Third Booster Dose Vaccine against Sars-Cov-2 in Primary Sjogren's Syndrome: Longitudinal Cohort from the Safer Study

Objectives: Few studies evaluate the immunogenicity and safety of different COVID-19 vaccine platforms in patients with primary Sjogren's Syndrome (pSS). The present study aims to assess the immunogenicity through anti-spike IgG antibodies after the COVID-19 vaccine dose in heterologous groups compared to homologous regimen in patients with pSS. Method(s): These data are from the SAFER study: 'Safety and efficacy of the COVID-19 vaccine in rheumatic disease', a real-life phase IV multicenter longitudinal study, evaluating patients since before the first dose. Pregnant women, those with a history of serious adverse events prior to any vaccine, and those with other causes of immunosuppression were excluded. Patients with pSS > 18 years, classified according to ACR/EULAR 2016 classification criteria were included. Antibodies against the Receptor Binding Domain - RBD portion of the Spike protein of SARS-CoV-2 (IgG-S) were measured by chemiluminescence (Architect SARS-CoV-2 Quanti II, Abbott), before the first dose and 28 days after the 2nd and 3rd dose. Seropositivity was defined as IgG-Spike titers >=7.1 BAU/mL. Patients received adenoviral vector (ChAdOx1, Astrazeneca), mRNA (Pfizer) or inactivated SARS-COV-2 (Coronavac). Non-parametric methods were used. The alpha level of significance was set at 5%. Result(s): 56 participants received 3 doses, 46 +/- 11 years old, disease duration 7.62 years, 92.9% female, 41.1% White and 55.4% Mixed. The homologous third-booster dose group (n = 15, all ChAdOx1) and heterologous group (n = 41) were homogeneous for age, sex, ethnicity, comorbidities, medication and baseline IgG-S median [IQR] titers. After primary vaccination (2 doses) IgG-S median and titers [IQR] were similar in homologous and heterologous groups (373.03 [179.58, 843.92] vs. 473.36 [119.05, 1059.60], p = 0.705). Third-booster dose induced higher IgG-S median [IQR] titers compared to only 2 doses (1229.54 [333.55, 4365.47] vs 464.95 [140.42, 1015.25], p alpha 0.001). Heterologous 3rd-booster induced higher IgG-S median [IQR] titers than homologous scheme with ChAdOx1 (1779.52 [335.83, 4523.89] vs 730.76 [303.37, 1858.98], p = 0.150), Fig 1 and 2, although not statistically significant. Conclusion(s): Third booster dose induced higher humoral immune response compared to two doses whichmay improve protection against COVID-19 in patients with pSS. Although not statistically significant, the response to the heterologous scheme tended to be better than the response to the homologous booster vaccination, which heterologous booster scheme tended to respond better than homologous booster vaccination, which is relevant in this immunosuppressed population. Increasing the sample size will help clarify this issue. .

Safety and Immunogenicity of Coronavac and Chadox1 Vaccines against Sars-Cov-2 in Patients with Rheumatoid Arthritis: Brazilian Multicentric Study

Objectives: To evaluate the safety and immunogenicity of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with Rheumatoid Arthritis (RA). Method(s): These data are from the 'SAFER (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases)' study, a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 vaccine in immunomediated rheumatic diseases (IMRDs). Adverse events (AEs) in patients with RA were assessed after two doses of ChAdOx1 or CoronaVac. Stratification of postvaccination AEs was performed using a diary, filled out daily. The titers of neutralizing antibodies against the receptor-biding domain of SARS-CoV-2 (anti-RBD) were measured by chemilumine scence test after each dose of immunizers. Proportions between groups were compared using the Chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test. Result(s): A total of 188 patients with RA were included in the study, most of them were female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed. The more common AEs after the first dose were pain at injection site (46,7%), headache (39,4%), arthralgia (39,4%) and myalgia (30,5%), and ChAdOx1 had a higher frequency of pain at the injection site (66% vs 32 %, p alpha 0.001) arthralgia (62% vs 22%, p alpha 0.001) and myalgia (45% vs 20%, p alpha 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection site (37%), arthralgia (31%), myalgia (23%) and headache (21%). Arthralgia (41,42 % vs 25 %, p = 0.02) and pain at injection site (51,43% vs 27%, p = 0.001) were more common with ChAdOx1. No patients had a flare after vaccination. The titers of anti-RBDafter two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p alpha 0,001). Conclusion(s): The frequency of local adverse effects, particularly pain at injection site, was high. AEs were more frequent with ChAdOx1, especially after the first dose. The use of the immunizers dis not change the degree of inflammatory activity of the disease. In patients with RA, ChAdOx1 was more immunogenic than CoronaVac. .

Safety of the Vaccine against Sars-Cov-2 in Patients with Systemic Lupus Erythematosus: Data from the Safer Study

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease which presents infections as one of the most frequent complications, including more severe outcomes of Coronavirus disease 2019 (COVID-19). Immunization of these patients has been strongly recommended, however, data on safety are still scarce. In this study we evaluate the safety after vaccination against SARS-CoV2 in patients with SLE. Method(s): Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease - the 'SAFER' study, is a longitudinal Brazilian multicenter phase IV study. In this study patients with SLE (according to the 2019 ACR/EULAR criteria), older than 18 years who received vaccination against SARS-CoV-2 CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) were included. The evaluation of adverse events (AEs) was done by telephone contact, symptom diaries and a face-to-face visit on the 28th day after each dose. Patients were followed up also by disease activity, assessed using SLEDAI-2 K score. Result(s): A total of 367 individuals with SLE were included, 207 received CoronaVac, 128 received ChadOx-1 and 32 received BNT162b2. Ninety percent of the subjects were female with a mean age of 37 years. About 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38%(140) of patients had zero SLEDAI-2Kat baseline and 41%(147) had zero SLEDAI-2 K 28 days after the 2nd dose. After the first and second dose the most frequent AEs were pain at injection site (58%/44%), headache (48%/33%) and pruritus (42%/37%). Comparing the three vaccines, after the first dose, local symptoms, myalgia, and fever were less frequent in patients who received CoronaVac (p alpha 0.001) as well as headache, tiredness (p = 0.001) and arthralgia (p = 0.003). After the second dose, only local symptoms such as pain at the application site and thickening of the skin around the application site were less frequent in the CoronaVac group (p alpha 0.05). Headache, tiredness, musculoskeletal symptoms and fever were more common in patients receiving AstraZeneca. No serious adverse events were reported regardless of the vaccination schedule used. Conclusion(s): This study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Neither severe AEs were reported nor worsening of disease activity were reported. Comparing the different vaccines, CoronaVac had fewer adverse events.

