Following Guidelines During a Crisis

The guidance states, "These preventative measures can include steps to prepare personnel such as: * "Educating employees on topics such as, in the case of a pandemic, personal hygiene (hand washing and coughing and sneezing etiquette), social distancing, and appropriate use of sick leave * "Encouraging employees to get immunized as appropriate by providing information on local vaccination services or by offering on-site vaccination services, if reasonable * "Providing information for and encouraging employees to develop family emergency preparedness plans * "Reviewing CGMP [current good manufacturing practice] regulations regarding appropriate sanitation practices and restriction of ill or sick employees from production areas (see 21 CFR [Code of Federal Regulations] 211.28)" (2). Examples include: * "Production equipment routine maintenance * "Utility system performance checks and maintenance (e.g., air temperature, lighting, compressed air) * "Environmental monitoring of facilities such as cell culture, harvesting, and purification rooms during production * "Stability testing for certain drug products and components * "Periodic examinations of data and of reserve samples" (2). EMA, Guidance on the Format of the Risk Management Plan (RMP) in the EU-in Integrated Format, EMA/164014/2018 Rev.2.0.1 accompanying GVP Module V Rev.2 Human Medicines Evaluation (EMA, 31 October 2018).

Vaccine hesitancy in primary care: Building bridges by understanding barriers.

Adult vaccination is an accepted part of health care and diabetes care. In spite of evidence regarding the efficacy and utility of vaccination in preventing disease, we continue to encounter vaccine hesitancy and vaccine skepticism. As physicians, it is our duty to encourage the public to get vaccinated. In this article, we create a simple framework which helps assess the barriers to vaccine acceptance, and create bridges to overcome vaccine hesitancy and skepticism. We use an interesting mnemonic, NARCO, to remind ourselves, and our readers, of the appropriate hierarchy of interviewing related to vaccine acceptance.

The relationship between SARS-CoV-2 vaccination and COVID-19 in children

Objective: To analyze the vaccination status of SARS-CoV-2 in children, and explore the relationship between SARS-CoV-2 vaccination and COVID-19 in children. Methods: A retrospective study was conducted to analyze the clinical data of 335 cases of SARS-CoV-2 Omicron variant infection from February 15, 2022 to March 18, 2022 in Shenzhen Third People's Hospital. Results: Among 335 children with SARS-CoV-2 infection, 174(51.9%) cases were vaccinated with the SARS-CoV-2 vaccine;33(31.4%) cases were vaccinated in the 3-<6 years old group;141(61.3%) cases were vaccinated in the 6-<14 years old group. There was a statistically significant difference in the proportion of SARS-CoV-2 vaccination between the 6-<14 years old group and the 3-<6 years old group (X2=26.1, P < 0.05). In the study cohort, 3-<6 years old group and 6-<14 years old group, there was no significant difference in the incidence of COVID-19 in the vaccinated group compared with the unvaccinated group (P > 0.05). In the study cohort, the proportion of confirmed cases of 1 dose of SARS-CoV-2 vaccine and 2 doses or more of SARS-CoV-2 vaccine was 89.5% (68 cases) and 77.6% (76 cases), respectively;in the 6~<14 years old group, the proportion of confirmed cases of 1 dose of SARS-CoV-2 vaccine and 2 doses or more of SARS-CoV-2 vaccine was 90.0% (54 cases) and 76.5% (62 cases), respectively;the differences were statistically significant (X2=4.264, P < 0.05;X2=4.279, P < 0.05). The IgG levels of 18.28 (6.61, 55.2) AU/mL and 58.3 (25.85, 131.41) AU/mL in the study cohort who were vaccinated for 1 dose, 2 doses and more, respectively;the IgG levels of 20.13 (8.33, 44.33) AU/mL and 56.57 (25.85, 150.07) AU/mL in the 6~<14 years old group who were vaccinated for 1 dose, 2 doses and more, respectively;and the differences were statistically significant (Z=-4.37, P < 0.05;Z=-3.96, P < 0.05). Conclusions: Children who received 2 doses of SARS-CoV-2 vaccine have a lower incidence of COVID-19 and higher levels of SARS-CoV-2 antibodies compared with who received 1 dose. It is recommended that children are advised to be vaccinated against the COVID-19.

