Real world experience of drug-drug interactions for HCV patients receiving pan-genotypic direct-acting antivirals in the era of COVID-19 pandemic

Background and Aims: The treatment of chronic hepatitis C (CHC) has evolved from genotype-specific to pan-genotypic direct acting antivirals (DAAs) with high efficacy and safety. However, drug-drug interactions (DDIs) must be avoided when used in combination with other medications, especially with the possible concomitant use of COVID-19 infection antivirals during the COVID-19 pandemic. This study aimed to access the potential DDIs of concomitant drugs with pan-genotypic DAAs and COVID-19 infection antivirals, and actual incidence of DDIs in real-world experience. Method(s): From January 2022 to October 2022, consecutive 116 HCV patients receiving pan-genotypic DAAs were retrospectively enrolled in Taipei Veterans General Hospital. The number of comedications and their potential DDIs with three pan-genotypic DAA regimens and three COVID-19 infection antivirals were analyzed. The actual incidence of DDIs during DAAs treatment were also investigated. Result(s): The mean age was 60.9 years old, with male predominant (55.2%). Of them, 12 (10.3%) patients had cirrhosis, and 24 (20.7%) patients had diabetes mellitus. Most patients were within Child-Pugh class A (109/116, 94.0%). The distribution of HCV genotypes was 8.6% in GT 1a, 36.2% in GT 1b, 39.7% in GT 2, 6.9% in GT 6, and 8.6% in indeterminate genotype, respectively. Of them, 43 (37.1%) patients received GLE/PIB, 69 (59.5%) received SOF/VEL 7plusmn;RBV, and 4 (3.4%) received SOF/VEL/VOX as DAAs regimen. Noteworthy, four patients had COVID-19 infection during DAAs treatment course. The rates of ETVR and SVR12 were 97.6% and 95.3%. The mean number of concomitant medications was 2.01. The distribution of concomitant drugs was 64.7% with no concomitant drug, 11.2% with 1-3 drugs, 11.2% with 4-6 drugs, 9.5% with 7-9 drugs, and 3.4% had more than 9 drugs, respectively. In potential contraindicated (red) DDI class, GLE/PIB was the most prevalent (7.3%), followed by SOF/VEL/VOX (6.4%), and SOF/VEL (1.8%) for non-cirrhosis and compensated cirrhosis patients;and no red DDI occurred in decompensated cirrhosis patients. In addition, the percentage of patients without potential DDIs was higher with SOF/VEL (79.8%) than with the other regimens. The potential red DDIs were predominantly with lipid-lowering agents for DAAs. For potential red DDI class with COVID-19 infection antivirals, Nirmatrelvir/Ritonavir was the most prevalent (6%), followed by Remdesivir (0.9%), and no potential DDIs with Molnupiravir. For COVID-19 antivirals, the potential red DDIs was mainly with central nervous system drugs. Finally, the actual incidence of DDIs during DAAs treatment showed no red DDI occurred for all patients, and GLE/PIB was the most prevalent (93%) of no potential DDIs. Conclusion(s): The potential DDIs between these comedications differed, with the most potential DDIs occurring with GLE/PIB and Nirmatrelvir/Ritonavir. After careful assessment of comedications and their potential DDIs, the actual incidence of DDIs could be reduced, and optimize safety in real-world practice.

Evaluation of clinical outcomes of COVID-19 in patients taking remdesivir in complex therapy in routine clinical practice