Evaluation of Homologous and Heterologous Vaccine against Sars-Cov-2 in Systemic Lupus Erythematosus Patients: Data from Safer Study

Objectives: To evaluate the immunogenicity of ChAdOx1, Coronavac and BNT162B2 vaccines in SLE patients, including homologous and heterologous immunizations. Method(s): The 'Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease-SAFER study' is a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 Vaccine in immune-mediated rheumatic diseases (IMRD) in real life, started on May 2021. SLE patients (according to the 2012 SLICC classification criteria), older than 18 years of age were recruited after 2 or 3 doses of vaccine against COVID-19 (ChAdOx1, BNT162b2 and CoronaVac) and were evaluated at baseline and on the 28th day after each dose. Homologous immunization was considered if they received three doses of the same vaccine and heterologous if a different one was applied. IgG antibody against SARS-CoV-2 spike receptor-binding domain were measured by chemiluminescence (SARS-CoV-2-IgG-II Quant assay, Abbott-Laboratories) at baseline and 28 days after the first, 2nd and 3rd doses (Seropositivity IgGSpike>= 7.1BAU/mL). Statistical analysis: ANOVA and pairwise comparisons tests Results: 316 SLE patients were included (255 heterologous and 61 homologous immunization), 89.2% were female and the mean age was 37.6 +/- 11.2 years. The two groups were homogeneous regarding demographical data, disease activity and immunosuppressive treatment. 49.7% used corticosteroids (alpha 5 mg/day in 52.3%), 83.5% antimalarials, 22.8% azathioprine and 20.3% mycophenolate mofetil. 207 patients received the first two doses with CoronaVac, 128 ChadOx-1 and 32 BNT162b2. Regarding the first two doses of the same vaccine, there was no difference in IgG titers over time between CoronaVac or ChadOx-1 (p = 0.313). IgG titers increased in all vaccine groups, with difference only after 2nd dose: 4.96 +/- 1.71BAU/mL CoronaVac vs. 6.00 +/- 1.99BAU/mL ChadOx-1 vs. 7.31 +/- 1.49BAU/mL BNT162b2 (p alpha 0.001). There was no difference in IgG titers over time between homologous or heterologous vaccine schedule (p = 0.872). IgG titers also increased in all groups, with difference only after 2nd dose: 5.49 +/- 1.96BAU/mL heterologous vs. 6.30 +/- 2.10BAU/mL homologous (p = 0.009). Conclusion(s): Induction of immunogenicity occurred in different vaccine regimens in SLE patients. Future research to explore different heterologous schemes in IMRD must be performed.

A Randomized Trial on Early Therapy in Covid-19 High-Risk Outpatients in Omicron Era

Background: Antivirals and monoclonal antibodies (mAbs) were approved for early treatment of COVID-19 based on data from trials conducted in unvaccinated people before the Omicron era. The comparative effectiveness of different treatments is unknown. We present the results of the interim analysis of MONET trial (EudraCT: 2021-004188-28). Method(s): In this ongoing multicenter, open-label, phase 4 trial, we randomly assigned, in a 1:1:1 ratio, non-hospitalized patients with early symptomatic Covid-19 (<=5 days after symptoms onset) and >=1 risk factor for disease progression, to receive 500 mg of intravenous sotrovimab (SOT) or 600 mg of intramuscular tixagevimab/cilgavimab (TIX/CIL) or oral 5-days course of NMV/r 300/100 mg BID. Primary outcome was hospitalization or death for any cause within 29 days after randomization, reported as cumulative incidence per 100 (95% CI), and P-value calculated by Fisher's exact test. Inflammatory marker (CRP, d-dimer, and neutrophils-to-lymphocytes ratio) and antibody level (serum anti-S IgG and anti-N IgG) analysed by mixed linear regression with random intercept and P-values for time trend calculated by ANOVA-style test with Bonferroni correction. Result(s): Prespecified interim analysis, including 400 patients (SOT =133, TIX/ CIL=130, NMV/r=137) enrolled from Mar 4 to Nov 16, 2022 (Fig.1A). Overall, 5 pts (3/5 immunosuppressed) had disease progression leading to hospitalization [1.25% (95% CI 0.4%-2.89%)], 1 in SOT (0.75%, 95% CI 0.01%-4.1%), 4 in TIX/CIL (3.08%, 95% CI 0.84%-7.69%) and none in NMV/r arm (P=0.030). No deaths or ICU admissions were observed. Among the hospitalized pts, 3 were infected with BA.2 (1 SOT, 2 TIX/CIL), one with BA.4/5, and one BQ.1.1 (both TIX/ CIL). No serious adverse events and no kidney or liver toxicity were reported. Temporal trend of inflammation markers was similar in the three arms, and their estimates are shown in Fig.1B. Kinetics of antibody was reported in Fig.1C. The plot shows a rapid increase of anti-S in both mAb arm and a linear increase of IgG in the NMV/r arm. Anti-N IgG kinetics was similar in the three arms. Conclusion(s): By these data the overall cumulative risk of clinical failure in mild Covid-19 occurring in the Omicron era is low. The hypothesis that differences in clinical progression among the three arms could be related to different activity against the Omicron subvariant observed in vitro should be further investigated. Type of treatment does not seem to influence the development of the natural antibody response.