COVID-19 breakthrough infection after four doses of the vaccines: a case report

The COVID-19 vaccines provide a high degree of protection against severe disease, hospitalisation, and death. However, no vaccine claimed 100% effectiveness and it is expected that a small proportion of vaccinated individuals may develop a breakthrough infection due to individual differences, virus variants and other factors. We conducted an epidemiological investigation and analysis of an imported case who had finished four doses of vaccination, and in order to provide a relevant reference for regular epidemic prevention and control in the post-pandemic era.

RHEUMATOID ARTHRITIS FLARE FOLLOWING COVID-19 VACCINATION IN MALAYSIAN POPULATION AND ITS ASSOCIATED RISK FACTORS

BackgroundFlare of Rheumatoid Arthritis (RA) following COVID-19 vaccination has been reported with a low occurrence observed in those patients with disease remission. However, no local data is available in our multi-ethnic Malaysian population.ObjectivesTo evaluate the prevalence of RA flare in Malaysian patients following COVID-19 vaccination and its associated risk factors.MethodsThis was a cross-sectional study assessing RA flare based on patient-reported disease flare through self-administered questionnaires and physician-reported flare. Patient self-reported disease flare was defined as ‘a sudden worsening of rheumatology condition or arthritis within 1 month post-vaccination' while physician-reported flare was defined as ‘an increment of disease activity score 28-joint documented within 3 months post-vaccination‘ from either a scheduled or unscheduled clinic visit. A total of 186 RA patients attended the rheumatology clinic in Hospital Putrajaya from May to July 2022 who completed the primary COVID-19 vaccination under the Malaysian National Vaccination Programme were recruited. Demographic data, disease parameters including serology for rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), cessation of disease modifying anti-rheumatic drugs (DMARDs) around vaccination, type of vaccines and adverse events were examined using descriptive and univariate analyses.ResultsMajority (93%) of RA patients enrolled were female with a mean age of 58 years old (standard deviation, SD 12.2) and mean disease duration was 12 years (SD 7.7). More than half were seropositive (66% RF, 63% ACPA) with 47.4% had double seropositivity (RF and ACPA positive). All patients received DMARDs with the majority (71%) were on methotrexate (MTX), 21.5% were on leflunomide, 17.7% on other DMARDs, with a small proportion (14%) of patients were receiving prednisolone. Only 4.8% of patients were on biologics or targeted synthetic disease modifying anti-rheumatic drugs. Half of the patients were in remission prior to vaccination. 62% of patients received Pfizer-BioNTech vaccine as the primary vaccine, followed by Sinovac-CoronaVac (24.6%) and Oxford-AstraZeneca (13.4%) vaccines. A booster dose had been administered to 80% of patients, of which 88.7% was Pfizer-BioNTech vaccine. MTX therapy were discontinued in 39.4% of patients (n=52) post-vaccination for a week duration. The prevalence of RA flare was only 12.9% (n=24) in which 14 were self-reported and 10 were physician-reported flares (4 severe flare, 6 mild-moderate flare). Flare rates were higher during the first and second dose of vaccination with 29.2% respectively, and only 12.5% were reported after booster vaccination. Common vaccine adverse effects were fever (16.8%), myalgia (8.6%) and arthralgia (6.4%). There were no significant differences in the occurrence of flare post-vaccination between age, gender, disease activity prior to vaccination, types of vaccine, usage of MTX and prednisolone, and discontinuation of MTX post-vaccination. Although seropositivity did not exhibit statistically significant flare rate post vaccination, sub-analysis revealed four times higher rate of flare in those who has double positivity compared to seronegative RA patients (12% vs 4%).ConclusionPrevelance of RA flare post-COVID-19 vaccination in Malaysian RA population is low. No significant associated risk factors were identified although double seropositivity appeared to have higher number of flares.References[1]Bixio, R., Bertelle, D., Masia, M., Pistillo, F., Carletto, A. and Rossini, M. (2021), Incidence of Disease Flare After BNT162b2 Coronavirus Disease 2019 Vaccination in Patients With Rheumatoid Arthritis in Remission. ACR Open Rheumatology, 3: 832-833.[2]Li X, Tong X, Yeung WWY, Kuan P, Yum SHH, Chui CSL, Lai FTT, Wan EYF, Wong CKH, Chan EWY, Lau CS, Wong ICK. Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong. Ann Rheum Dis. 2022 Apr;81(4):564-568.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Healthcare Resource Utilization and Costs Associated with Acute COVID in Adult Patients Managed in the Community or Hospital Setting in England: A Population-Based Study

