DOCSLIB.ORG

Insights Into Fungal Pathogenesis from the Iatrogenic Epidemic Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Insights Into Fungal Pathogenesis from the Iatrogenic Epidemic Of Fungal Genetics and Biology xxx (2013) xxx–xxx Contents lists available at ScienceDirect Fungal Genetics and Biology journal homepage: www.elsevier.com/locate/yfgbi Review Insights into fungal pathogenesis from the iatrogenic epidemic of Exserohilum rostratum fungal meningitis ⇑ David Andes a, Arturo Casadevall b, a The Departments of Medicine (Infectious Diseases) and Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53705-2281, United States b The Departments of Microbiology & Immunology and Medicine, Albert Einstein College of Medicine, Bronx, NY, United States article info abstract Article history: In 2012 the medical community in the United States faced an unprecedented outbreak of fungal menin- Received 15 July 2013 gitis caused by Exserohilum rostratum associated with injections of contaminated lots of methyprednil- Accepted 23 August 2013 sone acetate. Rapid response by public health authorities led to the identification of the cause of the Available online xxxx outbreak and the epidemic quickly abated, even though new cases were still being reported many months later. Although the cause of the outbreak is known there are many uncertainties regarding the Keywords: management of infected individuals and the long term risk for those who were exposed to this organism. Exserohilum rostratum The epidemic of E. rostratum infections illustrates how an organism that normally has low pathogenic Fungal potential for humans can transform into a very dangerous pathogen when conditions are changed such Meningistis that skin barriers are breached while it is simultaneously delivered with an immunosuppressive drug. Furthermore, this epidemic highlights the potential threats to human and animal health from the fungal kingdom. Ó 2013 Published by Elsevier Inc. In late 2012 the medical community in the United States was curred in individuals given injectable steroids contaminated with confronted by an outbreak of meningitis cases caused by an organ- fungal spores (Anonymous, 2002) and outbreak of Aspergillosis fol- ism that only very rarely caused disease in humans, a fungus lowed the use of a contaminated spinal anesthetic in Sri Lanka known as Exserohilum rostratum (Kainer et al., 2012; Kauffman (Rodrigo et al. 2007). Decades ago outbreaks of zygomycosis were et al., 2013; Kerkering et al., 2013; Smith et al., 2013). The cause associated with the use of contaminated bandages (Antoniadou, of the epidemic was eventually traced to the use of methyprednil- 2009). These episodes highlight the enormous potential of contam- sone acetate (MPA) injections contaminated with E. rostratum (tel- inating fungi to cause disease when inadvertently introduced into eomorph Setosphaeria) as a result of poor manufacturing practices the human host as part of contaminated therapies. In fact, as of at the New England Compounding Center (Lockhart et al., 2013). May 2013 the Centers for Disease Control (CDC, Atlanta, GA) was Cases were reported in 20 of the 23 states where the product investigating a new outbreak of fungal meningitis associated with was used. By mid-2013 the epidemic had abated as the contami- a different compounding pharmacy (Kuehn, 2013). nated MPA vials were withdrawn from clinical practice. However, In the United States there are over half a million epidural injec- as of July 1, 2013 the total case count stood at 749 with 61 deaths tions each year and infection is a rare complication that is usually and new cases continued to be reported, with three deaths in June caused by skin bacteria (Cooper and Sharpe, 1996; Hooten et al., 2013, many months after initial infection. This episode constitutes 2004). In contrast, the overall case rate for infection with E. rostra- the largest iatrogenic fungal outbreak in the United States. Hence, tum was near 4% of more than 13,500 exposed individuals, of this outbreak has a known cause and may not repeat itself but this which over 90% were exposed through an epidural, paraspinal, or tragic episode provides us with new insights into the potential for spinal injection, with the remainder having joint or peripheral fungi to cause disease and the conditions where fungal infection injections. Hence, the majority of the clinical manifestations ob- can progress to disease. Incidentally, the 2012–2013 fungal epi- served during the E. rostratum outbreak reflected the mode of demic from contaminated drugs was not the first time that such infection, which involved direct inoculation of the fungal cells into an iatrogenic disaster had occurred. Over a decade ago several normally sterile body sites. The distribution of clinical presenta- cases of Exophiala (Wangiella) dermatitides fungal meningitis oc- tions was as follows: 391 (52%) cases of meningitis, 323 (43%) cases of local paraspinal infections, 60 (15%) cases of arachnoiditis and 33 (4%) cases of septic arthritis. The total percentage exceeds ⇑ Corresponding author. Address: Albert Einstein College of Medicine, 1300 100% because some individuals had more than one condition. Morris Park Ave, Bronx, NY 10461, United States. The early cases mostly involved meningitis complicated by poster- E-mail address: [email protected] (A. Casadevall). 