Letter
Clinical Neurology
Aravind Ganesh, Steven Galetta
Summary: The study found lower total alpha-synuclein levels in the CSF of PD patients with high sensitivity but low specificity compared to HCs. Alpha-synuclein immunoreactivity in skin and submandibular gland was specific for PD but not sensitive. There are ongoing debates and uncertainties in methodology surrounding the detection of synuclein in tissue samples.
Article
Biochemistry & Molecular Biology
Yan-Yan Li, Tian-Tian Zhou, Yi Zhang, Nai-Hong Chen, Yu-He Yuan
Summary: This review summarizes the distribution of alpha-synuclein in the central nervous system and peripheral tissues of Parkinson's disease patients, and discusses the aggregation mechanism, providing a basis for early diagnosis and intervention.
NEUROCHEMICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jianmin Si, Chris van den Haute, Evy Lobbestael, Shaun Martin, Sarah van Veen, Peter Vangheluwe, Veerle Baekelandt
Summary: ATP13A2 loss impairs lysosomal membrane integrity and induces alpha-synuclein multimerization, while overexpression has a protective effect on alpha-synuclein by promoting ubiquitin-proteasome system activity and reducing alpha syn membrane association. Additionally, ATP13A2 promotes the secretion of alpha-synuclein through nanovesicles, suggesting a regulatory function independent of ATPase and transport activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Hao Gu, Xiuli Yang, Xiaobo Mao, Enquan Xu, Chen Qi, Haibo Wang, Saurav Brahmachari, Bethany York, Manjari Sriparna, Amanda Li, Michael Chang, Pavan Patel, Valina L. Dawson, Ted M. Dawson
Summary: The depletion of Lag3 in transgenic mice carrying human alpha-syn A53T mutation significantly reduces insoluble alpha-syn aggregates, delays disease progression, improves behavioral deficits, and prolongs survival, indicating the contribution of Lag3 to the pathogenesis in this model.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Zohra Rahmani, Satya Surabhi, Francisca Rojo-Cortes, Amina Dulac, Andreas Jenny, Serge Birman
Summary: The lack of Lamp1 in fruit flies increases susceptibility to oxidative stress and neurotoxicity caused by alpha-synuclein, suggesting a protective role of Lamp1 in Parkinson's disease models. Lamp1 promotes the formation of non-pathogenic aggregates, neutralizing the toxicity of alpha-synuclein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Alberto Delaidelli, Mette Richner, Lixiang Jiang, Amelia van der Laan, Ida Bergholdt Jul Christiansen, Nelson Ferreira, Jens R. Nyengaard, Christian B. Vaegter, Poul H. Jensen, Ian R. Mackenzie, Poul H. Sorensen, Asad Jan
Summary: The pathological accumulation of alpha-synuclein impairs redox homeostasis in the nervous system, leading to nuclear NRF2 accumulation and alterations in NRF2-responsive genes. Using a transgenic mouse model, it was observed that neuronal populations with phosphorylated aSyn showed increased nuclear NRF2 and abnormal anti-oxidant and inflammatory gene response in the affected neuraxis. Boosting neuronal anti-oxidant response may be a promising strategy to mitigate neurodegeneration in PD and related diseases.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
A. Anandhan, W. Chen, N. Nguyen, L. Madhavan, M. Dodson, D. D. Zhang
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the accumulation of alpha-synuclein and its negative effects on neuronal function and viability. This study demonstrates that loss of NRF2, a critical anti-ferroptotic mediator, increases markers of ferroptosis in PD-relevant brain regions. The increased ferroptosis is associated with age and genotype-dependent increase in alpha-syn pathology and behavioral deficits. The findings suggest targeting the vicious cycle of alpha-syn overexpression and NRF2 suppression as a potential means of preventing PD onset and progression.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Physical
Vinod Kumar Meena, Vijay Kumar, Shivani Karalia
Summary: The natural extract of Ocimum sanctum (OS) has been found to inhibit the aggregation of alpha-Synuclein (alpha-Syn), suggesting a potential therapeutic intervention against Parkinson's disease (PD) and other aggregation-related disorders. The study demonstrates the inhibitory and disaggregation effects of OS extract on alpha-Synuclein, as well as its protective effect on neuroblastoma cells against fibril-induced cytotoxicity. Docking studies also indicate the binding of OS extract with alpha-Synuclein, paving the way for further research on potential therapeutic strategies.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Cell Biology
Alice Prieto Huarcaya, Susy Drobny, Andre R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert, Denise Balta, Christian Werner, Tania Rizo, Lisa Gallwitz, Simon Bub, Iva Stojkovska, Nandkishore R. Belur, Jens Fogh, Joseph R. Mazzulli, Wei Xiang, Amitkumar Fulzele, Mario Dejung, Markus Sauer, Beate Winner, Stefan Rose-John, Philipp Arnold, Paul Saftig, Friederike Zunke
Summary: This study suggests that enhancing SNCA degradation through the application of rHsCTSD can reduce SNCA aggregates in the brains of PD patients and restore endo-lysosome and autophagy function.