Objectives: The COVID pandemic has imposed significant direct medical cost and resource use burden on healthcare systems. This study described the patient demographic and clinical characteristics, healthcare resource utilization and costs associated with acute COVID in adults in England. Method(s): This population-based retrospective study used linked primary care (Clinical Practice Research Datalink, CPRD, Aurum) and secondary care (Hospital Episode Statistics) data to identify: 1) hospitalized (admitted within 12 weeks of a positive COVID-19 PCR test between August 2020 and March 2021) and 2) non-hospitalized patients (positive test between August 2020 and January 2022 and managed in the community). Hospitalization and primary care costs, 12 weeks after COVID diagnosis, were calculated using 2021 UK healthcare reference costs. Result(s): We identified 1,706,368 adult COVID cases. For hospitalized (n=13,105) and non-hospitalized (n=1,693,263) cohorts, 84% and 41% considered high risk for severe COVID using PANORAMIC criteria and 41% and 13% using the UKHSA's Green Book for prioritized immunization groups, respectively. Among hospitalized cases, median (IQR) length of stay was 5 (2-7), 6 (4-10), 8 (5-14) days for 18-49 years, 50-64 years and >= 65 years, respectively;6% required mechanical ventilation support, and median (IQR) healthcare costs (critical care cost excluded) per-finished consultant episode due to COVID increased with age (18-49 years: 4364 (1362-4471), 50-64 years: 4379 (4364-5800), 65-74 years: 4395 (4364-5800), 75-84 years: 4473 (4364-5800) and 85+ years: 5800 (4370-5807). Among non-hospitalized cases, older adults were more likely to seek GP consultations (13% of persons age 85+, 9% age 75-84, 7% age 65-74, 5% age 50-64, 3% age 18-49). Of those with at least 1 GP visit, the median primary care consultation total cost in the non-hospitalized cohort was 16 (IQR 16-31). Conclusion(s): Our results quantify the substantial economic burden required to manage adult patients in the acute phase of COVID in England.Copyright © 2023

LONG-TERM AND BOOSTER VACCINATION RESPONSES IN PATIENTS WITH GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA

BackgroundVaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10mg/day prednisolone and methotrexate use were associated with reduced antibody concentrations four weeks after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) [1].ObjectivesHere, we performed a follow-up study to measure the decay of antibody concentrations over time and the immunogenicity of SARS-CoV-2 booster vaccination.MethodsGCA/PMR patients included in the primary vaccination (BNT162b2 or ChAdOx1) study were asked again to donate blood samples six months after primary vaccination (n=24) and one month after booster vaccination (n=46, BNT162b2 or mRNA1273). Data were compared to that of age-, sex-, and vaccine-matched controls (n=58 and n=42, respectively).ResultsAntibody concentrations decreased faster over time in GCA/PMR patients than in controls, but this decrease was not associated with treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post booster vaccination associated strongly with antibody concentrations post primary vaccination, but not with treatment during booster vaccination. However, the fold-change of post-booster vaccination showed a slight negative correlation with the post-primary vaccine antibodies.ConclusionThese results indicate that patients with impaired vaccine responses after primary vaccination, have slightly stronger increases in humoral immunity after booster vaccination, but this is not enough to reach a similar protection. The decrease in humoral immunity, and subsequent increase after booster vaccination, is likely not impacted by prednisolone or methotrexate treatment. Rather, these treatments put the patients at an immunogenic disadvantage during primary SARS-CoV-2 vaccination, which is not fully repaired by a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeat booster vaccination for patients that used >10mg/day prednisolone or methotrexate during primary vaccination.Reference[1]van Sleen Y, van der Geest, Kornelis SM, Reitsema RD, Esen I, Terpstra JH, Raveling-Eelsing E, et al. Humoral and cellular SARS-CoV-2 vaccine responses in patients with giant cell arteritis and polymyalgia rheumatica. RMD open 2022;8(2):e002479.Figure 1.Acknowledgements:NIL.Disclosure of InterestsYannick van Sleen: None declared, Kornelis van der Geest Speakers bureau: Speaker fees from Roche, Grant/research support from: Grant support from Abbvie, Annemarie Buisman: None declared, Maria Sandovici: None declared, Debbie van Baarle: None declared, Elisabeth Brouwer: None declared.