1087-1845/$ - see front matter Ó 2013 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fgb.2013.08.014 Please cite this article in press as: Andes, D., Casadevall, A. Insights into fungal pathogenesis from the iatrogenic epidemic of Exserohilum rostratum fungal meningitis. Fungal Genet. Biol. (2013), http://dx.doi.org/10.1016/j.fgb.2013.08.014 2 D. Andes, A. Casadevall / Fungal Genetics and Biology xxx (2013) xxx–xxx ior circulation stroke in 10% of affected individuals. Histological there were no prior reports of meningitis. Prior to the current out- analysis of post-mortem specimens demonstrated that E. rostratum break clinical experience with this organism was very limited. In was angioinvasive and elicited an inflammatory response with immunocompetent individuals with breaks in tissue integrity E. neutrophil predominance (Bell and Khabbaz, 2013). The incubation rostratum has been reported to cause cutaneous and corneal infec- period for the onset of meningitis after MPA injection ranged from tions. Disseminated E. rostratum disease had been reported in a 1 to 120 days (mean 23 days), with the longest times being compa- handful of immunocompromised individuals (Douer et al., 1987). rable to those described for the earlier Exophiala outbreak. As the The paucity of human cases suggests that E. rostratum has low outbreak has evolved later cases tended to present more com- pathogenic potential for humans. monly with infection of local tissues and these included a large The infection risk varied with the lot and one specific lot was number of paraspinal and epidural infections with a significantly associated with more infections. This lot was older than the others smaller number of joint and bone infections. For patients with and the likelihood of infection increased with vial age and was paraspinal infections the media number of days from injection to greatest for vials older than 60 days (Kainer et al., 2012). This could MRI diagnosis was 52 days for those that received one injection reflect a higher fungal contamination burden and/or growth of fun- and 43 for those that received several (Kontoyiannis et al., 2013). gi in the vials with time, possibly potentiated by the steroid. In this It is noteworthy that the time between infection and disease for regard, Aspergillus spp. have been reported to grow faster in the the soft tissue infections was significantly longer than that ob- presence of hydrocortisone (Ng et al., 1994). served with the meningitis cases, which may reflect differences An interesting aspect of this epidemic is a large subset of indi- in local immunity between the CNS and soft tissues and/or tissue viduals who have remained asymptomatic despite being known damage leading to symptomatology. The patients ranged in age to be infected. For example, 21% of 172 patients from a center in from 16 to 92 years with a mean age of 64. Older age (> 60) was Michigan who were found to have MRI imaging evidence for an ab- associated with 4-fold higher risk of disease (11.8% vs 2.9%) sug- scess at the injection site and have remained free of symptoms gesting the possibility that senescent immune system were less (Malani et al., 2013). Whether this reflects the injection of cortico- likely to control infection, especially in the presence of high con- steroids at the site or an indolent infection that will in time become centrations of corticosteroid in tissue (Kainer et al., 2012). symptomatic is not known. This situation represents a clear dis- One praiseworthy aspect of this iatrogenic tragedy was the ra- tinction between infection and disease. The word infection is often pid recognition of the outbreak and the decisive action taken by used synonymously with disease but they have been proposed to public health authorities, which is apparent by the timeline of represent different states whereby infection is the acquisition of events. On September 21, 2012 several fungal meningitis cases the microbe by the host and disease is an outcome whereby the were reported to the Center for Disease Control (Atlanta, Ga) and interaction of the host and microbe has resulted in sufficient dam- by October 4, 2012 that agency had associated the cases with age to impair homeostasis and produce clinical symptoms (Casa- MPA injections originating from the New England Compounding devall and Pirofski, 2000). Center, two days later the manufacturer recalled all vials and by The ability of the rarely pathogenic E. rostratum to cause infec- October 19, 2012 more than 99% of exposed individuals had been tion and disease after MPA injection reflects its deposition in nor- contacted. The investigation identified three contaminated lots mally sterile tissue sites in conjunction with an that included 17,675 vials that had been distributed to 76 health immunosuppressive drug in the form of MPA. In this regard, E. care facilities in 23 states.
