tobacco use or vaccination rates between the groups. In multivariable logistic regression, factors associated with seeking medical care post-Paxlovid were female sex (OR 4.6; 95% CI 1.4-15.3; p= 0.013), alcohol use (OR 0.4; 95% CI 0.2-0.9; p= 0.039), MI (OR 4.0; 95% CI 1.4-11.8; p=0.011), DM with complications (OR 6.9; 95% CI 2.0-23.3; p= 0.002), CLD (OR=3.9, 95% CI 1.1-13.5; p=0.03), at the time of Paxlovid treatments. Conclusion Independent risk factors for seeking medical care following Paxlovid treatment for COVID-19 were MI, CHF, CLD, and DM with complications while alcohol users were less likely to seek medical care following the Paxlovid treatment. Disclosures All Authors: No reported disclosures

COVID-19 update: New Novavax vaccine formulation for 2023-2024.

A new 2023-2024 formulation of the adjuvanted protein subunit COVID-19 vaccine manufactured by Novavax that was developed to more closely target currently circulating SARS-CoV-2 variants has been made available in the US under an FDA Emergency Use Authorization (EUA) for use in persons ≥12 years old. The original formulation of the Novavax vaccine is no longer authorized for use in the US. In September, updated formulations of the mRNA COVID-19 vaccines manufactured by Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) were licensed by the FDA for use in persons ≥12 years old and made available under EUAs for use in persons 6 months to 11 years old.

Surveillance on Adverse Events Following COVISHIELD (ChAdOx1 nCoV-19) vaccination in Goa, India: An Observational Study.

COVISHIELD, ChAdOx1 nCoV- 19 Corona Virus Vaccine was granted emergency use authorization (EUA) as the first vaccine in India in January 2021. Knowing what to anticipate after vaccination will reduce vaccine hesitancy in the public. This study aimed to identify and measure the adverse events following COVID-19 vaccination. A cross-sectional observational study was conducted at Goa Medical College, starting on February 21 till May 23, 2021. A total of 418 people were enrolled. We collected the data using the Microsoft Form and analyzed using Microsoft Excel and R-program. Of the 418 vaccine recipients, the incidence rate of AEFI (Adverse Events Following Immunization) was 54.31%. Fever, fatigue, and headache were the most commonly reported systemic AEFIs. Among these, 54.7% of AEFI were mild, 42.38% were of the moderate category, and only 2.96% were of grade 3 severity. None of the AEFIs were severe enough for hospitalization. Most of them developed symptoms within 24 hours of the first dose. Complete recovery from AEFIs took a median time of 24 hours. Most of our study findings were consistent with the phase 1, 2/3 trials findings of Oxford-AstraZeneca's ChAdOx1 vaccine. The AEFI symptoms were considered immune reactions to the vaccine. The AEFIs were more common among younger individuals and females. The chance of missing a serious adverse event like a thromboembolic phenomenon cannot be ruled out. We observed low AEFI rates with COVISHIELD in the Indian population compared to Oxford- AstraZeneca's ChAdOx1 vaccine in the UK-based population, which can be explained by preexisting immunity against adenovirus in the Indian population. However, based on the study findings, we may interpret that the COVISHIELD, Serum Institute of India, carries a good safety profile overall.

Use of Updated COVID-19 Vaccines 2023-2024 Formula for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices - United States, September 2023.

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.

Comparison between European Medicines Agency and US Food and Drug Administration in Granting Accelerated Marketing Authorizations for Covid-19 Medicines and their Utilized Regulations

BackgroundPrompted by the Covid-19 pandemic and the need to ensure timely and safe access to medicines during a pandemic, the aim of this study was to compare and contrast the EU and US regulations, processes, and outcomes pertaining to the granting of accelerated Marketing Authorizations (MAs) for COVID-19 vaccines and treatments with a view to determining how effective these regulations were in delivering safe medicines in a timely manner.MethodsMAs for medicines approved for Covid-related indications in the first two pandemic years (March 2020–February 2022) were identified using the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) websites. Authorization reports and utilized regulations were reviewed to determine and compare approval timelines, facilitated pathways, accepted clinical evidence, and effectiveness of the regulations by assessing them against time and safety standards.ResultsBy the end of February 2022, the EMA and FDA had granted 12 and 14 MAs, respectively. Two EU and two US approvals were issued in relation to new indications for already-approved treatments; the remaining ones were first-time approvals of novel vaccines and treatments. The median time to approval was 24 days for the EMA’s conditional MAs and 36 days for the USFDA’s Emergency Use Authorizations (EUA) for all Covid-19 medicines. This is compared with 23 and 28 days, respectively, specifically for first-time novel vaccines and treatments authorized by both USFDA and EMA. The USFDA and EMA differed markedly in terms of the time taken to approve new indications of already-approved treatment; the USFDA took 65 days for such approval, compared with 133 days for the EMA. Where MAs were issued by both authorities, USFDA approvals were issued before EMA approvals; applications for approval were submitted to the FDA before submission to the EMA. Three EU and two US MAs were based on data from two or more phase 3 clinical trials; the remaining ones were based on single trial data. Only six EU and four US trials had been completed by the time of authorization. This was in line with regulations. While the applicable regulations shared many similarities, there were marked differences. For instance, the EU’s conditional MA regulation pertains only to first approvals of new treatments. It does not cover new indications of already-approved treatments. This contrasts with the US, where the EUA regulation applies to both types of applications, something that may have impacted approval timelines.Overall, both EU and US utilized regulations were considered to be effective. For most cases, utilizing such regulations for Covid-19 MAs resulted in faster approval timelines compared to standard MAs. They were flexible enough to manage the process of granting emergency approvals while maintaining strict requirements and allowing comprehensive reviews of the supporting evidence.ConclusionUS and EU regulations were effective in ensuring timely accelerated market access to Covid-19 medicines during the pandemic without compromising the approval standards related to safety or efficacy. The population in both regions will receive comparable access to medicines during a pandemic if sponsors submit their applications to both authorities in parallel.

COVID-19 update: New Pfizer and Moderna vaccine formulations for 2023-2024.

New 2023-2024 formulations of the mRNA COVID-19 vaccines manufactured by Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) that more closely target currently circulating variants have been licensed by the FDA for use in persons ≥12 years old and made available under FDA Emergency Use Authorizations (EUAs) for use in persons 6 months to 11 years old. The bivalent (original and Omicron BA.4/5) formulations of the Pfizer and Moderna vaccines are no longer authorized for use in the US.

Effect of coronavirus disease 2019 on the vaccine development paradigm

Vaccines are prophylactic medical products effectively used against infectious diseases. Although a high amount of vaccine studies are conducted at the preclinical stage, the number of approved vaccines is less than 10%. Development of vaccines from the research stage to the approval of administrative institutions takes about 5 years to 10 years conventionally. However, this period of time for vaccine development is not convenient during public health emergencies because an effective vaccine is required in a short time to restrict the speed of high mortality and morbidity. The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had its catastrophic effects worldwide quickly. Therefore, an atypical process was followed for the development of COVID-19 vaccines. Great effort was spent in terms of cooperation among the governmental institutions, academia, and medical companies as well as a high amount of budget was allocated to develop effective vaccines against COVID-19. As of March 2023, the numbers of COVID-19 vaccines in clinical and preclinical development were 183 and 199, respectively. An emergency use authorization (EUA) process was applied to accelerate the approval of the vaccines. Consequently, vaccinations could be started in less than a year, which decelerated the speed of the pandemic. Although EUA caused hesitancy among some people questioning the safety and efficacy of the vaccines, the vast majority of the population was vaccinated. Currently, more than 5.5 billion people (about 70% of the world population) have received 13.38 billion doses of 11 different COVID-19 vaccines, and 73% of the doses were Comirnaty manufactured by Pfizer/BioNTech.