Research progress of nasal mucosal immunization vaccine against COVID-19

Respiratory mucosal immune system is the body's first line of defense against infection. Since the outbreak of novel coronavirus disease 2019 (COVID-19) in 2019, nasal mucosal immune vaccine, with its ability to induce cellular, humoral and mucosal triple immune responses, has become a research hotspot. This article focuses on novel coronavirus, with an understanding of its structure and pathogenesis, a brief introduction to the immune mechanism of nasal mucosa, a summary of the different types of nasal mucosal immune vaccines and their clinical research, aiming to provide some theoretical reference for the development of new vaccines, and exploration of the best methods and strategies to combat COVID-19.

THE KINETICS OF HUMORAL AND CELLULAR RESPONSES AFTER THE BOOSTER DOSE OF COVID-19 VACCINE IN INFLAMMATORY ARTHRITIS PATIENTS

BackgroundImpaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to unstudied kinetics of the immune response after booster vaccinations.ObjectivesThis study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster.MethodsIn 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2.ResultsIA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2).ConclusionOur study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Knowledge, attitudes, and willingness of adolescents towards coronavirus disease 2019 vaccine in Bangkok, Thailand

Background: The outbreak of coronavirus disease 2019 (COVID-19) was declared by the World Health Organization (WHO) as a COVID-19 pandemic on March 11, 2020. Therefore, the availability of vaccines will help develop immunity and protect people from this pandemic. The present systematic study examined knowledge, attitudes, and willingness of adolescents towards COVID-19 vaccine in Bangkok, Thailand. Objectives: The objective of the study was to evaluate the knowledge, attitudes, and willingness toward COVID-19 vaccine of key stage 4A-5 students at Satit Prasarnmit International Programme in Bangkok towards COVID-19 vaccine. Materials and Methods: The study was conducted using an online questionnaire. A total of 136 students participated. Knowledge, attitudes, and willingness of adolescents toward the COVID-19 vaccine were assessed. Differences between outcomes and socio-demographic characteristics of participants were analyzed through independent t-tests and the ANOVA. The level of willingness to vaccinate against COVID-19 was analyzed by a generalized linear model. Results: Students revealed moderate knowledge about COVID-19, correctly answering 11.08 out of 15 points (SD = 1.74), a low level of attitudes toward COVID-19 vaccine 8.49 out of 15 points (SD = 2.51), and low level of willingness to vaccinate against COVID-19 vaccine 2.29 out of 5 points (SD = 1.26), in total of 35 points (28 questions). There are statistically significant positive correlations shown between attitude towards COVID-19 vaccine and the level of willingness to vaccinate against COVID-19 vaccine (I2 = 0.384, P < 0.01%). Conclusion: This study revealed students in Satit Prasarnmit International Programme had moderate knowledge towards COVID-19, negative attitudes toward COVID-19 vaccine and low willingness to vaccinate against COVID-19. Furthermore, it indicates that there is a casual relationship between attitudes toward COVID-19 vaccine and the willingness of individuals to be vaccinated against COVID-19 vaccine. Thus, attitude toward COVID-19 vaccine acts as a major predictive factor toward the willingness to vaccinate against COVID-19 vaccine. Therefore, to increase peopleA's willingness to be vaccinated against COVID-19 vaccine, it is necessary to increase peopleA's attitude toward COVID-19 vaccine.

