SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis.

Introduction: T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co-stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell - B cell interactions. SAP and SLAMF are critical for TPH-dependent B cell maturation into autoantibody-producing plasma cells that characterize SLE pathogenesis. We hypothesized that SAP-expressing TPH cells are involved in the pathogenesis of lupus nephritis (LN). Methods: Peripheral blood mononuclear cells (PBMC) were isolated using density gradient separation from whole blood. Cells were stained for cell surface markers, followed by permeabilization and staining of intracellular SAP for spectral flow cytometry analysis. We also analyzed SAP expression from renal infiltrating LN T cells using the available single-cell RNA sequencing (scRNA seq) Accelerated Medicines Partnership (AMP) SLE dataset. Results: PBMC from 30 patients with SLE (34 ± 10 years old, 83% female), including 10 patients with LN, were analyzed. We found an increase in total SAP-positive CD4 and CD8 T cells in SLE compared with controls (55.5 ± 2.6 vs. 41.3 ± 3.4, p=0.007, and 52.5 ± 3.0 vs. 39.2 ± 2.8, p=0.007 respectively). In CD4 T cells, the highest SAP expression was in the TPH subset. The frequency of SAP+TPH in circulation correlated with disease activity; SLE patients with renal disease had higher levels of circulating SAP+TPH that remained significant after adjusting for age, sex, race, low complements, and elevated anti-dsDNA (p=0.014). scRNA-seq data of renal infiltrating T cells in LN identified SAP expression to localize to the TFH-like CD4 cluster and GZMK+ CD8 cluster. Increased SAP expression in LN was associated with the differential expression of SLAMF3 and SLAMF7 and granzyme K and EOMES. The existence of two predominant SAP-expressing subsets, the TFH-like CD4 T cells, and GZMK+ effector CD8 T cells, was verified using scRNA-seq data from a human transcriptomic atlas of fifteen major organs. Conclusion: The expansion of SAP-expressing T helper cells was associated with LN in our cohort and verified using scRNA-seq data of renal infiltrating T cells. Improved SLAM and SAP signaling understanding can identify new therapeutic targets in LN.

New and future therapies: Changes in the therapeutic armamentarium for SLE.

Following better understanding of molecular pathways involved in the pathogenesis of Systemic lupus erythematosus (SLE), pharmaceutical companies have been investigating new targeted drugs for SLE. The purpose of this scoping review is to provide an updated view of the most promising targeted therapies currently in clinical development or recently approved for SLE treatment as well as of the most promising potential future therapeutic strategies in SLE. In the past several years, two new drugs have been developed for lupus treatment along with an extended indication for belimumab. Anifrolumab, the anti-interferon medication, to treat non-renal lupus; voclosporin, a calcineurin inhibitor, for the treatment of lupus nephritis; and belimumab for lupus nephritis. More than 90 investigational drugs are currently in clinical development for SLE treatment, with various targets including inflammatory cytokines and their receptors, intracellular signaling, B cells or plasma cells, co-stimulation molecules, complement fractions, T cells, plasmacytoid dendritic cells as well as various other immunological targets of interest. Researchers are also actively engaged in the development of new therapeutic strategies, including the use of monoclonal antibodies in combination with bispecific monoclonal antibodies, nanobodies and nanoparticles, therapeutic vaccines, utilizing siRNA interference techniques, autologous hematopoietic stem-cell transplantation and Chimeric Antigens Receptor (CAR)-T cells. The therapeutic management and prognosis of SLE have profoundly evolved with changes in the therapeutic armamentarium. With the broad pipeline of targeted treatments in clinical development and new treatment strategies in the future, current challenges are transitioning from the availability of new drugs to the selection of the most appropriate strategy at the patient level.

Protocol for virtual physical examination in an observational, longitudinal study evaluating virtual outcome measures in SLE.

