Search

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Summary: Background: With the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need. Methods: Safety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.gov NCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021. Findings: The proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm. Interpretation: In this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia. Funding: The ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Abstract Background Collapsing glomerulopathy, characterized by marked hypertrophy and hyperplasia of the podocytes with eventual collapse of the glomerular tuft, is an important cause of end-stage renal disease. Among the many causes of collapsing glomerulopathy, autoimmune diseases, such as systemic lupus erythematosus, have been implicated. There are also rare reports of adult-onset Still’s disease, an autoinflammatory condition characterized by fever, rash, and inflammatory arthritis being associated with collapsing glomerulopathy. Case presentation Herein, we present a review of three published cases, and present a new case of a 15-year-old African American female patient with collapsing glomerulopathy who was diagnosed with adult-onset Still’s disease 12 years later when she presented with fevers, arthralgias, sore throat, lymphadenopathy, hepatocellular injury, and elevated serum ferritin. Her collapsing glomerulopathy was initially well controlled following induction therapy with cyclosporine and prednisone and maintenance therapy with losartan. However, after developing adult-onset Still’s disease, she had multiple flare-ups despite various immunosuppressive therapies and developed worsening renal function, eventually progressing to end-stage renal disease. Conclusions Our case-based review highlights a rare but important association between adult-onset Still’s disease and collapsing glomerulopathy, and postulates a possible pathophysiological link.

Abstract Background Global and country specific recommendations on Delayed umbilical cord clamping (DCC) are available, though guidance on their implementation in program settings is lacking. In India, DCC (clamping not earlier than 1 min after birth) is a component in the package of services delivered as part of the India Newborn Action Plan (INAP) supported by Nutrition International (NI) in two states. The objective of this case study was to document the learnings from implementation of DCC in these two states and to understand the health system factors that affected its operationalization. Methods Mixed methods were followed. Using the World Health Organization (WHO) Health Systems building blocks as a framework, 20 Key-Informant Interviews were conducted to explore facilitators and barriers to routine implementation of DCC in public health settings. Existing quantitative program data and secondary data from labour-room registers from eight NI- supported districts were analysed to assess the prevalence of DCC implementation in public health systems settings. Results A demonstrated commitment from the government to implement DCC at all delivery points in NI supported districts was observed. Funds were sufficient, trainings were optimal, knowledge of the health workforce was adequate and a recording mechanism was in place. According to record reviews, DCC was more likely to happen in facilities that provide Basic Emergency Obstetric services and among normal deliveries. It was less likely to be followed in babies delivered by Caesarean section (OR 0.03; 95%CI 0.02,0.05), birthweight

Sarcomatoid carcinoma of the adrenal gland is an uncommon presentation of malignant adrenal tumors and bilateral presentation is extremely rare. It is an extremely rare occurrence, unusual symptoms, and both epithelioid and sarcomatoid components in histology are a challenge to diagnose sarcomatoid carcinoma of adrenal origin. The majority of patients are diagnosed at a later stage while having metastatic disease and succumb due to disease within a few months of diagnosis due to the aggressive nature of the disease. Probably due to the advanced disease at the time of diagnosis; patients diagnosed having adrenal sarcomatoid tumor have a very poor prognosis. In nonmetastatic disease, adjuvant chemotherapy is suggested after the removal of the tumor. It is essential to diagnose these tumors earliest to treat with effective treatment modalities. The present study describes the rare case of sarcomatoid carcinoma involving the bilateral adrenal gland with metastasis to bones, lymph nodes, and pleura evaluated by 18F-FDG PET/CT.

Background: Metastasis to the maxilla is exceedingly rare and may be the presenting sign of either occult malignancy or development of distant disease. Primary tumors most commonly arise from the lung but have been reported from various other sites in the body. We report a case of a patient presenting with a maxillary mass found to be a metastasis from a rare, aggressive T1N1M1 lung tumor. Case presentation: A 58 year old male with significant smoking history presented to with progressively enlarging maxillary mass. Physical examination and contrast-enhanced CT revealed a 2cm maxillary mass with bony erosion, 4cm bilateral cervical lymphadenopathy, and 4.5cm left upper lobe lung mass. PET/CT showed hypermetabolic activity within the maxillary, cervical and lung lesions but also numerous metastases to the retroperitoneum, liver, and axial and appendicular skeleton.Punch biopsy was obtained. Histology showed a necrotic high-grade neoplasm with rhabdoid features. Immunohistochemistry was nonspecific, staining positively only for vimentin. Genetic analysis reported reduced to absent expression of SMARCA4 but intact SMARCB1. Clinical history and findings were consistent with SMARCA4-deficient thoracic sarcomatoid tumor with diffuse metastases. Conclusions: Metastasis to the maxilla requires a high index of suspicion; biopsy is required for definitive diagnosis. Maxillary metastasis should be considered in patients with maxillary lesions in the setting of either risk factors for or prior history of malignancy. We are the first to report maxillary metastasis as presenting sign of SMARCA4-deficient thoracic sarcomatoid tumor.

Sarcomatoid carcinoma of the adrenal gland is an uncommon presentation of malignant adrenal tumors and bilateral presentation is extremely rare. It is an extremely rare occurrence, unusual symptoms, and both epithelioid and sarcomatoid components in histology are a challenge to diagnose sarcomatoid carcinoma of adrenal origin. The majority of patients are diagnosed at a later stage while having metastatic disease and succumb due to disease within a few months of diagnosis due to the aggressive nature of the disease. Probably due to the advanced disease at the time of diagnosis; patients diagnosed having adrenal sarcomatoid tumor have a very poor prognosis. In nonmetastatic disease, adjuvant chemotherapy is suggested after the removal of the tumor. It is essential to diagnose these tumors earliest to treat with effective treatment modalities. The present study describes the rare case of sarcomatoid carcinoma involving the bilateral adrenal gland with metastasis to bones, lymph nodes, and pleura evaluated by 18F-FDG PET/CT. [ABSTRACT FROM AUTHOR]