Article
Neurosciences
Antonio Dominguez-Meijide, Valeria Parrales, Eftychia Vasili, Florencia Gonzalez-Lizarraga, Annekatrin Konig, Diana F. Lazaro, Annie Lannuzel, Stephane Haik, Elaine Del Bel, Rosana Chehin, Rita Raisman-Vozari, Patrick P. Michel, Nicolas Bizat, Tiago Fleming Outeiro
Summary: Doxycycline shows neuroprotective effects by reducing and inhibiting the aggregation of α-synuclein, attenuating oxidative stress in cells, and may be an effective strategy against synucleinopathies such as Parkinson's disease.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Clinical Neurology
Yuhua Chen, Wei Wu, Shuli Zhao, Xinyi Lv, Ji Hu, Chao Han, Guoping Wang, Shicun Wang, Pan Bo, Juan Zhang, Wei Gui, Qiqiang Tang, Qiang Liu, Shu Zhu, Feng Yu
Summary: This study found that chronic appendicitis-like lesions were detected in 53% of patients with PD, and patients with appendicitis-like lesions, impaired olfaction, and rapid eye movement sleep behavior disorder were at higher risk for PD. Additionally, histopathological analysis revealed structural changes associated with chronic appendicitis and alpha-Syn aggregation in PD patients with chronic appendicitis.
MOVEMENT DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Marco Greco, Chiara Carmela Spinelli, Lidia De Riccardis, Alessandro Buccolieri, Simona Di Giulio, Debora Musaro, Claudia Pagano, Daniela Manno, Michele Maffia
Summary: Copper dysregulation is linked to various neuropathologies such as Parkinson's disease; differentiated neurons express higher levels of CTR1 protein leading to increased copper uptake; copper treatment enhances phosphorylation of alpha-synuclein, potentially offering new opportunities for clinical intervention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Jun Ueda, Norihito Uemura, Masanori Sawamura, Tomoyuki Taguchi, Masashi Ikuno, Seiji Kaji, Yosuke Taruno, Shuichi Matsuzawa, Hodaka Yamakado, Ryosuke Takahashi
Summary: This study found that the antiepileptic drug perampanel can inhibit the transmission of alpha-synuclein in neurons by blocking macropinocytosis dependent on neuronal activity, thus potentially serving as a novel disease-modifying drug for Parkinson's disease.
MOVEMENT DISORDERS
(2021)
Article
Neurosciences
Federica Piancone, Marina Saresella, Francesca La Rosa, Ivana Marventano, Mario Meloni, Jorge Navarro, Mario Clerici
Summary: While alpha-syn did not activate the NLRP3 inflammasome, neuroinflammation in PD patients may be related to an imbalance between proinflammatory and anti-inflammatory cytokines.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Reito Nakamura, Ikumi Tomizawa, Atsushi Iwai, Tetsuo Ikeda, Kota Hirayama, Yung Wen Chiu, Takanobu Suzuki, Airi Tarutani, Tatsuo Mano, Atsushi Iwata, Tatsushi Toda, Youhei Sohma, Motomu Kanai, Yukiko Hori, Taisuke Tomita
Summary: Aggregation of alpha-synuclein into amyloid is a pathological hallmark of neurodegenerative disorders, and inhibiting this aggregation can be a potential therapeutic strategy. This study demonstrates that photo-oxygenation using a photocatalyst successfully inhibits alpha-synuclein aggregation by reducing its seeding ability. The oxidation of histidine residue in alpha-synuclein is found to be responsible for this inhibitory effect.