Remdesivir (GS-5734) is a new direct-acting antiviral drug in the nucleotide analogue class with antiviral activity against SARS-CoV-2 and the ability to inhibit RNA-dependent RNA polymerase. Preliminary results from phase III randomized clinical trials of remdesivir are inconsistent. Understanding the fact of the limited world experience with the use of remdesivir in COVID-19 required further study of its efficacy and safety in real clinical practice. The aim of the study is to evaluate the efficacy and safety of remdesivir in the treatment of patients with COVID-19. Material and methods. The study included 1422 patients with a novel coronavirus infection (COVID-19) who received remdesivir as part of complex therapy in a hospital setting at medical organizations of the Moscow public health system. Additionally, standard therapy was carried out, regulated by the Interim Guidelines "Prevention, Diagnosis and Treatment of Novel Coronavirus Infection (COVID-19)" of the Ministry of Healthcare of the Russian Federation, the current version. The efficacy of the drug was assessed based on primary and secondary efficacy points. Primary variable: 1) cumulative incidence of clinical outcomes in patients with COVID-19 treated with remdesivir as part of complex therapy;2) median time to clinical improvement according to the World Health Organization ordinal categorical scale (under clinical improvement, the patient is assumed to move >2 categories towards improvement in clinical condition). Secondary variables: 1) median time to achieve <2 NEWS scores lasting at least 24 hours or hospital discharge;2) mortality from all causes;3) duration of fever (>38 degreeC), days;4) duration of hospitalization, days;5) time to achieve elimination of the pathogen from the upper respiratory tract (no SARS-CoV-2 RNA), days. The safety of remdesivir was assessed based on the registration of adverse events using the method of spontaneous reports. Results. The analysis of clinical outcomes of treatment showed that 1195 (84.1%) patients recovered, death from all causes occurred in 227 (15.9%) patients. The median improvement in clinical status on the World Health Organization ordinal categorical scale was 6 days. The median time to reach a NEWS score of <2, lasting at least 24 hours, or hospital discharge was 4 days. The median duration of fever was 3 days from the start of remdesivir administration. The median length of hospital stays for patients included in the Register was 9 days. Adverse reactions associated with the use of remdesivir were recorded in 11 (0.7%) patients. Serious adverse reactions were not registered. During hospitalization, all adverse reactions were resolved. Conclusion. A retrospective analysis of data from the Registry of 1422 patients with COVID-19 who received remdesivir as part of complex therapy in medical organizations of the state healthcare system of Moscow in routine clinical practice showed clinical efficacy and a favorable safety profile of remdesivir (Remdeform, lyophilizate for solution for intravenous administration 100 mg, manufactured by JSC Pharmasyntez, Russia). The data obtained are consistent with previous randomized clinical trials of remdesivir and allow us to recommend its further use in patients with COVID-19 as part of complex therapy.Copyright © The Author(s), 2022.

Initiating Home Parenteral Nutrition Therapy in a Patient at High Risk of Refeeding Syndrome After COVID-19 Infection

Background: An emerging finding about COVID-19 is its effect on nutrition and weight loss. The COVID-19 symptoms of fatigue, altered taste or smell, and lack of appetite are well known. But COVID-19 may have a more profound effect on clinical nutrition status. Two recent studies have identified that approximately one-third of ambulatory COVID-19 patients are at risk of experiencing weight loss >= 5% (Anker, et al;di Filippo, et al). The case study presented here discusses home start total parenteral nutrition (TPN) in a patient recently diagnosed with COVID-19 at high risk for refeeding syndrome. Method(s): N/A Results: Case Study: A 92-year-old patient was diagnosed with COVID-19 on June 8, 2022. Over the next week, she was hospitalized twice to manage symptoms of acute mental status changes, lethargy, aphasia, hypotension, and loss of appetite. The patient received nirmatrelvir/ritonavir, remdesivir, and bebtelovimab to treat COVID-19 at different times between June 9, 2022, and June 18, 2022. She remained COVID positive and continued to deteriorate clinically. On June 20, 2022, the patient began receiving 24/7 homecare, including intravenous (IV) fluids of dextrose 5% in normal saline (D5NS) 1000 mL daily for three days. She continued to experience loss of appetite and had no bowel movement for 3 days. On June 23, 2022, she was referred to this specialty infusion provider to initiate TPN therapy in the home setting. The patient's BMI was 18.2 kg/m2. Lab results revealed potassium 3.0 mmol/L, phosphate 1.6 mg/dL, and magnesium 1.6 mg/dL. High risk of refeeding syndrome was identified by the level of hypophosphatemia and hypokalemia. The specialty infusion provider's registered dietitian recommended to discontinue D5NS and begin NS with added potassium, phosphate, and magnesium. Thiamine 200mg daily was added to prevent Wernicke's encephalopathy. The patient's clinical status and lab values were monitored closely each day until her electrolyte levels stabilized (Table 1). Home TPN therapy was initiated on June 28, 2022, with <10% dextrose and 50% calorie requirement with 85% protein and 1.0 g/kg lipids. Three-day calorie count and nutrition education were performed four days post TPN initiation. Oral intake met only 25% of estimated needs. Over several days, theTPN formula was gradually increased to goal calories and the infusion cycle was slowly decreased. The following week, the patient's oral intake improved to 60%-75% of estimated needs. Her constipation resolved, and she showed improvement in functional status and mobility. Her appetite drastically improved when the TPN was cycled. Another three-day calorie count was performed when TPN calories reached goals. Oral intake demonstrated 100% estimated calorie and protein needs. TPN therapy was ultimately discontinued on July 14, 2022. As of September 30, 2022, the patient has stabilized at her pre-COVID weight of 45 kg with full recovery of appetite, function, and cognition. Discussion(s): The ASPEN Consensus Recommendations for Refeeding Syndrome (da Silva, et al) describe the repletion of electrolyte levels before introducing calories to prevent end-organ damage associated with refeeding syndrome (respiratory muscle dysfunction, decreased cardiac contractility, cardiac arrhythmias, and encephalopathy). Conclusion(s): This case study highlights the successful initiation of home TPN therapy in a patient at high risk of refeeding syndrome post COVID-19 infection. Although home start TPN and the risk of refeeding syndrome are not new concepts, they must be considered in the setting of COVID-19. Given the effects COVID-19 has on taste, smell, and appetite and the recent finding that one-third of patients with COVID infection may experience weight loss of >= 5%, nutrition support and patient education are vital components of overall patient care. (Figure Presented).

