GM-CSF: Orchestrating the Pulmonary Response to Infection.

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

Black Fungus and beyond: COVID-19 associated infections.

Globally, many hospitalized COVID-19 patients can experience an unexpected acute change in status, prompting rapid and expert clinical assessment. Superimposed infections can be a significant cause of clinical and radiologic deviations in this patient population, further worsening clinical outcome and muddling the differential diagnosis. As thrombotic, inflammatory, and medication-induced complications can also trigger an acute change in COVID-19 patient status, imaging early and often plays a vital role in distinguishing the cause of patient decline and monitoring patient outcome. While the common radiologic findings of COVID-19 infection are now widely reported, little is known about the clinical manifestations and imaging findings of superimposed infection. By discussing case studies of patients who developed bacterial, fungal, parasitic, and viral co-infections and identifying the most frequently reported imaging findings of superimposed infections, physicians will be more familiar with common infectious presentations and initiate a directed workup sooner. Ultimately, any abrupt changes in the expected COVID-19 imaging presentation, such as the presence of new consolidations or cavitation, should prompt further workup to exclude superimposed opportunistic infection.

SEDATION AND PARALYSIS REQUIREMENTS IN MECHANICALLY VENTILATED PATIENTS WITH COVID-19

It was concluded that higher daily doses of sedative agents were used in COVID-19 patients compared to non-COVID patients. B Introduction: b Management of severe acute respiratory distress syndrome (ARDS) secondary to COVID-19 often requires deep sedation and paralysis to maintain oxygen saturation goals. Anecdotal findings suggest that patients with COVID-19 require higher doses of sedative agents to achieve target levels of sedation and maintain ventilator synchrony. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Severe Acute Respiratory Syndrome-Associated Coronavirus 2 Infection and Organ Dysfunction in the ICU: Opportunities for Translational Research.

OBJECTIVES: Since the beginning of the coronavirus disease 2019 pandemic, hundreds of thousands of patients have been treated in ICUs across the globe. The severe acute respiratory syndrome-associated coronavirus 2 virus enters cells via the angiotensin-converting enzyme 2 receptor and activates several distinct inflammatory pathways, resulting in hematologic abnormalities and dysfunction in respiratory, cardiac, gastrointestinal renal, endocrine, dermatologic, and neurologic systems. This review summarizes the current state of research in coronavirus disease 2019 pathophysiology within the context of potential organ-based disease mechanisms and opportunities for translational research. DATA SOURCES: Investigators from the Research Section of the Society of Critical Care Medicine were selected based on expertise in specific organ systems and research focus. Data were obtained from searches conducted in Medline via the PubMed portal, Directory of Open Access Journals, Excerpta Medica database, Latin American and Caribbean Health Sciences Literature, and Web of Science from an initial search from December 2019 to October 15, 2020, with a revised search to February 3, 2021. The medRxiv, Research Square, and clinical trial registries preprint servers also were searched to limit publication bias. STUDY SELECTION: Content experts selected studies that included mechanism-based relevance to the severe acute respiratory syndrome-associated coronavirus 2 virus or coronavirus disease 2019 disease. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Not applicable. CONCLUSIONS: Efforts to improve the care of critically ill coronavirus disease 2019 patients should be centered on understanding how severe acute respiratory syndrome-associated coronavirus 2 infection affects organ function. This review articulates specific targets for further research.

Anisocytosis is Associated With Short-Term Mortality in COVID-19 and May Reflect Proinflammatory Signature in Uninfected Ambulatory Adults.

BACKGROUND: Red cell distribution width (RDW), a measure of anisocytosis, is observed in chronic inflammation and is a prognostic marker in critically ill patients without COVID-19, but data in COVID-19 are limited. METHODS: Between March 12 and April 19, 2020, 282 individuals with confirmed COVID-19 and RDW available within 7 days prior to COVID-19 confirmation were evaluated. Individuals were grouped by quartiles of RDW. Association between quartiles of RDW and mortality was assessed using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. The association between RDW and all-cause mortality was further assessed using a Cox proportional hazards model. Plasma cytokine levels in uninfected ambulatory adults without cardiovascular disease (n=38) were measured and bivariate Spearman correlations and principle components analysis were used to identify relationships between cytokine concentrations with RDW. RESULTS: After adjusting for age, sex, race, cardiovascular disease, and hemoglobin, there was an association between RDW and mortality (Quartile 4 vs Quartile 1: HR 4.04 [1.08-15.07]), with each 1% increment in RDW associated with a 39% increased rate of mortality (HR 1.39 [1.21-1.59]). Remote RDW was also associated with mortality after COVID-19 infection. Among uninfected ambulatory adults without cardiovascular disease, RDW was associated with elevated pro-inflammatory cytokines (TNF-α, IL8, IL6, IL1b), but not regulatory cytokines (TGFb). CONCLUSIONS: Anisocytosis predicts short-term mortality in COVID-19 patients, often predates viral exposure, and may be related to a pro-inflammatory phenotype. Additional study of whether the RDW can assist in the early identification of pending cytokine storm is warranted.