Characteristics of liver injury in cases of COVID-19.

In novel coronavirus disease 2019 (COVID-19), liver injury was found at a high rate, and reports from outside Japan revealed that such injury was related to severity. We examined the characteristics of liver injury in 15 cases of COVID-19. Thirteen of these patients received antiviral therapy, such as favipiravir, remdesivir, and hydroxychloroquine. Liver injury was observed in eight cases at admission for COVID-19. The hepatic CT attenuation values at admission were significantly lower in nine patients who developed liver damage or showed its exacerbation during the treatment than in the remaining patients. Drug-induced liver injury due to antiviral drug was suspected in six cases. Liver injury due to COVID-19 may be related to low hepatic CT attenuation values and be modified by antiviral drugs.Copyright © 2021 The Japan Society of Hepatology.

Differences in Disease Burden and Treatment Utilization By Socioeconomic Status Among a Large Cohort of Patients with COVID-19 Diagnosis in the United States

Objectives: Social determinants of health (SDoH) including income, education, employment, and housing are known to affect health outcomes;while use in real-world database studies are limited. This study assessed socioeconomic differences in burden of disease and utilization of COVID-19 specific medications in a large cohort of patients in the US. Method(s): A total of 17,682,111 patients having a COVID-19 diagnosis between 4/1/2020 and 4/30/2022 were identified in the IQVIA longitudinal medical and pharmacy claims databases of >277 million patients. For SDoH, a 3-digit zip code median Area Deprivation Index (ADI) (v2.0 University of Wisconsin School of Medicine and Public Health 2015) was calculated for each patient, maintaining patient privacy. The ADI is a validated tool ranking neighborhoods by socioeconomic disadvantage. Medical and pharmacy utilization was assessed and stratified by ADI pentiles, where 0-20 was the least disadvantaged, and 81-100 was the most disadvantaged. Result(s): The proportion of patients having a claim with COVID-19 diagnosis was higher in the most disadvantaged (7.75%) compared to the least disadvantaged group (5.94%) (US overall: 6.37%). Medical claims prior to COVID-19 diagnosis were highest in the least disadvantaged, while prior pharmacy utilization was highest in the most-disadvantaged group. There was sparse use of COVID-19 medications overall;the least disadvantaged patients had the lowest use of COVID-19 specific medications. Casirivimab/imdevimab use was highest in the 61-80 (2.01%) and 81-100 (1.79%) ADI groups, and remdesivir use was highest in the moderately disadvantaged (ADI 41-60 and 61-80) groups (both 2.33%). Utilization of hydroxychloroquine (unapproved for COVID-19) increased from 0.91% in the least to 2.13% in the most disadvantaged groups. Conclusion(s): This study shows unequal burden of COVID-19 prevalence by SDoH, with the most disadvantaged having a higher disease burden and utilization of certain approved and unapproved COVID-19 medications, highlighting the need for further study of the reasons for these disparities.Copyright © 2023

Variation in Demographic Characteristics, Socioeconomic Status, Clinical Presentation and Selected Treatments in Mortality Among Patients with a Diagnosis of COVID-19 in the United States

Objectives: COVID-19 infected over 150 million people and caused over 1 million deaths in the US. This study evaluates several variables thought to be associated with mortality risk in the COVID-19 population. Method(s): The IQVIA longitudinal medical and pharmacy claims databases identified 17,682,111 patients with a COVID-19 diagnosis between 4/1/2020-4/30/2022 from a population of >277 million patients in the US. Patients were linked to Veritas Data Research fact-of-death records (90% complete compared to CDC reporting) and confirmed deaths were flagged. Confirmed mortality rates (CMR) were evaluated by age group, socioeconomic status (SES) using the Area Deprivation Index (v2.0, University of Wisconsin, 2015), co-morbidities and COVID-specific (approved and unapproved) treatments. Result(s): Of the 563,744 patients (3.2%) identified as dead (3.67% in men, 2.85% in women overall), CMR was lowest in patients aged 0-17 (0.08%), highest in age 65-75 (5.92%) and >75 (16.40%). Patients in the lowest 40% of SES had CMR of 4.43% while in the highest 20% was 1.56%. Respiratory failure, pneumonia and sepsis were the most common acute diagnoses accompanying COVID-19 deaths in all SES. In patients with comorbid dementia or Alzheimer's disease, CMR were 21.62% and 23.40% respectively. Additionally, congestive heart failure (15.79%), atrial fibrillation (15.50%), chronic kidney disease (15.30%) and COPD (12.19%) were associated with high CMR. Among patients receiving approved therapies, casirivimab/imdevimab and remdesivir had CMR of 1.41% and 12.63% respectively, while for those receiving unapproved therapies, ivermectin and hydroxychloroquine had CMR of 2.54% and 2.45%. Conclusion(s): Compared to the 1.1% case-mortality rate (Johns Hopkins 2023) among US COVID-19 patients, we found CMR exceeded 3% among those with a medical claim for COVID-19. Advanced age, dementia, and cardio-renal disease were associated with mortality. Patients with the lowest SES had approximately 3 times the confirmed mortality rate compared to those in the highest SES group.Copyright © 2023