Clinical Effectiveness and Adverse Events of Adjunctive Remdesivir Administration Vs Standard of Care in Adults with Severe and Critical Covid-19

Intro: The unavailability of specific treatment for COVID-19 prompted the empirical use of remdesivir, a viral RNA polymerase inhibitor. Since evidences present conflicting results, this study aims to determine the clinical effectiveness and adverse events of adjunctive remdesivir administration vs standard of care (non-remdesivir) in COVID-19 adult patients in a tertiary hospital in Baguio City, Philippines. Method(s): We performed a single-center, retrospective study of severe to critical COVID-19 patients admitted from September 2020 to September 2021. Stratified random sampling was employed and data collection was through chart review. Analysis was done with R Statistical Software version 4, utilizing paired T-test and McNemar test, with p-value of <0.05 considered as significant. Finding(s): A total of 318 patients were reviewed and classified into the remdesivir (n=159) and standard of care (non-remdesivir) (n=159) groups. Baseline characteristics were comparable except for co-morbidities (p<0.05). There were no noted significant differences between both groups in terms of morality (p=0.885) and reduction in chest radiograph infiltrates (p=0.182). However, the average number of days to clinical improvement (7 days vs 12 days) and recovery (16 days vs 21 days) were statistically lesser in the remdesivir group (p=0.00). Also, those who experienced diarrhea (p=0.33) and transaminitis (p=0.003) were significantly higher in those given remdesivir. Conclusion(s): There was no significant difference in terms of mortality in those given remdesivir vs standard of care alone. Nevertheless, remdesivir administration is associated with significantly faster time to clinical improvement and recovery. The drug is thought to facilitate faster lung viral load clearance and improved pulmonary function through inhibition of RNA polymerase. Though not potentially life-threatening, the drug may cause diarrhea and elevation in transaminases.Copyright © 2023

Updates in Nephrology for the Hospitalist

This chapter gives a broad overview of nephrology as it affects hospitalists while also hoping to answer a few of the essential questions hospitalists may ask their nephrology colleagues. Evaluation and treatment of both acute and chronic kidney disease is constantly evolving as the small but tight-knit community of hospital-nephrologists continue to collect, review, and research data. The majority of the chapter will be focused on discussing a few new updates in the field of nephrology and how these updates could potentially change hospital care. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Pre-existing chronic liver disease is associated with poor outcome in patients with SARS-CoV2 infection

COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Cirrhosis is characterized by immune dysregulation, leading to concerns that these patients may be at increased risk of complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-sixfold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. An international European registry study included 756 patients with chronic liver disease from 29 countries reports high mortality in patients with cirrhosis (32%). Data of 228 patients collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19 (APCOLIS study) showed that SARSCoV- 2 infection produces acute liver injury in 43% of CLD patients without cirrhosis. Additionally, 20% of compensated cirrhosis patients develop either ACLF or acute decompensation. In decompensated cirrhotics, the liver injury was progressive in 57% of patients, with 43% mortality. Patients with CLD and associated diabetes and obesity had a worse outcome. Liver related complications were seen in nearly half of the decompensated cirrhotics, which were of greater severity and with higher mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. In a subsequent study of 532 patients from 17 Asian countries was obtained with 121 cases of cirrhosis. An APCOLIS risk score was developed, which included presence of comorbidity, low platelet count, AKI, HE and respiratory failure predicts poor outcome and an APCOLIS score of 34 gave a sensitivity and specificity of 79.3%, PPV of 54.8% and NPV of 92.4% and predicted higher mortality (54.8% vs 7.6%, OR = 14.3 [95 CI 5.3-41.2], p<0.001) in cirrhosis patients with Covid-19. The APCOLIS score is helpful in triaging and prognostication of cirrhotics with Coivd-19. The impact of COVID-19 on patients with cirrhosis due to non-alcoholic fatty liver disease (NASH-CLD) was separately studied in 177 NASH-CLD patients. Obese patients with diabetes and hypertension had a higher prevalence of symptomatic COVID. Presence of diabetes [HR 2.27], fraility [HR 2.68], leucocyte counts [HR 1.69] and COVID-19 were independent predictors of worsening liver functions in patients with NASH-CLD. Severity of Covid in Cirrhosis could also be assessed by measuring ICAM1 the Intercellular Adhesion Molecule, an indicator of Endothelial Injury Marker. in Cirrhosis with Covid 19 Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir are found to be safe in limited studies in a patient with cirrhosis and COVID-19. And is safe in cirrhosis patients. However, flare of AIH has been reported in AIH patients. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic cause severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.

Clinical Approaches to the COVID-19 Pandemic

SARS-CoV-2 is a highly contagious virus that can affect almost any system in the body. New developments in understanding its transmissibility, management, and sequelae are unfolding almost daily. However, no medical publication in 2021 would be complete without a snapshot of the current status of this pandemic. The virus continues to mutate to more contagious, and therefore more dangerous, strains. The best path forward through this pandemic is vaccination against SARS-CoV-2 for all those who are eligible. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Outcomes of COVID-19 in children with cancer - Report from the Indian Pediatric Oncology Group (InPOG) COVID-19 registry in India

Introduction: The clinical outcomes of COVID-19 infection in children with cancer have been variable worldwide. Therefore, we aimed to collect data from all regions in India through a national collaborative study and identify factors that cause mortality directly related to COVID-19 infection. Method(s): Data was collected prospectively on children across India on cancer therapy and diagnosed with COVID-19 infections from 47 centers from April 2020 to October 2021. Information was recorded on the demographics, the number of children that required intervention, and the outcome of the infection. In addition, we analyzed the impact of the delta variant in 2021. Result(s): A total of 659 children were studied, of whom 64% were male and 36% were female. The data from the eastern region was sparse, and this was a collection bias. COVID-19 infection was predominantly seen in children less than five years. The delta variant had a higher impact in the southern region, and this was statistically significant. Of the 659 children, 30 children died (4.5%), however only 7 of the deaths were directly attributed to COVID-19 infection (1%). Conclusion(s): The study reports the largest nationally representative cohort of children with cancer and COVID-19 to date in India. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Complete characterization of the cohort has provided further insights into the effects of COVID-19 on cancer outcomes. The low mortality allows us to recommend that specific cancer treatments be continued without delays in therapy.Copyright © 2022

A free-standing children's hospital helps a post-partum woman needing VV-ECMO during COVID-19 Pandemic when ECMO resources were limited

Our case is a 21 y/o pregnant female, 26weeks gestation who presented to OB triage with COVID-19. She was admitted to OB/GYN unit in acute hypoxic respiratory failure and started on steroids and remdesivir. On hospital day 6, she underwent an emergent c-section for fetal distress due to increasing hypoxia and severe ARDS. As her arterial blood gas being ph 7.17/81/40/29.6/-0.4, lactate 6.8nmol/L with escalating vasoactive medication and ventilator settings;ECMO was decided. However, all adult ECMO resources were limited, even within other adult facilities in Central Florida. Through multidisciplinary discussions amongst OB/GYN, adult ICU, and our pediatric ECMO activation team, it was decided to transfer the patient to our free-standing pediatric hospital. The patient was successfully transferred and cannulated for VV-ECMO. Total ECMO run was 413 hours. On ECMO day #12 patient underwent a tracheostomy. On ECMO day # 17, patient developed headaches and seizure activity in which CT revealed a subdural hemorrhage. She was taken off ECMO and underwent an emergent decompressive craniectomy with hematoma evacuation by our pediatric neurosurgical team. Once stable enough, she was discharged post ECMO day #15 (PICU day #32) to rehabilitation center. Two weeks later she had her bone flap replaced, trach removed, and she walked out of our unit home. This case exudes two key points for discussion. The first point of understanding ECMO physiology allows a team to treat many different patient populations. Although this patient was unusual to our pediatric bedside providers being post-partum, our team knew we could help. The second key point is excellent multidisciplinary teamwork and that communication is essential. At Orlando Health Arnold Palmer Hospital, our ECMO activation team consists of surgeons, pediatric intensivists, CT surgeons, perfusionists, nursing, and administration. We meet virtually to discuss how to execute initiation and daily ECMO treatment plans. There were some on the virtual call that were hesitant in accepting care of this adult due to variety of reasons, saying no would have been the easier answer, but not the right thing to do. What we learned from this case may seem so obvious and simple but very difficult to execute;multidisciplinary teamwork, humility, and open communication gave this patient the ability to walk out of the hospital with her baby. Other pediatric ECMO teams can learn from this case is they too can help in extraordinary times such as during a pandemic when adult recourses are limited.