Load more

Recommended publications
  • 10 Top Researchers at AECOM
    TEN LEADING EINSTEIN RESEARCHERS AND THEIR ACCOMPLISHMENTS INFECTIOUS DISEASE John Blanchard, Ph.D., has identified a promising new treatment for extensively drug-resistant tuberculosis (XDR-TB), a dangerous form of the disease caused by strains of TB bacteria that have become resistant to virtually all antibiotics. In 2009, Dr. Blanchard reported that a combination of two drugs (clavulanate and meropenem) was highly effective in halting the growth of XDR-TB in John Blanchard, Ph.D. John Condeelis, Ph.D. Ekaterina Dadachova, Ph.D. laboratory culture. Since then, his drug combination has saved the lives of several patients with XDR-TB and will soon be formally evaluated in two human trials, in South Africa and Belgium. Dr. Blanchard is professor of biochemistry and the Dan Danciger Professor of Biochemistry. Arturo Casadevall, M.D., Ph.D., is one of the world’s leading microbiologists, well known for his diverse and innovative scientific inquiries. His work on Arturo Casadevall, M.D., Ph.D Vern Schramm, Ph.D. Joseph Sparano, M.D. fungal melanin, for example, has opened up the possibility of using this pigment in novel CANCER ways to protect against radiation exposure. Thanks to a highly John Condeelis, Ph.D., anatomy and structural biology Casadevall, M.D., Ph.D., Dr. productive research partnership is a leading expert on imaging department, scientific director of Dadachova developed radio- with colleague Ekaterina the tumor microenvironment— the analytical imaging facility, immunotherapy for metastatic Dadachova, Ph.D., he has the microscopic site where tumor co-director of the Gruss Lipper melanoma—a treatment developed a targeted therapy cells interact with surrounding Biophotonics Center, and the strategy that has shown promise for metastatic melanoma that cells.
    [Show full text]
  • Group Icon 2019 Speaker Biographies
    A University Symposium: Promoting Credibility, Reproducibility and Integrity in Research March 29, 2019 | Columbia University | Speaker Biographies Speaker Biographies* Howard Bauchner, MD was appointed the 16th Editor in Chief of JAMA and The JAMA Network in 2011. Prior to coming to JAMA, Howard was a Professor of Pediatrics and Public Health at Boston University School of Medicine and Editor in Chief of Archives of Disease in Childhood (2003- 2011). At BUSM he was Vice-Chair of Research for the Department of Pediatrics and Chief, Division of General Pediatrics. He is a member of the National Academy of Medicine (formerly the Institute of Medicine) and an honorary fellow of the Royal College of Paediatrics and Child Health, United Kingdom. At JAMA Howard has focused on improving and expanding clinical content, using electronic/digital approaches to enhance communication, and ensuring a commitment to innovation. Since his arrival in 2011 followers on social medical (twitter and Facebook) have increased from 13,000 to approximately 700,000 and the electronic table of contents is now distributed to close to 750,000 individuals each week. In print, via eTOC, and social media JAMA now reaches over 1.5M physicians each week worldwide. Views (PDF and HTML) have increased from 10M in 2011 to 32M in 2017 (50% from outside the U.S.) and podcast downloads have increased from 300,000 in 2014 to 2.2M in 2017. The print journal was redesigned for the first time in over 20 years and website has been updated twice. All 9 of the specialty journals were renamed (Archives of Pediatrics became JAMA Pediatrics), and 3 new journals have been launched – JAMA Oncology (2015), JAMA Cardiology (2016), and JAMA Network Open (2018).
