Estimates of actual and potential lives saved in the United States from the use of COVID-19 convalescent plasma

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies

Vomocytosis: Too Much Booze, Base, or Calcium?

Macrophages are well known for their phagocytic activity and their role in innate immune responses. Macrophages eat non-self particles, via a variety of mechanisms, and typically break down internalized cargo into small macromolecules. However, some pathogenic agents have the ability to evade this endosomal degradation through a nonlytic exocytosis process termed vomocytosis. This phenomenon has been most often studied for Cryptococcus neoformans, a yeast that causes roughly 180,000 deaths per year, primarily in immunocompromised (e.g., human immunodeficiency virus [HIV]) patients. Existing dogma purports that vomocytosis involves distinctive cellular pathways and intracellular physicochemical cues in the host cell during phagosomal maturation. Moreover, it has been observed that the immunological state of the individual and macrophage phenotype affect vomocytosis outcomes. Here we compile the current knowledge on the factors (with respect to the phagocytic cell) that promote vomocytosis of C. neoformans from macrophages

Estimating the size of fields in biomedical sciences

ABSTRACTScientific research output has increased exponentially over the past few decades, but not equally across all fields of study, and we lack clear methods for estimating the size of any given field of research. Understanding how fields grow, change, and are organized is essential to understanding how human resources are allocated to the investigation of scientific problems. In this study, we estimated the size of certain biomedical fields from the number of unique author names appearing in field-relevant publications in the PubMed database. Focusing on microbiology, where the size of fields is often associated with those who work on a particular microbe, we find large differences in the size of its subfields. We found that plotting the number of unique investigators as a function of time can show changes consistent with growing or shrinking fields. In general, the number of unique author names associated with a particular microbe correlated with the number of disease cases attributed to that microbe, suggesting that the microbiology field workforce is deployed in a manner consistent with the medical importance of the microbe in question. We propose that unique author counts can be used to measure the size of the workforce in any given field, analyze the overlap of the workforce between fields, and compare how the workforce correlates to available research funds and the public health burden of a field.IMPORTANCEScience and its individual fields are growing at spectacular rates along with the number of papers being generated each year. However, we lack methods to investigate the size of these fields, many times relying on anecdotal knowledge on which fields are “hot topics” or oversaturated. Thus, we developed a bibliometric method analyzing authorship information from PubMed to estimate the size of fields based on unique author counts. Our major findings are that unique author counts serve as an efficient measurement of the size of a given field. Additionally, the size of a biomedical science field correlates to its public health burden when compared to case numbers. This method allows us to compare growth rates, workforce distribution, and the allocation of resources between fields to understand how scientific fields self-regulate. These insights can, in turn, help guide policymaking, for example, in funding allocation, to ensure fields are not neglected

A food color-based colorimetric assay for Cryptococcus neoformans laccase activity

ABSTRACT Cryptococcus neoformans is a fungal pathogen that causes cryptococcosis primarily in immunocompromised patients, such as those with HIV/AIDS. One survival mechanism of C. neoformans during infection is melanin production, which catalyzed by laccase and protects fungal cells against immune attack. Hence, the comparative assessment of laccase activity is useful for characterizing cryptococcal strains. We serendipitously observed that culturing C. neoformans with food coloring resulted in degradation of some dyes with phenolic structures. Consequently, we investigated the color changes for the food dyes metabolized by C. neoformans laccase and by using this effect explored the development of a colorimetric assay to measure laccase activity. We developed several versions of a food dye-based colorimetric laccase assay that can be used to compare the relative laccase activities between different C. neoformans strains. We found that phenolic color degradation was glucose-dependent, which may reflect changes in the reduction properties of the media. Our food color-based colorimetric assay has several advantages, including lower cost, irreversibility, and not requiring constant monitoring , over the commonly used 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay for determining laccase activity. This method has potential applications to bioremediation of water pollutants in addition to its use in determining laccase virulence factor expression.IMPORTANCECryptococcus neoformans is present in the environment, and while infection is common, disease occurs mostly in immunocompromised individuals. C. neoformans infection in the lungs results in symptoms like pneumonia, and consequently, cryptococcal meningitis occurs if the fungal infection spreads to the brain. The laccase enzyme catalyzes the melanization reaction that serves as a virulence factor for C. neoformans. Developing a simple and less costly assay to determine the laccase activity in C. neoformans strains can be useful for a variety of procedures ranging from studying the relative virulence of cryptococci to environmental pollution studies

Dragotcytosis: Elucidation of the Mechanism for <i>Cryptococcus neoformans</i> Macrophage-to-Macrophage Transfer

Abstract Cryptococcus neoformans is a pathogenic yeast capable of a unique and intriguing form of cell-to-cell transfer between macrophage cells. The mechanism for cell-to-cell transfer is not understood. In this study, we imaged mouse macrophages with CellTracker Green 5-chloromethylfluorescein diacetate–labeled cytosol to ascertain whether cytosol was shared between donor and acceptor macrophages. Analysis of several transfer events detected no transfer of cytosol from donor-to-acceptor mouse macrophages. However, blocking Fc and complement receptors resulted in a major diminution of cell-to-cell transfer events. The timing of cell-to-cell transfer (11.17 min) closely approximated the sum of phagocytosis (4.18 min) and exocytosis (6.71 min) times. We propose that macrophage cell-to-cell transfer represents a nonlytic exocytosis event, followed by phagocytosis into a macrophage that is in close proximity, and name this process Dragotcytosis (“Dragot” is a Greek surname meaning “sentinel”), as it represents sharing of a microbe between two sentinel cells of the innate immune system.</jats:p