Spectroscopic investigation and structural simulation in human serum albumin with hydroxychloroquine/Silybum marianum and a possible potential COVID-19 drug candidate.

In this study, the interaction between human serum albumin (HSA) and the hydroxychloroquine/Silybum marianum (HCQ/SM) mixture was investigated using various techniques. The observed high binding constant (Kb) and Stern-Volmer quenching constant (KSV) indicate a strong binding affinity between the HCQ/SM mixture and HSA. The circular dichroism (CD) analysis revealed that HCQ/SM induced conformational changes in the secondary structure of HSA, leading to a decrease in the α-helical content. UV-Vis analysis exhibited a slight redshift, indicating that the HCQ/SM mixture could adapt to the flexible structure of HSA. The experimental results demonstrated the significant conformational changes in HSA upon binding with HCQ/SM. Theoretical studies were carried out using molecular dynamics simulation via the Gromacs simulation package to explore insights into the drug interaction with HSA-binding sites. Furthermore, molecular docking studies demonstrated that HCQ/SM-HSA exhibited favorable docking scores with the receptor (5FUZ), suggesting a potential therapeutic relevance in combating COVID-19 with a value of -6.24 kcal mol-1. HCQ/SM exhibited stronger interaction with both SARS-CoV-2 virus main proteases compared to favipiravir. Ultimately, the experimental data and molecular docking analysis presented in this research offer valuable insights into the pharmaceutical and biological properties of HCQ/SM mixtures when interacting with serum albumin.

Interferon Upregulation Associates with Insulin Resistance in Humans.

In humans, insulin resistance is a physiological response to infections developed to supply sufficient energy to the activated immune system. This metabolic adaptation facilitates the immune response but usually persists after the recovery period of the infection and predisposes the hosts to type 2 diabetes and vascular injury. In patients with diabetes, superimposed insulin resistance worsens metabolic control and promotes diabetic ketoacidosis. Pathogenic mechanisms underlying insulin resistance during microbial invasions remain to be fully defined. However, interferons cause insulin resistance in healthy subjects and other population groups, and their production is increased during infections, suggesting that this group of molecules may contribute to reduced insulin sensitivity. In agreement with this notion, gene expression profiles [transcriptomes] from patients with insulin resistance show a robust overexpression of interferon-stimulated genes [interferon signature]. In addition, serum levels of interferon and surrogates for interferon activity are elevated in patients with insulin resistance. Circulating levels of interferon-γ-inducible protein-10, neopterin, and apolipoprotein L1 correlate with insulin resistance manifestations, such as hypertriglyceridemia, reduced HDL-c, visceral fat, and homeostasis model assessment-insulin resistance. Furthermore, interferon downregulation improves insulin resistance. Antimalarials such as hydroxychloroquine reduce interferon production and improve insulin resistance, reducing the risk for type 2 diabetes and cardiovascular disease. In addition, diverse clinical conditions that feature interferon upregulation are associated with insulin resistance, suggesting that interferon may be a common factor promoting this adaptive response. Among these conditions are systemic lupus erythematosus, sarcoidosis, and infections with severe acute respiratory syndrome-coronavirus-2, human immunodeficiency virus, hepatitis C virus, and Mycobacterium tuberculosis.

Association of the medication protocols and longitudinal change of COVID-19 symptoms: a hospital-based mixed-statistical methods study.