Lack of efficacy of hydroxychloroquine in covid-19

Studies in mild-to-moderate cases as well as severe disease leave us still searching for a magic pill

Self-medication among university students during the COVID-19 pandemic: a comparative analysis of different faculties

Self-medication is a widespread public health concern. University students are likely to be more prone to it since self-medication rates increase with educational level. Studies have shown that self-medication rates vary among academics belonging to different faculties, and medical students have the highest self-medication rates. However, it is unknown whether this holds in a vulnerable situation, such as the COVID-19 pandemic. It is also unknown whether differences in technical knowledge of drugs influence self-medication rates among students. Thus, this study analyzes and compares prophylactic self-medication among graduate students of different faculties in the context of the COVID-19 pandemic. This cross-sectional observational study was conducted at a private university in southern Brazil. Students from the medicine, law, life sciences, and fine arts faculties were surveyed, and their responses were compared using a chi-square test. Among 396 respondents, 29.5% reported using preventive medication for COVID-19, and medical students were the least likely to do so. The self-medication rate was 13.6% among respondents, and self-medication did not differ significantly between students of different faculties. Of the students who self-medicated 63% reported having studied the medication before using them. Furthermore, the media did not induce drug use among 81.8% respondents. These results show that medical students used fewer preventive medications during the pandemic and refute the assertion that self-medication rates are higher among medical students. They also show that self-medication rates during the pandemic were significantly lower than those before the pandemic. These revelations show a new aspect of self-medication.Copyright © 2021 Muslim OT et al.

EFFECTS OF DMARD TREATMENT ON SARS-CoV-2 mRNA VACCINATION IN PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASE: A MATCHED, PROSPECTIVE COHORT STUDY