A Randomized, Controlled Trial of Trifarotene Plus Doxycycline for Severe Acne Vulgaris

OBJECTIVE: We evaluated the efficacy and safety of trifarotene plus oral doxycycline in acne. METHOD(S): This was a randomized (2:1 ratio) 12-week, double-blind study of once-daily trifarotene cream 50microg/g plus enteric-coated doxycycline 120mg (T+D) versus trifarotene vehicle and doxycycline placebo (V+P). Patients were aged 12 years or older with severe facial acne (>=20 inflammatory lesions, 30 to 120 non-inflammatory lesions, and <=4 nodules). Efficacy outcomes included change from baseline in lesion counts and success (score of 0/1 with >=2 grade improvement) on investigator global assessment (IGA). Safety was assessed by adverse events and local tolerability. RESULT(S): The study enrolled 133 subjects in the T+D group and 69 subjects in the V+P group. The population was balanced, with an approximately even ratio of adolescent (12-17 years) and adult (>=18 years) subjects. The absolute change in lesion counts from baseline were: -69.1 T+D versus -48.1 V+P for total lesions, -29.4 T+D versus -19.5 V+P for inflammatory lesions, and -39.5 T+D versus -28.2 for non-inflammatory lesions (P<0.0001 for all). Success was achieved by 31.7 percent of subjects in the T+D group versus 15.8 percent in the V+P group (P=0.0107). The safety and tolerability profiles were comparable between the T+D and V+P arms. CONCLUSION(S): T+D was demonstrated to be safe and efficacious as a treatment option for patients with severe acne.Copyright © 2022 Matrix Medical Communications. All rights reserved.

34th Annual Meeting of the Japanese Society for Neuroimmunology (JSNI)

The proceedings contain 14 papers. The topics discussed include: MOG-positive anti-NMDA receptor encephalitis with no demyelinating lesions: two case reports;safety and tolerability of rozanolixizumab in the randomized phase 3 MycarinG study;Outcomes from RAISE: A randomized, phase 3 trial of zilucoplan in generalized myasthenia gravis;efficacy and safety of zilucoplan in myasthenia gravis: responder analysis from the randomized Phase 3 RAISE trial;distinct effects among calcium-binding proteins for microglia to produce chemokines associated with the clinical severity of ALS;astroglial connexin 43 is a novel therapeutic target for a chronic multiple sclerosis model;targeting lymphocytes in SPMS: Th cell populations as a biomarker to predict the efficacy of Siponimod;CSF lysophospholipids as a novel biomarker in relapsing-remitting multiple sclerosis;the immune response to SARS-COV-2 MRNA vaccines in siponimod-treated patients with secondary progressive multiple sclerosis;patient characteristics of siponimod-treated SPMS patients in Japan: interim results from post-marketing surveillance;and efficacy of ravulizumab across sex and age subgroups of patients with generalized myasthenia gravis: a post hoc analysis of the CHAMPION MG study.

Higher Immunogenicity of a Third Heterologous Dose with BNT262b2 Mensanger RNA Vaccine Compared to a Homologous Dose in Kidney Transplant Recipients Fully Vaccinated with Inactivated Whole- Virion CoronaVac Vaccine

Purpose: This study aims to compare the immunogenicity of a third dose of the heterologous BNT262b2 mRNA vaccine versus the homologous inactivated wholevirion CoronaVac vaccine in adult kidney transplant recipients (KTR). Method(s): This prospective, single-center, phase 4 interventional study included KTR aged 30-69 years, with more than 30days of transplantation, and no previous confirmed COVID-19. The patients received the 3rd heterologous (BNT162b2 mRNA) or homologous dose, at least four weeks after the standard two-dose schedule of CoronaVac vaccine, at the transplant center. Antibody response immediately before and after the 3rd dose was assessed by the AdviseDx SARS-CoV-2 IgG II assay. For those positive assays, neutralizing anti-SARS-CoV-2 antibodies were assessed through the cPassTM SARS-CoV-2 Neutralization Antibody Detection Kit. Result(s): There were 307 patients in the heterologous group and 777 patients in the homologous group. KTR in the heterologous group were older (median age 54 vs. 50 years,p<0.0001), with a lower prevalence of diabetes (7% vs. 11%,p=0.032), lower percentage of deceased donors (60% vs. 68%,p=0.006) and longer time since transplant (median 11 vs. 6 years,p< 0.0001).Immediately before the 3rd dose, seroprevalence for IgG antibodies (36% vs. 34%,p=0.597) and the median antibody titers among those seroprevalent (246 AU/mL vs. 268 AU/mL,p=0.279) were similar. At a median of 25 days after the heterologous and 35 days after the homologous 3rddose vaccine, seroconversion rate was higher in the heterologous group (49% vs. 32%,p<0.0001), resulting in a higher seroprevalence rate (67% vs. 55%,p=0.0003). Overall, 42% remained seronegative after the third dose. The median antibody titers after booster among those seroprevalent patients was higher in those in whom the 3rd heterologous vaccine was administered (7,771 AU/mL vs 599 AU/mL,p<0.0001). The analysis of the neutralizing activity is ongoing. Conclusion(s): This prospective interventional study suggests that a 3rd heterologous dose is associated with a higher seroconversion rate and median antibody titers compared to a homologous dose in kidney transplant recipients fully vaccinated with inactivated whole-virion CoronaVac vaccine. In addition, 42% of subjects did not produce humoral immune response after the third dose, urging the development of alternative strategies.

