The combination effects of theophylline and corticosteroids in COVID-19

Late in 2019, the novel coronavirus disease (COVID-19) became pandemic. The disease has associated with severe inflammatory symptoms of the respiratory epithelial cells and the dysfunction of several organs of the body. Studies have shown that theophylline plays an important role in acute inflammation and has a synergistic effect on low therapeutic concentrations with corticosteroid drugs and amplifies anti-inflammatory effect of corticosteroids by activating histone deacetylase-2 (HDAC2), which decreases corticosteroid resistance by increasing the affinity of corticosteroid receptors to corticosteroid drugs. Therefore, theophylline could be considered as an adjunctive anti-inflammatory drug in combination with corticosteroids in the treatment of patients with COVID-19.Copyright © 2020 by the Author(s).

Clinical Approaches to Minimize Readmissions of Patients with COPD: A Narrative Review

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease and also a lead-ing cause of morbidity and mortality worldwide. The frequent readmissions of patients with COPD may reduce lung function, mental health, and quality of life;it also increases the cost of treatment and mortality rate. Some common factors that may increase the readmission frequency of COPD patients include delay of diagnosis, advanced lung function decline, lack of adherence for COPD treatment, ineffective management of comorbidities, acute exacerbation or stable COPD, and infec-tions. However, these factors might be well controlled with appropriate approaches to minimize the readmission of patients with COPD. In this review, we propose a strategy with a seven-step approach to reduce the readmission in COPD patients, including early diagnosis of COPD, optimal treatment for stable COPD, targeted management of comorbidities, adequate therapy for acute ex-acerbations, individualized action plans for COPD patients, effective prevention of bacterial and viral infections, and adaptive program of pulmonary rehabilitation. Thus, implementing this approach may reduce the risk of readmission in patients with COPD.Copyright © 2023 Bentham Science Publishers.

Molecularly imprinted polymer-modified carbon paste electrodes (MIP-CPE): A review on sensitive electrochemical sensors for pharmaceutical determinations

Recent years have been associated with the development of various sensor-based technologies in response to the undeniable need for the rapid and precise analysis of an immense variety of pharmaceuticals. In this regard, special attention has been paid to the design and fabrication of sensing platforms based on electrochemical detection methods as they can offer many advantages, such as portability, ease of use, relatively cheap instruments, and fast response times. Carbon paste electrodes (CPEs) are among the most promising conductive electrodes due to their beneficial properties, including ease of electrode modification, facile surface renewability, low background currents, and the ability to modify with different analytes. However, their widespread use is affected by the lack of sufficient selectivity of CPEs. Molecularly imprinted polymers (MIPs) composed of tailor-made cavities for specific target molecules are appealing complementary additives that can overcome this limitation. Accordingly, adding MIP to the carbon paste matrix can contribute to the required selectivity of sensing platforms. This review aims to present a categorized report on the recent research and the outcomes in the combinatory fields of MIPs and CPEs for determining pharmaceuticals in complex and simple matrices. CPEs modified with MIPs of various pharmaceutical compounds, including analgesic drugs, antibiotics, antivirals, cardiovascular drugs, as well as therapeutic agents affecting the central nervous system (CNS), will be addressed in detail.Copyright © 2023 Elsevier B.V.

Practicing Telemedicines in India

The great use of telecommunication technology propels new healthcare system of telemedicine through which diagnosis as well as treatment can be done in the remote areas. The ancient Greek language explain the terminology of telemedicine in the phrase of distance healing. As per WHO, Telemedicine is the delivery of health-care services, where distance is a critical factor, by all health-care professionals using information and communications technologies for the exchange of valid information for diagnosis, treatment and prevention of disease and injuries, research and evaluation, and the continuing education of health-care workers, with the aim of advancing the health of individuals and communities. Historically the concept of teleconsultation was evolved in the first half of twentieth century when the data of ECG was communicated through telephone lines, this can be traced as first evidence of this unique healthcare system. Further the introduction of electrical system of telegraph as well as evolution of telephone revolutionized this system of healthcare. when the Technology of telemedicine help both patients as well as service providers in multiple ways involving physicians, surgeons, pharmacists, paramedical staff, IT and electronics engineers, government, hospitals and end user public Location is now a days no problem and therefore there is no limitation of the availability of healthcare facilities to such location or remote location. The biggest role in such development is played by the communication technology which may provide healthcare services to every nook and corner of the location. It can decrease the health staff pressure because in India WHO guidelines ask to maintain the ratio 1:1000 of doctor and Indian public compared to present 0.62:1000 ratio of doctor and public. The great advantage of this system is that in case of epidemic or pandemic like COVID 19 Telemedicine can keep the health staff are well general public free from contagious infection (COVID-19). There are a number of networking communication modes that can be applied, which may improve the patient compliance,dosage regimen can be managed in better fashion thus increase the longevity of person life. Disasters management during pandemics present unique challenges which can be addressed effectively as happened during the lockdown. This technology-based practice can break the infectivity chain of the transmission of communicable diseases This chapter incorporates basic concept of telemedicine, its origin and types, communication technologies, services by telemedicine, types of telemedicine, tools of telemedicine, telemedicine software's and guidelines related to practicingtelemedicine in reference to Indian context. Copyright © RJPT All right reserved.