The objective of this study was to identify the relationship between hospitalization treatment strategies leading to change in symptoms during 12-week follow-up among hospitalized patients during the COVID-19 outbreak. In this article, data from a prospective cohort study on COVID-19 patients admitted to Khorshid Hospital, Isfahan, Iran, from February 2020 to February 2021, were analyzed and reported. Patient characteristics, including socio-demographics, comorbidities, signs and symptoms, and treatments during hospitalization, were investigated. Also, to investigate the treatment effects adjusted by other confounding factors that lead to symptom change during follow-up, the binary classification trees, generalized linear mixed model, machine learning, and joint generalized estimating equation methods were applied. This research scrutinized the effects of various medications on COVID-19 patients in a prospective hospital-based cohort study, and found that heparin, methylprednisolone, ceftriaxone, and hydroxychloroquine were the most frequently prescribed medications. The results indicate that of patients under 65 years of age, 76% had a cough at the time of admission, while of patients with Cr levels of 1.1 or more, 80% had not lost weight at the time of admission. The results of fitted models showed that, during the follow-up, women are more likely to have shortness of breath (OR = 1.25; P-value: 0.039), fatigue (OR = 1.31; P-value: 0.013) and cough (OR = 1.29; P-value: 0.019) compared to men. Additionally, patients with symptoms of chest pain, fatigue and decreased appetite during admission are at a higher risk of experiencing fatigue during follow-up. Each day increase in the duration of ceftriaxone multiplies the odds of shortness of breath by 1.15 (P-value: 0.012). With each passing week, the odds of losing weight increase by 1.41 (P-value: 0.038), while the odds of shortness of breath and cough decrease by 0.84 (P-value: 0.005) and 0.56 (P-value: 0.000), respectively. In addition, each day increase in the duration of meropenem or methylprednisolone decreased the odds of weight loss at follow-up by 0.88 (P-value: 0.026) and 0.91 (P-value: 0.023), respectively (among those who took these medications). Identified prognostic factors can help clinicians and policymakers adapt management strategies for patients in any pandemic like COVID-19, which ultimately leads to better hospital decision-making and improved patient quality of life outcomes.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic.

This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir.

Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. When introduced after viral adsorption, BPR3P0128 significantly decreased SARS-CoV-2 replication; however, it did not affect the early entry stage, as evidenced by a time-of-drug-addition assay. This suggests that BPR3P0128's primary action takes place during viral replication. We also found that BPR3P0128 effectively reduced the expression of proinflammatory cytokines in human lung epithelial Calu-3 cells infected with SARS-CoV-2. Molecular docking analysis showed that BPR3P0128 targets the RdRp channel, inhibiting substrate entry, which implies it operates differently-but complementary-with remdesivir. Utilizing an optimized cell-based minigenome RdRp reporter assay, we confirmed that BPR3P0128 exhibited potent inhibitory activity. However, an enzyme-based RdRp assay employing purified recombinant nsp12/nsp7/nsp8 failed to corroborate this inhibitory activity. This suggests that BPR3P0128 may inhibit activity by targeting host-related RdRp-associated factors. Moreover, we discovered that a combination of BPR3P0128 and remdesivir had a synergistic effect-a result likely due to both drugs interacting with separate domains of the RdRp. This novel synergy between the two drugs reinforces the potential clinical value of the BPR3P0128-remdesivir combination in combating various SARS-CoV-2 variants of concern.

Look after the COVID-19 pandemic: Mortality rates among patients with rheumatic diseases.

AIM: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may have a more severe course in patients with underlying disease or who have had immunosuppression. In this study, it was aimed to determine the frequency of coronavirus disease 2019 (COVID-19) and the mortality rates related to COVID-19 among patients with rheumatic disease. METHODS: The patients who were followed up with rheumatic disease in the rheumatology outpatient clinic in a tertiary hospital were retrospectively assessed if they had COVID-19 infection or not between March 2020 and January 2022. RESULTS: A total of 10 682 patients were evaluated. There were 2928 (27.4%) COVID-19-positive and 7754 (72.6%) COVID-19-negative patients. The mean age of COVID-19-positive patients was 46.2 ± 14.6 years, and 65.8% were female. Forty-two (1.4%) patients died due to COVID-19. Among COVID-19-negative patients, 192 patients died. The most common rheumatic disease among patients with COVID-19 was spondyloarthritis (SpA) (30.4%). Corticosteroids were the most common treatment agent in COVID-19-positive patients regardless of mortality. Thirty-one (73.8%) patients were receiving corticosteroids, and 35 (83.3%) patients were receiving immunosuppressive agents among patients with mortality. According to the logistic regression analysis, older age, male gender, and receiving corticosteroid, hydroxychloroquine, mycophenolate mofetil, tofacitinib, rituximab, and cyclophosphamide were found to be related to increased mortality. CONCLUSION: COVID-19 is a serious infection and the current study emphasized that patients with rheumatic diseases had increased mortality rates, particularly in patients who were old, male, and on immunosuppressive treatments.