Is Remdesivir-Induced Symptomatic Bradycardia Persistent? A Two Case Report of COVID-19 Infection

As of May 2022, a total of over 528 million cases of coronavirus 19 disease (COVID-19) worldwide with over 6 million deaths. Remdesivir is a broad-spectrum antiviral medication approved worldwide;it acts by inhibiting the RNA-dependent RNA polymerase, used for moderate-to-severe COVID-19 which requires supplemental oxygen but not intubation. Not shown to improve mortality but shorten the recovery time, especially if given within the first 10 days of symptom initiation. Despite its worldwide use, its cardiovascular safety profile has not been determined as yet. Herein, we report two cases of COVID-19 infection who develop symptomatic bradycardia on a 5-day course of remdesivir.Copyright © 2022 Annals of Clinical Cardiology Published by Wolters Kluwer - Medknow.

Clinical features and acute management in adults

COVID-19 is a multisystem disease that requires holistic management. Most patients will experience mild symptoms including cough, fever and mild dyspnoea. A small proportion of patients will have severe manifestations including respiratory failure, ARDS and multiorgan failure. Extrapulmonary features are common and include gastrointestinal, thromboembolic, neurological, cardiac, renal, endocrine and dermatological manifestations. The care of COVID-19 patients requires close attention to these features. This includes respiratory support (such as supplemental oxygen, NIV and awake proning);fluid, electrolyte and nutrition management;prevention, detection and treatment of thrombotic events;management of diabetic complications;review of medications;appropriate use of antibiotics;and evidence-based use of therapeutic agents such as corticosteroids, antivirals such as remdesivir and other emerging therapies such as immunomodulating agents. Early planning for treatment escalation and decision making around the appropriateness of cardiopulmonary resuscitation are crucial as deterioration can be rapid. Prolonged symptoms occur in a minority of patients and longitudinal follow-up is required.Copyright © ERS 2021.

Liver injury caused by SARS-CoV-2 delta and omicron-variant in Taiwan

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has recently emerged and spread globally. An outbreak of coronavirus disease 2019 (COVID-19) caused by the Delta variant occurred in Southern Taiwan in June 2021 and has been eliminated [1]. However, in April 2022, there was an outbreak of the Omicron variant in Taiwan. Fifteen patients with Omicron variant were admitted to our hospital from April 26 to May 1, 2022. We compared the clinical characteristics of the patients with the Delta variant in June 2021 and the Omicron variant in April 2022 (Table 1). These laboratory data were the first laboratory data at admission, and no anti-COVID-19 therapy was prescribed before these data. There were no differences in age (59.9 vs. 57.1 years, P = 0.96), male gender (63.6 vs. 60.0%, P = 1.00), diabetes ratio (27.3 vs. 35.7%, P = 1.00), body mass index (25.0 vs. 26.0 kg/m2, P = 1.00), pneumonia ratio (18.2 vs. 40.0%, P = 0.40) between the Delta and Omicron variants. There were also no differences in serum levels of aspartate aminotransferase (AST) (40.1 vs. 25.8 IU/L, P = 0.24) and alanine aminotransferase (ALT) (26.3 vs. 27.2 IU/L, P = 0.64) between the two groups. All the patients with the Omicron variant were symptomatic. The most common symptoms were upper respiratory tract infections (60.0%) (Supplementary Table 1). Six patients developed pneumonia without mechanical ventilator support requirement during admission (40.0%). Remdesivir, Paxlovid, or Molnupiravir were prescribed to patients according to their clinical conditions. Among the patients with the Omicron variant, nine (60.0%) had past medical history of diabetes, four (26.7%) had hypertension, three had chronic kidney disease (20.0%), and three had malignancy history (20.0%). COVID-19 might cause liver injury and lead to a more unfavorable prognosis [2]. In this study, about one-fifth of the patients suffered from liver injury, which was similar to previous studies [3]. There was no difference in liver injury between the Delta and Omicron variants in our study, which echoes previous research [4]. COVID-19 vaccination might protect against symptomatic diseases caused by the Omicron variant [5]. Vaccination rates have increased since 2021. In the study, over ninety percent of the patients have received at least two doses of vaccination. In conclusion, we demonstrated no difference in liver injury ratio between the Delta and Omicron variants. To our knowledge, this is the first report that compares the Delta and Omicron variants in Taiwan.

