SARS-CoV-2 infection of the placenta

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Abstract

Background. The effects of Covid-19 in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic Covid-19 complicated by severe preeclampsia and placental abruption. Methods. We analyzed placenta for the presence of SARS-CoV-2 through molecular and immunohistochemical assays and by and electron microscopy, and we measured the maternal antibody response in blood to this infection. Results. SARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the maternal-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for vasculopathy typically associated with preeclampsia. Conclusion. This case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with Covid-19.

Authors

Hillary Hosier, Shelli F. Farhadian, Raffaella A. Morotti, Uma Deshmukh, Alice Lu-Culligan, Katherine H. Campbell, Yuki Yasumoto, Chantal B.F. Vogels, Arnau Casanovas-Massana, Pavithra Vijayakumar, Bertie Geng, Camila D. Odio, John Fournier, Anderson F. Brito, Joseph R. Fauver, Feimei Liu, Tara Alpert, Reshef Tal, Klara Szigeti-Buck, Sudhir Perincheri, Christopher P. Larsen, Aileen M. Gariepy, Gabriela Aguilar, Kristen L. Fardelmann, Malini Harigopal, Hugh S. Taylor, Christian M. Pettker, Anne L. Wyllie, Charles S. Dela Cruz, Aaron M. Ring, Nathan D. Grubaugh, Albert I. Ko, Tamas L. Horvath, Akiko Iwasaki, Uma M. Reddy, Heather S. Lipkind

Early safety indicators of COVID-19 convalescent plasma in 5,000 patients

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Abstract

BACKGROUND. Convalescent plasma is the only antibody based therapy currently available for COVID 19 patients. It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. METHODS. Thus, we analyzed key safety metrics after transfusion of ABO compatible human COVID-19 convalescent plasma in 5,000 hospitalized adults with severe or life threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma. RESULTS. The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%). Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (TACO; n = 7), transfusion-related acute lung injury (TRALI; n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 (of 36) SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The seven-day mortality rate was 14.9%. CONCLUSION. Given the deadly nature of COVID 19 and the large population of critically-ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.

Authors

Michael J. Joyner, R. Scott Wright, DeLisa Fairweather, Jonathon W. Senefeld, Katelyn A. Bruno, Stephen A. Klassen, Rickey E. Carter, Allan M. Klompas, Chad C. Wiggins, John R.A. Shepherd, Robert F. Rea, Emily R. Whelan, Andrew J. Clayburn, Matthew R. Spiegel, Patrick W. Johnson, Elizabeth R. Lesser, Sarah E. Baker, Kathryn F. Larson, Juan G. Ripoll, Kylie J. Andersen, David O. Hodge, Katie L. Kunze, Matthew R. Buras, Matthew N.P. Vogt, Vitaly Herasevich, Joshua J. Dennis, Riley J. Regimbal, Philippe R. Bauer, Janis E. Blair, Camille M. van Buskirk, Jeffrey L. Winters, James R. Stubbs, Nigel S. Paneth, Nicole C. Verdun, Peter Marks, Arturo Casadevall

New York City COVID-19 resident physician exposure during exponential phase of pandemic

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Abstract

Background From March 2-April 12, 2020, New York City (NYC) experienced exponential growth of the COVID-19 pandemic due to novel coronavirus (SARS-CoV-2). Little is known regarding how physicians have been affected. We aimed to characterize COVID-19 impact on NYC resident physicians. Methods IRB-exempt and expedited cross-sectional analysis through survey to NYC residency program directors (PDs) April 3–12, 2020, encompassing events from March 2–April 12, 2020. Results From an estimated 340 residency programs around NYC, recruitment yielded 91 responses, representing 24 specialties and 2,306 residents. 45.1% of programs reported at least one resident with confirmed COVID-19: 101 resident physicians were confirmed COVID-19-positive, with an additional 163 residents presumed positive for COVID-19 based on symptoms but awaiting or unable to obtain testing. Two COVID-19-positive residents were hospitalized, with one in intensive care. Among specialties with >100 residents represented, negative binomial regression indicated that infection risk differed by specialty (p=0.039). 80% of programs reported quarantining a resident. 90/91 programs reported reuse or extended mask use, and 43 programs reported that personal protective equipment (PPE) was suboptimal. 65 programs (74.7%) have redeployed residents elsewhere to support COVID-19 efforts. Conclusion Many resident physicians around NYC have been affected by COVID-19 through direct infection, quarantine, or redeployment. Lack of access to testing and concern regarding suboptimal PPE are common among residency programs. Infection risk may differ by specialty. Funding AHA, MPB, RWSC, CGM, LRDG, JDH: NEI Core Grant P30EY019007, RPB Unrestricted Grant. ACP and JS: Parker Family Chair. SXX: University of Pennsylvania.