Incident use of hydroxychloroquine for the treatment of rheumatoid arthritis and systemic lupus erythematosus during the COVID-19 pandemic.

OBJECTIVE: We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (IMASIS) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population, and in RA and SLE patients. Methotrexate (MTX) was use was estimated as a control. RESULTS: Over 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS respectively, to decrease in May 2020. Usage rates of HCQ went back to pre-pandemic trends in Spain, but remained high in the US, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment. CONCLUSIONS: Use of HCQ increased dramatically in the general population in both Spain and the US during March and April 2020. While Spain returned to pre-pandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the US. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the US. This article is protected by copyright. All rights reserved.

COVID-19 in patients with Down syndrome: A systematic review.

INTRODUCTION: Down syndrome (DS) is associated with multiple comorbid conditions and chronic immune dysfunction. Persons with DS who contract COVID-19 are at high risk for complications and have a poor prognosis. We aimed to study the clinical symptoms, laboratory and biochemical profiles, radiologic findings, treatment, and outcomes of patients with DS and COVID-19. METHOD: We systematically searched PubMed, MEDLINE, Web of Science, Scopus, and the Cochrane Library using the keywords COVID-19 or coronavirus or SARS-CoV-2 and DS or trisomy 21. Seventeen articles were identified: eight case reports and nine case series published from December 2019 through March 2022, with a total of 55 cases. RESULTS: Patients averaged 24.8 years (26 days to 60 years); 29 of the patients were male. The most common symptoms were fever, dyspnea, and cough. Gastrointestinal and upper respiratory tract symptoms were commonly reported for pediatric patients. The most common comorbidities present in patients with DS were obesity (49.0%), hypothyroidism (21.6%) and obstructive sleep apnea (15.6%). The patients were hospitalized for a mean of 14.8 days. When the patients were compared with the general COVID-19 population, the mean number of hospitalized days was higher. Most patients had leukopenia, lymphopenia, and elevated inflammatory markers (d-dimer and C-reactive protein). Bilateral infiltrations and bilateral ground-glass opacifications were frequently seen in chest radiographs and chest computed tomographic imaging. Most of the patients were treated with methylprednisolone, macrolides, and hydroxychloroquine. Of the 55 patients, 22 died. The mean age of the patients who died was 42.8 years. Mortality rate was higher in individuals with DS over 40 years of age. CONCLUSION: More studies are needed to better understand COVID-19 infections among persons with DS. In addition, the study was limited by a lack of statistical analyses and a specific comparison group.

Recent findings about antimalarials in cutaneous lupus erythematosus: What dermatologists should know.

Antimalarials (AMs), particularly hydroxychloroquine (HCQ) and chloroquine (CQ), are the cornerstone of the treatment for both systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). HCQ and CQ are recommended as first-line oral agents in all CLE guidelines. Initially thought to have potential therapeutic effects against COVID-19, HCQ has drawn significant attention in recent years, highlighting concerns over its potential toxicity among patients and physicians. This review aims to consolidate current evidence on the efficacy of AMs in CLE. Our focus will be on optimizing therapeutic strategies, such as switching from HCQ to CQ, adding quinacrine to either HCQ or CQ, or adjusting HCQ dose based on blood concentration. Additionally, we will explore the potential for HCQ dose reduction or discontinuation in cases of CLE or SLE remission. Our review will focus on the existing evidence regarding adverse events linked to AM usage, with a specific emphasis on severe events and those of particular interest to dermatologists. Last, we will discuss the optimal HCQ dose and the balance between preventing CLE or SLE flares and minimizing toxicity.

Quality-by-design ecofriendly potentiometric sensor for rapid monitoring of hydroxychloroquine purity in the presence of toxic impurities.

