Hydroxychloroquine Sulfate Research Articles

A Retrospective Analysis of the Impact of the Coronavirus Disease 2019 Pandemic on Health Care Workers in a Tertiary Hospital in Turkey

IntroductionSeveral vaccines have been developed and approved for use against severe acute respiratory syndrome coronavirus-2; however, the use of personal protective equipment remains important owing to the lack of effective specific treatment and whole community immunity. Hydroxychloroquine sulfate was a treatment option in the early days of the pandemic; however, it was subsequently removed owing to a lack of evidence as an effective treatment.We aimed to evaluate the testing and infection characteristics of coronavirus disease 2019 among health care personnel and determine the effectiveness of prophylactic hydroxychloroquine sulfate use to prevent transmission. MethodsThis retrospective observational study was conducted between May 1 and September 30, 2020. The health care personnel included in the study were physicians, nurses, and paraprofessional support personnel. The health records of health care personnel who had been tested for severe acute respiratory syndrome coronavirus-2 using polymerase chain reaction were retrospectively analyzed. ResultsIn total, 508 health care personnel were included in the study. A total of 152 (29.9%) health care personnel were diagnosed with coronavirus disease 2019. The positive polymerase chain reaction rate was 80.3% (n = 122). A comparison of infected and uninfected health care personnel showed a difference in age and occupation and no difference in sex, working area, and prophylactic hydroxychloroquine sulfate use. DiscussionProtective measures in low-risk areas of our hospital require improvements. All health care personnel should be trained on personal protective equipment use. There was no evidence to support the effectiveness of prophylactic hydroxychloroquine sulfate against severe acute respiratory syndrome coronavirus-2 transmission.

Potential of betacyanin as inhibitor of SARS-CoV-2 revealed by molecular docking study

Covid-19 is a global pandemic where an effective drug has yet to be found. A new coronavirus species, SARS-CoV-2 causes this disease. Several studies have been conducted on medicinal plant-based lead compounds to find antidotes for this virus. One of the fruits that with a high betacyanin content is super red dragon fruit produced by plant Hylocereus costaricensis. Betacyanin, besides having anti-inflammatory and immunomodulatory activities, also has antiviral activity. Therefore, this study aimed to evaluate betacyanin’s interaction with several SARS-CoV-2 receptors by observing its binding affinity and compared it with the nelfinavir and hydroxychloroquine sulfate that have been recommended for treating COVID-19. This research was an in silico study using computer software to assess binding affinity simulations based on molecular docking. The results of this study indicated that betacyanin had a good affinity with several receptors so that it has the potential to be developed as a lead compound to overcome COVID-19. Based on its binding affinity value, betacyanin’s ability was comparable to nelfinavir and hydroxychloroquine sulfate recommended by WHO as a therapeutic agent for COVID-19.

Phase 1 Randomized Placebo-Controlled Study in Healthy Adult Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate – A Potential Treatment for COVID-19

The airways and lungs are the primary sites of SARS-CoV-2 entry, replication, and damage, so there is reason to administer drugs to these regions. Oral hydroxychloroquine (oHCQ) has produced mixed results in COVID-19, despite reported antiviral activity in vitro (EC50=0.72-119 μM). We tested the hypothesis that aerosolized HCQ sulfate (aHCQ) tolerably, safely, and rapidly achieves high respiratory tissue concentrations, while minimizing systemic toxicity. aHCQ was administered via Aerogen nebulizer (oral inhalation, nasal exhalation) to healthy volunteers in a Phase 1 study to assess tolerability, safety, and pharmacokinetics. 10 volunteers (age 55±13 years, 60% female) were randomized to Placebo (n=2), or aHCQ (20 mg, n=2; 50 mg, n=6); all completed the inhalation. 6/8 receiving aHCQ had adverse events (all mild; 75% transient dysgeusia, 25% dizziness). FEV1 and FVC were essentially unchanged from baseline after 15-360 minutes and 1 and 7 days. QT segments were minimally changed from baseline (maximum change 34 msec) after 1-6 hours, and 1 and 7 days; all were ≤455 msec. Pharmacokinetics of 50 mg: Area Under the Blood Curve 0-24 hours post-inhalation was 377±127 ng*hr/mL, <15% of that reported for oHCQ 200 mg; Pharmacokinetic modelling predicts initial epithelial lining fluid concentrations in excess of reported EC50s, and peak respiratory tissue concentrations of 0.5 mM, decreasing to 0.01 mM at 24 hours as HCQ slowly releases into blood. aHCQ was safe, well-tolerated, and appears to be sequestered in respiratory tissues. Administering aHCQ at a fraction of oral dosing may rapidly achieve respiratory tract concentrations sufficient to inhibit SARS-CoV-2.

