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The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids.

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Problem considered: Coronavirus disease(COVID-19) outbroke towards the end of December 2019 in China, soon it started spreading rapidly to various countries leading to an outburst of pandemic. Due to the restrictions imposed to control the spread of the infection, globally the manufacturing, import and export of medicine and the healthcare services to patients with chronic illness had been affected. This study aimed to explore the perspectives of the pharmacists on the medicine supply chain for patients with chronic diseases during COVID-19 pandemic in India. Methods: This study is a prospective, qualitative research involving telephonic, semi-structured in-depth interviews. An interview guide for pharmacists was prepared and validated using "Interview Protocol Refinement" method. Purposive sampling method was used to recruit the pharmacists; a telephonic oral consent was obtained. The interview session was audio recorded and the recordings were transcribed verbatim. Further, transcripts were validated and later analysed using NVivo software. Results: A total of 8 participants were interviewed during our study. Thematic analysis of the transcripts resulted in seven main themes. The study showed that there was deficiency in medicine supply during the COVID-19 pandemic and the pharmacists faced several challenges in procuring and storing the medication, arranging for unavailable medicines, medication dispensing and provision of the services such as medicine delivery, patient counselling. There was also scarcity of manpower leading to extra workload and working overtime. Conclusion: Uninterrupted supply of essential medicine is the backbone of health care system. An effective plan and appropriate strategies are vital to combat such future emergencies.

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Background: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any. Methods: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire. Finding: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19. Interpretation: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae. Funding: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.

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Objective: The study purpose was to compare the anti- novel coronavirus disease 2019 (COVID-19) property of chlorogenic acid (CGA) and Zinc oxide nanoparticles (ZnO-NP) with the new valid synthesized complex of ZnO /CGA-NPs. Methods: The facile mixing method was utilized to prepare ZnO/CGA-NPs. The in vitro effect of different ZnO/CGA-NPs concentrations on papain-like protease (PLpro) and spike protein- receptor-binding domain (RBD) was measured by ELISA technique. The compounds effects on SARS-CoV2 were determined on viral entry, replication, and assembly by using plaque reduction assay, qPCR, and ELISA techniques. Their individual effects or mixed with hydroxychloroquine (HCQ) on erythrocytes (RBCs) and leukocytes (WBCs) were evaluated by routine cell culture technique. Finally, turbidity and agar well diffusion assays were done to evaluate their antimicrobial properties against Escherichia. coli, klebsila pneumonia, Streptococcus pyogenes, Staphylococcus aureus, and Candida albicans. Results: The results confirmed that the uniformly dispersed ZnO-NPs were converted to aggregated form of ZnO/CGA-NPs upon the addition of CGA. The inhibitory concentration 50 (IC50) of ZnO /CGA-NPs against RBD, angiotensin-converting enzyme 2 (ACE2) and PLpro were 1647.7, 323.3 µg/mL and 38.7 µg/mL, respectively. Also, it inhibited E-gene, RdRp gene, E-protein, and spike protein with an IC50 of 0.11, 0.13, 0.48, and 0.37 µg/mL, respectively. It acted as an antimicrobial against all tested organisms with a minimum inhibitory concentration (MIC) of 26 µg/mL. Finally, ZnO/CGA-NPs Complex (0.1 IC50) prevented the cytotoxic effect of HCQ on RBCs and WBC by 92.3 and 90 %, respectively. Conclusion: ZnO/CGA-NPs Complex can be considered as a new anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) compound.

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Hydroxychloroquine (HCQ) is an anti-malarial drug but also widely used to treat autoimmune diseases like arthritis and lupus. Although there have been multiple reports of the adverse effect of prolonged HCQ usage on the outer retina, leading to bull's-eye maculopathy, the effect of HCQ toxicity on the inner retina as well as on overall visual functions has not been explored in detail. Furthermore, lack of an established animal model of HCQ toxicity hinders our understanding of the underlying molecular mechanisms. Here, using a small clinical study, we confirmed the effect of HCQ toxicity on the inner retina, in particular the reduction in central inner retinal thickness, and established a mouse model of chronic HCQ toxicity that recapitulates the effects observed in human retina. Using the mouse model, we demonstrated that chronic HCQ toxicity results in loss of inner retinal neurons and retinal ganglion cells (RGC) and compromises visual functions. We further established that HCQ treatment prevents autophagosome-lysosome fusion and alters the sphingolipid homeostasis in mouse retina. Our results affirm the notion that HCQ treatment causes early damage to the inner retina and affects visual functions before leading to characteristic toxicity in the macular region of the outer retina, 'bull's-eye maculopathy.' We also provide insights into the underlying molecular mechanisms of HCQ retinal toxicity that may involve autophagy-lysosomal defects and alterations in sphingolipid metabolism.