Hydroxychloroquine (HCQ) is prescribed to treat malaria and certain autoimmune diseases. Recent studies questioned its efficiency in relieving COVID-19 symptoms and improving clinical outcomes. This work presents a quality-by-design approach to develop, optimize, and validate a potentiometric sensor for the selective analysis of HCQ in the presence of its toxic impurities (key starting materials), namely 4,7-Dichloroquinoline (DCQ) and hydroxynovaldiamine (HND). The study employed a custom experimental design of 16 sensors with different ion exchangers, plasticizers, and ionophores. We observed the Nernstian slopes, correlation coefficients, quantification limit, response time, and selectivity coefficient for DCQ and HND. The computer software constructed a prediction model for each response. The predicted responses strongly correlate to the experimental ones, indicating model fitness. The optimized sensor achieved 93.8% desirability. It proved a slope of 30.57 mV/decade, a correlation coefficient of 0.9931, a quantification limit of 1.07 × 10-6 M, a detection limit of 2.18 × 10-7 M, and a fast response of 6.5 s within the pH range of 2.5-8.5. The sensor was successfully used to determine HCQ purity in its raw material. The sensor represents a potential tool for rapid, sensitive, and selective monitoring of HCQ purity during industrial production from its starting materials.

An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase.

The main proteinase (Mpro) of SARS-CoV-2 plays a critical role in cleaving viral polyproteins into functional proteins required for viral replication and assembly, making it a prime drug target for COVID-19. It is well known that noncompetitive inhibition offers potential therapeutic options for treating COVID-19, which can effectively reduce the likelihood of cross-reactivity with other proteins and increase the selectivity of the drug. Therefore, the discovery of allosteric sites of Mpro has both scientific and practical significance. In this study, we explored the binding characteristics and inhibiting process of Mpro activity by two recently reported allosteric inhibitors, pelitinib and AT7519 which were obtained by the X-ray screening experiments, to probe the allosteric mechanism via molecular dynamic (MD) simulations. We found that pelitinib and AT7519 can stably bind to Mpro far from the active site. The binding affinity is estimated to be -24.37 ± 4.14 and - 26.96 ± 4.05 kcal/mol for pelitinib and AT7519, respectively, which is considerably stable compared with orthosteric drugs. Furthermore, the strong binding caused clear changes in the catalytic site of Mpro, thus decreasing the substrate accessibility. The community network analysis also validated that pelitinib and AT7519 strengthened intra- and inter-domain communication of Mpro dimer, resulting in a rigid Mpro, which could negatively impact substrate binding. In summary, our findings provide the detailed working mechanism for the two experimentally observed allosteric sites of Mpro. These allosteric sites greatly enhance the 'druggability' of Mpro and represent attractive targets for the development of new Mpro inhibitors.

Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review.

Background: Hydroxychloroquine and Azithromycin combination was used rampantly in management of COVID-19 patients in different countries. Present review was conducted to evaluate the efficacy of Hydroxychloroquine and Azithromycin combination compared to the control (standard care) and any adverse effect following this combination use in COVID-19 patients if any. Material and Methods: We included all the systematic review with or without meta-analysis reporting the effect of Hydroxychloroquine (HCQ) and Azithromycin (AZM) combination use in COVID-19 patient using three databases namely PubMed, medline, CINHAL, Web of Science from July 2020 till Jan 2022. Results: The systematic search strategy has identified 104 studies in total, after removal of duplicates only 4 systematic reviews were included in the qualitative synthesis. The various tools for assessing and reporting the data in the reviews were PRISMA, ROBINS-I, Robs2, AMSTAR, MASTER checklists. Mortality among the hydroxychloroquine with azithromycin combination group was significantly higher than among the Standard Care group. The duration of hospital stay in days was shorter in the Standard Care group in comparison with the hydroxychloroquine group or the hydroxychloroquine and azithromycin combination group. Of the 4 systematic reviews included, 3 had low risk of bias and one had unclear risk of bias using the ROBIS tool. Chloroquine or Hydroxychloroquine combination did not shorten the duration of hospital stay. Conclusion: Rampant use of Chloroquine or Hydroxychloroquine alone or with Azithromycin combination caused adverse effects like QT prolongation. Finally, there is no evidence to support use of either Hydroxychloroquine with or without Azithromycin, for the treatment of COVID-19.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

Impact of COVID-19 Medication (Favipiravir and Hydroxychloroquine) on High Frequency Hearing.