PATHOPHYSIOLOGY OF LACTIC ACIDOSIS IN PATIENTS WITH ASTHMA

SESSION TITLE: Challenges in Asthma SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Asthma is a chronic illness affecting 334 million people worldwide[1]. Asthma affects the respiratory gas exchange, which plays a significant role in acid-base balance. Acid-base disorders in asthma involve respiratory alkalosis, respiratory acidosis, and AG acidosis[2]. CASE PRESENTATION: A 37 years old Hispanic male with a PMH of intermittent asthma presents with progressive dyspnea for three days, worse with activity and decreases with rest. He reported no [cough, fever, rhinorrhea, chest pain]. No orthopnea. He is vaccinated for COVID ( 2 Pfizer doses), has no sickness exposure, and works as a driver. The patient is not a smoker. Physical Exam: Blood pressure 124/72 mmHg. Heart Rate 100 PPM. Temperature 97.1 F.Respiratory Rate 21BPM.SPO2 90% General appearance: acute distress with nasal flaring. Heart: Normal S1, S2. RRR. Lung: Poor air entry with diffuse wheeze bilaterally. He was placed on a 6 LPM NC. CBC and differential were unremarkable. He was started on methylprednisone, Ceftriaxone, and azithromycin. The patient was started on inhaled Salbutamol and Budesonide. Chest X-ray was unremarkable, Chemistry was unremarkable except for elevated Lactic acid 4.7, There was no concern for reduced tissue perfusion or hypoxia, with no evidence of an infectious process because both viral and bacterial causes for pneumonia were excluded, and antibiotics were stopped. A serial lactic acid level trend was 4.5/4.3/ 4.1/ 4 on the first day, while on the next day, it was 3.1/ 2.9/ 2.7/ 2.5/ 3.5, we stopped trending his lactic acid level. He improved and was discharged on an oral taper steroid and inhaled steroids with a B2 agonist. DISCUSSION: There are two types of Lactic acidosis in patients with asthma: 1- Type-A results from impaired oxygen delivery to tissues and reduced tissue perfusion in severe acute asthma may be accompanied by reduced cardiac output. 2- Type B where oxygen delivery is normal, but the cellular function is impaired due to increased norepinephrine in plasma, increasing metabolic rate and lactate production, drugs like beta-agonists increase glycogenolysis leading to an increased pyruvate concentration;pyruvate is converted to lactic acid. B2 agonist increases lipolysis and increases Acetyl CoA, this increase in Acetyl CoA inhibits the conversion of pyruvate to Acetyl CoA, increasing pyruvate which will be converted to lactic acid[2], Theophylline is a non-selective 5'-phosphodiesterase inhibitor and potentiates the activity of ß-adrenergic agents by increasing the intracellular concentration of cAMP, Glucocorticoids are also known to increase the ß-receptor's sensitivity to ß-adrenergic agonists. CONCLUSIONS: Providers are increasingly challenged by hyperlactatemia,it is not harmful but elevated Lactic acid levels and clearance rate is used for prognostication,hyperlactatemia might be misleading,and all possible causes of elevated lactic acid levels must be explored. Reference #1: 10.5334/aogh.2412 Reference #2: https://doi.org/10.3390/jcm8040563 Reference #3: Edwin B. Liem, Stephen C. Mnookin, Michael E. Mahla;Albuterol-induced Lactic Acidosis. Anesthesiology 2003;99:505–506 doi: https://doi.org/10.1097/00000542-200308000-00036 DISCLOSURES: No relevant relationships by Vasudev Malik Daliparty No relevant relationships by Abdallah Khashan No relevant relationships by Samer Talib No relevant relationships by MATTHEW YOTSUYA