OBJECTIVE: There is a lack of data on the use of telemedicine (TM) in SLE. SLE outcome measures remain complex, and clinicians and clinical trialists have raised concerns about the accuracy of virtual disease activity measures. This study evaluates the level of agreement between virtual SLE outcome measures and face-to-face (F2F) encounter. Here, we describe the study design, virtual physical examination protocol and demographics for the first 50 patients evaluated. METHODS AND ANALYSIS: This is an observational, longitudinal study of 200 patients with SLE with varying levels of disease activity from 4 academic lupus centres serving diverse populations. Each study participant will be evaluated at a baseline and a follow-up visit. At each visit, participants are evaluated by the same physician first via a videoconference-based TM and then a F2F encounter. For this protocol, virtual physical examination guidelines relying on physician-directed patient self-examination were established. SLE disease activity measures will be completed immediately after the TM encounter and repeated after the F2F encounter for each visit. The degree of agreement between TM and F2F disease activity measures will be analysed using the Bland-Altman method. An interim analysis is planned after the enrolment of the first 50 participants. ETHICS AND DISSEMINATION: This study has been reviewed by the Columbia University Medical Center Institutional Review Board (IRB Protocol #: AAAT6574). The full results of this study will be published after the final data analysis of 200 patients. The abrupt shift to TM visits due to the COVID-19 pandemic disrupted clinical practice and clinical trials. Establishing a high level of agreement between SLE disease activity measures obtained with videoconference TM and F2F at the same time point, will allow for improved assessment of disease activity when F2F data cannot be acquired. This information may guide both medical decision-making and provide reliable outcome measures for clinical research.

The Role of Phytochemicals and Gut Microbiome in Atherosclerosis in Preclinical Mouse Models.

Gut microbiome alterations have recently been linked to many chronic conditions including cardiovascular disease (CVD). There is an interplay between diet and the resident gut microbiome, where the food eaten affects populations of certain microbes. This is important, as different microbes are associated with various pathologies, as they can produce compounds that are disease-promoting or disease-protecting. The Western diet negatively affects the host gut microbiome, ultimately resulting in heightened arterial inflammation and cell phenotype changes as well as plaque accumulation in the arteries. Nutritional interventions including whole foods rich in fiber and phytochemicals as well as isolated compounds including polyphenols and traditional medicinal plants show promise in positively influencing the host gut microbiome to alleviate atherosclerosis. This review investigates the efficacy of a vast array of foods and phytochemicals on host gut microbes and atherosclerotic burden in mice. Reduction in plaque by interventions was associated with increases in bacterial diversity, reduction in the Firmicutes/Bacteroidetes (F/B) ratio, and upregulation of Akkermansia. Upregulation in CYP7 isoform in the liver, ABC transporters, bile acid excretion, and the level of acetic acid, propionic acid, and butyric acid were also noted in several studies reducing plaque. These changes were also associated with attenuated inflammation and oxidative stress. In conclusion, an increase in the abundance of Akkermansia with diets rich in polyphenols, fiber, and grains is likely to reduce plaque burden in patients suffering from CVD.

State-of-the-art advancement of surface functionalized layered double hydroxides for cell-specific targeting of therapeutics.

Over the years, layered double hydroxides (LDHs) hold a specific position in biomedicine due to their tunable chemical composition and appropriate structural properties. However, LDHs lack adequate sensitivity for active targeting because of less active surface area and low mechanical strength in physiological conditions. The exploitation of eco-friendly materials, such as chitosan (CS), for surface engineering of LDHs, whose payloads are transferred only under certain conditions, can help develop stimuli-responsive materials owing to high biosafety and unique mechanical strength. We aim to render a well-oriented scenario toward the latest achievements of a bottom-up technology relying on the surface functionalization of LDHs to fabricate functional formulations with promoted bio-functionality and high encapsulation efficiency for various bioactives. Many efforts have been devoted to critical aspects of LDHs, including systemic biosafety and the suitability for developing multicomponent systems via integration with therapeutic modalities, which are thoroughly discussed herein. In addition, a comprehensive discussion was provided for the recent progress in the emergence of CS-coated LDHs. Finally, the challenges and future perspectives in the fabrication of efficient CS-LDHs in biomedicine are considered, with a special focus on cancer treatment.

