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.S. EDs (doi:10.1111/acem.14258). Patients with ABSSSI, without an unstable comorbidity or infection complication requiring complex management, were treated with a single dose of dalbavancin. At the emergency physicians' discretion, patients were either discharged and received outpatient follow-up or were hospitalized for continued management. A decision analytic cost-effectiveness model was developed from the U.S. healthcare's perspective to evaluate costs associated with the dalbavancin pathway compared with inpatient usual care. Costs (2021 USD) were modeled over a 14-day horizon and included ED visits, drug costs, inpatient stay, and physician visits. One-way and probabilistic sensitivity analyses examined input parameter uncertainty. RESULTS: Driven largely by the per diem inpatient cost and LOS for usual care, the dalbavancin pathway was associated with savings of $5133.20 per patient and $1211.57 per hospitalization day avoided, compared with inpatient usual care. The results remained robust in sensitivity and scenario analyses. CONCLUSION: The new single-dose dalbavancin ED pathway for ABSSSI treatment, which was previously implemented at 11 U.S. EDs, offers robust cost savings compared to inpatient usual care.

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design Setting and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast. Interventions: Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov ( NCT04885530 ).

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. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024. Exposure: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg). Main Outcomes and Measures: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity. Results: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P < .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P < .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P < .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure. Conclusions and Relevance: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Variable aging and storage of dissolved black carbon in the ocean.

During wildfires and fossil fuel combustion, biomass is converted to black carbon (BC) via incomplete combustion. BC enters the ocean by rivers and atmospheric deposition contributing to the marine dissolved organic carbon (DOC) pool. The fate of BC is considered to reside in the marine DOC pool, where the oldest BC 14C ages have been measured (>20,000 14C y), implying long-term storage. DOC is the largest exchangeable pool of organic carbon in the oceans, yet most DOC (>80%) remains molecularly uncharacterized. Here, we report 14C measurements on size-fractionated dissolved BC (DBC) obtained using benzene polycarboxylic acids as molecular tracers to constrain the sources and cycling of DBC and its contributions to refractory DOC (RDOC) in a site in the North Pacific Ocean. Our results reveal that the cycling of DBC is more dynamic and heterogeneous than previously believed though it does not comprise a single, uniformly "old" 14C age. Instead, both semilabile and refractory DBC components are distributed among size fractions of DOC. We report that DBC cycles within DOC as a component of RDOC, exhibiting turnover in the ocean on millennia timescales. DBC within the low-molecular-weight DOC pool is large, environmentally persistent and constitutes the size fraction that is responsible for long-term DBC storage. We speculate that sea surface processes, including bacterial remineralization (via the coupling of photooxidation of surface DBC and bacterial co-metabolism), sorption onto sinking particles and surface photochemical oxidation, modify DBC composition and turnover, ultimately controlling the fate of DBC and RDOC in the ocean.

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. The protease inhibitor nirmatrelvir in combination with ritonavir has proven effective in patients who are high risk for progression to severe COVID-19, but there are no approved therapies for standard-risk patients, who now comprise the majority of the population. Simnotrelvir appears to be effective in standard-risk patients, including those who have completed primary vaccination against COVID-19 and have received a booster dose. This manuscript examines the rationale for the development of simnotrelvir and explores how this drug may be used in the future to treat COVID-19.

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. However, the role of IVIG in the treatment of post-COVID-19 conditions is uncertain. This manuscript examines what is known about IVIG in the treatment of long COVID and explores how this therapeutic agent may be used in the future to address this condition.

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. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Dominant heterocyclic composition of dissolved organic nitrogen in the ocean: A new paradigm for cycling and persistence.

Marine dissolved organic nitrogen (DON) is one of the planet's largest reservoirs of fixed N, which persists even in the N-limited oligotrophic surface ocean. The vast majority of the ocean's total DON reservoir is refractory (RDON), primarily composed of low molecular weight (LMW) compounds in the subsurface and deep sea. However, the composition of this major N pool, as well as the reasons for its accumulation and persistence, are not understood. Past characterization of the analytically more tractable, but quantitatively minor, high molecular weight (HMW) DON fraction revealed a functionally simple amide-dominated composition. While extensive work in the past two decades has revealed enormous complexity and structural diversity in LMW dissolved organic carbon, no efforts have specifically targeted LMW nitrogenous molecules. Here, we report the first coupled isotopic and solid-state NMR structural analysis of LMW DON isolated throughout the water column in two ocean basins. Together these results provide a first view into the composition, potential sources, and cycling of this dominant portion of marine DON. Our data indicate that RDON is dominated by 15N-depleted heterocyclic-N structures, entirely distinct from previously characterized HMW material. This fundamentally new view of marine DON composition suggests an important structural control for RDON accumulation and persistence in the ocean. The mechanisms of production, cycling, and removal of these heterocyclic-N-containing compounds now represents a central challenge in our understanding of the ocean's DON reservoir.