Authors

Mark P. Breazzano, Junchao Shen, Aliaa H. Abdelhakim, Lora Dagi Glass, Jason Horowitz, Sharon X. Xie, C. Gustavo De Moraes, Alice Chen-Plotkin, Royce W.S. Chen

Clinical trials for COVID-19 should include sex as a variable

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This Viewpoint calls on investigators that are developing and testing therapeutic and prophylactic approaches for COVID-19 to design studies that are inclusive of male-female differences.

Authors

Evelyne Bischof, Jeannette Wolfe, Sabra L. Klein

Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists

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Medications that target catecholamine-associated inflammation may prevent cytokine storm syndrome associated with COVID-19 and other diseases.

Authors

Maximilian F. Konig, Michael A. Powell, Verena Staedtke, Ren-Yuan Bai, David L. Thomas, Nicole M. Fischer, Sakibul Huq, Adham M. Khalafallah, Allison Koenecke, Ruoxuan Xiong, Brett Mensh, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Joshua T. Vogelstein, Susan Athey, Shibin Zhou, Chetan Bettegowda

Prototype pathogen approach for pandemic preparedness: world on fire

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Improved pandemic preparedness could be achieved by proactively managing emerging virus threats using available technologies.

Authors

Barney S. Graham, Kizzmekia S. Corbett

Panic prescribing has become omnipresent during the COVID-19 pandemic

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Lessons from the Ebola outbreak shows that it is possible to develop rapid and effective clinical research responses without relying on anecdote.

Authors

Arthur L. Caplan, Ross Upshur

Deployment of convalescent plasma for the prevention and treatment of COVID-19

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e. “convalescent”) plasma refers to plasma that is collected from individuals, following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy to confer immediate immunity to susceptible individuals. There are numerous examples, where convalescent plasma has been used successfully as post-exposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East Respiratory Syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads and improved survival. Globally, blood centers have robust infrastructure to undertake collections and construct inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, from evidence of benefit, regulatory considerations, logistical work flow and proposed clinical trials, as scale up is brought underway to mobilize this critical resource.

Authors

Evan M. Bloch, Shmuel Shoham, Arturo Casadevall, Bruce S. Sachais, Beth Shaz, Jeffrey L. Winters, Camille van Buskirk, Brenda J. Grossman, Michael Joyner, Jeffrey P. Henderson, Andrew Pekosz, Bryan Lau, Amy Wesolowski, Louis Katz, Hua Shan, Paul G. Auwaerter, David Thomas, David J. Sullivan, Nigel Paneth, Eric Gehrie, Steven Spitalnik, Eldad Hod, Lewis Pollack, Wayne T. Nicholson, Liise-anne Pirofski, Jeffrey A. Bailey, Aaron A.R. Tobian

Kidney diseases in the time of COVID-19: major challenges to patient care

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The current COVID-19 pandemic has affected everyone, but presents profound consequences for patients with kidney disease, health care providers, and biomedical researchers. In this Viewpoint, I will discuss a number of kidney-specific aspects of COVID-19 infection, noting therapeutic and basic research opportunities.

Authors

Hamid Rabb

The COVID-19 pandemic and research shutdown: staying safe and productive

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This viewpoint addresses the major impact of the COVID-19 pandemic on biomedical research, the challenges created by the COVID-19 pandemic for research-intensive institutions, and what investigators can do to maintain some level of research activity while keeping their coworkers and trainees safe and engaged.

Authors

M. Bishr Omary, Jeetendra R. Eswaraka, S. David Kimball, Prabhas V. Moghe, Reynold A. Panettieri, Jr., Kathleen W. Scotto