Tiaochang Xiaoyan extract tablets ameliorate chronic inflammation by activating macrophage lysosomes in chronic colitis rats.

Tiaochang Xiaoyan tablet (TCXYT) is a traditional Chinese medicine prescription derived from the Xianglian pill, which is a traditional Chinese medicine for treating chronic dysentery recorded in the Taiping Huimin Heji Bureau [1078-1085]. For many years, TCXYT has been used to treat ulcerative colitis, however, its therapeutic mechanism is still unclear. In the present study, we used colonic lamina propria macrophages (LPM) and mouse-derived macrophage cell line RAW264.7 cells as the research objects, with the aim of exploring the therapeutic effects and mechanisms of TCXYT on colitis. We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce a rat model of chronic colitis, and normal rats as the control. The disease activity index (DAI) and colonic histopathological changes of rats were used to evaluate the severity of colitis. Rats were divided into the control group; model group; high, middle-, and low-dose TCXYT group; and the hydroxychloroquine sulfate group. TCXYT was administered by gavage on the 3rd day after model replication and lasted for 7 days. The doses used for the high-, middle-, and low-dose TCXYT groups were 0.8, 0.4 and 0.2 g/kg, respectively. Enzyme-linked immunosorbent assay was used to detect the serum concentration of cytokines. Western blot was used to detect the expressions of Toll-like receptor 9 (TLR9), myeloid differentiation primary response 88 (MyD88), interleukin (IL) receptor-associated kinase (IRAK) 1, and IRAK4 in colonic LPM and RAW264.7 cells. Immunofluorescence was used to detect lysosomal activity. The chemical constituents of TCXYT were separated and identified based on Q-Orbitrap high resolution LC/MS data. TCXYT promoted the repair of colonic mucosal injury, attenuated inflammation, increased lysosome activity in macrophages, and decreased the DAI in rats with colitis compared with those in the model group. TCXYT decreased the serum concentrations of IL-1β and tumor necrosis factor-α (TNF-α), increased those of IL-4 and IL-10, and decreased the TLR9, MyD88, IRAK1, and IRAK4 protein levels in LPM and RAW264.7 cells compared to the model group. TCXYT could ameliorate colon inflammation and CD11c+ macrophage infiltration in rats with chronic colitis. This effect may be mediated by activating lysosomes in macrophages by inhibiting the TLR9/MyD88/IRAK signaling pathway.

Accurate and sensitive determination of hydroxychloroquine sulfate used on COVID-19 patients in human urine, serum and saliva samples by GC-MS

A rapid, accurate, and sensitive analytical method, ultrasonication-assisted spraying based fine droplet formation–liquid phase microextraction–gas chromatography–mass spectrometry (UA-SFDF-LPME-GC-MS), was proposed for the determination of trace amounts of hydroxychloroquine sulfate in human serum, urine, and saliva samples. To determine the best extraction strategy, several liquid and solid phase extraction methods were investigated for their efficiencies in isolation and preconcentration of hydroxychloroquine sulfate from biological matrices. The UA-SFDF-LPME method was determined to be the best extraction method as it was operationally simple and provided accurate results. Variables such as the extraction solvent, spraying number, sodium hydroxide concentration and volume, sample volume, mixing method, and mixing period were optimized for the proposed method using the one-variable-at-a-time approach. In addition, Tukey's method based on a post hoc comparison test was employed to evaluate the significant difference between the parameters inspected. After the optimization studies, the limit of detection (LOD) and limit of quantification (LOQ) were determined to be 0.7 and 2.4 μg/kg, respectively. The sensitivity of the GC-MS system based on the LOD was enhanced approximately 440-fold when the UA-SFDF-LPME method was employed. Spiking experiments were also conducted for the human serum, urine, and saliva samples to determine the applicability and accuracy of the proposed method. Recoveries for the human serum, urine, and saliva samples were found to be in the ranges of 93.9%–101.7%, 95.2%–105.0%, and 93.1%–102.3%, respectively. These results were satisfactory and indicated that the hydroxychloroquine sulfate level in the above biological samples could be analyzed using the proposed method.