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. The primary outcome was the time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Key secondary outcomes included hospitalization or death by day 28 and a composite outcome of the need for an urgent-care or emergency department visit or hospitalization or death through day 28. RESULTS: Of the 1407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, were included in the analysis. There was no evidence that the use of fluticasone furoate resulted in a shorter time to recovery than placebo (hazard ratio, 1.01; 95% credible interval, 0.91 to 1.12; posterior probability of benefit [defined as a hazard ratio >1], 0.56). A total of 24 participants (3.7%) in the fluticasone furoate group had urgent-care or emergency department visits or were hospitalized, as compared with 13 participants (2.1%) in the placebo group (hazard ratio, 1.9; 95% credible interval, 0.8 to 3.5). Three participants in each group were hospitalized, and no deaths occurred. Adverse events were uncommon in both groups. CONCLUSIONS: Treatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among outpatients with Covid-19 in the United States. (Funded by the National Center for Advancing Translational Sciences and others; ACTIV-6 ClinicalTrials.gov number, NCT04885530.).

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 (SARS­CoV­2), the virus that causes Coronavirus (COVID-19). More than 200 symptoms have been associated with long COVID, potentially affecting nearly all body systems, and current estimates suggest that between 7 million and 23 million Americans have developed long COVID. However, there are no approved treatments for this condition. EXPERT OPINION: The first prospective, randomized study of the RECOVER research initiative, RECOVER-Vital, will evaluate the SARS-CoV-2 antiviral nirmatrelvir/ritonavir (Paxlovid) as a potential treatment for long COVID. This manuscript explores what is known about Paxlovid to treat and prevent long COVID and examines the rationale for addressing this condition with an antiviral agent.

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. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

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 (GohibicTM) 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. This manuscript explores what is known about vilobelimab and explores how this treatment may be used in the future to treat severe COVID-19.

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. EXPERT OPINION: Although the mechanism of action has not been fully elucidated, metformin is known to alter glucose metabolism and is under investigation as an antiviral agent, demonstrating in vitro and in vivo activity against SARS-CoV-2. Recent work suggests metformin may also serve as a therapeutic option for patients with COVID-19 as well as those with post-acute sequelae of SARS-CoV-2 infection, known more commonly as 'long COVID-19.' This manuscript examines what is known about metformin for the treatment of COVID-19 and explores how this drug may be used in the future to address the SARS-CoV-2 pandemic.

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. EXPERT OPINION: Interferons have been used to treat viral infections, including hepatitis B and hepatitis C, and malignancies such as non-Hodgkin's lymphoma, as well as the autoimmune condition multiple sclerosis. This manuscript examines what is known about the role of interferon lambda in the treatment of COVID-19, including potential limitations, and explores how this approach may be used in the future.

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. Novel therapeutic options are urgently needed. EXPERT OPINION: On 28 December 2022, a phase 3, observer-blinded, randomized trial was published evaluating 771 symptomatic adults with mild-to-moderate COVID-19 with a high risk of progression to severe disease. Participants were assigned to receive a 5-day course of either Paxlovid)\, which is recommended by the World Health Organization for treating mild-to-moderate COVID-19, or VV116 and the primary end point was the time to sustained clinical recovery through day 28. Among study subjects, VV116 was found to be noninferior to Paxlovid with respect to the time to sustained clinical recovery and with fewer safety concerns. This manuscript examines what is known about VV116 and explores how this novel treatment option may be used in the future to address the ongoing SARS-CoV-2 pandemic.

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. A literature search of PubMed was performed to identify all relevant studies of montelukast and SARS-CoV-2 through 27 January 2023. EXPERT OPINION: Montelukast has been the subject of small studies of SARS-CoV-2 and will be included in a large, randomized, double-blind, placebo-controlled study of outpatients with COVID-19 sponsored by the United States National Institutes of Health known as Accelerating COVID-19 Therapeutic Interventions and Vaccines-6. This paper reviews what is known about montelukast, an inexpensive, well-tolerated, and widely available medication, and examines the rationale for using this drug to potentially treat patients with COVID-19.

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. This manuscript examines what is known about the role of IL-1 receptor antagonism in the treatment of patients with COVID-19 and examines how anakinra may be used in the future to address the SARS-CoV-2 infection pandemic.