DRUG-INDUCED PNEUMONITIS IN THE SETTING OF SARS-COV-2 INFECTION

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Interstitial pneumonitis (ILD) is inflammation of lung interstitium leading to scarring and pulmonary fibrosis. Various etiologies include idiopathic, connective tissue disorders, sarcoidosis and drug induced1. Many chemotherapy agents have been implicated in drug related ILD such as bleomycin, taxanes. However, newer chemotherapeutic drugs such as molecular agents such as anti-VEGF, anti-EGFR (panitumumab) could be causative of drug induced ILD. CASE PRESENTATION: A 75-year-old female with stage IV sigmoid colon cancer treated with surgery, adjuvant FOLFOX chemotherapy and Panitumumab. She presented to the emergency department with shortness of breath and hypoxia after known COVID-19 exposure. Initial imaging with chest radiography showed bilateral ground glass opacities. A chest CT pulmonary embolism protocol was negative for pulmonary embolism but showed bilateral ground glass opacities (GGOs) and some interstitial thickening (L>R) not typical of COVID-19 infection. She was treated with remdesivir and dexamethasone, however her oxygen requirements continued to rapidly escalate. A repeat CT chest without contrast showed bilateral asymmetric interstitial thickening and GGOs. Given persistence of CT chest abnormalities, workup for interstitial lung disease was initiated. The results include ANA titer 1:80, otherwise negative ANCA profile, rheumatoid factor, anti-CCP, Scl-70, Sjogren antibodies. Given clinical history and imaging findings, diagnosis of ILD was suspected, and she was started on solumedrol 1 mg/kg. Her oxygen requirements decreased significantly over the next 2 days, and she was discharged home on oral steroid taper and pneumocystis pneumonia prophylaxis. DISCUSSION: Panitumumab is a fully humanized monoclonal antibody against EGFR. Approved by the US Food and Drug Administration in 2006 for advanced or recurrent colorectal cancer exhibiting wild-type KRAS mutation.2 ILD is rarely reported with panitumumab monotherapy, but higher incidence when used as a combination treatment such as with FOLFOX or FOLFIRI. A Japanese post-marketing surveillance study from 2010-2015 showed an ILD incidence of 1.3% but mortality rates of 51.3%.2 EGFR is expressed on basal cells and non-cilia cells of the bronchioles and type II cells of the alveolus. EGFR mediated mechanisms are important in tissue repair.3 Therefore inhibition of this pathway has been postulated to play a role in development of ILD. Another mechanism was decreased surfactant production by type II cells in pre-clinical study.4,5 ILD secondary to Panitumumab can occur at any point during therapy and up to 1 year after administration of drug.6 The role of infectious processes, in this case, COVID-19 pneumonia, could synergistically worsen ILD presentation. CONCLUSIONS: Although the incidence of ILD is low, the mortality rate is high, therefore early recognition and treatment is associated with improved clinical outcomes. Reference #1: Mudawi D, Heyes K, Hastings R, Rivera-Ortega P, Chaudhuri N. An update on interstitial lung disease. Br J Hosp Med (Lond). Jul 2 2021;82(7):1-14. Reference #2: Osawa M, Kudoh S, Sakai F, et al. Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study. Int J Clin Oncol. Dec 2015;20(6):1063-1071. Reference #3: The FASEB Journal - 2000 - Puddicombe - Involvement of the epidermal growth factor receptor in epithelial repair in asthma.pdf. DISCLOSURES: No relevant relationships by Navitha Ramesh No relevant relationships by Uba Udeh

EFFECTS OF BENRALIZUMAB ON AIRWAY DYNAMICS IN SEVERE EOSINOPHILIC ASTHMA USING FUNCTIONAL RESPIRATORY IMAGING PARAMETERS: THE BURAN STUDY DESIGN

SESSION TITLE: Imaging Across the Care Spectrum SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Eosinophilic airway inflammation and mucus plugs are common in asthma patients. Eosinophil depletion may reduce mucus plugging and improve airway patency and airflow distribution. This study will investigate the short-term benefits of sustained depletion of airway eosinophils by benralizumab, an anti-IL-5Rα monoclonal antibody, on airway structure and dynamics using functional respiratory imaging (FRI) in adults with severe eosinophilic asthma (SEA). METHODS: A multicenter, single-arm, open-label, phase 4 study enrolling approximately 138 patients. Screening will be followed by a run-in period of up to 21 days, before administration of subcutaneous benralizumab 30 mg at Weeks 0, 4 and 8, final assessment at Week 13, and a 2-week follow-up period. RESULTS: Key inclusion criteria: age 18-70 years with diagnosed SEA inadequately controlled by high-dose inhaled corticosteroid and long-acting β2-agonist (ICS-LABA) treatment +- oral corticosteroids (OCS) or other asthma controllers;documented post-bronchodilator (BD) reversibility;≥2 exacerbations in prior 12 months;baseline peripheral blood eosinophil count ≥300/μL (≥150 cells/μL if OCS-dependent);pre-BD forced vital capacity (FVC) <65% predicted, pre-BD FEV1 <80% predicted and Asthma Control Questionnaire (ACQ-6) ≥1.5. Key exclusion criteria: exacerbation/pulmonary infection 6 weeks pre-screening;smokers or ex-smokers who stopped smoking ≤12 months pre-screening and/or history of >10 pack-years;positive for COVID-19 at or ≤6 weeks before screening, or severe COVID-19 at any time.The primary endpoint is mean change from baseline in specific airway volume measured at total lung capacity. Secondary objectives include change from baseline in airway dynamics (lung, airway and blood vessel volumes, airflow distribution, airway resistance, air trapping, ventilation/perfusion mapping) and mucus plug scores, and correlations with conventional lung function measurements (FVC, FEV1) at baseline and Week 13. FRI will be via computed tomography scans assessed using computer modelling. Exploratory objectives include: relationships between airway dynamics and patient-reported outcomes (PROs) such as the Asthma Impairment and Risk Questionnaire (AIRQ), ACQ-6, and St George's Respiratory Questionnaire (SGRQ) at baseline, from baseline to Week 13, and change from baseline in Central/Peripheral (C/P) lung deposition ratio of inhaled drugs. Safety and tolerability will also be assessed. CONCLUSIONS: This study will advance understanding of the eosinophil-depletion effects of benralizumab on airway structure, dynamics, and mucus plugs and could provide additional useful insights into the relationship of PROs with changes in airway dynamics and structure. CLINICAL IMPLICATIONS: Our results may help further characterize physiologic changes resulting from eosinophil depletion with benralizumab and better delineate the impact of changes in lung function and structure on PROs. DISCLOSURES: stockholder relationship with AstraZeneca Please note: 2 years Added 03/31/2022 by Donna Carstens, value=Salary No relevant relationships by Wilfried De Backer Employee relationship with AstraZeneca LP Please note: Since 2014 by Eduardo Genofre, value=Salary Shareholder relationship with AstraZeneca LP Please note: Since 2014 by Eduardo Genofre, value=LTIs Employee relationship with FLUIDDA Inc Please note: Aug 2021 - Present Added 04/12/2022 by Patrick Muchmore, value=Salary Advisory Committee Member relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/20 2 by Reynold Panettieri Advisory Committee Member relationship with RIFM Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with RIFM Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Genetech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Genetech Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Sanofi/Regeneron Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with Bayer Please note: 24 months by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with Theravance Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with Novartis Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Optikira Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Medimmune Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Maven Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Evelobio Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Contracted Research relationship with Johnson & Johnson Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with AstraZeneca;RIFM;Equillium;Genentech;Thervance Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca;RIFM;Equillium;Bayer Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca;Sanofi/Regeneron;Genentech Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Novartis;Optikira;Medimmune;Maven;Evelobio Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Johnson & Johnson;AstraZeneca;RIFM;Equillium;Genentech Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Theravance Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with AstraZeneca Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with AstraZeneca Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with MedImmune Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 0 /29/2022 by Reynold Panettieri Principal Investigator relationship with MedImmune Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Reseaerch Institute for Fragrance Materials Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Reseaerch Institute for Fragrance Materials Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Equillium Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Theravance Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Avillion Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Speaker/Speaker's Bureau relationship with Sanofi/Regeneron Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Genentech Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationshipwith OncoArendi Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Metera Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Speaker/Speaker's Bureau relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Consultant relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with Genentech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with Genentech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Consultant relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Equillium Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Novartis Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Medimmune Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator r lationship with Origo Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with ACTIV-1 Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Janssen Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Vault Health Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Speaker/Speaker's Bureau relationship with Sanofi Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Speaker/Speaker's Bureau relationship with Merck & Co Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Employee No relevant relationships by Vivian Shih Shareholder relationship with AstraZeneca Please note: >5 years by Frank Trudo, value=Shares