Formulation and stability study of hydroxychloroquine sulfate oral suspensions

Hydroxychloroquine is an antimalarial drug indicated in the treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also used for the treatment of rheumatoid arthritis, discoid and systemic lupus erythematosus, and more recently proposed in COVID-19 therapy. Hydroxychloroquine is only available in tablets which are not easy to administer for pediatric and geriatric patients, and patients unable to swallow such as patients found in intensive care units. The aim of this work was to develop and optimize a ready to use liquid hydroxychloroquine formulation and to carry out the corresponding chemical and microbiological stability studies. The formulation was evaluated for ease of preparation, physical properties, and palatability. Its stability was performed at ambient temperature and under refrigeration. After 6 months of stability testing, the results showed no pH change, no drug loss, no microbial development, and no visual change. The formulation, employing excipients in a range that EMA has recommended, showed chemical and microbiological stability for at least 6 months even in the worst storage conditions.

In vitro Dissolution Profile at Different Biological pH Conditions of Hydroxychloroquine Sulfate Tablets Is Available for the Treatment of COVID-19.

Hydroxychloroquine sulfate is one of an extensive series of 4-aminoquinolines with antimalarial activity. Moreover, it is used for the treatment of rheumatoid arthritis. Sometimes, hydroxychloroquine sulfate is beneficial for the treatment of autoimmune diseases. Based on recent clinical experiments, it is exploited for the treatment of COVID-19, coronavirus across the globe. The chromatogram separation was achieved by using Agilent, Zorbax C8, 250 mm × 4.6 mm i.d., column. The buffer consists of 0.01 M of 1-pentane sulfonic acid and 0.02% of orthophosphoric acid in purified water. Mixed buffer, acetonitrile, and methanol (800:100:100 v/v). The flow rate was 1.0 ml min−1, and injection volume was 10 μl. Detection was made at 254 nm by using a dual absorbance detector (DAD). The reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated as per the current International Conference on Harmonization (ICH) guidelines to estimate hydroxychloroquine sulfate tablets. As part of method validation, specificity, linearity, precision, and recovery parameters were verified. The concentration and area relationships were linear (R2 > 0.999) over the concentration range of 25–300 μg ml−1 for hydroxychloroquine (HCQ). The relative standard deviations for precision and intermediate precision were <1.5%. The proposed RP-HPLC generic method was applied successfully to evaluate the in vitro dissolution profile with different pH conditions such as 0.1 N HCl, pH 4.5 acetate buffer, and pH 6.8 phosphate buffers as US-marketed reference products.

Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: Molecular docking and DFT calculations

Structure−activity relationships for hydroxychloroquine compound and its derivatives resulted in a potent antiviral activity. Where hydroxychloroquine derivatives showed an apparent efficacy against coronavirus related pneumonia. For this reason, the current study is focused on the structural properties of hydroxychloroquine and hydroxychloroquine sulfate. Optimized structures of these molecules have been reported by using DFT method at B3LYP/6-31G* level of theory. The geometric were determined and compared with the experimental crystal structure. The intra and intermolecular interactions which exist within these compounds are analyzed by different methods namely the topological analysis AIM, ELF and the reduced gradient of the density. These approaches make it possible in particular to study the properties of hydrogen bonds. The highest occupied molecular orbital and the lowest unoccupied molecular orbital energy levels are constructed and the corresponding frontier energy gaps are determined to realize the charge transfer within the molecule. The densities of state diagrams were determined to calculate contributions to the molecular orbitals. The molecular electrostatic potential surfaces are determined to give a visual representation of charge distribution of these ligands and to provide information linked to electrophilic and nucleophilic sites localization. Finally, these derivatives were evaluated for the inhibition of COVID-19 activity by using the molecular docking method.