BackgroundPatients suffering from systemic autoimmune rheumatic disease (SARD) display poor antibody development after two doses of mRNA vaccinations leaving these patients with only limited humoral protection against severe SARS-CoV-2 disease courses. Of key interest is the effect of conventional synthetic (csDMARD) and biological/ targeted drugs (b/tsDMARDs) disease modifying antirheumatic drugs on the time of protection.ObjectivesTo compare antibody titer development in patients with vasculitis and connective tissue disease (CTD) with healthy controls 6 months after two mRNA vaccinations and after third immunization. To analyze factors, that affect the velocity of titer decline, well as qualitative humoral response.MethodsPatients with SARD were enrolled and matched for gender and age with healthy control subjects (HC) and the humoral response after 6 months to two doses of mRNA vaccine BNT162b2 in terms of SARS-COV-2 antibody titer was assessed. In addition to binding antibody units (BAU) we also analyzed neutralizing antibodies. Patients receiving B-cell depleting therapy and those with prior SARS-CoV-2 infection (via detection of nucleocapsid antibodies) were excluded. Differences between two groups were calculated with Wilcoxon signed-rank test.ResultsA total of 53 patients with SARD (42 patients suffering from connective tissue disease and 11 with vasculitis respectively) and 73 HC were analysed. Interestingly only patients receiving a combination therapy of different csDMARDs/ b/tsDMARDs demonstrated diminished antibody titers 6 months after two doses of mRNA vaccine (p-value p-value<0,001), whereas patients receiving only csDMARD as monotherapy displayed comparable antibody levels to healthy controls. This effect was equalized after a third booster vaccination (p-value=0,13). Concerning disease entities, patients with vasculitis seemed to have lower BAU than HC (p-value<0,05) and patients suffering from CTD. After third vaccination both patient groups had lower antibody levels than HC (vasculitis: p-value <0,0001;CTD: p-value p-value<0,01). Lower antibody levels before third vaccination correlated with lower antibodies after third immunization.ConclusionPatients with autoimmune rheumatic diseases undergoing combination therapy may be more vulnerable to SARS-CoV-2 infection, due to reduced antibody levels 6 months following two doses of mRNA vaccine. Our data strongly recommends antibody measurements in patients receiving combination therapy and individualized earlier booster vaccination.Figure 1.Anti-SARS-Cov-2 S antibody titers. A: Antibody titers measured 6 months after two doses of mRNA vaccination in patients with connective tissue disease, vasculitis and healthy controls. B, Antibody levels according to disease entity. AB: antibody;BAU: binding antibody unit;CTD: connective tissue disease;HC: healthy control;mono: disease modifying anti-rheumatic drug monotherapy;combination: combination therapy of disease modifying anti-rheumatic drugs;RBD: receptor binding domain;[Figure omitted. See PDF]Table 1.Demographic parameters and therapy of study participants.SARD (n=53)HC (n=73)Age, mean (standard deviation)53.55 (±14.04)51.27 (±14.07)Female45 (84.9%)47 (64.4%)Connective tissue disease42 (79%)Vasculitis11 (21%)csDMARD or b/tsDMARD monotherapy22 (41%)csDMARD and/or b/tsDMARD combination therapy13 (25%)No therapy18 (34%)Methotrexate8 (15%)Mycophenolate mofetil10 (19%)Hydroxychloroquine17 (32%)Azathioprine8 (15%)Belimumab3 (6%)Tocilizumab3 (6%)Glucocorticoid dose 1. vaccination, mean (standard deviation)2.8 (±10.8)Glucocorticoid dose 2. vaccination, mean (standard deviation)2.6 (±10.7)SARD: Systemic autoimmune rheumatic disease, HC: Healthy controls, csDMARD: conventional synthetic disease modifying antirheumatic drugs and b/tsDMARD: biological/ targeted drugs disease modifying antirheumatic drugsREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsElisabeth Simader Speakers bureau: Lilly, Thomas Deimel: None declared, Felix Kartnig: None declared, Selma Tobudic: None declared, Helmuth Hasla her Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Thomas Maria Karonitsch: None declared, Daniel Mrak: None declared, Thomas Nothnagl: None declared, Thomas Perkmann: None declared, Helga Lechner-Radner: None declared, Judith Sautner: None declared, Florian Winkler: None declared, Heinz Burgmann Speakers bureau: speaker fees from Shionogi, Pfizer, MSD, Paid instructor for: advisory boards for Valneva, MSD, Gilead, Consultant of: consulting fees from MSD, Pfizer, Takeda, Gilead, Daniel Aletaha Speakers bureau: other from Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: grants from Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Stefan Winkler: None declared, Stephan Blüml Speakers bureau: personal fees from Abbvie, personal fees from Novartis, Peter Mandl Speakers bureau: reports speaker fees from AbbVie, Janssen and Novartis, Grant/research support from: research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB.

Pilot Study Evaluating the Trends in Utilization of Compounded Products Pre- and Post- COVID-19 Pandemic

Objectives: To assess utilization differences in compounded products before and after the COVID-19 pandemic. Secondary objectives were to understand if there were changes in patient cost sharing and types of products compounded pre- and post- pandemic. Method(s): A cross-sectional study was completed using a large national claims database for patients who received at least one COVID-related vaccine, test, or treatment from October 2015 to July 2022. Claims included in the analysis are those identified as paid, listed as compounded, and were filled in 2019, 2020, or 2021. Chi-Square and T-Tests were used to determine if there are differences between each year. Result(s): The prevalence of paid claims for compounded products was 0.00055% (14,101) in 2019, 0.00042% (11,551) in 2020, and 0.00048% (14,005) in 2021. In each year, most claims for compounded products were through commercial insurance 70% in 2019, 62% in 2020, and 65% in 2021. On average there were approximately 2 claims per patient. The most frequently compounded product was lidocaine hydrochloride 20mg/ML topical solution. In 2020 there was an increase in utilization of naltrexone hydrochloride, a treatment for opioid use disorder (OUD). Between 2019 and 2020 the number of compounded claims decreased 17.6% while the number of total claims increased by 9.01%. From 2020 to 2021 the number of claims for compounded products returned to pre-pandemic levels with a 21.24% increase. In the same period, the total number of claims increased 5.86%. The average patient cost sharing for compounded products was $42.57 (SD: $60.02) in 2019, $40.07 ($80.36) in 2020, and $42.61 ($60.02) in 2021. Conclusion(s): We found that there were fewer patients receiving compounded products following the COVID-19 pandemic. We found no change in the number of compounded claims for hydroxychloroquine and ivermectin, though in 2020, there was a notable increase in the number of claims for naltrexone hydrochloride.Copyright © 2023

IMPACT OF THE COVID-19 PANDEMIC ON ADHERENCE TO DISEASE MODIFYING DRUGS AMONG PATIENTS WITH RHEUMATIC DISEASES: A POPULATION-BASED, INTERRUPTED TIME SERIES ANALYSIS