Development of vaccines and vaccines for pandemic threats (in particular for COVID19)

Vaccines, currently used for prophylactic purposes, prevent more than three million deaths every year from diseases like diphtheria, pertussis, tetanus, poliomyelitis, measles and influenza. The general six stages of the development of a new vaccine are: i) Exploratory stage;ii) Pre-clinical stage;iii) Clinical development;iv) Regulatory review and approval;v) Manufacturing;vi) Quality control. Clinical development is a three/four-phase process. During Phase I, small groups of people receive the trial vaccine. In Phase II, the clinical study is expanded. In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety. Many vaccines undergo Phase IV formal, ongoing studies after the vaccine is approved and licensed. Phase IV studies, also referred to as postmarketing surveillance studies (PMS). These processes are very similar to drug developments. However, there are several differences compared to drug development, namely: i) unlike drugs, which are given to patients, vaccines are received by healthy individuals, thus the safety margin should be very high;ii) as vaccines have to be stored under refrigeration, there are always logistical challenges during clinical trials;iii) Adjuvants are incorporated into vaccine formulations to modulate and improve the immune response (antigen/adjuvant formulation are important aspects of clinical development);iv) The immune response primarily measured during early stages of vaccine development (Phase I/II) should evaluate: Humoral/ cell-mediated/ cross-reactive antibodies or immune complexes/ immune landscape. A challenge in responding to pandemic diseases is that vaccines may not exist for them. For newly emerging threats without licensed vaccines, such as SARS, MERS, Marburg virus, Nipah virus, SARS CoV-2 and the like, the time required to develop and produce a safe, effective vaccine is unknown and would depend on the nature of the threat and the state of current vaccine research for that threat. In almost all cases, several months would be needed to respond with the first doses of vaccines. Unfortunately, six month later than WHO declared the public health emergency of international concern (27/01/2020) there are five important questions, essential for vaccine development that remain open for scientists, namely: 1) Why do people respond so differently to infection? 2)Has the virus developed any worrying mutations? 3)How well will a vaccine work? 4)Can we develop immunity and if so, how long does it last? 5)What is the origin of the virus? Until a safe, effective vaccine was ready, other public health and medical measures (social distancing, quarantine, and aspecific medications) would need to be employed to try to limit disease spread.

IMMUNOGENICITY and SAFETY of the CHADOX 1 COVID-19 VACCINE in PATIENTS with AUTOIMMUNE DISEASES and HEALTHY CONTROLS: DATA from SAFER STUDY

