The editors of JCI and JCI Insight have revised the editorial process to address the impact of the COVID-19 pandemic on the global research community. Highlights:
Background: Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Anti-viral immune response is crucial to achieve pathogen clearance, however in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. Methods: We performed a flow cytometric characterization of immune cells subsets from 30 COVID-19 patients and correlated these data with clinical outcomes. Results: COVID-19 patients showed decreased numbers of circulating T, B and NK cells, and exhibited a skewing of CD8+ T cells towards a terminally differentiated/senescent phenotype. In agreement, T CD4+, T CD8+ but also NK cells displayed reduced anti-viral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in COVID-19 patients, particularly in those that required intensive care. The latter group of patients showed also increased serum IL-6 levels, that correlated to the frequency of granzyme-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. Conclusion: In conclusion, the association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore anti-viral mechanisms. Funding: This study was supported by funds of Dept. of Experimental and Clinical Medicine of University of Florence (ex-60%) derived from Ministero dell’Istruzione, dell’Università e della Ricerca (Italy).
Alessio Mazzoni, Lorenzo Salvati, Laura Maggi, Manuela Capone, Anna Vanni, Michele Spinicci, Jessica Mencarini, Roberto Caporale, Benedetta Peruzzi, Alberto Antonelli, Michele Trotta, Lorenzo Zammarchi, Luca Ciani, Leonardo Gori, Chiara Lazzeri, Andrea Matucci, Alessandra Vultaggio, Oliviero Rossi, Fabio Almerigogna, Paola Parronchi, Paolo Fontanari, Federico Lavorini, Adriano Peris, Gian Maria Rossolini, Alessandro Bartoloni, Sergio Romagnani, Francesco Liotta, Francesco Annunziato, Lorenzo Cosmi
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.
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
In COVID-19, complement activation may contribute to hemostatic activation leading to pathological features such as microvascular injury and coagulopathy.
Wen-Chao Song, Garret A. FitzGerald
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.
Evelyne Bischof, Jeannette Wolfe, Sabra L. Klein
Barney S. Graham, Kizzmekia S. Corbett
Maximilian F. Konig, Mike Powell, Verena Staedtke, Ren-Yuan Bai, David L. Thomas, Nicole 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
Arthur L. Caplan, Ross Upshur
Severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2), the cause of coronavirus disease 2019 (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 for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure 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 for undertaking collections and constructing 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, including evidence of benefit, regulatory considerations, logistical work flow, and proposed clinical trials, as scale-up is brought underway to mobilize this critical resource.
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 A. Hod, Lewis Pollack, Wayne T. Nicholson, Liise-anne Pirofski, Jeffrey A. Bailey, Aaron A.R. Tobian
M. Bishr Omary, Jeetendra Eswaraka, S. David Kimball, Prabhas V. Moghe, Reynold A. Panettieri Jr., Kathleen W. Scotto
Arturo Casadevall, Liise-anne Pirofski
The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological characteristics between moderate and severe COVID-19. The authors found that respiratory distress on admission is associated with unfavorable outcomes. Increased cytokine levels (IL-6, IL-10, and TNF-α), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-γ expression in CD4+ T cells are associated with severe COVID-19. Overall, this study characterized the cytokine storm in severe COVID-19 and provides insights into immune therapeutics and vaccine design.
Savannah F. Pedersen, Ya-Chi Ho
BACKGROUND Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODS In this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTS The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSION The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATION This is a retrospective observational study without a trial registration number.FUNDING This work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).
Guang Chen, Di Wu, Wei Guo, Yong Cao, Da Huang, Hongwu Wang, Tao Wang, Xiaoyun Zhang, Huilong Chen, Haijing Yu, Xiaoping Zhang, Minxia Zhang, Shiji Wu, Jianxin Song, Tao Chen, Meifang Han, Shusheng Li, Xiaoping Luo, Jianping Zhao, Qin Ning
The editors of JCI and JCI Insight are revisiting our editorial processes in light of the strain that the COVID-19 pandemic places on the worldwide scientific community. Here, we discuss adjustments to our decision framework in light of restrictions placed on laboratory working conditions for many of our authors.
Rexford S. Ahima, Sarah Jackson, Arturo Casadevall, Gregg L. Semenza, Gordon Tomaselli, Kathleen L. Collins, Andrew P. Lieberman, Donna M. Martin, Pavan Reddy