The first five years of SARS-CoV-2: inpatient treatment updates and future directions.

Introduction: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in adults with pneumonia in Wuhan, China.

Areas Covered: It is now believed that several billion humans have been infected with SARS-CoV-2 and more than ten million have died from coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2.

Expert Opinion: The first five years of the SARS-CoV-2 pandemic have been marked by unfathomable suffering as well as remarkable scientific progress.

Single Intravenous Dose Dalbavancin Pathway for the Treatment of Acute Bacterial Skin and Skin Structure Infections: Considerations for Emergency Department Implementation and Cost Savings.

Background: A pathway for the treatment of acute bacterial skin and skin structure infections (ABSSSI) with a single intravenous (IV) dose of dalbavancin was previously shown to reduce hospital admissions and shorten inpatient length of stay (LOS).

Objectives: To describe pathway implementation at the emergency department (ED) and evaluate cost-effectiveness of a single-dose dalbavancin administered to ED patients who would otherwise be hospitalized to receive usual care with multidose IV antibiotics.

Methods: The dalbavancin pathway was previously implemented at 11 U.

Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial.

Importance: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

Objective: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

Design, Setting, And Participants: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021.

Simnotrelvir as a potential treatment for COVID-19.

Introduction: Simnotrelvir is a selective 3-chymotrypsin-like oral protease inhibitor with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Areas Covered: On 18 January 2024, results of a double-blind, randomized, placebo-controlled trial of simnotrelvir as a treatment for mild-to moderate COVID-19-were published, indicating the drug, when given in combination with ritonavir, shortened the time to resolution of symptoms.

Expert Opinion: Treatment options for most outpatients with mild-to-moderate COVID-19 are limited.

Intravenous immunoglobulin as a potential treatment for long COVID.

Introduction: On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United States National Institutes of Health (NIH) opened enrollment for the therapeutic arm of the RECOVER initiative, a prospective, randomized study to evaluate new treatment options for long coronavirus disease 2019 (long COVID).

Areas Covered: One of the first drugs to be studied in this nationwide initiative is intravenous immunoglobulin (IVIG), which will be a treatment option for subjects enrolled in RECOVER-AUTO, a randomized trial to investigate therapeutic strategies for autonomic dysfunction related to long COVID.

Expert Opinion: IVIG is a mixture of human antibodies (human immunoglobulin) that has been widely used to treat a variety of diseases, including immune thrombocytopenia purpura, Kawasaki disease, chronic inflammatory demyelinating polyneuropathy, and certain infections such as influenza, human immunodeficiency virus, and measles.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.

Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.

Design, Setting, And Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19.

Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19.

Background: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear.

Methods: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 μg once daily for 14 days or placebo.

Paxlovid as a potential treatment for long COVID.

Introduction: On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United States National Institutes of Health opened enrollment for RECOVER-Vital, a randomized study to evaluate new treatment options for long Coronavirus (long COVID).

Areas Covered: The RECOVER Initiative is a $1.15 billion research platform intended to describe, categorize, treat, and prevent long-term symptoms following infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2), the virus that causes Coronavirus (COVID-19).

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19.

Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

Design, Setting, And Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia.

Optimizing the use of vilobelimab for the treatment of COVID-19.

Introduction: On 4 April 2023i4 April 2023, the United States Food and Drug Administration issued an emergency use authorization for the use of vilobelimab (Gohibic) for the treatment of COVID-19 in hospitalized adults when initiated within 48 hours of receiving invasive mechanical ventilation or extracorporeal membrane oxygenation.

Areas Covered: Vilobelimab is a human-mouse chimeric IgG4 kappa antibody that targets human complement component 5a, a part of the immune system that is thought to play an important role in the systemic inflammation due to SARS-CoV-2 infection that leads to COVID-19 disease progression.

Expert Opinion: A pragmatic, adaptive, randomized, multicenter phase II/III study evaluating vilobelimab for the treatment of severe COVID-19 found that patients receiving invasive mechanical ventilation and usual care who were treated with vilobelimab had a lower risk of death by day 28 and day 60 compared to those receiving placebo.