    [Show full text]
  • Antibodies and Fungi: an Evolving Paradigm with Opportunities for the Development of New Antifungal Therapies and Vaccines
    2 Rev Iberoam Micol 1997; 14: 2-3 Forum Micológico Antibodies and fungi: an evolving paradigm with opportunities for the development of new antifungal therapies and vaccines Arturo Casadevall Departments of Medicine (Division of Infectious Diseases) and Microbiology & Immunology of the Albert Einstein College of Medicine, Bronx, New York, USA The role of antibody immunity in protection with the function of protective antibodies [8]. Hence there against fungal infections has been uncertain for decades. is now evidence for "good" and "bad" antibodies against This is in sharp contrast to bacteria, viruses, and protozoa fungi. where antibody immunity is widely acknowledged to con- Protection studies with mAbs suggest an explana- tribute to protection. This raises the questions: Do protec- tion for the inconclusive and often contradictory results tive antibodies against fungi exist?; Why has it been so obtained from experiments with polyclonal sera [2]. difficult to demonstrate conclusively that antibody immu- Polyclonal antibody preparations contain antibodies of nity protects against fungi?; Does antibody immunity multiple specificities and isotypes. MAb preparations dif- influence the course of fungal infections? fer from polyclonal antibodv preparations in that they The issue of whether antibody immunity contribu- contain one antibody type of a defined specificity and tes to host defense against fungi is no longer academic. In isotype. The discovery that protective, non-protective and recent years there has been a marked increase in fungal deleterious mAbs exist suggests that the efficacy of poly- infections associated with the HIV epidemic and immuno- clonal antibody preparations reflects their relative propor- suppressive therapies. Systemic mycoses in immunocom- tion of these types of antibodies.
    [Show full text]
  • 2018 Resources Seminar Slides.Pdf
    Special Seminar 21 September 2018 Resources and Opportunities Johns Hopkins Malaria Research Institute Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Connection with MMI Since 2001 Bloomberg Philanthropies has given $125 million to the Bloomberg School to fund a state-of-the-art research facility to mount a broad program of basic-science research to treat and control malaria, develop a vaccine and find new drug targets to prevent and cure this deadly disease. Diane Griffin, MD, PhD Founding Director, JHMRI Former Chair, MMI Dept The Institute resides in the Department of Molecular Microbiology and Immunology (MMI). Arturo Casadevall, MD, PhD Current Chair, MMI Dept 2 Leadership George Dimopoulos, PhD, MBA Bill Moss, MD, MPH Professor, JHMRI Deputy Director, Professor, JHMRI Deputy Director, Parasite Core Director & ICEMR Program Director Peter Agre, MD Bloomberg Distinguished Professor & JHMRI Director Sean Prigge, PhD Photini Sinnis, MD Professor, JHMRI Deputy Director, Professor & JHMRI Deputy & Co-Director Biophysics Core Director 3 21 Faculty/Labs Core Facilities School of Public Health • Insectary – Molecular Microbiology • Parasite Core & Immunology • Biophysics Core – Epidemiology • Spatial Science Core • MMI Genetic Analysis & School of Medicine Sequencing Facility Cell Biology – • MMI Imaging & Microscopy – Neuroscience • MMI Flow Cytometry/Cell – Pharmacology Sorting Core Field Site Macha, Zambia 4 Macha Research Trust Southern Province, Zambia Field station in rural Zambia Molecular laboratory Insectary Malaria “sphere” Flight cage 5 JHBSPH Staff Based in Macha Dr. Phil Thuma, MD Dr. Jennifer Stevenson, PhD Senior Scientific advisor Lead Entomologist 6 3 Biophysics Core Facility Co-Directors Scott Bailey, PhD Email: [email protected] Sean Prigge, PhD Email: [email protected] Biophysics Core Johns Hopkins Bloomberg School of Public Health 615 N.