BackgroundAlthough studies have quantified adherence to medications among patients with rheumatic diseases (RD) during the COVID-19, lack of direct pre-pandemic comparison precludes understanding of impact of the pandemic.ObjectivesOur objective was to evaluate the effect of the COVID-19 pandemic on adherence to disease modifying drugs (DMARDs) including conventional synthetic (csDMARDs) and targeted synthetic (tsDMARDs).MethodsWe linked population-based health data on all physician visits, hospital admissions, and all dispensed medications, regardless of payer in British Columbia from 01/01/1996 to 3/31/2021. We identified prescriptions for csDMARDs (including methotrexate, hydroxychloroquine) and tsDMARDs, namely anti-TNFs (including infliximab, etanercept, adalimumab) and rituximab using drug identification numbers among indicated individuals with RD. We defined March 11, 2020, as the ‘index date' which corresponded to the date that mitigation measures for the COVID-19 pandemic were first introduced. We assessed adherence as proportion days covered (PDC), calculated monthly in the 12 months before and 12 months after the index date. We used interrupted time-series models, namely segmented regression to estimate changes and trends in adherence before and after the index date.ResultsOur analysis showed that the mean PDCs for all included DMARDs stayed relatively steady in the 12 months before and after mitigation measures were introduced (see Table 1). Adherence was highest among anti-TNFs, methotrexate, and azathioprine. Anti-TNFs were on a downward trajectory 12 months prior to the index date. Interrupted time-series modeling demonstrated statistically significant differences in the trends in PDCs post- vs. pre-mitigation measures for all anti-TNFS (slope [∂]: 1.38, standard error [SE]: 0.23), infliximab (∂: 1.35, SE: 0.23), adalimumab (∂: 0.82, SE: 0.25), and etanercept (∂: 1.07, SE: 0.25) (see Figure 1a). Conversely, the csDMARDs were on a flatter trajectory, and methotrexate (∂: -0.53, SE: 0.16), leflunomide (∂: 0.43, SE: 0.08), mycophenolate (∂: -1.26, SE: 0.48), cyclophosphamide (∂: 0.29, SE: 0.05), minocycline (∂: 0.04, SE: 0.02), chloroquine (∂: 0.02, SE: 0.00) showed statistically significant changes in estimated PDC trajectory after mitigation measures were introduced (see Figure 1b).ConclusionThis population-based study demonstrates that messaging and pandemic mitigation measures did not affect adherence to DMARDs.Table 1.Mean PDC 1 year before and after mitigation measures for the COVID-19 pandemic were introduced.MedicationMean PDC (%) 12 months before index dateMean PDC (%) 12 months after index datecsDMARDsmethotrexate28.926.8azathioprine21.819.5sulfasalazine16.214.9leflunomide14.313.0cyclosporine13.711.5hydroxychloroquine10.59.6mycophenolate4.52.9antimalarials4.43.9penicillamine3.53.4cyclophosphamide1.50.7chlorambucil1.20.4minocycline1.10.9gold0.50.2chloroquine0.10.0tsDMARDsanti-TNFs52.149.2infliximab41.838.3adalimumab40.336.8etanercept31.828.9rituximab3.42.9REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Inhibition of Spike Protein of SARS-CoV2 from (Merremia mammosa (Lour) Hall. F.) Bioactive Compounds: Molecular Docking and ADMET Study

Spike protein is a receptor protein that has e role in the entry step of SARS-CoV2. This protein will bind to the ACE2 receptor in the human body and activate TMPRSS2. Inhibition of this protein will prevent the binding of the virus to host cells to spread the infection. This study aims to identify the activity of bioactive compounds of Merremia mammosa (Lour) tuber obtained from LC-MS/MS QTOF analysis of a previous study against the Spike protein of SARS-CoV2 using molecular docking and ADMET analysis. Molecular docking was conducted using SARS-CoV2 spike protein (PDB id. 6M0J) using Maestro Schrodinger software. Results showed that from 206 compounds there are 8 compounds of Merremia mammosa (Lour) that have lower predictive binding energies than standard drugs arbidol, hydroxychloroquine, and chloroquine. Result(s): 206 compounds of Merremia mammosa (Lour) tuber were successfully docked, there were 8 compounds that have docking scores more negative than standard drugs. It indicates that 8 compounds are more active than the positive controls. ADMET study revealed all of those potential ligands had the possibility to be developed as drugs. Conclusion(s): Molecular docking simulations were successfully utilized to identify the potential compounds from Merremia mammosa (Lour) tuber with the activity as an inhibitor for spike protein of SARS-CoV2. Further in vitro assay and purification are needed for future research.Copyright © 2021 Muslim OT et al.