EVALUATION OF RESPONSE TO ADJUVANTED RECOMBINANT ZOSTER VACCINATION IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB: RESULTS FROM A RANDOMIZED TRIAL SUB-STUDY

BackgroundUpadacitinib (UPA) is an oral JAK inhibitor (JAKi) approved for the treatment of RA. JAKi have been associated with an elevated risk of herpes zoster (HZ) in patients (pts) with RA. The adjuvanted recombinant zoster vaccine (RZV, Shingrix) was shown to be well-tolerated and effective in preventing HZ in adults aged ≥ 50 years.[1] The efficacy and safety of RZV have not been studied in pts with RA while on UPA in combination with MTX.ObjectivesTo assess the immunogenicity of RZV in pts with RA receiving UPA 15 mg once daily (QD) with background MTX.MethodsEligible adults aged ≥ 50 years with RA enrolled in the ongoing SELECT-COMPARE phase 3 trial (NCT02629159) received two RZV doses, administered at the baseline and week (wk) 12 visits. Pts should have been on stable doses of UPA 15 mg QD and background MTX for ≥ 8 wks before the first vaccination and ≥ 4 wks after the second vaccination. Antibody titers were collected pre-vaccination (baseline), 4 wks post-dose 1 vaccination (wk 4), and 4 wks post-dose 2 vaccination (wk 16). The primary endpoint was the proportion of pts with a humoral response to RZV defined as ≥ 4-fold increase in pre-vaccination concentration of anti-glycoprotein E [gE] titer levels at wk 16. Secondary endpoints included humoral response to RZV at wk 4 and the geometric mean fold rise (GMFR) in anti-gE antibody levels at wks 4 and 16. Cell-mediated immunogenicity to RZV was an exploratory endpoint evaluated by the frequencies of gE-specific CD4+ [2+] T cells (CD4+ T cells expressing ≥ 2 of 4 activation markers: IFN-γ, IL-2, TNF-α, and CD40 ligand) measured by flow cytometry at wks 4 and 16 in a sub-cohort of pts.ResultsOf the 95 pts who received ≥ 1 RZV dose, 93 (98%) received both RZV doses. Pts had a mean (standard deviation) age of 62.4 (7.5) years. The median (range) disease duration was 11.7 (4.9–41.6) years and duration of UPA exposure was 3.9 (2.9–5.8) years. At baseline, all but 2 pts were receiving concomitant MTX and half (50%) were taking an oral corticosteroid (CS) at a median daily dose of 5.0 mg. One pt discontinued UPA by wk 16. Blood samples were available from 90/93 pts. Satisfactory humoral responses to RZV occurred in 64% (95% confidence interval [CI]: 55–74) of pts at wk 4 and 88% (81–95) at wk 16 (Figure 1). Age (50–< 65 years: 85% [95% CI: 75–94];≥ 65 years: 94% [85–100]) and concomitant CS (yes: 87% [77–97];no: 89% [80–98]) use at baseline did not affect humoral responses at wk 16. GMFR in anti-gE antibody levels compared with baseline values were observed at wks 4 (10.2 [95% CI: 7.3–14.3]) and 16 (22.6 [15.9–32.2]). Among the sub-cohort of pts, nearly two-thirds achieved a cell-mediated immune response to RZV (wk 4: n = 21/34, 62% [95% CI: 45–78];wk 16: n = 25/38;66% [51–81]). Within 30 days post-vaccination of either RZV dose, no serious adverse events (AEs) (Table 1) or HZ were reported. AEs that were possibly related to RZV were reported in 17% of pts. One death occurred more than 30 days after wk 16 due to COVID-19 pneumonia.ConclusionMore than three-quarters (88%) of pts with RA receiving UPA 15 mg QD on background MTX achieved a satisfactory humoral response to RZV at wk 16. In a subgroup of pts, two-thirds (66%) achieved a cell-mediated immune response to RZV at wk 16. Age and concomitant CS use did not negatively affect RZV response.Reference[1]Syed YY. Drugs Aging. 2018;35:1031–40.Table 1. Safety Results Through 30-Days Post-RZV Vaccination in UPA-Treated PatientsEvent, n (%)UPA 15 mg QD (N = 95)Any AE38 (40%)AE with reasonable possibility of being related to UPAa13 (14%)AE with reasonable possibility of being related to RZVa16 (17%)Severe AEb1 (1%)Serious AE0AE leading to discontinuation of UPA0Death0AE, adverse event;QD, once daily;RZV, adjuvanted recombinant zoster vaccine;UPA, upadacitinib.aAs assessed by the investigator.bHypersensitivity.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Yanxi Liu Shareholder of: AbbVie, Employee of: AbbVie, CONRADO GARCIA GARCIA: None declared, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Alvin F. Wells Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Novartis, Pfizer, and Sanofi, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Michael Chen Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Anthony Cunningham Consultant of: GSK, Merck Sharp & Dohme, and BioCSL/Sequirus.