Background: Patients with autoimmune infammatory diseases (AID) have been prioritized for urgent vaccination to mitigate COVID-19 risk. However, few studies in the literature assessed the immunogenicity and safety of the COVID-19 vaccine in patients with AID. Objectives: In this context, the present study aims to evaluate the immunogenic-ity and safety of the vaccine against COVID-19 in patients with AID. Methods: These data are from 'Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease'-SAFER study, a Brazilian multicentric prospective phase IV study to evaluate COVID-19 Vaccine in AID, in the real-life, in Brazil. Immunogenicity and adverse events (AE) from a single center were assessed, after 2 doses of ChAdOx1 (Oxford/AstraZeneca), 8 weeks of interval, in patients with AID and healthy controls (HC). Inclusion criteria were age ≥ 18 years and fulflling criteria according to international classifcation for AID. Exclusion criteria: pregnancy, previous severe AE to any vaccine, other immunosuppression causes. Stratifcation of post-vaccination AE was performed using a diary, flled out daily and returned at the end of 28 days for each dose. Participants were followed up through blood collection for measurement of IgG antibodies against SARS-CoV-2 spike receptor-binding domain by chemiluminescence (SARS-CoV-2 IgG II Quant assay, Abbott Laboratories, Abbott Park, IL, USA) at baseline and 28 days after the second dose. The seropositivity was defned for titers ≥50 AU/mL. Quantitative analyses were presented as observed frequency, percentage, central tendency, and variability measurements. The sample's normal distribution was verifed through the Shapiro-Wilk test. The Kruskal-Wallis test and the post-hoc Dwass-Steel-Critchlow-Fligner pairwise comparisons test were used to compare the IgG-S titers between the groups through the evaluation period. Categorical data were addressed using the Fisheŕs exact or Chi-squared (χ2) test. An alpha level of 5% signifcance was used in all analyses. Results: A total of 377 volunteers with AID and 50 HC were included in the study. Patients with spondyloarthritis (N=64), systemic lupus erythematosus (N=63), rheumatoid arthritis (N=61), primary Sjögren's syndrome (N=61), vasculitis (N=31), systemic sclerosis (N=14), inflammatory myopathy (N=9), Crohńs disease (N=49), ulcerative colitis (N=11) and other systemics AID (N=12) were evaluated. Both groups had female predominance (73.5% vs. 74.0%, p=0.937) and were homogeneous for age (43.5 vs. 41.7,p=0.308). The seroconversion among those not reactive (IgG-S negative at baseline) (46 HC and 191 AID), 28 days after second dose was 97.1% for spondyloar-thritis (p=0.425), systemic lupus erythematosus 88.2% (0.006), rheumatoid arthritis 93.5% (0.158), primary Sjögren's syndrome 92.6% (0.133), systemic sclerosis or inflammatory myopathy 47.1% (0.001), inflammatory bowel disease 100% (0.999) and vasculitis 80% (0.006), while in healthy control was 100%. In comparison with HC, there was a statistically significant difference in IgG-S titles only in systemic sclerosis or inflammatory myopathy (1.694 AU/ml vs. 3.719 AU/ml;p=0.006). Both groups only presented mild AE. Pain at the injection (85.7% vs. 78.4%, p=0.239), headache (67.3% vs. 53.8, p=0.074) and fatigue (59.2% Vs. 46.2%, p=0.089) were more common in HC than AID. Overall, reactions like arthralgia (52.6 vs. 22.4%, p<0.001), hematoma (14.1 vs. 4.1%, p=0.05), cutaneous rash (9.5 vs. 0%, p=0.024) were more frequent in AID. Most participants related that they felt safer after receiving a COVID-19 vaccination, and 52.4% did not reported a worse patient global assessment (PGA) index. Conclusion: In conclusion, our data indicated that ChAdOx1 vaccine is safe and induced high titers and seroconversion rate in AID. More severe AID, such as vasculitis, systemic lupus erythematosous, and systemic sclerosis and myositis showed a lower seroconversion rate. Further analysis will explore the association between immunossupressant and reactivity, and booster dose.

ABATACEPT VERSUS HYDROXYCHLOROQUINE in PALINDROMIC RHEUMATISM: A MULTICENTER RANDOMIZED CLINICAL TRIAL (PALABA STUDY): TRIAL DESIGN and PATIENTS CHARACTERISTICS

Background: Many patients with palindromic rheumatism (PR), mainly those with positive autoantibodies, evolve to rheumatoid arthritis (RA). Management of PR is empirical, and hydroxychloroquine (HCQ) is the most used antirheumatic drug. Abatacept (ABA) has been investigated in preclinical RA with good results. There are no randomized clinical trials in PR. Objectives: To present the design of a randomized clinical trial in PR (PALABA study). To describe the characteristics of the patients at study entry. The main objective is to test the hypothesis that ABA can reduce the progression of RA in seropositive (ACPA+ and/or RF+) PR patients in comparison with HCQ. Methods: Phase IV multicenter open label randomized controlled clinical trial with 42 months duration. The enrollment period was 18 months and the open randomized period 24 months. Fourteen spanish centers were included. The sample size was 70 patients (35 per arm). ABA sc 125 mg/week frst year, 125 mg eow second year and HCQ oral 5mg/Kg daily were administered, both therapies in monotherapy. The main inclusion criteria were age >18 years with PR according to Guerne and Weissman modifed criteria and disease evolution >3 and <36 months. Positive ACPA (ELISA or chemiluminescence (CCP2) and/or RF tests are required. Patients with arthritis in ≥1 joint >1 week at baseline, with criteria of other rheumatic diseases, radiographic erosions or previous antirheumatic therapy with synthetic DMARDS were excluded. The main outcome measure is achievement of RA classifcation criteria (EULAR/ACR 2010) at any time during the 24-month follow-up. Secondary outcomes were the number and intensity of joint attacks, adverse events, and effects on serum ACPA and anti-carbamylated antibodies at 0,3,12,24 months of follow-up. STATISTICS: Modifed Full Analysis Set and Per Protocol Population analysis. Results: Patient one was included in June 2018. The inclusion period has been extended until April 2022 due to low recruitment rates, partly due to the COVID-19 pandemic. As of 15 Jan 2022, 51 patients have been randomized and 49 (37F/12M) have received at least one drug dose. The mean onset of symptoms was 9.9±6.3 months. In 22 patients the follow-up time was greater than 12 months. RF and ACPA (CCP2) were positive in 81.6% and 89.8% of patients respectively;24 patients were included in the ABA arm and 25 in the HCQ arm. Seven patients withdrew from the study during follow-up due to: progression to RA (n=3), adverse events (n=2) and other reasons (n=2). The demographic, clinical and laboratory characteristics of PR patients at study entry are shown in Table 1. No signifcant differences in patients' characteristics between arms were observed at enrollment except a higher prevalence of CCP2 in the HCQ arm. Conclusion: We present the design of the frst randomized clinical trial in PR of the efficacy of antirheumatic drugs (ABA vs HCQ) to avoid progression towards RA in patients with a high risk (recent onset PR and positive autoantibody status) of persistent arthritis. The characteristics of patients included until now are similar to those reported in recent onset PR.