Rigidity and Flexibility of Pyrazole, s-Triazole, and v-Triazole Derivative of Chloroquine as Potential Therapeutic against COVID-19

Based on the core unit of chloroquine, new types of N-heterocyclic compounds that are fused together have been made. The compounds were put into two groups. In series A, the five-member hetero-rings were directly connected to the core unit, while in series B, the CH2 group was used to make the five-member ring more flexible (series B). Using the Gaussian 09 programme, the DFT method with hybrid correlation functional (B3LYP) and 6-311 (d, p) basis sets were used to figure out how to optimize and measure the quantum chemical properties of molecules. The molecular overeating environment (MOE) programme is used to study molecular docking. The binding of flexible compounds shows that AC8, AC10, AC3, and AC5 have the strongest binding affinities compared to the other candidates, while the rigid molecules ARC10 and ARC6 have the lowest binding affinities. In general, the results of the binding affinity showed that the drugs and receptors being studied might have anti-Covid-19 properties. Likewise, the flexible compounds AC8, AC10, AC3, and AC5 had the lowest Ki values of those made and could be used as a treatment. Our virtual physicochemical evaluation of all compounds in series A and B showed that all of them met the limits for molecular weight, lipophilicity (MLogP 4.15, the octanol-water partition coefficient), and water solubility. In addition to MR, the number of H-bond acceptors and the PSA were both within the acceptable range. It seems that the number of rotatable bonds is the only physicochemical property that separates the compounds in series B. The scores of compounds AC3, AC4, AC7, AC8, AC11, and AC12 are outside the acceptable range when compared to the results of chloroquine as the parent compound. © 2023 by SPC (Sami Publishing Company).

SARS-CoV-2 infection (COVID-19) in children.

Since the outbreak in December 2019, the SARS-CoV-2 pandemic virus has been a major public health problem in all countries of the world. The virus is transmitted by inhalation of respiratory droplets from the patient or asymptomatic carrier and is highly contagious. The clinical disease in children is similar to any acute respiratory infection with predominant upper respiratory symptoms, but occasionally can progress to pneumonia with acute respiratory distress syndrome and multiorgan failure. The disease is milder in children than in adults, with low mortality, and it appears that infants and young children have a somewhat more severe clinical course. Diagnosis is made by detecting the virus from respiratory samples (mainly nasopharyngeal and oropharyngeal swabs) using polymerase chain reaction. Treatment is usually symptomatic, and in severe and critical forms, the use of one of the antiviral drugs (lopinavir-ritonavir, remdesivir, hydroxychloroquine) may be consideredCopyright © 2020 Croatian Paediatric Society. All rights reserved.

Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data

ObjectiveTo assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.DesignComparative observational study using data collected from routine care.SettingFour French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020.Participants181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care.InterventionsHydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group).Main outcome measuresThe primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting.ResultsIn the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.ConclusionsHydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.

SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundBelimumab (BLM) is a monoclonal antibody that inhibits B-lymphocyte stimulating factor (BlyS) approved as a specific treatment for systemic lupus erythematosus (SLE) in 2011. We present the experience with BLM in a Spanish cohort with more than 460 patients.ObjectivesTo describe demographic characteristics, efficacy and safety of BLM in patients with SLE in Spanish population since its approval.MethodsDescriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding SLE patients treated with BLM were collected from medical records (2011-2022). Demographic features, efficacy, laboratory variables, SLEDAI, renal involvement, steroid dose, administration routes and safety were assessed. To see whether a trend in BLM prescription had changed or not over time, two periods of time were analyzed: 2011-2016 (period1) and 2017-2022 (period2).ResultsBaseline characteristics of patients are summarized in Table 1.A total of 462 patients (36 hospitals) were included, 50.9% were on intravenous (IV), 34% on subcutaneous (SC) and 15.1% switched from IV to SC route. The median number of pre-BLM csDMARD use was 2.0 (2.0-3.0), being hydroxychloroquine (HCQ) the most frequently used (94.5%). Fifty-two patients were treated with IV cyclophosphamide with a median of 6 bolus received. At the time of BLM start, 443 patients were on prednisone with a median dose of 6.2 mg (5.0-10.0). Significant decreases in prednisone dose, SLEDAI and anti-DNA antibodies were observed from baseline until the last visit, whereas complement C3 and C4 values raised (Figure 1). A total of 118 patients (27.4%) had renal involvement with a median proteinuria of 1.0 g/day (0.5-2.4). Renal biopsy was done in 102 out of 118 patients, being class IV (33%), class III (21%) and class V (16%) the most frequently reported. After BLM, 73.3% of these patients improved (median proteinuria of 0.2 g/day (0.1-0.7).In period1, 100 patients started BLM compared to 362 in period2. The median time from SLE diagnosis to BLM begin was 7.1 (4.0-13.7) and 6.2 (2.1 -14.4) years in period1 and period2, respectively (p=0.454). We found a trend to use more csDMARD before BLM treatment in period1: 2.5 (2-3) vs. 2 (2-3) (p=0.088).A total of 143 (30.5%) patients discontinued treatment mostly due to inefficacy (55.9%) and infections (11.9%). In fact, 116 patients developed infections, mostly mild;2 patients died, 16 had COVID-19 and 4 patients developed tumors requiring discontinuation of the drug.ConclusionIn our cohort of SLE patients in a real-world setting, BLM has been effective, safe and seems to be a good choice to treat renal involvement.References[1]Navarra SV, Guzmán RM, Gallacher AE, et al. Lancet. 2011;377(9767):721-31.[2]Stohl W, Hiepe;rt al. Arthritis Rheum. 2012;64(7):2328-37.[3]Furie R, Rovin BH, Houssiau F, et al. N Engl J Med. 2020;383(12):1117-1128.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