Investigation of Promising Antiviral Candidate Molecules based on Algal Phlorotannin for the Prevention of COVID-19 Pandemic by in silico Studies

Background: Coronavirus disease 19 (COVID-19) is a highly contagious and pathogenic viral infection. Research has been stepped up due to the lack of vaccine for this viral infection and no effective treatment against this new virus. In order to control the spread, the effectiveness of algal phlorotannin-derived natural molecules on COVID-19, which are easy to obtain, maintainable and have antiviral efficacy by focusing on the Spike (S) protein of the virus, was investigated by in silico methods. Materials and methods: In this study, molecular docking was performed to highlight the emerging role of the top three molecules amongst the selected 11 compounds against SARS CoV-2-RBD/ACE2 and SARS CoV-2-Spike/TMPRSS2. Results and Discussion: An in silico model of algal molecules interactivity on SARS CoV-2-RBD/ACE2 and SARS CoV-2-Spike/TMPRSS2 receptor was observed. Results suggested that based on in silico model, out of algal phlorotannin ligands, only a diecol showed good binding affinity toward SARS CoV-2-RBD/ACE2 interface, compared as remdesivir, chloroquine and hydroxychloroquine sulfate. Moreover within these potential molecules based phlorofucofuroeckol B can also be protector for only TMPRSS2. Conclusion: In future, these results may be aid to direction of the design and development of potent drugs for COVID-19 treatment based on the severity of infection.

Coexistence of Severe Acute Respiratory Syndrome-Coronavirus-2 and Human Metapneumovirus in a Child with Severe Pneumonia

Coronavirus disease-2019 (COVID-19) is a respiratory system disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). In cases with COVID-19 pneumonia, other respiratory viral agents may be simultaneously present. An 11-monthold male patient diagnosed with hydrocephalus, epilepsy and mental-motor retardation was referred to our hospital with fever, cough, and vomiting. The nasopharyngeal swab sample was positive for SARS-CoV-2 and human metapneumovirus. The patient's respiratory distress increased on the third day of the follow-up, and hydroxychloroquine sulfate was added to his treatment. On day 11 of follow-up, based on the deteriorating general condition of the patient and increased acute phase reactants, sepsis secondary to nosocomial infection was considered. Acinetobacter baumannii growth was seen in the blood culture. After antibiotic treatment, the patient's clinical condition improved. Our findings support the idea that COVID-19 can be severe in young children when it coexists with viruses that cause other respiratory tract infections.

Effect of Pre-admission Hydroxychloroquine Treatment on COVID-19-related Intensive Care Follow-up in Geriatric Patients

Objective: The admission rates to intensive care units and mortalities in geriatric patients are higher than the rest of the population with COVID-19 infection. Although the efficacy of hydroxychloroquine sulfate has been recognized, especially when started early during infection, its effectiveness at these early time points in geriatric patients has not been investigated. In this study, our primary aim was to investigate the effects of early treatment of hydroxychloroquine sulfate on COVID-19 positive geriatric patients, according to their clinical symptoms, situation before the intensive care, and patient survival.

COVID-19: The Patients' Perspectives.

COVID-19: The Patients' Perspectives.

Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study.

Since the outbreak of the COVID-19 (coronavirus disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants using a molecular docking approach to inhibit the main protease (Mpro) and spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina (AV) as a docking engine. A rule of five (Ro5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was performed by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding/ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine, and hydroxychloroquine sulfate (antimalarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. This finding implied that several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate, which so far are recommended in the treatment of COVID-19. From quantum chemical DFT calculations, the ascending order of chemical reactivity of selected compounds was pectolinarin > hesperidin > rhoifolin > morin > epigallocatechin gallate. All isolated compounds' C=O regions are preferable for an electrophilic attack, and O-H regions are suitable for a nucleophilic attack. Furthermore, Homo-Lumo and global descriptor values indicated a satisfactory remarkable profile for the selected compounds. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development of drugs to treat infections caused by SARS-CoV-2. The present study identified plant-based compounds that can be further investigated in vitro and in vivo as lead compounds against SARS-CoV-2.

Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.

Background: Hydroxychloroquine (HCQ) is one of the repurposed drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, all the published clinical trials involve oral administration of the drug, although the disease is primarily a respiratory one. Direct inhaled delivery could reduce the side effects associated with oral use and ensure a high concentration of the drug in the lungs. In this study, inhalable HCQ powders were prepared and characterized for potential COVID-19 therapy. Methods: Hydroxychloroquine sulfate (HCQ-sul) was jet milled (JM) followed by conditioning by storage at different relative humidities (43%, 53%, 58%, and 75% RHs) for 7 days. The solid-state properties, including particle morphology and size distribution, crystallinity, and vapor moisture profiles of HCQ-sul samples, were characterized by scanning electron microscopy, laser diffraction, X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, and dynamic water vapor sorption. The aerosol performance of the HCQ-sul powders was assessed using a medium-high resistance Osmohaler coupling to a next-generation impactor (NGI) at a flow rate of 60 L/min. Results: The jet-milled powder showed a volume median diameter of 1.7 μm (span 1.5) and retained the same crystalline form as the raw HCQ-sul. A small amount of amorphous materials was present in the jet-milled HCQ-sul, which was convertible to the stable, crystalline state after conditioning at 53%, 58%, and 75% RH. The recovered fine particle fraction (FPF)recovered and the emitted fine particle fraction (FPFemitted) of the HCQ-sul sample immediately after jet milling and the samples after conditioning at 43%, 53%, and 58% RH were similar at ∼43% and 61%, respectively. In contrast, the sample having conditioned at 75%RH showed lower corresponding values at 33% and 26% respectively, due to the formation of solid bridges caused by excessive moisture. Conclusion: Inhalable crystalline powders of HCQ-sul were successfully prepared, which can be used for clinical testing as a potential inhaled COVID-19 treatment.