Metformin as a potential treatment for COVID-19.

Introduction: Early treatment for SARS-CoV-2 infection is essential to limit the clinical progression of COVID-19. However, limited therapeutic options are available for standard-risk patients, including those under age 50 who have received the primary series of COVID-19 vaccination as well as a bivalent booster.

Areas Covered: Metformin is a widely used, inexpensive antihyperglycemic for the treatment of diabetes mellitus type 2 as well as polycystic ovarian syndrome, with a well-described safety profile.

Interferon lambda as a potential treatment for COVID-19.

Introduction: Pegylated interferon lambda substantially reduced the risk of COVID-19-related hospitalizations or emergency room visits in a recent phase 3, multi-center, randomized, double-blind, placebo-controlled study of high-risk, non-hospitalized adult patients with SARS-CoV-2 infection compared to treatment with placebo.

Areas Covered: Interferons are a family of signaling molecules produced as part of the innate immune response to viral infections. The administration of exogenous interferon may limit disease progression in patients with COVID-19.

VV116 as a potential treatment for COVID-19.

Introduction: VV116 is a chemically-modified version of the antiviral remdesivir with oral bioavailability and potent activity against SARS-CoV-2.

Areas Covered: The optimal treatment of standard-risk outpatients who develop mild-to-moderate COVID-19 is controversial. While several therapeutic are currently recommended, including nirmatrelvir-ritonavir (Paxlovid), molnupiravir, and remdesivir, these treatments have substantial drawbacks, including drug-drug interactions and questionable efficacy in vaccinated adults.

Montelukast as a potential treatment for COVID-19.

Introduction: Montelukast is a leukotriene inhibitor that is widely used to treat chronic asthma and allergic rhinitis. The drug interferes with molecular signaling pathways produced by leukotrienes in a variety of cells and tissues throughout the human body that lead to tightening of airway muscles, production of aberrant pulmonary fluid (airway edema), and in some cases, pulmonary inflammation.

Areas Covered: Montelukast has also been noted to have anti-inflammatory properties, suggesting it may have a role in the treatment of coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been noted to induce misfiring of the immune system in some patients.

Anakinra as a potential treatment for COVID-19.

On November 8, 2022, the United States Food and Drug Administration (FDA) issued an emergency use authorization for the interleukin-1 (IL-1) inhibitor anakinra for the treatment of patients with COVID-19 pneumonia. The authorization was specifically intended for patients requiring supplemental oxygen who are at risk of progression to respiratory failure and are likely to have an elevated plasma soluble urokinase plasminogen activator receptor. Anakinra is a modified, recombinant human IL-1 receptor antagonist used to treat rheumatoid arthritis, neonatal-onset multisystem inflammatory disease and other inflammatory diseases.

Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether ivermectin, with a maximum targeted dose of 600 μg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19.

Objective: To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19.

Design, Setting, And Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19.

Meeting the Challenges of Sepsis in Severe Coronavirus Disease 2019: A Call to Arms.

Sepsis is a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis may be caused by bacterial, fungal, or viral pathogens. The clinical manifestations exhibited by patients with severe coronavirus disease 2019 (COVID-19)-related sepsis overlap with those exhibited by patients with sepsis from secondary bacterial or fungal infections and can include an altered mental status, dyspnea, reduced urine output, tachycardia, and hypotension.

Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear.

Objective: To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US.

Design, Setting, And Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19.

Effect of Ivermectin 600 μg/kg for 6 days vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial.

Background: Whether ivermectin, with a maximum targeted dose of 600 μg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) remains unknown. Our objective was to evaluate the effectiveness of ivermectin, dosed at 600 μg/kg, daily for 6 days compared with placebo for the treatment of early mild to moderate COVID-19.

Methods: ACTIV-6, an ongoing, decentralized, randomized, double-blind, placebo-controlled, platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are spp.