CLINICAL CHARACTERISTICS & OUTCOMES AMONG PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES AND SARS-CoV-2 INFECTION: 2-YEAR DATA FROM A TERTIARY RHEUMATOLOGY CENTRE IN GREECE

BackgroundPatients with autoimmune rheumatic diseases (ARDs) under moderate/severe immunosuppression are considered a high-risk population to develop severe Covid-19 infection.ObjectivesThe aim of our study was to describe the clinical characteristics and the outcome of patients with ARD who contracted a Sars-Cov-2 infection.MethodsAmong patients with ARD being followed in our tertiary outpatient rheumatology clinic, we retrospectively identified those infected with SARS-CoV-2 between the beginning of the pandemic and August 2022. Patients' medical files were reviewed for demographics (age, gender and comorbidities) and disease-related characteristics, as well as coronavirus disease (COVID-19) characteristics, including vaccination status, treatment, and outcomes (covid-19 severity, hospitalization, death).ResultsA total of 209 cases of ARD patients with confirmed Covid-19 infection were recorded. Most of them were women (62.7%), with a mean age of 52.4± 13.8 years. The most prevalent ARDs were seronegative spondyloarthropathies (28.7%), systematic lupus erythematosus (21.5%), rheumatoid arthritis (16.5%), and systemic sclerosis (11.5%). More than half of the patients received corticosteroids (57.8%), while the most frequently used immunosuppressants were hydroxychloroquine (30.9%), TNF inhibitors (26.5%), mycophenolate mofetil (24.0%), methotrexate (19.1%) and rituximab (15.2%). One hundred and fifty-eight (76%) patients were either on remission or had mild disease activity. Most of the patients (131/209) had at least one comorbidity, more commonly arterial hypertension (48.5%) and pulmonary disease (45.2%). Most of the patients were vaccinated against Sars-Cov-2 (73.7%), either with two doses (38.0%), three doses (57.0%) or four doses (5.0%) of mRNA-based vaccines. The big majority of the patients (83.3%) were asymptomatic or had mild Covid-19 disease. About half of the patients (53.1%) reported to have received Covid-19 treatment. Thirty-two of them (15.3%) needed hospitalization, and five death cases were reported overall. Among the demographic characteristics, age (p<0.0001 for hospitalization) and comorbidities were associated with worse covid-19 outcomes. In particular, cardiovascular disease (OR 5.37, p=0.001 for covid-19 severity, OR 6.89, p=0.001 for hospitalization), pulmonary disease (OR 3.02, p=0.006 for hospitalization), and obesity (OR 3.46, p=0.044 for hospitalization) had the stronger associations. Non-vaccination status was also associated with a higher risk for hospitalization (OR 2.68, p=0.015). In relation to ARD-related factors, treatment with rituximab (OR 4.11, p=0.002 for hospitalization), systemic sclerosis diagnosis (OR 3.45, p=0.03 for Covid-19 severity) and myositis diagnosis (OR 4.91, p=0.033 for hospitalization) were associated with worse Covid-19 outcomes. On the other hand, spondyloarthropathies appear to be negatively associated with Covid-19 severity (OR=0.27, p=0.035).ConclusionAccording to our study, most ARD patients recovered uneventfully from Covid-19. However, there are several indications that we should be vigilant for patients who remain unvaccinated, are older, have a systemic sclerosis or myositis diagnosis, and/or receive intense immunosuppressive regiments such as rituximab.References[1]Papagoras C, Fragoulis GE, et al. Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases. Ann Rheum Dis. 2021 Nov 10.[2]Strangfeld A, Schäfer M, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2021 Jul;80(7):930-942.Table 1.N=209ARD Diagnosisn (%)Rheumatoid arthritis34 (16.3)Seronegative spondyloarthropathies60 (28.7)Systemic lupus erythematosus45 (21.5)Systemic sclerosis24 (11.5)Sjogren's syndrome15 (7.2)Vasculitis19 (9.1)Myositis9 (4.3)Other3 (1.4)Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Chilblain lupus erythematosus associated with systemic lupus erythematosus: A classic diagnosis in a current epidemiological context