Effects of Berries, Phytochemicals, and Probiotics on Atherosclerosis through Gut Microbiota Modification: A Meta-Analysis of Animal Studies.

Atherosclerosis is a major cause of death and disability. The beneficial effects of phytochemicals and probiotics on atherosclerosis have gained significant interest since these functional foods can improve inflammation, oxidative stress, and microbiome dysbiosis. The direct effect of the microbiome in atherosclerosis, however, needs further elucidation. The objective of this work was to investigate the effects of polyphenols, alkaloids, and probiotics on atherosclerosis using a meta-analysis of studies with mouse models of atherosclerosis. Identification of eligible studies was conducted through searches on PubMed, Embase, Web of Science, and Science Direct until November 2022. The results showed that phytochemicals reduced atherosclerosis, which was significant in male mice, but not in females. Probiotics, on the other hand, showed significant reductions in plaque in both sexes. Berries and phytochemicals modulated gut microbial composition by reducing the Firmicutes/Bacteroidetes (F/B) ratio and by upregulating health-promoting bacteria, including Akkermansia muciniphila. This analysis suggests that phytochemicals and probiotics can reduce atherosclerosis in animal models, with a potentially greater effect on male animals. Thus, consumption of functional foods rich in phytochemicals as well as probiotics are viable interventions to improve gut health and reduce plaque burden in patients suffering from cardiovascular disease (CVD).

The Effect of Ginger (Zingiber officinale) on Improving Blood Lipids and Body Weight; A Systematic Review and Multivariate Meta-analysis of Clinical Trials.

BACKGROUND: Beneficial effects of ginger consumption on metabolic biomarkers has been reported previously. The current research aimed to investigate the effects of ginger supplementation on lipid profile and body weight using a meta-analysis of randomized, controlled trials. METHODS: Online databases PubMed, Embase, Web of Science, and Science Direct were searched until December 2021 to identify eligible articles. Twenty-six trials were included. RESULTS: The results showed that ginger consumption could significantly improve lipid profile including total triglyceride (-12.54 (-20.01 to -5.08)), cholesterol (-6.53 (-10.76 to -2.31)), LDL (-5.14 (-8.79 to -1.50)), and HDL (1.13 (0.35 to 1.91)). Moreover, ginger supplementation could significantly decrease body mass index (BMI) (-0.49 (-0.79 to -0.18)). However, the small number of sample studies that investigated reductions in body weight (-0.52 (-1.48 to 0.43)) were not statistically significant. Sub-group analysis of treatment dose and duration showed that in most of the analyzed lipid profiles, both ≤1500 and >1500 mg/d for both of ≤8 and >8 weeks could be effective; however, in the case of weight control dose of >1500 mg/d for more than 8 weeks was more effective. Besides, the results of multivariate meta-analysis revealed the effect of the intervention on all lipid profiles simultaneously. CONCLUSION: The present meta-analysis and review revealed that ginger supplementation can improve lipid profile and body weight if used at the appropriate dose and duration. More studies are needed to fully evaluate the effect of ginger supplements' different doses and duration on lipid profile and BMI.

Combination of surgery and laser for the treatment of extensive VIN3 and vulval condyloma: A case report.

Introduction and importance: Vulval intraepithelial neoplastic lesions (VINs) are rare lesions that appear with limited signs of pre-malignancy restricted to the vulvar epithelium. One of the principal causes of VINs is the human papillomavirus (HPV) infection, especially in people with weakened immune systems and young women. Case presentation: A 35-year-old woman presented with VIN3 who had severe immunosuppression and was under corticosteroid treatment. Her lesions were treated with a laser and surgical excision. Clinical discussion: Pathological findings indicated full thickness dysplasia and HPV infection. Follow-up after 5 years showed complete recovery and no recurrence, with a restoration of the vulva esthetics. Conclusion: Due to the increasing prevalence of VIN malignancy in young women and the importance of maintaining normal anatomy and function of the genitalia, a combination of surgery and laser can be used instead of extensive surgery only.