FDA CAUGHT IN POLITICAL CROSSFIRE

FDA's oversight of medical devices and diagnostics has put it in the hot seat for shortages of critical products for protecting medical personnel and for providing fast and accurate public testing for COVID infection. The result is that the White House has delayed in selecting an FDA commissioner, even though federal rules require Woodcock to vacate her acting position by mid-November unless the administration nominates a new commissioner, permitting her to continue on during the Senate confirmation process. The approval decision by CDER officials was blasted by members of Congress, the medical community and even some patient groups, but justified by the reviewers as likely to provide some benefit to some patients who lacked any alternative treatment for this devastating disease.

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

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

Injecting Innovation into Drug Packaging

According to Jens Kürten, group senior director, Communication and Marketing, Gerresheimer, there are nine megatrends that will both characterize and influence the pharmaceutical packaging market. Whether the drug be injected intravenously or subcutaneously, at home or in a hospital setting, there are various needs that should be considered prior to choosing the 'best-fit' packaging, he adds. [...]packaging requirements for pharmaceuticals change over time as the lifecycle of the drug continues," Stöcker states. [...]customers request more eco-friendly options to reduce or avoid plastic. [...]it has been necessary to design the packaging for the vaccines with these specific requirements in mind to ensure the safety and efficacy of the therapeutic product are protected.

The Elephant (or Donkey) in the Room

With the United States presidential election merely days away (set to take place on 3 Nov. 2020), the world's gaze has shifted to the race for the White House and whether there will be a Republican or Democrat taking office. [...]if this circumstance were to change, there would be potential consequences for European pharma companies that have a presence in or deal with the US. If the Democrats win the presidency and have control over Congress, it is expected that foreign and generic-drug manufacturers would benefit as a result of lower market entrance barriers.

POSSIBLE ROLE OF PEPTIDE EPITOPES OF COVID-19 BNT-162B2 MRNA VACCINE IN FOMENTING AUTOIMMUNITY: AN IN SILICO ANALYSIS

BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Vaccine Administration: The Growing Role of Prefilled Syringes

(Note: The MIDAS database reflects vaccine doses that are dispensed with a prescription in retail or hospital settings, so the COVID-19 vaccines and other public-health-administered vaccines are not fully reflected in that data set.) Stamoran adds, "However, across the rest of the world, vial-based vaccines still make up the majority of the volume dispensed." [...]there is plenty of room for growth for this newer administration device. [...]PFS are now widely used for annual flu shots, heparin injections, and a growing list of injectable therapies across multiple disease states. According to a 2021 article authored byGuillaume Lehee, R&D Innovation Leader for BD Medical-Pharmaceutical Systems, the use of PFS to vaccinate 300 million individuals in the United States in the event of a future pandemic could save more than three million hours of healthcare practitioners' time (1). [...]today's PFS are not yet proven to be compatible with ultrafrozen temperatures as the existing glass materials and other components may not stand up to the extremely low required temperatures," explains Stamoran.