BILATERAL PNEUMOTHORAX, PNEUMOMEDIASTINUM, AND SUBCUTANEOUS EMPHYSEMA: A CASE OF A RARE SYNCHRONOUS TRIAD IN ASTHMA EXACERBATION

SESSION TITLE: Obstructive Lung Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Individual cases of pneumothorax, pneumomediastinum and subcutaneous emphysema have been reported in asthma attacks, but rarely coincide. Pathophysiology is secondary to obstruction in the minor airways leading to air-trapping and barotrauma of distal airways with subsequent alveolar rupture. This case illustrates a case of asthma exacerbation with a synchronous triad of rare complications. CASE PRESENTATION: 65-year-old female with a history of breast cancer, asthma and hypertension presented with shortness of breath, wheezing, and productive cough since four days ago. Vital signs were remarkable for tachypnea and saturation of 91%. Physical examination revealed respiratory distress, and auscultation disclosed diffuse inspiratory and expiratory wheezing. Limited bedside ultrasound showed B-lines compatible for pulmonary edema. Arterial blood gases were compatible with respiratory acidosis and hypoxemia. Laboratories showed leukocytosis, hypotonic hyponatremia, normal brain natriuretic peptide, and negative COVID-19 PCR test. Chest Xray (CXR) demonstrated changes concerning for pneumonia with superimposed pleural effusion. The patient was admitted with the impression of asthma exacerbation versus community acquired pneumonia. Initially, the patient was placed in bi-level positive airway pressure to aid in respiratory discomfort, broad spectrum antibiotic regimen, and diuresis therapy. On follow up, she was found hypoxic with periorbital edema, dyspnea, and subcutaneous emphysema in neck, upper extremities, and thorax for which emergent intubation was performed. CXR and Thoracic CT confirmed pneumomediastinum, large right sided pneumothorax and a moderate left sided pneumothorax requiring tube thoracostomy. At the Intensive Care Unit, treatment included combination therapies with levalbuterol, ipratropium, terbutaline, theophylline, budesonide, IV steroids and magnesium without appropriate response. Mechanical ventilator was set to protective lung parameters to avoid worsening barotrauma. Subsequently, she was paralyzed for 48 hours to aid in synchrony and allow adequate pulmonary gas exchange. Nonetheless, severe bronchoconstriction was persistent along with depressed neurological status. Two months later, the patient passed away. DISCUSSION: We believe our patient developed barotrauma secondary to a cough attack combined with positive airway pressure. Similarities in presentation such as dyspnea, tachycardia, and hypoxia may prove difficult in differentiation. Although each of these pathologies separately can generally be self-limiting depending on size and hemodynamic compromise, the combination can be mortal and clinical suspicion is important in fast diagnosis and treatment. CONCLUSIONS: Our case demonstrates the importance of suspicion of barotrauma in patients with asthma attacks not responding adequately to therapy or developing worsening hypoxia which can be detrimental. Reference #1: Franco, A. I., Arponen, S., Hermoso, F., & García, M. J. (2019). Subcutaneous emphysema, pneumothorax and pneumomediastinum as a complication of an asthma attack. The Indian journal of radiology & imaging, 29(1), 77–80. https://doi.org/10.4103/ijri.IJRI_340_18 Reference #2: Zeynep Karakaya, Şerafettin Demir, Sönmez Serkan Sagay, Olcay Karakaya, Serife Özdinç, "Bilateral Spontaneous Pneumothorax, Pneumomediastinum, and Subcutaneous Emphysema: Rare and Fatal Complications of Asthma", Case Reports in Emergency Medicine, vol. 2012, Article ID 242579, 3 pages, 2012.https://doi.org/10.1155/2012/242579 Reference #3: Subcutaneous Emphysema in Acute Asthma: A Cause for Concern? Patrick D Mitchell, Thomas J King, Donal B O'Shea Respiratory Care Aug 2015, 60 (8) e141-e143;DOI: 10.4187/respcare.03750 DISCLOSURES: No relevant relationships by Juan Adams-Chahin No relevant relationships by Gretchen Marrero No relevant relationships by natalia Mestres No relevant relationships by Are is Morales Malavé No relevant relationships by Carlos Sifre No relevant relationships by Paloma Velasco No relevant relationships by Mark Vergara-Gomez

Evolution of Therapeutic Drug Monitoring requests in a tertiary University Hospital in the last 16 years

