Remdesivir Use in the Real-World Setting: An Overview of Available Evidence.

In the years of Coronavirus Disease 2019 (COVID-19), various treatment options have been utilized. COVID-19 continues to circulate in the global population, and the evolution of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has posed significant challenges to the treatment and prevention of infection. Remdesivir (RDV), an anti-viral agent with in vitro efficacy against coronaviruses, is a potent and safe treatment as suggested by a plethora of in vitro and in vivo studies and clinical trials. Emerging real-world data have confirmed its effectiveness, and there are currently datasets evaluating its efficacy and safety against SARS-CoV-2 infections in various clinical scenarios, including some that are not in the SmPC recommendations according for COVID-19 pharmacotherapy. Remdesivir increases the chance of recovery, reduces progression to severe disease, lowers mortality rates, and exhibits beneficial post-hospitalization outcomes, especially when used early in the course of the disease. Strong evidence suggests the expansion of remdesivir use in special populations (e.g., pregnancy, immunosuppression, renal impairment, transplantation, elderly and co-medicated patients) where the benefits of treatment outweigh the risk of adverse effects. In this article, we attempt to overview the available real-world data of remdesivir pharmacotherapy. With the unpredictable course of COVID-19, we need to utilize all available knowledge to bridge the gap between clinical research and clinical practice and be sufficiently prepared for the future.

COVID-19 Pharmacotherapy in Pregnancy: A Literature Review of Current Therapeutic Choices.

The clinical management of COVID-19 in pregnant women, who are considered a vulnerable population, remains uncertain even as the pandemic subsides. SARS-CoV-2 affects pregnant individuals in multiple ways and has been associated with severe maternal morbidity and mortality, as well as neonatal complications. The unique anatomy and physiology of gestation make managing COVID-19 in this population a complex and challenging task, emphasizing the importance of spreading knowledge and expertise in this area. Therapeutic interventions require distinct clinical consideration, taking into account differences in pharmacokinetics, vertical transmission, drug toxicities, and postnatal care. Currently, there is limited data on antiviral and immunomodulating COVID-19 pharmacotherapy in pregnancy. Some medication has been shown to be safe and well tolerated among pregnant women with COVID-19; however, the lack of randomized clinical trials and studies in this patient population is evident. Available vaccines are considered safe and effective, with no evidence of harm to the fetus, embryo development, or short-term postnatal development. Pregnant women should be counseled about the risks of SARS-CoV-2 infection and informed of available ways to protect themselves and their families. Effective treatments for COVID-19 should not be withheld from pregnant individuals, and more research is needed to ensure the best outcomes.

Commonalities Between ARDS, Pulmonary Fibrosis and COVID-19: The Potential of Autotaxin as a Therapeutic Target.

Severe COVID-19 is characterized by acute respiratory distress syndrome (ARDS)-like hyperinflammation and endothelial dysfunction, that can lead to respiratory and multi organ failure and death. Interstitial lung diseases (ILD) and pulmonary fibrosis confer an increased risk for severe disease, while a subset of COVID-19-related ARDS surviving patients will develop a fibroproliferative response that can persist post hospitalization. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling lysophospholipid with multiple effects in pulmonary and immune cells. In this review, we discuss the similarities of COVID-19, ARDS and ILDs, and suggest ATX as a possible pathologic link and a potential common therapeutic target.

Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels, Endothelial Dysfunction Biomarkers, and Impaired Functions of Dendritic Cells.

Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signaling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNA sequencing datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, which exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, suggesting that its pharmacological targeting might represent an additional therapeutic option, both during and after hospitalization.

Protracted severe COVID-19 pneumonia following rituximab treatment: caution needed.

The outcomes of COVID-19 in patients treated with biologic agents are a subject of intense investigation. Recent data indicated that patients under rituximab (RTX) may carry an increased risk of serious disease. We performed an electronic search in Medline and Scopus using the keywords rituximab and COVID-19. We present a rare case of severe, protracted COVID-19 pneumonia in a patient with mixed connective tissue disease (MCTD) who was infected a few days following RTX treatment. In a relevant literature search, we identified 18 cases of patients with rheumatic diseases (6 RA, 8 ANCA vasculitis, 3 systemic sclerosis and 1 polymyositis) treated with RTX who experienced an atypical and/or prolonged course of COVID-19 pneumonia with no evidence of cytokine storm. Our case indicates that RTX may unfavorably affect outcomes following SARS-CoV-2 infection. B cell depletion may dampen the humoral response against the virus; we may hypothesize that B cell-depleted patients may be protected from cytokine storm but on the other hand may have difficulties in virus clearance leading to a protracted course. Taking into account that COVID-19 vaccines are available we may consider delaying RTX infusions at least in patients without life threatening disease, until vaccination is completed.