Dysgeusia and Appetite Loss: Thinking Beyond MDD and COVID-19

Background: Dysgeusia is a distortion of taste sensation. Etiologies can include medications and Covid-19, among others. Dysgeusia may lead to appetite loss which is nonspecific and can have multiple causes, including major depressive disorder (MDD) (Coulter, 1988). Although post-marketing data revealed no association between nifedipine and dysgeusia (Ackerman, 1997), case reports of dysgeusia from nifedipine exist (Ackerman, 1997). We present a case of nifedipine-induced dysgeusia mistaken for depression. Case Report: A 42-year-old man with hypertension and diabetes was admitted to the hospital following right thalamocapsular and intraventricular hemorrhages. Hypertension was managed with metoprolol, lisinopril, nifedipine, and chlorthalidone. Levetiracetam was started for seizure prophylaxis. Medications included pantoprazole, simethicone, transdermal lidocaine, insulin, metformin, docusate, senna, and subcutaneous heparin. Psychiatric consultation was requested out of concern that appetite loss indicated depression. The day before psychiatric evaluation, mirtazapine 15 mg at bedtime for mood and appetite was started. Nifedipine 90 mg daily had been started 9 days prior to his first complaint of decreased appetite. The patient reported feeling disconnected from his family and “sad" for ∼10 years, complaining that family members “talk behind his back.” He was otherwise without paranoia. He denied insomnia, anhedonia, hopelessness, poor concentration, suicidal ideation, homicidal ideation, guilt, mania, or hallucinations. He reported poor appetite due to epigastric discomfort and bad taste to foods. Covid-19 testing was not yet widely available. No other signs or symptoms suggestive of Covid-19 were present. Although alert and fully oriented, concentration was impaired with sometimes tangential thought processes. Affect was full without depression. A diagnosis of adjustment disorder was made. The psychiatry team suspected nifedipine-induced dysgeusia and advised discontinuing nifedipine. Appetite improved two days later. Discussion: This case highlights the importance of considering alternative causes of nonspecific symptoms of depression, including decreased appetite, that may have non-psychiatric causes. Dysgeusia is widely recognized as a symptom of Covid-19. Other causes, including medications may be underrecognized and amenable to intervention. Conclusion: It would be helpful to consider medication side-effects as potential causes for taste distortion alongside psychiatric diagnoses, and COVID-19. References: 1. Coulter DM: Eye pain with nifedipine and disturbance of taste with captopril: a mutually controlled study showing a method of post marketing surveillance BMJ 1988;296: 1086–8. 2. Ackerman BH, Kasbekar N: Disturbances of taste and smell induced by drugs. Pharmacotherapy 1997;17(3):482-96.

Clinical Outcomesin Patients With COVID-19 During Two Phase IV Studies of Cladribine Tablets for Treatment of Multiple Sclerosis: An Update

Objective: Report on clinical outcomes in patients with multiple sclerosis (MS) who developed COVID-19 during two ongoing Phase IV studies of cladribine tablets (CladT): CLARIFY-MS ( NCT03369665) and MAGNIFY-MS (NCT03364036). Background: The COVID-19 pandemic has prompted various guidelines on the appropriate use of disease-modifying therapy for MS, including CladT. Design/Methods: CLARIFY-MS is investigating the effect of CladT on health-related quality of life in patients with highly active relapsing MS, while MAGNIFY-MS is evaluating the onset of action of CladT in this population. Both studies have an open-label, single-arm, multicenter design in which patients receive CladT 3.5 mg/kg cumulative dose over 2 years. A total of 485 and 270 patients, respectively, have been enrolled to CLARIFY-MS and MAGNIFY-MS. Cases of suspected or confirmed COVID-19 in these studies were identified from adverse event (AE) reports and reviewed in terms of patient characteristics, COVID-19 severity and outcomes. Results: From the combined population (n=755), 30 patients aged 19-55 years were identified with either suspected (n=2) or confirmed (n=28) COVID-19 (CLARIFY-MS, n=16;MAGNIFYMS, n=14). Time to infection since last CladT dose was 0-11 months. The majority of patients were female (25 out of 30 patients) and experienced mild (20 patients) or moderate (8 patients) COVID-19. Three cases were reported as serious AEs, including two patients who were hospitalized. No patient required mechanical ventilation and there were no deaths. At time of reporting, 27 out of 30 patients had recovered and 3 patients recovered with sequelae. Conclusions: Findings show that the small number of CladT-treated MS patients who acquired COVID-19 in these Phase IV studies typically experienced mild disease with no increased risk of serious outcomes.

Safety of the use of methylprednisolone pulses versus dexamethasone in patients with pneumonia due to SARS-CoV-2 infection: Preliminary results

Objective: To assess the safety of high-dose bolus methylprednisolone versus intermediate-dose dexamethasone in COVID-19 patients with non-critical respiratory failure (RF). Material and/or methods: Low-intervention, phase IV, open-label, randomized 1:1, low-intervention clinical trial (CT): • Arm 1: Dexamethasone 6 mg/24 h/10 days. • Arm 2: Methylprednisolone boluses 250 mg/24 h/3 days Safety preliminary results are presented for 127 patients. This CT has been approved by the Spanish Medicines Agency and the Medicines Ethics Committee of the Salamanca Health Area. EudraCT Number: 2020-005026-28. Results: 127 hospitalized patients, diagnosed with acutephase SARS-CoV-2 infection and non-critical RF, were recruited between January and August 2021. The mean age was 59.5 years and 66.14% were male. The 93.70% were in stage 5 disease according to WHO criteria and 6.30% in stage 4. There were 55 serious adverse events (SAEs) (32 patients, 78% men) and 7 of them (12.7%) were considered serious adverse reactions (SARs), all of them expected. Six patients died (three in the methylprednisolone group). Of these seven SARs, two (28.5%) belonged to the methylprednisolone group, all in men (mean age 67.5 years) and none resulted in death. The classification by organ and system (SOC) of the registered 55 AEs and SAEs, was as follows: 5 vascular disorders cases (methylprednisolone arm: 2), 21 respiratory, thoracic and mediastinal disorders cases (methylprednisolone arm: 12), 2 gastrointestinal disorders cases (methylprednisolone arm: 0), 1 nervous system disorders case (methylprednisolone arm), 26 infections and infestations cases (methylprednisolone arm: 13) and 1 cardiac disorders case no related with methylprednisolone. For the seven adverse reactions reported, the classification by SOC was as follows: one infections and infestations case and one gastrointestinal disorders case no related with methylprednisolone and five vascular disorders cases (methylprednisolone arm: 2). Conclusions: Based on the results obtained, there is no evidence of safety risks associated with high-dose methylprednisolone bolus versus intermediate-dose dexamethasone in patients with COVID-19 with non-critical respiratory failure.