Objectives: Chilblain lupus erythematosus (LE) is a rare chronic cutaneous lupus erythematosus (CCLE) characterized by the appearance of violaceous plaques in acral regions most exposed to cold. The isolated form affects middle-aged women, while the familial form manifests in early childhood and is associated with mutations in the TREX1 gene. Result(s): A 13-year-old adolescent, with no relevant family history, was referred in March 2021 for suspected chilblain-like lesions associated with COVID-19 infection. The patient presented with multiple violaceous papules on hands and feet. The lesions were slightly painful. Small hyperkeratotic papules were also observed on finger pads. Physical examination also revealed some aphthae affecting the lips. No other systemic symptoms were reported. A skin biopsy and blood tests were performed due to presumed chilblain LE with probable systemic involvement. Histology revealed basal vacuolar damage and intense perivascular and periadnexal lymphocytic inflammatory dermal infiltrate. Remarkably, mucin was noted among the collagen bundles. Leukopenia and positive ANA antibodies (titre 1:320) were detected. Complement levels were normal. SARS-CoV2 infection was ruled out. Skin lesions disappeared within 1 month under topical corticosteroids. Hydroxychloroquine was afterwards started by Rheumatology without recurrence of skin symptoms until last follow-up. Discussion(s): We present an uncommon case of an adolescent with systemic LE presenting as chilblain LE. Chilblain LE can be accompanied by other discoid CCLE. It can progress to systemic LE in up to 20% of patients, especially when concomitant CCLE is present. This rare presentation of CCLE should be differentiated from typical chilblain and other resembling lesions, such as SARS-CoV2-associated chilblain and acral purpuric lesions (COVID toes). The Mayo Clinic diagnostic criteria can be helpful, particularly in this last SARS-CoV2 outbreak scenario, when the reporting of similar skin lesions has been significant.

The effect of hydroxychloroquine in COVID-19 patients who did not receive corticosteroids

Background and Objective: At the beginning of the pandemic, Hydroxychloroquine (HCQ) was one of the most widely used drugs prescribed to patients admitted to hospitals with coronavirus disease 2019 (COVID-19). We try to find the effect of HCQ on the severity and mortality of patients who did not receive corticosteroids. Methods: In this retrospective study, patients with COVID-19 disease were collected from February 20, 2020, to July 21, 2020, at Rouhani Hospital in Babol. Patients were followed up until December 6, 2021. In this study, 170 patients in case and control groups were studied. We used logistic and COX regression models to explore the effects of drugs. Data were analyzed by SPSS version 22. Findings: The use of HCQ did not affect mortality (p=0.46, 95%CI= 0.63 to 2.71, OR= 1.31) and final severity (p= 0.75, 95%CI= 0.59 to 2.06, OR= 1.10) at admission time. However, azithromycin remained in the final model but did not have a significant effect (P= 0.08, HR= 0.28, 95%CI= 0.06 to 0.18). Heparin use was not associated with severity improvement (p= 0.06, 95%CI= 0.97 to 2.81, HR= 1.65), while ceftriaxone remained a factor affecting severity in the model (p = 0.03, 95% CI= 0.29 to 0.95, HR = 0.52). Conclusion: In this study, HCQ harmed mortality admission time and was ineffective in the long term. The use of ceftriaxone compared to other drugs showed protective effects against the mortality hospitalization time. Heparin is not recommended without considering the risk of bleeding in COVID-19 patients.

