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:
Convalescent plasma is a leading treatment for COVID-19, but there is a paucity of data identifying therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to spike(S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain(S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101(80%) had detectable neutralizing antibody(nAb) titers. Using nAb titers as the reference, the IgG ELISAs confirmed between 95-98% of the nAb positive, but only 20-32% of the nAb negative samples. Male sex, older age, and hospitalization with COVID-19 were associated with increased antibody responses across the serological assays. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses.
Sabra L. Klein, Andrew Pekosz, Han-Sol Park, Rebecca L. Ursin, Janna R. Shapiro, Sarah E. Benner, Kirsten Littlefield, Swetha Kumar, Harnish Mukesh Naik, Michael Betenbaugh, Ruchee Shrestha, Annie A. Wu, Robert M. Hughes, Imani Burgess, Patrizio Caturegli, Oliver Laeyendecker, Thomas C. Quinn, David J. Sullivan, Shmuel Shoham, Andrew D. Redd, Evan M. Bloch, Arturo Casadevall, Aaron A. R. Tobian
Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyper-inflammation and thrombotic microangiopathy, thereby increasing COVID-19 mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies and NETs/human aortic endothelial cell (HAEC) co-cultures. Increased plasma levels of NETs, tissue factor (TF) activity and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAEC. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against SARS-CoV-2 that exploit complement or NETosis inhibition.
Panagiotis Skendros, Alexandros Mitsios, Akrivi Chrysanthopoulou, Dimitrios C. Mastellos, Simeon Metallidis, Petros Rafailidis, Maria Ntinopoulou, Eleni Sertaridou, Victoria Tsironidou, Christina Tsigalou, Maria G. Tektonidou, Theocharis Konstantinidis, Charalampos Papagoras, Ioannis Mitroulis, Georgios Germanidis, John D. Lambris, Konstantinos Ritis
This Viewpoint describes how physicians and researchers can utilize approaches based on relationship-centered care and structural competence to reduce racism and enhance trustworthiness in health care and biomedical research.
Lisa A. Cooper, Deidra C. Crews
An alarming increase in children presenting with fever, hyperinflammation and multiorgan dysfunction frequently requiring intensive care has been observed after SARS-CoV-2 infection. The illness resembles Kawasaki Disease (KD) with coronary dilatation and aneurysm occurring in some. However, the cardiovascular manifestations were typically on the severe end of the KD spectrum with cardiogenic shock a common presentation together with other features. This led to defining a unique syndrome named multisystem inflammatory syndrome in Children (MIS-C). In this issue of the JCI, Lee and Day-Lewis et al. and Diorio et al. explored the clinical profiles associated with COVID-19 in children. We posit that while splitting MIS-C into a separate disease may aid clinical management decisions, lumping it into the KD pot may better serve to understand pathobiology.
Rae S.M. Yeung, Polly J. Ferguson
Background: Initial reports from the Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to Coronavirus Disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed Multisystem Inflammatory Syndrome in Children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology. Methods: We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8 and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. Cts and burr cells on blood smears also differentiated between patients with severe COVID-19 and those with MIS-C. Conclusion: Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and severe COVID-19.
Caroline Diorio, Sarah E. Henrickson, Laura A. Vella, Kevin O. McNerney, Julie M. Chase, Chakkapong Burudpakdee, Jessica H. Lee, Cristina Jasen, Fran Balamuth, David M. Barrett, Brenda Banwell, Kathrin M. Bernt, Allison M. Blatz, Kathleen Chiotos, Brian T. Fisher, Julie C. Fitzgerald, Jeffrey S. Gerber, Kandace Gollomp, Christopher Gray, Stephan A. Grupp, Rebecca M. Harris, Todd J. Kilbaugh, Audrey R. Odom John, Michele P. Lambert, Emily J. Liebling, Michele Paessler, Whitney Petrosa, Charles A. Phillips, Anne F. Reilly, Neil Romberg, Alix E. Seif, Deborah Sesok-Pizzini, Kathleen Sullivan, Julie Vardaro, Edward M Behrens, David T. Teachey, Hamid Bassiri
Background: Pediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail. Methods: We retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS). Results: Twenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range 1 month to 17 years); 50% of patients had pre-existing conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) requiring inotrope support. Seven patients (25%) met criteria for complete or incomplete KD and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6 and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to MIS-C patients included IVIG (71%), corticosteroids (61%) and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort. Conclusion: MIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from Kawasaki disease and macrophage activation syndrome. Funding: This work was supported by the National Institute of Health / National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) K08-AR074562 (PYL), K08-AR AR073339 (LAH), R01-AR065538, R01-AR073201 and P30-AR070253 (PAN); National Institute of Allergy and Infectious Diseases 5T32AI007512-34 (JL, JR, TB, AAN and RWN); Rheumatology Research Foundation Investigator Awards (PYL and LAH) and Medical Education Award (JSH); Boston Children’s Hospital Faculty Career Development Awards (PYL and LAH), the McCance Family Foundation (JWN), and the Samara Jan Turkel Center (JC, RPS, MBS).