Introduction: TDM has been widely used in clinical practice for many years and has application in various groups of drugs,mainly in drugs with pharmacokinetic variability, concentration related therapeutic and adverse effects, narrow therapeutic index, defined therapeutic concentration range and desired therapeutic effect difficult to monitor. Objectives: The aim of this study is to assess the evolution of TDM application throughout the years and its usefulness and necessity nowadays in a tertiary University Hospital. Methods: Data of Therapeutic Drug Monitoring requests were collected for the years 2005, 2010, 2015, 2019, 2020 and 2021 from the records of the Laboratory of Pharmacology General University Hospital of Alexandroupolis. Drugs monitored included digoxin, valproic acid, carbamazepine, phenytoin, phenobarbital, cyclosporine, tacrolimus, amikacin, gentamycin, vancomycin, serum benzodiazepines, methotrexate, cortisol, acetaminophen, salicylate, theophylline, tobramycin and primidone. More specifically, the data collected were the drug's level measurement and the clinic that requested the specific drug order. Results: A total of 1357 drug level measurement records were found for 2005, 1442 for 2010, 766 for 2015, 520 for 2019, 442 for 2020 and 622 for 2021. During these years the most frequent drug requested for TDM was digoxin (2005), cyclosporine (2010, 2019), valproic acid (2015, 2020), and tacrolimus (2021). In regards to the drugs requested, digoxin was predominantly requested by Cardiology and Pathology, cyclosporine and tacrolimus by Nephrology and valproic acid by Psychiatry. Furthermore, the percentage of non optimal therapeutic levels that required dose adjustments were calculated and will be presented. Conclusion: TDM retains a degree of its value as shown by the number of incidents requiring dose modifications. In addition, the presented results obtained from 2005 to 2021 show that there is a notable decrease in the number of requests for TDM per year. This can be imputed to several reasons such as the replacement of specific drugs with new therapeutic regimens and the evolution of therapeutic drug protocols in several diseases. Another major factor was the measures taken against the Covid-19 pandemic in the last two years which resulted to a substantial decrease of routine health examinations and scheduled appointments in the Hospital.

A CASE REPORT ON COVID- 19: REVIEW OF MEDICATIONS

Rationale: COVID-19 is also known as Novel coronavirus 2019 or acute respiratory syndrome caused due to coronavirus or SARS-CoV-2 is an RNA virus belongs to β- Coronaviridae family.COVID also causes severe pneumonia and acute respiratory distress syndrome (ARDS), which can result in difficulty breathing and necessitate mechanical ventilation and intensive care unit management. Patient concerns: A 47-yearmale with a history of hypertension who was presented to hospital with worsening fevers, cough, and respiratory distress. Diagnosis: CT scan of the chest showed multiple subsegmental patchy ill, defined broncho centric and sub-pleural areas of ground glass opacities with septal thickening are seen in both the lungs and test of COVID also turned positive. Interventions: He was being treated aggressively in the intensive care unit with intravenous Prednisolone, Felbinac, Piperacillin/tazobactam.He also received a loading dose of remdesivir however was unable to complete the course due to sudden droppage of SP02. Outcomes: He remained critically ill and eventually passed away. Lessons: COVID-19 has become a global pandemic and a major hit to our healthcare systems, with a rapidly rising death rate. There is currently no approved treatment regimen for COVID-19 infections. The alarming increase in cases per day keeps researchers busy to find a cure and to reduce the global mortality rate.

Role of etophylline and theophylline prolonged release tablet in COVID-19 associated sinus node dysfunction

During COVID-19 pandemic, one of the most common arrythmia reported with this illness is sinus bradycardia. Treatment for COVID-19 and associated cardiac dysfunction is still evolving. Temporary pacemaker insertion is difficult due to pandemic and risk of spread of infection to the additional staff involved. Orciprenaline stimulates the sino-atrial and atrioventricular nodes and accelerates atrioventricular conduction. Theophylline improves sinus node function in subjects with sinus bradycardia and enhances atrioventricular nodal conduction We report a case series of 10 patients admitted in dedicated COVID-19 ICUs and developed sinus node dysfunction. All of these patients were started on etophylline and theophylline prolonged release tablet (150 mg) once a day. On subsequent follow up after 72 hours, all patients reported heart rate well within normal range. COVID-19 virus directly involves the myocardium by entering the cardiac myocytes resulting in inflammation and injury. As the sinus bradycardia due to COVID-19 is usually transient and respond well this drug, short course of this drug could be added to treat this arrythmia in future.

Theophylline: Old Drug in a New Light, Application in COVID-19 through Computational Studies.

Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged the development of effective pharmacological treatments to directly attack the development of new variants of the SARS-CoV-2 virus and possess a therapeutical battery of compounds that could improve the current management of the disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, and potentially antiviral mechanisms, is an interesting proposal as an adjuvant in the treatment of COVID-19 patients. Nevertheless, it is essential to understand how this compound could behave against such a disease, not only at a pharmacodynamic but also at a pharmacokinetic level. In this sense, the quickest approach in drug discovery is through different computational methods, either from network pharmacology or from quantitative systems pharmacology approaches. In the present review, we explore the possibility of using theophylline in the treatment of COVID-19 patients since it seems to be a relevant candidate by aiming at several immunological targets involved in the pathophysiology of the disease. Theophylline down-regulates the inflammatory processes activated by SARS-CoV-2 through various mechanisms, and herein, they are discussed by reviewing computational simulation studies and their different applications and effects.

Infection Prevention during Use of a Warm Zone Model in Cohort Patient Care Locations during the COVID-19 Pandemic

Background. The COVID-19 pandemic required hospitals to care for influxes of patients in cohort locations during critical shortages of personal protective equipment (PPE). Safety zones can be used to protect healthcare workers caring for patients with infectious pathogens. During the COVID-19 pandemic, our hospital developed a Warm Zone model (WZM) to streamline the care of patients with COVID. We established specific areas in our COVID cohort units where staff were permitted to bridge between rooms without doffing gowns, but still doffing gloves and performing hand hygiene between patients. We recognized that a WZM could inadvertently increase risk of nosocomial transmission of pathogens if gowns acted as fomites. For this reason, patients with known infectious pathogens were excluded from the WZM. To measure for unintended harmful consequences of the WZM, our Infection Prevention (IP) department performed surveillance for hospital onset (HO) Clostridioides difficile (CDI), Carbapenemresistant enterobacteriaceae (CRE) and Methicillin-resistant Staphyloccocus aureus (MRSA) bloodstream infections on units that implemented the WZM. Methods. Two intensive care units and 3 wards where COVID positive patients were cohorted were included in surveillance. The timeframe for this analysis was 7/1/2020 - 3/31/2021. An electronic surveillance system was used to measure HO infections. The National Healthcare Surveillance Network (NHSN) LabID definitions were used when determining HO CDI and MRSA bloodstream infections (BSI). Results. During the study period, there were no HO CRE, 1 HO CDI, and 2 HO MRSA BSI in cohort units. There was no evidence to suggest that the HO CDI or HO MRSA BSI were associated with use of a WZM. During this time period, there were 14 cases of community onset (CO) CDI, 2 cases of CO MRSA BSI, and one CO CRE. Conclusion. During use of a WZM in COVID cohort units, IP did not identify significant increase in HO CDI, CRE, or MRSA BSI compared to non-cohort units. We were limited in our ability to measure acquisition of pathogens because active surveillance screening for colonization was not performed. However, we were able to safely employ a WZM to streamline patient care in COVID cohort areas without evidence of causing nosocomial infections via patient-to-patient transmission.

Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction.

OBJECTIVE: To evaluate the efficacy and safety of intranasal theophylline saline irrigation on olfactory recovery in patients with post-viral olfactory dysfunction (PVOD). METHODS: Between May 2019 and April 2020, we conducted a double-blinded, placebo-controlled randomized clinical trial of adults with 6-36 months of PVOD. Patients were randomized to nasal theophylline saline irrigation or placebo saline irrigation twice a day for 6 weeks. The primary outcome was the Global Rating of Smell Change. Secondary outcomes were changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). RESULTS: Twenty-two patients (n = 12, theophylline; n = 10, placebo) completed the study. Slightly more patients in the theophylline group (33%) reported improved smell compared to the placebo group (30%, difference 3.3%, 95% CI -35.6% to 42.3%). The median differences in pre- and post-treatment UPSIT and QOD-NS change between the two groups were 1 (95% CI -3 to 5) and -10 (95% CI -15 to -4), respectively in favor of theophylline. Three patients receiving theophylline and 2 receiving placebo had clinically meaningful improvements on the UPSIT (difference 5%, 95% CI -30% to 40%). There were no adverse events, and serum theophylline levels were undetectable in 10/10 patients. CONCLUSIONS: While safe, there were no clinically meaningful differences in olfactory change between the two groups except for olfaction-related quality of life, which was better with theophylline. The imprecise estimates suggest future trials will need substantially larger sample sizes or treatment modifications, such as increasing the theophylline dose, to observe larger treatment effects.