Regional Variation in Patient Characteristics and Treatment Patterns for over 17 Million COVID-19 Patients in the United States

Objectives: According to the CDC, as of December 2022, almost one in three Americans had confirmed COVID-19 infection;yet only a small portion generated healthcare claims related to COVID-19. Higher burden of COVID-19 cases in Northeastern states compared to other US regions has been documented. This study examined the regional variation in demographic characteristics and treatment patterns among patients with a claim for COVID-19 in a nationwide US claims database. Method(s): Analysis of data from over 277 million patients in IQVIA's longitudinal medical and pharmacy claims databases resulted in a cohort of 17,682,111 patients with COVID-19 diagnosis between 4/1/2020 and 4/30/2022. Demographic characteristics and treatment rates for key approved and un-approved COVID-19 therapies were assessed and stratified by region. Result(s): Among patients in the database, 6.4% had a COVID-19 diagnosis. The proportion was higher in the Northeast (7.1%) and South (6.9%) compared with the West (4.8%). The highest proportion of patients were aged 18-44 years (32.7% in South to 35.2% in West). Over a fifth of the patients were >= 65 years old (US overall= 23.7%;22.5% in Northeast to 25.8% in Midwest). Approximately 57% of the patients nationally and within each region were women. For approved medications, utilization ranged from 1.7% in Northeast to 2.7% in Midwest (overall:2.2%) for remdesivir;0.7% in Northeast to 2.2% in South (overall: 1.5%) for casirivimab/imdevimab. For unapproved medications, utilization ranged from 0.9% in Northeast to 1.6% in South (overall:1.3%) for hydroxychloroquine and 0.4% in Northeast to 1.8% in South (overall:1.1%) for ivermectin. Conclusion(s): Less than one in five US cases of COVID-19 had a claim with diagnosis of COVID-19. Use of COVID-19 specific medications remained low throughout the pandemic. Despite the higher disease burden, proportion of patients with claims and receiving COVID-19 treatment were low nationally, particularly in the northeast US region.Copyright © 2023

Differential of antiviral activity between chloroquine and hydroxychloroquine sulfate against SARS-CoV-2 in vitro.

Objective To investigated the in vitro antiviral activity of chloroquine and hydroxychloroquine sulfate against different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Prototype, Beta, Delta, Omicron) by changing the sequence of drug and virus introduction. Methods Prophylactic treatment: Vero E6 cells were treated with Chloroquine or hydroxychloroquine sulfate (200.00, 150.00, 100.00, 50.00, 16.70, 5.55, 1.85, 0.62, 0.21 micromol.L-1) for 1 h, then the virus was added and incubated for another 2 h. The virus-drug mixture was repalced with fresh medium until the end of the experiment. Post-entry treatment: Vero E6 cells were incubated with virus for 2 h, then the virus was removed and the cells were cultured with drug-containing medium until the end of the experiment. Full-time treatment: Vero E6 cells were pretreated with the drug for 1 h ahead, then virus was added and incubated for another 2 h. The virus-drug mixture was discarded and the cells were cultured with drug-containing medium until the end of the experiment. After 72 h of culture, the cells were observed to see whether they became round and shed to determine the cytopathic situation, and the semi-maximum effect concentration (EC50) and drug selection index (SI) were calculated. Results Both drugs were less effective in preventing SARS-CoV-2. Chloroquine/hydroxychloroquine sulfate showed good antiviral activity under both therapeutic and full-time treatment. EC50 of hydroxychloroquine sulfate was less than chloroquine, SI was greater than chloroquine, antiviral effect of hydroxychloroquine sulfate was better than chloroquine. The antiviral effect of chloroquine (EC50 = 0.904 micromol.L-1) and hydroxychloroquine sulfate (EC50 = 0.143 micromol.L-1) was more significant against Omicron variant than other variants under therapeutic and full-time treatment conditions. Conclusion Chloroquine/hydroxychloroquine sulfate showed good antiviral activity under both therapeutic and full-time treatment, and both drugs were significantly more active against the Omicron variant than the other variants.Copyright © 2023 Authors. All rights reserved.

Pharmacokinetic evaluation of drug-drug interactions in the treatment of COVID-19.

Objective: The COVID-19 pandemic, which started in Wuhan, China and affected the whole world, still represents a unique global challenge with its contagiousness and lethality. The symptoms of COVID-19 patients may differ depending on the severity of the disease. According to the report published by the Ministry of Health Coronavirus Research Advisory Board on the diagnosis, treatment and control of COVID-19, drug combination therapy (hydroxychloroquine, lopinavir / ritonavir and favipiravir) is recommended by health authorities. Drug-drug interaction is a possible situation as a result of simultaneous use of these drugs, which are metabolized by cytochrome P 450 enzymes (CYP), which are mostly found in the liver, with some other drugs. In this review, we aimed to show the pharmacokinetic drug-drug interactions of the drugs used in the treatment of COVID-19, especially by indicating the metabolism pathways. Result and Discussion: The COVID-19 pandemic adversely affects social life, economic and financial markets worldwide. Appropriate treatment protocols are of great importance but taking drug-drug interactions into account in treatment practices prevents unwanted results in patient treatment.Copyright © 2021 University of Ankara. All rights reserved.