Pui Y. Lee, Megan Day-Lewis, Lauren A. Henderson, Kevin Friedman, Jeffrey Lo, Jordan E. Roberts, Mindy S. Lo, Craig D. Platt, Janet Chou, Kacie J. Hoyt, Annette L. Baker, Tina Banzon, Margaret H. Chang, Ezra Cohen, Sarah de Ferranti, Audrey Dionne, Saddiq Habiballah, Olha Halyabar, Jonathan S. Hausmann, Melissa Hazen, Erin Janssen, Esra Meidan, Ryan W. Nelson, Alan A. Nguyen, Robert P. Sundel, Fatma Dedeoglu, Peter A. Nigrovic, Jane W. Newburger, Mary Beth F. Son
A retrospective look at how clinical research trials were prioritized in New York City in the wake of the COVID-19 pandemic provides insights for future clinical research efforts.
Roy M. Gulick, Magdalena E. Sobieszczyk, Donald W. Landry, Anthony N. Hollenberg
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.
Arturo Casadevall, Michael J. Joyner, Liise-anne Pirofski
The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients’ plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.
Yanqun Wang, Lu Zhang, Ling Sang, Feng Ye, Shicong Ruan, Bei Zhong, Tie Song, Abeer N. Alshukairi, Rongchang Chen, Zhaoyong Zhang, Mian Gan, Airu Zhu, Yongbo Huang, Ling Luo, Chris KP Mok, Manal M. Al Gethamy, Haitao Tan, Zhengtu Li, Xiaofang Huang, Fang Li, Jing Sun, Yanjun Zhang, Liyan Wen, Yuming Li, Zhao Chen, Zhen Zhuang, Jianfen Zhuo, Chunke Chen, Lijun Kuang, Junxiang Wang, Huibin Lv, Yongliang Jiang, Min Li, Yimin Lin, Ying Deng, Lan Tang, Jieling Liang, Jicheng Huang, Stanley Perlman, Nanshan Zhong, Jingxian Zhao, J.S. Malik Peiris, Yimin Li, Jincun Zhao
New York City has been described as the epicenter of the COVID-19 pandemic in the United States. While health care workers are notably at increased risk for COVID-19 infection, the impact on resident physicians remains unclear. In this issue of the JCI, Breazzano et al. surveyed resident physicians for their exposure to COVID-19 during the exponential phase of the COVID-19 pandemic. The researchers also assessed how personal protective equipment and COVID-19 testing protected health care workers from infection. This study highlights resident physician experiences of the first COVID-19 wave that can inform and improve preparedness for upcoming COVID-19 surges and other future epidemics.
Lauren I. Shapiro, Grace R. Kajita, Julia H. Arnsten, Yaron Tomer
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.
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
BACKGROUND Convalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). 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 5000 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), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (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 7-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.TRIAL REGISTRATION ClinicalTrials.gov NCT04338360.FUNDING Mayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.
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
Leonard Angka, Marisa Market, Michele Ardolino, Rebecca C. Auer
BACKGROUND Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral 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 cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTS Patients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A–expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSION The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDING This study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the “Excellence Departments 2018–2022 Project”) 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, 2020, to 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 the COVID-19 impact on NYC resident physicians.METHODS IRB-exempt and expedited cross-sectional analysis through survey to NYC residency program directors April 3–12, 2020, encompassing events from March 2, 2020, to April 12, 2020.RESULTS From an estimated 340 residency programs around NYC, recruitment yielded 91 responses, representing 24 specialties and 2306 residents. In 45.1% of programs, at least 1 resident with confirmed COVID-19 was reported. One hundred one 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 1 in intensive care. Among specialties with more than 100 residents represented, negative binomial regression indicated that infection risk differed by specialty (P = 0.039). In 80% of programs, quarantining a resident was reported. Ninety of 91 programs reported reuse or extended mask use, and 43 programs reported that personal protective equipment (PPE) was suboptimal. Sixty-five programs (74.7%) 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 National Eye Institute Core Grant P30EY019007; Research to Prevent Blindness Unrestricted Grant; Parker Family Chair; University of Pennsylvania.
Mark P. Breazzano, Junchao Shen, Aliaa H. Abdelhakim, Lora R. Dagi Glass, Jason D. Horowitz, Sharon X. Xie, C. Gustavo de Moraes, Alice Chen-Plotkin, Royce W.S. Chen, on behalf of the New York City Residency Program Directors COVID-19 Research Group
Wen-Chao Song, Garret A. FitzGerald
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