Smart active-targeting of lipid-polymer hybrid nanoparticles for therapeutic applications: Recent advances and challenges.

The advances in producing multifunctional lipid-polymer hybrid nanoparticles (LPHNs) by combining the biomimetic behavior of liposomes and architectural advantages of polymers have provided great opportunities for selective and efficient therapeutics delivery. The constructed LPHNs exhibit different therapeutic efficacies for special uses based on characteristics of different excipients. However, the high mechanical/structural stability of hybrid nano-systems could be viewed as both a negative property and a positive feature, where the concomitant release of drug molecules in a controllable manner is required. In addition, difficulties in scaling up the LPHNs production, due to involvement of several criteria, limit their application for biomedical fields, especially in monitoring, bioimaging, and drug delivery. To address these challenges bio-modifications have exhibited enormous potential to prepare reproducible LPHNs for site-specific therapeutics delivery, diagnostic and preventative applications. The ever-growing surface bio-functionality has provided continuous vitality to this biotechnology and has also posed desirable biosafety to nanoparticles (NPs). As a proof-of-concept, this manuscript provides a crucial review of coated lipid and polymer NPs displaying excellent surface functionality and architectural advantages. We also provide a description of structural classifications and production methodologies, as well as the biomedical possibilities and translational obstacles in the development of surface modified nanocarrier technology.

The Impact of Telemedicine on Rheumatology Care.

Background: The pandemic disrupted the care of patients with rheumatic diseases; difficulties in access to care and its psychological impact affected quality of life. Telemedicine as an alternative to traditional face-to-face office visits has the potential to mitigate this impact. Objective: To evaluate patient and provider experience with telemedicine and its effect on care. Methods: We surveyed patients with rheumatic diseases and their rheumatology providers. The surveys were conducted in 2020 and repeated in 2021. We assessed data on quality of care and health-related quality of life. Results: Hundred patients and 17 providers responded to the survey. Patients reported higher satisfaction with telemedicine in 2021 compared to 2020 (94 vs. 84%), felt more comfortable with (96 vs. 86%), expressed a stronger preference for (22 vs. 16%), and higher intention to use telemedicine in the future (83 vs. 77%); patients thought physicians were able to address their concerns. While providers' satisfaction with telemedicine increased (18-76%), 14/17 providers believed that telemedicine visits were worse than in-person visits. There were no differences in annualized office visits and admissions. Mean EQ-5D score was 0.74, lower than general population (0.87) but equivalent to a subset of patients with SLE (0.74). Conclusion: Our data showed a high level of satisfaction with telemedicine. The lower rheumatology provider satisfaction raises concern if telemedicine constitutes an acceptable alternative to in-person care. The stable number of office visits, admissions, and the similar quality of life to pre-pandemic level suggest effective management of rheumatic diseases using telemedicine/in-person hybrid care.

Nuts as a Part of Dietary Strategy to Improve Metabolic Biomarkers: A Narrative Review.

Background: Nuts are in the spotlight because of their association with improved health outcomes. We aimed to summarize the findings of previous studies to evaluate the impact of nuts consumption on glycaemic and lipid profile, inflammation, and oxidative stress. Methods: Electronic searches for observational and intervention studies were undertaken in PubMed, Embase, Web of Science, and Science Direct until 2022 for searching the studies aiming the application of different types of nuts and the beneficial effects of nuts in improving glycemia, dyslipidemia, inflammation, and oxidative stress. Results: Results from 56 interventional, 9 narrative and 3 systematic reviews, and 12 meta-analysis studies, aiming at the evaluating beneficial effects of different types of nuts on metabolic markers, showed that nut consumption could improve metabolic markers, including glycaemic factors, lipid profile, and inflammatory and oxidative stress parameters in both healthy and individuals with metabolic disorders in a type-, dose- and duration-dependent manner. According to their unique nutrient components, nuts can be known as a part of a healthy diet, resulting in improved metabolic biomarkers. Conclusion: Considering the efficacy of nuts in improving metabolic markers, incorporation of, incorporating nuts the effectiveness of nuts in improving metabolic markers, incorporating nuts in the diet may prevent the incidence or aggravation of chronic metabolic diseases. Considering the health benefits of the nuts' components, including essential micronutrients, if consumed in the appropriate dose and duration to provide the necessary amount of effective micronutrients to improve health, we will see an improvement in metabolic factors. At the same time, more research is required to determine the optimal type, dose, and duration of nut intervention with regards to metabolic control and reducing the risk of developing metabolic disorders.