Hydroxychloroquine for the treatment and prophylaxis of COVID-19: The journey so far and the road ahead

As mortality and morbidity from novel coronavirus disease (COVID-19) continue to mount worldwide, the scientific community as well as public health systems are under immense pressure to contain the pandemic as well as to develop effective medical countermeasures. Meanwhile, desperation has driven prescribers, researchers as well as administrators to recommend and try therapies supported by little or no reliable evidence. Recently, hydroxychloroquine-sulfate (HCQS) has got significant media and political attention for the treatment as well as prophylaxis of COVID-19 despite the lack of convincing and unequivocal data supporting its efficacy and safety in these patients. This has unfortunately, yet foreseeably led to several controversies and confusion among the medical fraternity, the patient community as well as the general public. Based on the available studies, many with high risk of bias, relatively small sample sizes, and abbreviated follow-ups, HCQS is unlikely to be of dramatic benefit in COVID-19 patients and yet has the potential to cause harm, particularly when used in combination with azithromycin or other medications in high risk individuals with comorbidities. Although definitive data from larger well-controlled randomized trials will be forthcoming in the future, and we may be able to identify specific patient subpopulations likely to benefit from hydroxychloroquine, till that time it will be prudent to prescribe it within investigational trial settings with close safety monitoring. Here we review the current evidence and developments related to the use of HCQS in COVID-19 patients and highlight the importance of risk-benefit assessment and rational use of HCQS during this devastating pandemic.

Preparation and physicochemical stability of 50 mg/mL hydroxychloroquine oral suspension in SyrSpendⓇ SF PH4 (dry)

In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, hydroxychloroquine has been proposed as a potential agent to treat patients with COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 infection. Older adults are more susceptible to COVID-19 and some patients may require admission to the intensive care unit, where oral drug administration of solid forms may be compromised in many COVID-19 patients. However, a liquid formulation of hydroxychloroquine is not commercially available. This study describes how to prepare a 50 mg/mL hydroxychloroquine oral suspension using hydroxychloroquine sulfate powder and SyrSpendⓇ SF PH4 (dry) suspending vehicle. Moreover, a fully validated stability-indicating method has been developed to demonstrate the physicochemical stability of the compounded hydroxychloroquine oral suspension over 60 days under refrigeration (5 ± 3 °C). Finally, use of the proposed oral suspension provides a reliable solution to perform safe and accurate administration of hydroxychloroquine to patients with SARS-CoV-2 infection.

Association between Hydroxychloroquine and Bacterial Pneumonia in Rheumatic Patients: A Population-Based Propensity Score Matching Cohort Study

Background: Association between hydroxychloroquine (HCQ) and bacterial infections required to be determined. Whether hydroxychloroquinehad use could reduce lesser risk of bacterial infections are unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. Methods: The Longitudinal Health Insurance Database (LHID), a one million extract from Taiwan National Health Insurance Research Database (NHIRD) of 23 million Taiwanese populations was used. We included patients who newly diagnosed rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012.HCQ users and nonusers were then matched according to age, sex, urbanization level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. Results: There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulfate had no difference to that of patient without the use of HCQ sulfate in propensity score matched cohort, (Log-rank test: p-value=0.5). However, patients used HCQ sulfate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR=0.55, 95% CI=0.35, 0.89) in the cohort matched, with regarding HCQ nonusers as a reference. Conclusion: Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400 days was associated with lower risk of bacteria pneumonia. Funding Statement: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW109-TDU-B-212-114004), China Medical University Hospital (CMU107-ASIA-19, DMR-109-231); MOST Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-), Tseng-Lien Lin Foundation, Taichung, Taiwan. No additional external funding was received for this study. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board of the China Medical University Hospital (CMUH104-REC2-115(AR-4)).