COVID-19 VACCINE PERCEPTION AND HESITANCY AMONG PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASE (AIRD) IN MALAYSIA

BackgroundPatients with autoimmune rheumatic disease (AIRD) are at risk of severe COVID-19 infection and vaccine has been demonstrated to be able to reduce the severity of infection. Malaysia has a low flu vaccination coverage rate (approximately 3%) and hence it is important to assess the perception and hesitancy of COVID-19 vaccine especially among the vulnerable group.ObjectivesTo study the perception of COVID-19 vaccine and to determine the prevalence of vaccine hesitancy among AIRD patients in Malaysia.MethodsThis was a cross-sectional survey using online Google Forms® that was conducted among adult AIRD patients (18 years and older) from August 2021 until February 2022. Patients were recruited from the outpatient clinics as well as distribution of the survey through social medias. The survey was in English and Malay language. The survey collected data on the socio-demographic background, prior history of other vaccination after the age of 18 and COVID-19 vaccination with reasons of hesitancy, defined as being unsure or unwilling to be vaccinated. The survey also assessed the patients' perception by specifying the level of agreement to COVID-19 vaccine statements using the Likert response scale: 1-Strongly disagree;2- Disagree;3-Neither agree nor disagree;4-Agree;5-Strongly agree.ResultsA total of 162 patients participated in the survey and majority of them were females (87.7%). Our multi-racial cohort consisted of Malay (n=103, 63.5%), followed by Chinese (n=38, 23.5%), Sabahan Bumiputra (n=12, 7.4%) and Indian (n=7, 4.3%). More than half (n=107,66.6%) have not had any history of other vaccination after the age of 18. Only 16.7% (n=27) agreed/strongly agreed that COVID-19 vaccine can be given to patients with co-morbidities and 24.1 (n=39) agreed/strongly agreed that COVID-19 vaccine can be given to patients who have history of allergy to other drugs or food. At the time of the survey, vast majority of the respondents have received at least the 1st dose of Covid-19 vaccine (n=148, 91.4%). A total of 9 (5.6%) patients were hesitant to be vaccinated (6 were unsure and 3 patients were not willing to be vaccinated). The commonest reasons of being unsure or not willing to be vaccinated was worried of the vaccine's adverse effects (66.7%), worried of the blood clot complication (33,3%), worried of disease flare post-vaccine (33,3%), worried of allergic reaction (22.2%), lack of information on the safety of the vaccine in patients with AIRD from government and media (22.2%), face mask and social distancing measures were adequate (22.2%). Statistical analysis revealed that more patients who had vaccine hesitancy were from the lower socioeconomic status (income <1066 Euro/month), 88.9% vs 11.1%, p=0.03 but no association with ethnicity, education status, marital status or place of residence (urban vs rural).ConclusionCOVID-19 vaccine hesitancy is low in Malaysian patients with AIRD but patients with a low socioeconomic status are prone to have vaccine hesitancy. More education on the vaccine's efficacy and safety especially among patients with co-morbidities are warranted.Reference[1]Knowledge, acceptance and perception on COVID-19 vaccine among Malaysians: A web-based survey. Mohamed NA, Solehan HM, Mohd Rani MD, Ithnin M, Che Isahak CI (2021) Knowledge, acceptance and perception on COVID-19 vaccine among Malaysians: A web-based survey. PLOS ONE 16(8): e0256110.Acknowledgements:NIL.Disclosure of InterestsSyahrul Sazliyana Shaharir Speakers bureau: Pfizer,Novartis, Lydia Kamaruzaman: None declared, Theepa Nesam Mariamutu: None declared, Mohd Shahrir Mohamed Said: None declared, Azmawati Mohammed Nawi: None declared, Wan Syamimee Wan Ghazali: None declared, Malehah Mohd Noh: None declared.