The Effects of Curcumin Supplementation on Metabolic Biomarkers and Body Mass Index in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Curcumin is one of the most commonly used indigenous molecules endowed with various shielding functionalities that protect the liver. In the present research, we aimed to investigate the effects of curcumin on metabolic factors and body mass index (BMI) in patients with non-alcoholic fatty liver disease (NAFLD) using a meta-analysis of randomized, controlled trials. METHODS: Online databases PubMed, Embase, Web of Science, and Science Direct were searched until April 2021 to identify eligible articles. Fourteen trials were included. RESULTS: The results showed that curcumin consumption can significantly reduce AST (-0.35, (-0.57 to -0.14)), total cholesterol (-0.81, (-1.34 to -0.27)), TG (-0.49, (-0.71 to -0.27)), and FBS (-0.28, (-0.46 to -0.09)) in patients with NAFLD. However, the improvements in ALT (-0.29, (-0.58 to 0.00)), LDL (-0.48, (-0.97 to 0.01)), HDL (0.03, (-0.38 to 0.44)), and BMI (-0.13, (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of curcumin consumption for patients with NAFLD is <500 mg/d for less than 10 weeks. CONCLUSION: The present study suggests that consuming curcumin can improve liver enzymes, lipid profile, FBS, and BMI in patients with NAFLD. Moreover, curcumin supplementation may provide beneficial effects on metabolic biomarkers and body weight if used at the appropriate dose and duration. Further RCTs are required to confirm our findings.

Effect of n-3 (Omega-3) Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers and Body Weight in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of RCTs.

Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM), using a meta-analysis of randomized, controlled trials (RCTs). Online databases PubMed, Embase, Web of Science, and Science Direct were searched until 2021 to identify eligible articles. Thirty trials were included. The results showed that n-3 consumption can significantly reduce glycemic factors including fasting blood sugar (FBS) (-0.36 (-0.71 to -0.01)), glycated hemoglobulin (HbA1c) (-0.74 (-1.13 to -0.35)), and homeostatic model assessment of insulin resistance (HOMA.IR) (-0.58 (-1.13 to -0.03)). Furthermore, significant improvement in lipid profile including triglycerides (TG) (-0.27 (-0.37 to -0.18)), total cholesterol (-0.60 (-0.88 to -0.32)), low density lipoprotein (LDL) (-0.54 (-0.85 to -0.23)), and high-density lipoprotein (HDL) (0.60 (0.23 to 0.96)) levels were found in the present meta-analysis. The reduction in the inflammatory marker's tumor necrosis factor-alpha (TNF-α) (-0.13 (-0.75 to 0.48)) and c-reactive protein (CRP) (-0.72 (-1.70 to 0.27)), as well as weight (-0.09 (-0.24 to 0.07)) and BMI (-0.13 (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of n-3 consumption for patients with T2DM is 1000-2000 mg/d for more than 8 weeks. The present meta-analysis and review reveals that n-3 supplementation can improve glycemic factors and lipid profile in patients with T2DM. Furthermore, n-3 supplementation may provide beneficial effects on inflammatory markers and body weight if used at the appropriate dose and duration.

The Use of COVID-19 Vaccines in Patients with SLE.