During the initial phase of the COVID-19 pandemic, there was ongoing investigation into potentially effective treatments. Antiviral medications such as Favipiravir and Hydroxychloroquine were employed to treat COVID-19 infections. However, limited studies have examined the adverse effects of these medications on hearing, particularly at extended high frequencies. This study included 10 subjects who had received medications like Azithromycin, a combination of Favipiravir and Hydroxychloroquine, and Hydroxychloroquine alone as part of their COVID-19 treatment. These subjects had previously undergone extended high-frequency audiometry testing (from 8 to 20 kHz) as part of another project conducted by the same department before contracting COVID-19. Post-COVID-19 extended high-frequency audiometry was performed 1 month after the patients received a negative RT-PCR report. The results were then compared using a Paired t-test. A significant shift in the thresholds of high frequencies above 8-20 kHz is found in subjects who had received Favipiravir and Hydroxychloroquine medications. We observed a significant impact of COVID-19 medications on high-frequency hearing, which tends to go unnoticed in regular pure-tone audiometry evaluations. Therefore, our study emphasizes the need for regular follow-ups, including detailed audiological assessments that incorporate extended high-frequency testing, at least once every 3 months for patients who have taken medications for COVID-19 treatment.

Characteristics and Outcomes of Stem Cell Transplant Patients during the COVID-19 Era: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to identify the outcomes of stem cell transplant (SCT) patients during the COVID-19 era. Pooled event rates (PER) were calculated, and meta-regression was performed. A random effects model was utilized. In total, 36 eligible studies were included out of 290. The PER of COVID-19-related deaths and COVID-19-related hospital admissions were 21.1% and 55.2%, respectively. The PER of the use of hydroxychloroquine was 53.27%, of the receipt of immunosuppression it was 39.4%, and of the use of antivirals, antibiotics, and steroids it was 71.61%, 37.94%, and 18.46%, respectively. The PER of the time elapsed until COVID-19 infection after SCT of more than 6 months was 85.3%. The PER of fever, respiratory symptoms, and gastrointestinal symptoms were 70.9, 76.1, and 19.3%, respectively. The PER of acute and chronic GvHD were 40.2% and 60.9%, respectively. SCT patients are at a higher risk of severe COVID-19 infection and mortality. The use of dexamethasone improves the survival of hospitalized SCT patients with moderate to severe COVID-19 requiring supplemental oxygen or ventilation. The SCT patient group is a heterogeneous group with varying characteristics. The quality of reporting on these patients when infected with COVID-19 is not uniform and further prospective or registry studies are needed to better guide clinical care in this unique setting.

Acro-Ischemia Associated With SARS-CoV-2: A Case Report.

COVID-19 is known to cause various cutaneous lesions, including acro-ischemic lesions (AIL), which are associated with poor prognosis. Anticoagulant therapy has shown positive responses in AIL patients. However, in this case study, we present a fatal AIL case despite anticoagulant therapy. We propose different treatment approaches based on the limited current data on acro-ischemia pathogenesis related to SARS-CoV-2. The clinical case involved a 59-year-old male with severe COVID-19 symptoms, including acrocyanosis and right hemiparesis. Despite receiving anticoagulant therapy, the patient's condition worsened, leading to necrosis in the left foot. The discussion focuses on the high-risk nature of AIL, the potential link between angiotensin-converting enzyme 2 (ACE2) receptors and vasculitis or thromboembolic manifestations, and the role of immune clots in AIL pathogenesis. Behçet syndrome is referenced as a model of inflammation-induced thrombosis, guiding the suggestion for immunosuppressant-based treatment in addition to anticoagulants. Additionally, three substances, N-acetyl cysteine, sulodexide, and hydroxychloroquine, are proposed.