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Coronavirus disease is caused by the SARS-CoV-2 virus. The virus first appeared in Wuhan (China) in December 2019 and has spread globally. Till now, it affected 269 million people with 5.3 million deaths in 224 countries and territories. With the emergence of variants like Omicron, the COVID-19 cases grew exponentially, with thousands of deaths. The general symptoms of COVID-19 include fever, sore throat, cough, lung infections, and, in severe cases, acute respiratory distress syndrome, sepsis, and death. SARS-CoV-2 predominantly affects the lung, but it can also affect other organs such as the brain, heart, and gastrointestinal system. It is observed that 75 % of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. The most common reported comorbidities are hypertension, NDs, diabetes, cancer, endothelial dysfunction, and CVDs. Moreover, older and pre-existing polypharmacy patients have worsened COVID-19 associated complications. SARS-CoV-2 also results in the hypercoagulability issues like gangrene, stroke, pulmonary embolism, and other associated complications. This review aims to provide the latest information on the impact of the COVID-19 on pre-existing comorbidities such as CVDs, NDs, COPD, and other complications. This review will help us to understand the current scenario of COVID-19 and comorbidities; thus, it will play an important role in the management and decision-making efforts to tackle such complications.

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BACKGROUND & AIMS: Polycystic liver disease (PLD) is characterised by increased autophagy and reduced miRNA levels in cholangiocytes. Given that autophagy has been implicated in miRNA regulation, we tested the hypothesis that increased autophagy accounts for miRNA reduction in PLD cholangiocytes (PLDCs) and accelerated hepatic cystogenesis. METHODS: We assessed miRNA levels in cultured normal human cholangiocytes (NHCs), PLDCs, and isolated PLDC autophagosomes by miRNA-sequencing (miRNA-seq), and miRNA targets by mRNA-seq. Levels of miR-345 and miR-345-targeted proteins in livers of animals and humans with PLD, in NHCs and PLDCs, and in PLDCs transfected with pre-miR-345 were assessed by in situ hybridisation (ISH), quantitative PCR, western blotting, and fluorescence confocal microscopy. We also assessed cell proliferation and cyst growth in vitro, and hepatic cystogenesis in vivo. RESULTS: In total, 81% of miRNAs were decreased in PLDCs, with levels of 10 miRNAs reduced by more than 10 times; miR-345 was the most-reduced miRNA. In silico analysis and luciferase reporter assays showed that miR-345 targets included cell-cycle and cell-proliferation-related genes [i.e. cell division cycle 25A (CDC25A), cyclin-dependent kinase 6 (CDK6), E2F2, and proliferating cell nuclear antigen (PCNA)]; levels of 4 studied miR-345 targets were increased in PLDCs at both the mRNA and protein levels. Transfection of PLDCs with pre-miR-345 increased miR-345 and decreased the expression of miR-345-targeted proteins, cell proliferation, and cyst growth in vitro. MiR-345 accumulated in autophagosomes in PLDCs but not NHCs. Inhibition of autophagy increased miR-345 levels, decreased the expression of miR-345-targeted proteins, and reduced hepatic cystogenesis in vitro and in vivo. CONCLUSION: Autophagy-mediated reduction of miR-345 in PLDCs (i.e. miRNAutophagy) accelerates hepatic cystogenesis. Inhibition of autophagy restores miR-345 levels, decreases cyst growth, and is beneficial for PLD. LAY SUMMARY: Polycystic liver disease (PLD) is an incurable genetic disorder characterised by the progressive growth of hepatic cysts. We found that hepatic cystogenesis is increased when the levels of miR-345 in PLD cholangiocytes (PLDCs) are reduced by autophagy. Restoration of miR-345 in PLDCs via inhibition of autophagy decreases hepatic cystogenesis and thus, is beneficial for PLD.

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Chronic use of hydroxychloroquine can result in cardiomyopathy and conduction disturbances. Here, we describe a case of hydroxychloroquine cardiotoxicity in a patient with heart failure with preserved ejection fraction and severe chronotropic incompetence. (Level of Difficulty: Intermediate.).