PURPOSE OF REVIEW: Three COVID-19 vaccines obtained emergency authorization from the Food and Drug Administration (FDA) and are widely used in the USA. Unfortunately, there is a paucity of evidence on the safety and efficacy of these vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD), as these patients were excluded from all phases of vaccine development. Here we reviewed current data on COVID-19 vaccination in patients with AIIRD, with emphasis on systemic lupus erythematosus (SLE), and provided a comprehensive update on the benefits and risks of vaccination. RECENT FINDINGS: Patients with SLE have worse immune responses following SARS-CoV-2 vaccination than healthy controls. The efficacy of the COVID-19 vaccines seems to be further reduced by immunosuppressive medications, such as glucocorticoids (GC), methotrexate (MTX), mycophenolate/mycophenolic acid (MMF), and rituximab (RTX). However, these data do not substantiate that AIIRD patients are at greater risk of disease flares or have a higher incidence of side effects following vaccination. There is no significant safety concern for the use of COVID-19 vaccines in patients with AIIRD. The benefits of vaccination far outweigh the risks in patients with AIIRD, including SLE. More data are needed to determine the necessity of a booster vaccine dose and appropriate adjustment of immunosuppressants around the administration of vaccine.

Evaluation of SLE arthritis using frequency domain optical imaging.

OBJECTIVES: Systemic lupus erythematosus (SLE) affects the joints in up to 95% of patients. The diagnosis and evaluation of SLE arthritis remain challenging in both practice and clinical trials. Frequency domain optical imaging (FDOI) has been previously used to assess joint involvement in inflammatory arthritis. The objective of this study was to evaluate FDOI in SLE arthritis. METHODS: Ninety-six proximal interphalangeal (PIP) joints from 16 patients with SLE arthritis and 60 PIP joints from 10 age-matched, gender-matched and race/ethnicity-matched controls were examined. A laser beam with a wavelength of 670 nm, 1 mm in diameter and intensity modulated at 300 MHz and 600 MHz was directed onto the dorsal surface of each joint, scanning across a sagittal plane. The transmitted light intensities and phase shifts were measured with an intensified charge-coupled device camera. The data were analysed using Discriminant Analysis and Support Vector Machine algorithms. RESULTS: The amplitude and phase of the transmitted light were significantly different between SLE and control PIPs (p<0.05). Receiver operating characteristic (ROC) analysis of cross-validated models showed an Area Under the ROC Curve (AUC)of 0.89 with corresponding sensitivity of 95%, specificity of 79%, and accuracy of 80%. CONCLUSION: This study is the first evaluation of optical methods in the assessment of SLE arthritis; there was a statistically significant difference in the FDOI signals between patients with SLE and healthy volunteers. The results show that FDOI may have the potential to provide an objective, user-independent, evaluation of SLE PIP joints arthritis.

Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in Systemic Lupus Erythematosus.

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4-24.0] vs. 4.0 [2.5-8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = -0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC50) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.

The Rise and Fall of Hydroxychloroquine with the COVID-19 Pandemic: Narrative Review of Selected Data.

Since the first outbreak of Coronavirus Disease-2019 (COVID-19) in January 2020, the medical community has been pursuing effective countermeasures. Early in the pandemic, several small clinical and in vitro studies from France and China reported on the efficacy of chloroquine (CQ) and hydroxychloroquine (HCQ) against SARS-CoV-2 infections, which generated global attention towards these decades-old antimalarials (AM) and heralded numerous studies investigating their role in treating COVID-19. Despite several observational studies early in the pandemic affirming their beneficial role in treating COVID-19, 12 clinical studies reported no mortality benefits for CQ/HCQ in COVID-19 patients. The excitement over CQ/HCQ was ultimately quenched after three large randomized clinical trials, the COALITION-I trial in Brazil, the RECOVERY trial in the United Kingdom (UK), and the SOLIDARITY trial from World Health Organization (WHO) consistently reported no beneficial effects for CQ/HCQ in hospitalized COVID-19 patients. While initial studies suggested that CQ/HCQ might have a role in treating the early phases of infection, the results from three rigorously designed studies investigating their role in non-hospitalized COVID-19 patients were equivocal and inconsistent. Here we review the major social events related to the therapeutic use of CQ/HCQ in COVID-19, and the data from selected clinical studies evaluating their efficacy in hospitalized and non-hospitalized COVID-19 patients along with the major safety concerns.