    [Show full text]
  • Arturo Casadevall, MD Phd (BA ’79 Chemistry, Queens College )
    The Distinguished Speaker Seminar at presents a public lecture by Arturo Casadevall, MD PhD (BA ’79 Chemistry, Queens College ) Johns Hopkins Bloomberg School of Public Health Johns Hopkins School of Medicine Bloomberg Distinguished Professor of Molecular Microbiology, Immunology & Infectious Diseases Thoughts on Martians, Mammals and the Origin of Microbial Virulence ConEdison STEM Lecture Hall at Queens College C-201 Science Building April 7, 2017 - 10:00 AM Guests welcome Supported by Consolidated Edison, Inc. and the QC Division of Math & Natural Sciences Arturo Casadevall was born in Sanc, Spíritus, Cuba in 1957. He moved to Elmhurst, Queens, New York City in 1968 and became a U.S. ci,zen in 1976. Casadevall received his Bachelor of Arts degree in Chemistry from Queens College, City University of New York in 1979, and his M.S. and Ph.D. in Biochemistry from New York University in 1983 and 1984. He then received his M.D. from New York University in 1985. Casadevall completed his internship and residency in internal medicine at the Bellevue Hospital Center, and a fellowship in infec,ous diseases at the Montefiore Medical Center of the Albert Einstein College of Medicine. He completed a postdoctoral fellowship in cell biology at the Albert Einstein College of Medicine from 1989-1991. In March 2015, Casadevall was named a Bloomberg Dis,nguished Professor at Johns Hopkins University for his accomplishments as an interdisciplinary researcher and eXcellence in teaching, holding appointments in the Bloomberg School of Public Health’s Department of Molecular Microbiology and Immunology and the Johns Hopkins School of Medicine’s Department of Infec,ous Diseases.
    [Show full text]
  • Shaking up Science
    NEWSFOCUS Shaking Up Science Two journal editors take a hard look at honesty in science and question the ethos of their profession FERRIC FANG AND ARTURO CASADEVALL ARE AN UNLIKELY DUO. covery for its own sake was being sidelined by a push to publish They live a continent apart and barely speak on the phone. (“There in high-impact journals. Funding was scarcer than ever. Scientists were a couple of times that I failed to immediately recognize his focused on narrow fi elds and often couldn’t communicate their pro- voice,” Fang admits.) Fang grew up in Los Angeles, the son of a doc- fessional passions at a cocktail party. tor, and attended Harvard University. Casadevall fl ed Cuba for the None of this is new. But Fang and Casadevall decided to try to do United States at 11, was reunited with his family in New York, and something about it—to recapture what brought them to science in the never left. He enrolled at Queens College of the City University of fi rst place, the thrill of the chase, of being part of something bigger New York because the fi rst year there was free and worked at McDon- than oneself. They wanted to ask: Are we doing science the best way ald’s and as a bank teller to earn spending money. “I never thought we can? And if not, what’s in our power to change? about a career in science,” Casadevall says. “I didn’t know you could get paid to do research.” The partnership Despite their differences, they rose on parallel tracks through “The 99%, the majority of scientists, are really driven by fear,” Fang on January 24, 2013 the ranks of microbiology and immunology, running large labs and says.
    [Show full text]
  • Fungal Virulence, Vertebrate Endothermy, and Dinosaur Extinction: Is There a Connection?
    Fungal Genetics and Biology 42 (2005) 98–106 www.elsevier.com/locate/yfgbi Commentary Fungal virulence, vertebrate endothermy, and dinosaur extinction: is there a connection? Arturo Casadevall* Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA Department of Microbiology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA Received 14 November 2004; accepted 30 November 2004 Abstract Fungi are relatively rare causes of life-threatening systemic disease in immunologically intact mammals despite being frequent pathogens in insects, amphibians, and plants. Given that virulence is a complex trait, the capacity of certain soil fungi to infect, persist, and cause disease in animals despite no apparent requirement for animal hosts in replication or survival presents a paradox. In recent years studies with amoeba, slime molds, and worms have led to the proposal that interactions between fungi and other environmental microbes, including predators, select for characteristics that are also suitable for survival in animal hosts. Given that most fungal species grow best at ambient temperatures, the high body temperature of endothermic animals must provide a thermal barrier for protection against infection with a large number of fungi. Fungal disease is relatively common in birds but most are caused by only a few thermotolerant species. The relative resistance of endothermic vertebrates to fungal diseases is likely a result of higher body temperatures combined with immune defenses. Protection against fungal diseases could have been a powerful selec- tive mechanism for endothermy in certain vertebrates. Deforestation and proliferation of fungal spores at cretaceous–tertiary boundary suggests that fungal diseases could have contributed to the demise of dinosaurs and the flourishing of mammalian species.