Disease-Modifying Medications in Patients with Rheumatoid Arthritis in the USA: Trends from 2016 to 2021.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), since their introduction in 1990, have revolutionized the management of rheumatoid arthritis. Newer DMARDs have recently been approved, influencing treatment patterns and clinical guidelines. OBJECTIVE: To update the current prescribing patterns of DMARDs in the pharmacotherapy of rheumatoid arthritis (RA) to include the pandemic era. METHODS: This was a retrospective cross-sectional multi-year study. Using Optum's Clinformatics® Data Mart Database, we summarized trends in the prevalence of DMARD use in the USA from 2016 to 2021 by year for adult patients ≥ 18 years old with at least one medical RA claim and one pharmacy/medical claim of a DMARD medication. Trends included type of DMARD, class of DMARD (conventional (csDMARDs), biologics [tumor necrosis factor (TNFi) and Non-TNFi), and Janus kinase inhibitors (JAKs)], and triple therapy [methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SUL)] used. RESULTS: The total sample from 2016 to 2021 was 670,679 commercially insured patients. The average age was 63.7 years (SD 13.6), and 76.7% were female and 70% were White. csDMARDs remain the most prescribed (ranging from 77.2 to 79.2%). Although JAKs were the least prescribed DMARD class, their proportion more than doubled from 2016 (1.5%) to 2021 (4%). MTX utilization declined from 40% in 2016 to 34% in 2021. In contrast, HCQ use increased during the pandemic era from < 25% in 2018 to 30% in 2021. Although there is evidence of the therapeutic benefit of triple therapy, its use was very low (~ 1%) compared to biologics only (~ 17%) or biologics+MTX (~ 10%). CONCLUSION: About half of patients with RA were on DMARDs. As expected, csDMARDs were highly used consistently. The COVID-19 pandemic might have influenced the use of HCQ and infusion DMARDs. Triple therapy use remains low.

Effect of pulse methylprednisolone on prognosis in SARS-CoV-2 patients with severe pneumonia.

OBJECTIVE: This study aimed to evaluate the effect of pulse methylprednisolone treatment on prognosis in severe COVID-19 pneumonia. PATIENTS AND METHODS: This retrospective cohort study included 128 patients hospitalized in our clinic for severe COVID-19 between March 2020 and February 2021. Standard treatment (plaquenil, favipravir, low molecular weight heparin, and antibiotics when necessary) was given to the patients in accordance with the Turkish Ministry of Health guidelines. After steroid treatment was included in the guidelines, dexamethasone 6 mg/day was administered along with standard treatment. In patients whose clinical condition did not improve despite this treatment, 250 mg/day methylprednisolone (pulse steroid therapy) was administered intravenous (i.v.) for 3 days, followed by a 40 mg/day maintenance dose. The group receiving methylprednisolone 250 mg/day for 3 days and the group receiving standard treatment without steroids were compared in terms of symptoms, comorbidities, laboratory and radiological findings, length of hospitalization, prognosis, intensive care unit (ICU) admission, and intubation. RESULTS: Of the 128 patients included in the study, 85 (66.4%) were male, and the mean age was 61.7 ± 13.2 years (min: 25; max: 88). A total of 50 (39.1%) patients were transferred to the ICU, while the number of intubated patients was 37 (28.9%). Pulse methylprednisolone treatment was given to 98 (76.6%) patients, compared to the 30 (23.4%) patients who received only standard treatment. In total, 37 patients (28.9%) died. The presence of comorbid diseases (34.3% vs. 1.5%, p = 0.012), advanced age (67.7 vs. 59.3, p = 0.001), and not receiving steroid treatment (p = 0.046) significantly increased mortality. The mortality rate was 24.4% (24/98 patients) in the steroid therapy group and 43.3% (13/30 patients) in patients not receiving steroid therapy, and the difference was statistically significant (p = 0.046). Pulse steroid therapy also significantly decreased the rate of intubation (p = 0.014) and ICU admission (p = 0.007). In the logistic regression analysis that included comorbidity, advanced age, and pulse steroid therapy, advanced age (p = 0.022) and pulse steroid therapy (p = 0.048) were found to be effective independent variables of mortality. CONCLUSIONS: The results showed that pulse i.v. methylprednisolone significantly reduced mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with severe pneumonia requiring hospitalization, in addition to significantly reducing the need for intensive care and intubation. In SARS-CoV-2 patients with severe pneumonia, pulse i.v. methylprednisolone may be useful as a standard treatment in patients who do not respond to dexamethasone.