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OBJECTIVES: The use of complementary and alternative medicine (CAM) by patients with rheumatoid arthritis (RA) is highly prevalent. The relationship of these remedies with disease therapy are not fully studied. We aimed to explore the relationship between different anti-rheumatic drug therapy and CAM use in RA patients. METHODS: The study used an interview-based cross-sectional survey in two major referral centres in Riyadh, Saudi Arabia. Patients were adults with confirmed RA that attended rheumatology clinics. Information on the utilization of CAM, RA duration, drug therapy, and laboratory parameters were obtained. Descriptive statistics as well as adjusted odds ratio using bivariate logistic regression were used to explore the different factors related to CAM use, including drug therapy. RESULTS: A total of 438 adult patients with RA were included. The mean (±SD) age of the patients was 49 (±15.0) years. The majority were women 393 (89.7%). Two hundred and ninety-two patients (66.7%) had used CAM. The CAM users who had a longer disease duration (AOR 1.041 [95% CI: 1.011, 1.073]; p = 0.008) were more likely to be female (AOR 2.068 [95% CI: 1.098, 3.896]; p = 0.024), and use methotrexate (AOR 1.918 [95% CI: 1.249, 2.946]; p = 0.003) as opposed to celecoxib (AOR 0.509 [95% CI: 0.307, 0.844]; p = 0.009) and biologic monotherapy (AOR 0.443 [95% CI: 0.224, 0.876]; p = 0.019). Other factors related to CAM were meloxicam use (AOR 2.342 [95% CI: 1.341, 4.089]; p = 0.003) and traditional therapy (AOR 2.989 [95% CI: 1.647, 5.425]; p = 0.000). The remaining factors were not significant. CONCLUSION: CAM use is prevalent in patients with RA. Understanding patients and disease related factors associated with higher use of CAM is warranted to improve RA management and provide more rational use of these remedies.

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The global outbreak of coronavirus disease and rapid spread of the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent a significant threat to human health. A key mechanism of human SARS-CoV-2 infection is initiated by the combination of human angiotensin-converting enzyme 2 (hACE2) and the receptor-binding domain (RBD) of the SARS-CoV-2-derived spike glycoprotein. Despite the importance of these protein interactions, there are still insufficient detection methods to observe their activity at the cellular level. Herein, we developed a novel fluorescence resonance energy transfer (FRET)-based hACE2 biosensor to monitor the interaction between hACE2 and SARS-CoV-2 RBD. This biosensor facilitated the visualization of hACE2-RBD activity with high spatiotemporal resolutions at the single-cell level. Further studies revealed that the FRET-based hACE2 biosensors were sensitive to both exogenous and endogenous hACE2 expression, suggesting that they might be safely applied to the early stage of SARS-CoV-2 infection without direct virus use. Therefore, our novel biosensor could potentially help develop drugs that target SARS-CoV-2 by inhibiting hACE2-RBD interaction.

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BACKGROUND: Among many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin. AIMS: This meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19. METHODS: A comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio. RESULTS: A total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59-17.82%, I2 - 92%), 10.22% (6.01-16.85%, I2 - 79%), and 0.72% (0.34-1.51, I2 - 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22-15.52, I2 - 59%) and 8.61% (4.52-15.79, I2 - 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77-1.93, I2 - 0%) & 1.51 (0.79-2.87, I2 - 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition). CONCLUSION: The use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.

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BACKGROUND AND AIMS: Treatment options for PsA, following non-steroidal anti-inflammatory drugs (NSAIDs), include conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), particularly methotrexate (MTX). The present study was performed to determine the non-adherence and discontinuation rates of different methotrexate (MTX) formulations in psoriatic arthritis (PsA). APPROACH AND RESULTS: We performed a retrospective-cohort study on patients with PsA identified by disease-specific code in the administrative-health-databases of a Northern Italian region (Lombardy) between 2004 and 2015. Subjects were defined as non-adherent if less than 80% of the prescribed MTX dose was taken based on the time between each prescription. Discontinuation rates were calculated using the time between the first and the last MTX prescription over an observation period of 120 months. Among 8952 patients with PsA, 33% were treated with MTX (mean dosage 10 mg/week ± 2.5 mg standard deviation), more frequently (59%) in its parenteral formulation at a 10 mg weekly dosage (35%). Oral glucocorticoids were prescribed to 21% of patients, while non-steroidal anti-inflammatory drugs to 45%. Approximately 37% of patients with PsA were defined as non-adherent to MTX, with the oral formulation associated with an increased risk of non-adherence (hazard ratio 2.08, 95% confidence interval 1.84-2.35, p < 0.001) compared with parenteral 10-15 mg weekly doses. Oral MTX was discontinued in 52% of cases without a significantly increased risk of discontinuation compared to parenteral formulations which, at higher dosages, had a more favorable retention rate. CONCLUSION: Oral MTX formulation is associated with a 2-fold risk of non-adherence compared to MTX parenteral route in PsA.