Theophylline in Treatment of COVID-19 Induced Sinus Bradycardia.

This is a retrospective case series of two patients with laboratory-confirmed coronavirus 2 (SARS-CoV-2) infection, presented to the University of Arkansas for Medical Sciences in January 2021. Medical records of these patients were reviewed using the EPIC electronic health record system. Clinical, laboratory, and treatment data were reviewed against periods of bradycardia in each patient. Both of the patients presented with dizziness and presyncope related to sinus bradycardia in which they received treatment with 1 mg of IV atropine and theophylline 200 mg orally. We share these two cases of theophylline treatment in COVID-19 induced sinus bradycardia. The first patient was a 39-year-old female, with a past medical history of polycystic ovarian syndrome, who presented to the emergency department with lightheadedness and dizziness. Two weeks prior to her presentation, she was tested positive for COVID-19 infection that was treated with azithromycin, dexamethasone and aspirin. Upon presentation, her ECG showed sinus bradycardia at a rate of 48 bpm. The second patient, a 21-year-old female with no significant past medical history, presented with presyncope. Three weeks prior to her presentation, she tested positive for COVID-19 infection that was treated symptomatically at her home. Upon presentation, her ECG showed junctional rhythm at a heart rate of 51 bpm.

Pentoxifylline or theophylline use in hospitalized COVID-19 patients requiring oxygen support.

INTRODUCTION: The phosphodiesterase inhibitors theophylline and pentoxifylline have anti-inflammatory properties that may make them useful in COVID-19 pneumonia. We conducted a retrospective review of hospitalized COVID-19 patients requiring oxygen who received these drugs. OBJECTIVES: To examine the potential efficacy and safety of theophylline and pentoxifylline in COVID-19 pneumonia patients. METHODS: Adults with a positive test for SARS-COV2 and were hospitalized due to pneumonia requiring either high flow nasal cannula or mechanical ventilation were included. Patients with a history of asthma or chronic obstructive pulmonary disease were preferentially given theophylline. All other patients received pentoxifylline 400 mg orally TID. A group of hospitalized COVID-19 patients receiving standard of care acted as a comparison group. The coprimary outcomes were a change in C-reactive protein (CRP) and ROX score between groups from day 1 to day 4 of therapy. RESULTS: Two hundred and nine inpatients were reviewed. Fifty-eight patients received pentoxifylline/theophylline, with 151 patients serving as the comparison group. Active therapy was associated with an increase in the ROX score (mean: 2.9 (95% CI: 0.6, 5.1)) and decrease in CRP (mean: -0.7 (95% CI: -4.7, 3.2). Mortality rates were theophylline/pentoxifylline 24% and comparison group had a 26%, respectively. CONCLUSION: In this retrospective study, theophylline and pentoxifylline were associated with an increase in ROX score and nominal decreases in CRP and mortality. Treatment was safe with few adverse reactions documented. We believe that this study could the basis for randomized-controlled trials to further explore these drugs' role in COVID-19.

Antiviral potential of some novel structural analogs of standard drugs repurposed for the treatment of COVID-19.

SARS-CoV-2 pandemic has claimed millions of lives across the world. As of June 2020, there is no FDA approved antiviral therapy to eradicate this dreadful virus. In this study, drug re-purposing and computational approaches were employed to identify high affinity inhibitors of SARS-CoV-2 Main protease (3CLpro), Papain-like protease (PLpro) and the receptor domain of Spike protein. Molecular docking on 40 derivatives of standard drugs (Remdesivir, Lopinavir and Theophylline) led to the identification of R10, R2 and L9 as potential inhibitors of 3CLpro, PLpro and Spike protein, respectively. The binding affinity of R10, R2 and L9 towards 3CLpro, PLpro and Spike protein were 4.03 × 106, 3.72 × 104 and 1.31 × 104M-1, respectively. These inhibitors interact with the active site or catalytic amino acid residues of 3CLpro, PLpro and Spike protein. We also examined the stability and dynamic behavior of protein-inhibitor complex by employing molecular dynamics simulation. RMSDs, RMSFs and variation in secondary structure of target proteins alone or in complex with their respective inhibitors were used to ascertain the integrity of proteins' structure during simulation. Moreover, physicochemical and ADMET properties of R10, R2 and L9 along with Remdesivir, Lopinavir and Theophylline were determined. In vitro and In vivo studies are needed to further validate the potential of these derivatives before they can be developed into potential drug molecules.Communicated by Ramaswamy H. Sarma.