    [Show full text]
  • Climate Change Brings the Specter of New Infectious Diseases
    Climate change brings the specter of new infectious diseases Arturo Casadevall J Clin Invest. 2020;130(2):553-555. https://doi.org/10.1172/JCI135003. Viewpoint Climate change will bring major changes to the epidemiology of infectious diseases through changes in microbial and vector geographic range. Human defenses against microbial diseases rely on advanced immunity that includes innate and adaptive arms and endothermy, which creates a thermal restriction zone for many microbes. Given that microbes can adapt to higher temperatures, there is concern that global warming will select for microbes with higher heat tolerance that can defeat our endothermy defenses and bring new infectious disease. New microbial threats in a changing climate Almost three decades ago, experts began to sound the alarm that climate change could be associated with changes to the epidemiology of infectious diseases (1, 2). Since then a large body of literature has accumulated on this subject focused primarily on how climate will affect locations of pathogenic microbes and vectors of infectious diseases. In this Viewpoint, I focus on another threat: the strong possibility that new, previously unknown infectious diseases will emerge from warmer climates as microbes adapt to higher global temperatures that can defeat our endothermy thermal barrier. The field of infectious diseases has the unenviable distinction of being the only subdiscipline of medicine that routinely has to deal with new diseases and where therapies lose their potency and value from drug resistance. New infectious diseases caused by pathogenic microbes not previously […] Find the latest version: https://jci.me/135003/pdf The Journal of Clinical Investigation VIEWPOINT Climate change brings the specter of new infectious diseases Arturo Casadevall Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.
    [Show full text]
  • New Way out for Cryptococcus
    RESEARCH HIGHLIGHTS FUNGAL PATHOGENESIS New way out for Cryptococcus Macrophages are part of the innate to cause disease in immunocom- main virulence factor of C. neofor- immune armoury that responds to promised individuals, but because mans is the capsule, and the greatly pathogen invasion. Usually, mac- it is a model for the switch from a reduced extrusion of an acapsular rophages ingest and kill pathogens, benign environmental organism to mutant led Alvarez and Casadevall to but some pathogens multiply inside a voracious pathogen of mammals propose that capsular polysaccharide the phagocyte, then exit by lysing and amoebae. contributes to the exit mechanism. and killing it. Two reports published The phagosome is a vacuole that Several bacterial pathogens can in Current Biology reveal a third is formed around a pathogen after manipulate the cytoskeleton during outcome of pathogen ingestion by ingestion by phagocytosis. When the pathogenesis, including members of macrophages: Cryptococcus neoform- phagosome fuses with a lysosome the Legionella, Listeria and Shigella ans can replicate after phagocytosis the ingested pathogen is killed by genera. As C. neoformans cells were and then exit by a novel mechanism a combination of enzyme action propelled out of the macrophages, that leaves both the macrophage and and oxidative burst. Alvarez and both groups proposed a role for the pathogen intact. Casadevall, and Ma et al. noticed that the cytoskeleton in pathogen exit. Cryptococcosis has come to after ingestion by macrophages, the However, inhibiting actin polymeri- prominence owing to the ability of phagosomes containing replicated zation only increased the frequency the causative agent, C. neoformans, to C.
    [Show full text]
  • SARS-Cov-2 Viral Load and Antibody Responses: the Case for Convalescent Plasma Therapy
    SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy Arturo Casadevall, … , Michael J. Joyner, Liise-anne Pirofski J Clin Invest. 2020. https://doi.org/10.1172/JCI139760. Commentary In-Press Preview Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy. Find the latest version: https://jci.me/139760/pdf SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy Arturo Casadevall1, Michael J. Joyner2 and Liise-anne Pirofski3 1Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD, USA; 2Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, USA; 3Division of Infectious Diseases, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA Address correspondence: Arturo Casadevall Department of Molecular Microbiology and Immunology Johns Hopkins School of Public Health 615 N.