Bibliometric analysis of publication trends in the COVID-19 pandemic

Purpose of Study The COVID-19 pandemic has presented a major challenge to the global medical community resulting in many necessary changes in worldwide research publication trends. As focus and funding of research have shifted throughout the pandemic, so too have publication types, topics, and country-wide research output. While changes during the pandemic have undoubtedly had an impact on publications, these impacts and their implication for long-term research have been poorly characterized. We aim to illustrate these shifting changes in publications during the COVID-19 pandemic. Methods Used Publications were accessed using PubMed Advanced Search Criteria. The beginning of the COVID-19 pandemic was set as the date of the first reported case in Wuhan on 12/31/2019. Searches were conducted on 9/10/ 2021. We generated searches based on type of publication, country affiliation of the first author, date ranges, and specific topics such as 'COPD' or 'Diabetes'. We analyzed the changes in publications during the 4 months before the first case of COVID-19 and every 4 months thereafter. Results were analyzed using SPSS. Summary of Results In the two years before the pandemic, 3541.9 PubMed-indexed articles were published per day, while 4379.9 such articles have been published each day during the pandemic. Covid-19 resulted in net increases relative to baseline in case reports, reviews, and retracted publications with net decreases in clinical trials, multicenter studies, and randomized control trials in most yearly tertiles relative to the 4 months before Covid-19. Meta-analysis and observational studies demonstrated initial net increases followed by subsequent net decreases. The largest percent decrease in publication type relative to baseline has been seen in Phase I (- 82.6%) and Phase IV (-80.5%) clinical trials. In the first yearly tertile, China had the largest percent increase in publications relative to baseline (38.4%) followed by Italy in the second tertile (32.0%) and India in the third tertile (43.5%). Increases in daily publications were seen in many research topics including diabetes (32.8/day), asthma (4.6/day), heart disease (2.9/day), and COPD (2.4/day). Conclusions COVID-19 has caused a shift in research focus and funds towards pandemic-related research. This has emphasized lower evidence research, such as case reports, and shifted focus away from high evidence studies, such as clinical trials and meta-analysis. Production of high-evidence studies does not appear to be recovering as the pandemic continues. Research output of individual countries appears to coincide with COVID-19 related infection surges in each respective country. Despite new emphasis on Covid-related research, many important topics such as diabetes and heart disease have experienced increases in publications.

Early efficacy results of montelukast as add on treatment of hospitalized patient with COVID-19 pneumonia: An investigator-initiated open labelled randomized controlled ongoing clinical trial

Background: Leukotriene receptor antagonists might have a role in viral infections, either by improving lung injury and inflammation, or by acting on 3CL proteinase of the HCoV-19. Thus, we hypothesised that montelukast may be an adjuvant drug in HCoV-19 infection treatment. This study aims to evaluate the efficacy and safety of montelukast in the adjuvant treatment of COVID-19 pneumonia. Method: We are conducting a randomized, controlled, parallel, open-label trial involving hospitalized adult patients with confirmed COVID-19. Patients were randomly assigned in a 1:1 ratio to receive either montelukast 10 mg, once a day for 14 days, in addition to standard of care (SoC), or SoC alone. SoC follows the best practice for treating these patients, according to updated recommendations. The primary outcome is time to recovery. Participants are assessed using diary cards to capture data on treatment-related improvements in an 8-point ordinal scale (COVID-19 scale). Secondary endpoints include changes in NEWS (National Early Warning Score), respiratory and inflammatory parameters. Mann-Whitney U test for continuous variables and Ficher's exact test for categorical variables were used to compare differences between groups. This phase IV clinical trial takes place at the University Hospital of São João, Porto. EudraCT number: 2020-001747-21. Results: Eighteen patients (11 males, mean age 60 years, age range 42-89, table 1) enrolled and completed the trial. The trial is still open for the recruitment of participants. The participants from the active group spent less time hospitalized than control group [median (P25-75): 3.0 (3-6) vs 7.5 (4.75-17.75) days, p = 0.03]. The number of days to achieve 7 (not hospitalized, limitation on activities) or 8 points (not hospitalized, no limitations) in the COVID-19 scale was also statistically significant. The number of patients in need of supplemental high flux oxygen and the NEWS score followed the same trend (table 1). Conclusion: In conclusion, early efficacy results from this ongoing clinical trial suggest montelukast may have a role in treating COVID-19 patients as an adjuvant treatment by diminishing hospitalization days until discharge. Data were presented as median (25th percentile-75th percentile) unless otherwise states. Bpm: beats per minute;cpm: cycles per minute;NEWS: National Early Warning Score);SoC: standard of care. NEWS is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness), and is being used as an efficacy measure. Higher points represent higher risk of poor outcomes. COVID-19 scale is as follows: (1) Death;(2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);(3) Hospitalized, on non-invasive ventilation or high flow oxygen devices;(4) Hospitalized, requiring supplemental oxygen;(5) Hospitalized, not requiring supplemental oxygen-requiring ongoing medical care (COVID-19 related or otherwise);(6) Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care;(7) Not hospitalized, limitation on activities and/or requiring home oxygen;(8) Not hospitalized, no limitations on activities. (Figure Presented).