Bronchoscopy during the COVID-19 pandemic: effect on current practices and strategies to reduce procedure-associated transmission.

Introduction: Bronchoscopy and related procedures have unambiguously been affected during the Corona Virus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS COV-2). Ordinary bronchoscopy practices and lung cancer services might have changed over this pandemic and for the years to come.Areas covered: This manuscript summarizes the utility of bronchoscopy in COVID-19 patients, and the impact of the pandemic in lung cancer diagnostic services, in view of possible viral spread during these We conducted a literature review of articles published in PubMed/Medline from inception to November 5th, 2020 using relevant terms.Expert opinion: Without doubt this pandemic has changed the way bronchoscopy and related procedures are being performed. Mandatory universal personal protective equipment, pre-bronchoscopy PCR tests, dedicated protective barriers and disposable bronchoscopes might be the safest and simpler way to perform even the most complicated procedures.

Increased Red Cell Distribution Width Is Associated With Disease Severity in Hospitalized Adults With SARS-CoV-2 Infection: An Observational Multicentric Study.

Background: There is an amenable need for clinically applicable biomarkers in patients with SARS-CoV-2 infection. Red Cell Distribution Width (RDW) has been recently suggested as a prognostic biomarker for COVID-19. Methods: This was an observational study enrolling patients between February 26 and May 15 2020. We aimed to validate the association of the previously published RDW threshold of 14.5% with markers of disease progression and mortality. Results: A total number of 193 hospitalized patients with COVID-19 were enrolled and analyzed. Median age was 61 years (95% CI: 58-64). Patients with baseline RDW ≥14.5% (n = 41, 19.2%) presented with more progressive disease compared to patients with baseline RDW <14.5% (n = 156, 80.8%) as indicated by significant differences in maximum FiO2% during hospitalization (median: 100, 95% CI: 45.2-100, vs. 35, 95% CI: 31-40, p = 0.0001, respectively). Values of RDW ≥14.5% were also strongly associated with increased risk of mortality (HR: 4.1, 95% CI: 0.88-19.23), (p = 0.02). Conclusion: Our study provides evidence to support reproducibility and validity of a specified cut-off threshold of RDW as biomarker of disease severity and mortality in patients with COVID-19.

False Positive COVID-19 Antibody Test in a Case of Granulomatosis With Polyangiitis.

Collateral damage due to 2019 novel coronavirus disease (COVID-19) represents an emerging issue. Symptoms of COVID-19 are not disease-specific. Differential diagnosis is challenging and the exclusion of other life-threatening diseases has major caveats. In the era of this pandemic, diagnosis of other life-threatening diseases might delay treatment. The Food and Drug Administration has recently authorized the first antibody-based test for COVID-19; however, RT-PCR of nasopharyngeal or oropharyngeal swabs remains the recommended test for diagnosis. We present the first report of a false positive COVID-19 antibody test in a case of Granulomatosis with Polyangiitis (GPA). Specifically, the case concerns an 82-year-old female, never smoker, who was admitted to our hospital with symptoms of fever and general fatigue that had lasted 7 days. She already had a positive IgM test for COVID-19, yet multiple RT-PCR tests had returned as negative for SARS-CoV-2. In the following days, her renal function deteriorated, while hematuria and proteinuria with active urinary sediment developed. Based on high clinical suspicion for ANCA-associated vasculitis, we performed a complete immunologic profile which revealed positive c-ANCA with elevated titers of anti-PR3. Pulses of methylprednisolone along with cyclophosphamide were applied. At day 10, treatment response was noticed as indicated by respiratory and renal function improvement. This report highlights the need for meticulous patient evaluation in order to avoid misdiagnosis in the era of COVID-19.