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Background In patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. Methods This investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov , NCT04399980 , NCT04463004 , and NCT04492514 . Findings Between May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43–5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups. Interpretation There was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed. Funding Kiniksa Pharmaceuticals.

Rationale The INCREASE study of inhaled treprostinil met its primary endpoint of change in 6-minute-walk distance at Week 16. In addition, there were significantly fewer clinical worsening events in patients receiving inhaled treprostinil. However, the incidence of multiple events in the same patient is unknown. Objectives This post hoc analysis evaluated the effect of continued treatment with inhaled treprostinil on the frequency and impact of multiple disease progression events. Methods Patients enrolled in INCREASE were analyzed for disease progression events, defined as at least 15% decline in 6-minute-walk distance, exacerbation of underlying lung disease, cardiopulmonary hospitalization, lung transplantation, at least 10% decline in forced vital capacity, or death during the duration of the 16-week study. Measurements and Main Results In total, 147 disease progression events occurred in the inhaled treprostinil group (89/163 patients, 55%) compared with 215 events (109/163 patients, 67%) in the placebo group ( P = 0.018). There was a lower incidence of each disease progression component in the inhaled treprostinil group: 6-minute-walk distance decline (45 vs. 64 events), lung disease exacerbation (48 vs. 72 events), FVC decline (19 vs. 33), cardiopulmonary hospitalization (23 vs. 33 events), and death (10 vs. 12). Fewer patients receiving inhaled treprostinil had multiple progression events compared with those receiving the placebo (35 vs. 58, 22% vs. 36%; P = 0.005). Conclusions Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared with patients receiving placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice.

Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies, which is characterized by reduced serum immunoglobulin levels and B-lymphocyte dysfunction. There are many clinical manifestations of this disease, the most common of which are recurrent respiratory tract infections. Among the most recently recognized autoimmune manifestation of CVID is a disease described as granulomatous-lymphocytic interstitial lung disease (GLILD), where CVID coexists with a small airway lymphoproliferative disorder, mimicking follicular bronchiolitis, or lymphocytic interstitial pneumonitis (LIP) on histology specimens. We herein describe the clinical and radiological features of GLILD in a 55-year-old woman where the diagnosis of CVID was actively pursued and eventually confirmed after her lung biopsy showed characteristic features of GLILD. The patient had dramatic response to treatment with IVIG and corticosteroids for 3 months followed by Mycophenolate mofetil for maintenance therapy. K E Y W O R D Scommon variable immunodeficiency, follicular bronchiolitis, granulomatous-lymphocytic interstitial lung disease, lymphoproliferative disorder, lymphocytic interstitial pneumonitis | I NTR ODU CTI ONCommon variable immunodeficiency (CVID) is estimated to affect 1/25,000 to 1/50,000 individuals worldwide. Approximately, 20% of CVID patients have associated autoimmune diseases, including hemolytic anemia, thrombocytopenia, neutropenia, rheumatoid arthritis, vitiligo, pyoderma gangrenosum, and others. [1][2][3][4][5][6][7] Granulomatous-lymphocytic interstitial lung disease (GLILD) is a pathologic diagnosis characterized by granulomas with benign lymphoproliferative infiltrates involving diffuse areas of the pulmonary parenchyma. [8][9][10] It is the most common cause of diffuse parenchymal lung disease in patients with CVID, occurring in approximately 10%-30% of all patients. 8-13 GLILD can be detected on lung biopsies many years prior to the diagnosis of CVID, 14 and is often associated with other organ granulomas, splenomegaly, adenopathy, and autoimmune cytopenias. 12,15 | C AS E PR ES ENTATI ONA 55-year-old woman was evaluated in the pulmonary clinic for progressively worsening dyspnea on exertion for 3 months. Her symptoms began with a dry cough, which failed to respond to two courses of antibiotics that were prescribed by her primary care physician for a possible respiratory tract infection. Her medical history was significant for Hashimoto's thyroiditis, Type I diabetes mellitus and Morphea-form skin rash. She had no history of smoking, recurrent infections, or chronic respiratory diseases, with no significant occupational or Figure 1) showed bilateral lower lung zone patchy and nodular opacities. Her pulmonary function test showed mild restriction with a moderately reduced diffusing capacity of the lung for carbon monoxide (DLCO). On chest computed tomography (CT) scan (Figure 2) diffuse bilateral ground glass opacities with bulky mediastinal and hilar lymphadenopathy was noted. Other ...

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