    [Show full text]
  • Coronavirus: Where We Are and the Path Forward on This Fight, the Investigation of Two Bolivian Scientists in the USA
    Coronavirus: where we are and the path forward on this fight, the investigation of two Bolivian scientists in the USA By: Milenka Arévalo, and Karen Gomez Drs. Milenka Arévalo and Karen Gomez are scientists who were born in Bolivia. Both moved to the U.S. to pursue their graduate degrees and have been living there ever since. With the objective of helping Bolivia, they interviewed a diverse panel of U.S. scientist and medical experts who shared their expertise and knowledge about the new coronavirus. This publication is intended for most readers with a desire to obtain up-to-date scientific information. However, some sections of this article provide details that are more appropriate for people with a scientific background. Interviews for this article were conducted from April 27th to May 1st. Since then, and since the time this publication was prepared, more information continues to be uncovered. The New Coronavirus, Its Spread, and Symptoms of the Disease it Causes On February 11, 2020, The International Committee on Taxonomy of Viruses and the World Health Organization (WHO) announced the name of the new coronavirus that had been spreading around the world. It was called “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” and coronavirus disease 19 (COVID-19) was the name of the disease it caused. Dr. Alan Schenkel, an Associate Professor in the Department of Microbiology, Immunology and Pathology at Colorado State University in Fort Collins, Colorado indicates that although “there are seven coronaviruses that infect humans (four cause the common cold, and three cause acute respiratory distress syndrome), SARS-CoV-2 is different because it has a very long shedding period (10-40 days) and long incubation time (4-14 days).” We now know that these features contribute to its rapid spread and make it very contagious.
    [Show full text]
  • NCFS Summary Report: Appendix A
    Reflecting Back—Looking Toward the Future Appendix A. National Commission on Forensic Science Commissioners and Biographies Co-Chairs: Gregory Champagne Julia Leighton Sally Q. Yates Gregory Czarnopys Hon. Bridget Mary Willie E. May, Ph.D. Deirdre Daly McCormack Vice-Chairs: M. Bonner Denton, Ph.D. Peter Neufeld Nelson Santos Jules Epstein Phil Pulaski John Butler, Ph.D. Stephen Fienberg, Ph.D. Matthew Redle John Fudenberg Sunita Sah, Ph.D. Commission Staff: S. James Gates, Jr., Ph.D. Michael “Jeff” Salyards, Ph.D. Andrew J. Bruck Dean Gialamas Ex-Officio Members: Victor Weedn, M.D. Paul Giannelli Rebecca Ferrell, Ph.D. Jonathan McGrath, Ph.D. Randy Hanzlick, M.D. David Honey, Ph.D. Danielle M. Weiss Hon. Barbara Hervey Marilyn Huestis, Ph.D. Lindsay DePalma Susan Howley Gerald LaPorte Commission Members: Ted Hunt Patricia Manzolillo Thomas Albright, Ph.D. Linda Jackson Hon. Jed Rakoff Suzanne Bell, Ph.D. Hon. Pam King Frances Schrotter Frederick Bieber, Ph.D. Troy Lawrence Kathryn Turman Arturo Casadevall, Ph.D. Marc LeBeau, Ph.D. Cecelia Crouse, Ph.D. NCFS Co-Chairs Sally Q. Yates Sally Quillian Yates became Acting Deputy Attorney General on January 10, 2015. President Obama formally nominated her for the position on January 8, 2015. Previously, Ms. Yates was nominated by President Obama to serve as U.S. Attorney for the Northern District of Georgia and was confirmed by the U.S. Senate on March 10, 2010. She was the first woman to serve as U.S. Attorney in the Northern District of Georgia. As the chief federal law enforcement official for the district, she oversaw the prosecution of all federal crimes and the litigation of civil matters in which the government had an interest in a district encompassing more than 6 million residents.
    [Show full text]