S2688 COVID-19-Induced Acute Hepatitis Treated Successfully With N-Acetylcysteine: Case Report

INTRODUCTION: Mild liver impairment is widely reported in patients with COVID19. However, Acute hepatitis (AH) was reported in only one case found in a 99-case series published in China.N- acetylcysteine (NAC) is a known medication used in acetaminophen-induced hepatitis, works as a hepatoprotective agent via multiple mechanisms, including restoring hepatic glutathione as well as an antioxidant. It seems that its therapeutic use could be extended to manage cases of AH induced by other medical conditions like COVID 19 as in our case. CASE DESCRIPTION/METHODS: 64 years old male presented with progressive dyspnea, fever, and myalgia. He was diagnosed with COVID19 at a different facility two days prior to the current presentation and was sent home to self-quarantine. On presentation, the patient was mildly hypoxia that responded to nasal oxygen, but never hypotensive. Laboratory results were significant for elevated aspartate transaminase (AST) and alanine transaminase (ALT) at 1,264, 767 Units/L respectively. Alkaline phosphates showed a 1.5-fold increase from his baseline. Total bilirubin, Albumin, prothrombin time, partial thromboplastin time, international normalized ratio (INR) were all normal throughout hospitalization. Viral hepatitis panel and autoimmune hepatitis panel (including anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, and immunoglobulin G level were also negative. Serum salicylate and acetaminophen levels, urine toxicology screening test, and respiratory viral panel (novel Coronavirus not included) were all negative. Serum ferritin was elevated at 20,325 ng/mL, while serum iron was 40 mcg/dL and total iron-binding capacity was 282 mcg/dL. Upon admission, the patient was given a loading dose of NAC followed by maintenance doses. Two days later, AST and ALT started to trend down. Two days later, alkaline phosphatase followed suit. The patient was also placed on the COVID19 treatment regimen used in our facility, including Azithromycin, Hydroxychloroquine, and Zinc sulfate. Systemic corticosteroids were initiated on day 6 due to worsening hypoxia. Eventually, the patient’s inflammatory markers normalized on day 9. Hypoxia improved and he was successfully discharged home. DISCUSSION: We reported a rare case of COVID19 induced AH along with our observation of possible benefit from using NAC in treating this condition. NAC is known for its safety profile. Hence, we believe that more studies need to investigate the role of NAC in treating cases of AH.Figure 1.: Liver enzymes trending over time. ALT( alanine transaminase), AST Aspartate transferase, ALk Pho (alkaline phosphatase).Figure 2.: Patient vital signs during admission.

Application of Artificial Intelligence in Early Diagnosis of Spontaneous Preterm Labor and Birth.

This study reviews the current status and future prospective of knowledge on the use of artificial intelligence for the prediction of spontaneous preterm labor and birth (“preterm birth” hereafter). The summary of review suggests that different machine learning approaches would be optimal for different types of data regarding the prediction of preterm birth: the artificial neural network, logistic regression and/or the random forest for numeric data; the support vector machine for electrohysterogram data; the recurrent neural network for text data; and the convolutional neural network for image data. The ranges of performance measures were 0.79–0.94 for accuracy, 0.22–0.97 for sensitivity, 0.86–1.00 for specificity, and 0.54–0.83 for the area under the receiver operating characteristic curve. The following maternal variables were reported to be major determinants of preterm birth: delivery and pregestational body mass index, age, parity, predelivery systolic and diastolic blood pressure, twins, below high school graduation, infant sex, prior preterm birth, progesterone medication history, upper gastrointestinal tract symptom, gastroesophageal reflux disease, Helicobacter pylori, urban region, calcium channel blocker medication history, gestational diabetes mellitus, prior cone biopsy, cervical length, myomas and adenomyosis, insurance, marriage, religion, systemic lupus erythematosus, hydroxychloroquine sulfate, and increased cerebrospinal fluid and reduced cortical folding due to impaired brain growth.

Hydroxychloroquine and Chloroquine Prescribing Patterns by Provider Specialty Following Initial Reports of Potential Benefit for COVID-19 Treatment - United States, January-June 2020.

Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use† and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.§ Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.¶ In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks.