Anti-Granulocyte-Macrophage Colony-Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial.

Rationale: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [-6 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

Exophiala pneumonia requiring pneumonectomy in a post-renal transplant patient.

Exophiala is a rare fungus that can cause fatal infections in patients who are immunocompromised. This case describes a 55-year-old post-renal transplant patient undergoing active treatment for multiple myeloma who presented to the emergency room with complaints of cough and dyspnea. She was found to have a cavitary lesion in the left upper lobe of her lung, and direct sampling via bronchoscopy revealed an invasive fungal infection with an Exophiala species. Despite initial improvement on antifungal therapy, her clinical course deteriorated requiring pneumonectomy and formation of brain abscess. This case emphasizes the challenge of invasive fungal infections and the importance of broad differentials in patients who are immunocompromised.

Candida parapsilosis endocarditis in an immunocompetent host.

This case describes an 83-year-old immunocompetent woman who presented to the emergency department with complaints of nausea, vomiting, and dizziness. She was found to have evidence of embolic stroke secondary to Candida parapsilosis endocarditis. This case emphasizes the challenge of diagnosing fungal endocarditis, as it can be difficult to culture, and the importance of broad differentials even in patients with no obvious risk factors.

Varicella-zoster virus causing a ring-like cerebral lesion in AIDS.

We report a 50-year-old man with a possible stroke 3 months earlier, recurrent shingles outbreaks, and male-who-has-sex-with-men status who presented to the emergency department with worsening confusion, lower-extremity weakness, gait imbalance, and incontinence. Given his clinically immunocompromised state, the patient was started on intravenous acyclovir. A human immunodeficiency virus (HIV) test returned positive, magnetic resonance imaging of the brain showed a ring-enhancing lesion, and lumbar puncture was positive for varicella-zoster virus. Eventual brain biopsy of the ring-enhancing lesion confirmed vasculitis. This case highlights the broad differential of a ring-enhancing lesion and the importance of early HIV screening.

Streptococcus intermedius causing infective endocarditis and abscesses: a report of three cases and review of the literature.

BACKGROUND: Streptococcus intermedius is a member of the Streptococcus anginosus group. Clinical disease with S. intermedius is characterized by abscess formation and rarely endocarditis. Identification of Streptococcus intermedius is difficult, leading to the development of molecular methods to more accurately identify and characterize this organism. CASE PRESENTATION: Over a period of 6 months we encountered three cases of invasive Streptococcus intermedius infection presenting as hepatic abscesses, brain abscess, and endocarditis. We confirmed our microbiologic diagnosis through 16S sequencing and found a common virulence gene in each case. CONCLUSION: Our report illustrates three different clinical manifestations due to Streptococcus intermedius infection that can be encountered in healthy individuals in a community hospital setting. To our knowledge, this is the first case of Streptococcus intermedius endocarditis confirmed by 16S sequencing analysis. The use of molecular methods may allow a better understanding of the epidemiology and pathogenesis of this organism.