High mortality among patients with severe COVID-19 and Do Not Intubate orders

INTRODUCTION. Moderate to severe respiratory distress among patients with COVID-19 is associated with a high mortality. This study evaluated ventilator support and mortality by Do Intubate (DI) or Do Not Intubate (DNI) orders. METHODS. This was a retrospective study of patients with COVID-19 and a supplemental oxygen requirement of 15 l/min. The patients were divided into two groups corresponding to the first and second wave of COVID-19 and were subsequently further divided according to DI and DNI orders and analysed regarding need of ventilator support and mortality. RESULTS. The study included 178 patients. The mortality was 24% for patients with DI orders (n = 115) and 81% for patients with DNI orders (n = 63) increasing to 98% (n = 46) for patients with DNI orders and very high flow oxygen requirements ( 30 l/min.). From the first to the second wave of COVID-19, the use of constant continuous positive airway pressure (cCPAP) increased from 71% to 91% (p < 0.001), whereas the use of mechanical ventilation decreased from 54% to 28% (odds ratio = 0.38 (95% confidence interval: 0.17-0.85)). CONCLUSION. The mortality was high for patients with DNI orders and respiratory distress with very high levels in supplemental oxygen in both the first and second wave of COVID-19 despite an increase in use of cCPAP and treatment with dexamethasone and remdesivir during the second wave. Hence, careful evaluation on transition to palliative care must be considered for these patients.

Case of acute vision loss after injectable remdesivir with anticoagulants and overdose of antibiotics: A late report.

A woman reported decreased vision in the right eye since hospitalization for COVID-19. Vision in the right eye was 6/18 and in the left eye was counting fingers. Her left eye had cataract and right eye was pseudophakic with earlier documented good recovery. In the right eye, she had branch retinal vein occlusion (BRVO) with macular edema documented on optical coherence tomography (OCT). It was suspected that it might be an ocular manifestation of COVID-19 which had not been reported and had worsened. An overdose of antibiotics or remdesivir might also be responsible for the same. She was advised anti-VEGF injections and was kept under treatment.

Triple combination therapy with two antivirals and monoclonal antibodies for persistent or relapsed SARS-CoV-2 infection in immunocompromised patients.

INTRODUCTION: Severely immunocompromised patients are at risk for prolonged or relapsed COVID-19 leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients. METHODS: We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with two antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (Mabs), between February and October 2022. The main outcomes were virological response at day 14 (negative SARS-CoV-2 swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up. RESULTS: Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of two antivirals and Mabs and 4 received two antivirals only; in 20/22 (91%) two antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received second course of combination treatment. Response rate at day 14, 30 and last follow-up was, respectively, 75% (15/20 evaluable), 73% (16/22) and 82% (18/22). Day 14 and 30 response rates were significantly higher when combination therapy included Mabs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects: bradycardia leading to remdesivir discontinuation and myocardial infarction. CONCLUSION: Combination therapy including two antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and Mabs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

COVID-19: A review of therapeutics under investigation.

The COVID-19 outbreak has disrupted global health care networks and caused thousands of deaths and an international economic downturn. Multiple drugs are being used on patients with COVID-19 based on theoretical and in vitro therapeutic targets. Several of these therapies have been studied, but many have limited evidence behind their use, and clinical trials to evaluate their efficacy are either ongoing or have not yet begun. This review summarizes the existing evidence for medications currently under investigation for treatment of COVID-19, including remdesivir, chloroquine/hydroxychlorquine, convalescent plasma, lopinavir/ritonavir, IL-6 inhibitors, corticosteroids, and angiotensin-converting enzyme inhibitors.