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OBJECTIVE: To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19). METHODS: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled patients with COVID-19 treated with CQ or HCQ, with or without azithromycin, and reported on cardiac toxic effects. We performed a meta-analysis using the arcsine transformation of the different incidences. RESULTS: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of torsades de pointes arrhythmia, ventricular tachycardia, or cardiac arrest was 3 per 1000 (95% CI, 0-21; I 2 =96%) in 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5% (95% CI, 1-11; I 2 =98%). The pooled incidence of change in QTc from baseline of 60 milliseconds or more or QTc of 500 milliseconds or more was 9% (95% CI, 3-17; I 2 =97%). Mean or median age, coronary artery disease, hypertension, diabetes, concomitant QT-prolonging medications, intensive care unit admission, and severity of illness in the study populations explained between-studies heterogeneity. CONCLUSION: Treatment of patients with COVID-19 with CQ or HCQ is associated with an important risk of drug-induced QT prolongation and relatively higher incidence of torsades de pointes, ventricular tachycardia, or cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. Patients with COVID-19 who are treated with antimalarials for other indications should be adequately monitored.

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The COVID-19 pandemic has required clinicians to urgently identify new treatment options or the re-purposing of existing drugs. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ). The aims of this systematic review are to systematically identify and collate 24 studies describing the use of CQ and HCQ in human clinical trials and to provide a detailed synthesis of evidence of its efficacy and safety. Of clinical trials, 100% showed no significant difference in the probability of viral transmission or clearance in prophylaxis or therapy, respectively, compared to the control group. Among observational studies employing an endpoint specific to efficacy, 58% concurred with the finding of no significant difference in the attainment of outcomes. Three-fifths of clinical trials and half of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Of the total papers focusing on cardiac side-effects, 44% found a greater incidence of QTc prolongation and/or arrhythmias, 44% found no evidence of a significant difference, and 11% mixed results. The strongest available evidence points towards the inefficacy of CQ and HCQ in prophylaxis or in the treatment of hospitalised COVID-19 patients.

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BACKGROUND: Pharmacological treatments including antivirals (Lopinavir/Ritonavir), Immuno-modulatory and anti-inflammatory drugs including, Tocilizumab and Hydroxychloroquine (HCQ) has been widely investigated as a treatment for COVID-19.Despite the ongoing controversies, HCQ was recommended for managing mild to moderate cases in Saudi Arabia . However, to our knowledge, no previous studies have been conducted in Saudi Arabia to assess its effectiveness. METHODS: A hospital-based retrospective cohort study involving 161 patients with COVID-19 was conducted from March 1 to May 20, 2020. The study was conducted at Prince Mohammed bin Abdul Aziz Hospital (PMAH).The population included hospitalized adults (age ≥ 18 years) with laboratory-confirmed COVID-19. Each eligible patient was followed from the time of admission until the time of discharge. Patients were classified into two groups according to treatment type: in the HCQ group, patients were treated with HCQ; in the SC group, patients were treated with other antiviral or antibacterial treatments according to Ministry of Health (MOH) protocols.The outcomes were hospitalization days, ICU admission, and the need for mechanical ventilation.We estimated the differences in hospital length of stay and time in the ICU between the HCQ group and the standard care (SC) group using a multivariate generalized linear regression. The differences in ICU admission and mechanical ventilation were compared via logistic regression. All models were adjusted for age and gender variables. RESULTS: A total of 161 patients fulfilled the inclusion criteria. Approximately 59% (n = 95) received HCQ-based treatment, and 41% (n = 66) received SC. Length of hospital stay and time in ICU in for patients who received HCQ based treatment was shorter than those who received SC. Similarly, there was less need for ICU admission and mechanical ventilation among patients who received HCQ based treatment compared with SC, (8.6% vs. 10.7 and 3.1% vs. 9.1%). However, the regression analysis showed no significant difference between the two groups in terms of patient outcomes. CONCLUSION: HCQ had a modest effect on hospital length stay and days in ICU compared with SC. However, these results need to be interpreted with caution. Larger observational studies and RCTs that evaluate the efficacy of HCQ in COVID-19 patients in the Saudi population are urgently needed.

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The outbreak of SARS-CoV-2 started in Hubei province of China in December 2019 and rapidly spread all over the world. It has infected more than 7 million people worldwide and has pushed half of the world in a state of lockdown. There is an urgent unmet need of interventions both for prevention and treatment of this disease and more than 500 clinical trials are ongoing in this regard. At present, no study with robust methodology have clearly demonstrated benefits of hydroxychloroquine for treatment, preexposure prophylaxis in healthcare workers or post exposure prophylaxis in COrona VIrus Disease-2019. Remdesivir has been shown to have modest benefits in moderate to severe disease, if administered early. Given the rapid pace of clinical information and discoveries, it is important for clinicians to be up to date with the latest, evidence-based treatment options available for this novel disease. Keeping up with this current pace of information, we review the clinical studies of different therapeutic options available to treat SARS-CoV-2.