Article
Genetics & Heredity
Megan Null, Josee Dupuis, Pezhman Sheinidashtegol, Ryan M. Layer, Christopher R. Gignoux, Audrey E. Hendricks
Summary: Identification of rare-variant associations is crucial for understanding the genetic architecture of complex traits and diseases. Existing simulation methods have limitations in using real-variant annotation and accurately estimating the number of rare variants. This study presents a flexible and accurate rare-variant simulation algorithm, RAREsim, that can simulate the expected variant distribution and provide real-variant annotations.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Immunology
Yijia Li, Linda J. Harrison, Kara W. Chew, Judy S. Currier, David A. Wohl, Eric S. Daar, Teresa H. Evering, Ryan Wu, Mark Giganti, Justin Ritz, Arzhang Cyrus Javan, Robert W. Coombs, Carlee Moser, Michael D. Hughes, Joseph J. Eron, Davey M. Smith, Jonathan Z. Li
Summary: This exploratory analysis of placebo recipients in the ACTIV2/A5401 platform trial showed that high anterior nasal RNA levels and detectable plasma RNA were associated with delayed symptom improvement in acute Coronavirus Disease 2019.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Babafemi O. Taiwo, Kara W. Chew, Carlee Moser, David Alain Wohl, Eric S. Daar, Jonathan Z. Li, Alexander L. Greninger, Christoph Bausch, Thomas Luke, Keila Hoover, Gene Neytman, Mark J. Giganti, Maxine Olefsky, Arzhang Cyrus Javan, Courtney Fletcher, Joseph J. Eron, Judith S. Currier, Michael D. Hughes, Davey M. Smith
Summary: SAB-185, a novel IgG polyclonal immunoglobulin product, showed antiviral activity and safety in nonhospitalized adults with mild-moderate COVID-19.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Correction
Multidisciplinary Sciences
Kara W. Chew, Carlee S. Moser, Eric S. A. Daar, David A. Z. Wohl, Jonathan Z. W. Li, Robert W. Coombs, Justin Ritz, Mark Giganti, Arzhang Cyrus Javan, Yijia C. Li, Manish C. Choudhary, Rinki Deo, Carlos Malvestutto, Paul Klekotka, Karen Price, Ajay Nirula, William Fischer, Veenu M. Bala, Ruy M. S. Ribeiro, Alan S. V. Perelson, Courtney V. J. Fletcher, Joseph J. S. Eron, Judith S. D. Currier, Michael D. M. Hughes, Davey M. Smith
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Teresa H. Evering, Kara W. Chew, Mark J. Giganti, Carlee Moser, Mauricio Pinilla, David Alain Wohl, Judith J. Currier, Joseph Eron, Arzhang Cyrus Javan, Rachel Bender Ignacio, David Margolis, Qing Zhu, Ji Ma, Lijie Zhong, Li Yan, Ulises D'Andrea Nores, Keila Hoover, Bharat Mocherla, Manish C. Choudhary, Rinki Deo, Justin Ritz, William A. Fischer, Courtney Fletcher, Jonathan Z. Li, Michael D. Hughes, Davey Smith, Eric S. Daar
Summary: This randomized controlled trial assessed the safety and efficacy of amubarvimab plus romlusevimab. The combination treatment significantly reduced the risk of hospitalization and/or death among nonhospitalized adults with mild to moderate SARSCoV-2 infection at high risk for progression to severe disease.
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Medicine, General & Internal
Rinki Deo, Manish C. Choudhary, Carlee Moser, Justin Ritz, Eric S. Daar, David A. Wohl, Alexander L. Greninger, Joseph J. Eron, Judith S. Currier, Michael D. Hughes, Davey M. Smith, Kara W. Chew, Jonathan Z. Li
Summary: The study retrospectively analyzed untreated outpatients with mild to moderate COVID-19 and found that symptom and viral rebound were common, but the combination of symptom and viral rebound was rare.
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Immunology
Elizabeth Hastie, Carlee Moser, Xin Sun, Jeffrey Lennox, Priscilla Y. Hsue, Ronald J. Bosch, Steven Deeks, Milenka Meneses, Michael M. Lederman, Peter Hunt, Timothy J. Henrich, Vincent C. Marconi, Sara Gianella
Summary: The immune-modulators ruxolitinib and sirolimus did not have a significant effect on CMV DNA shedding in people with HIV on suppressive antiretroviral therapy. However, higher CMV DNA levels were associated with immune markers related to HIV persistence and mortality rates. CMV is a known contributor to the persistent inflammation and immune dysfunction observed in HIV.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Clinical Neurology
Yuankai Zhang, Xue Liu, Kerri L. Wiggins, Nuzulul L. Kurniansyah, Xiuqing Guo, Amanda L. Rodrigue, Wei Zhao, Lisa R. Yanek, Scott M. Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patino, Tamar Sofer, Dan E. Arking, Thomas R. Austin, Alexa S. Beiser, John Blangero, Eric E. Boerwinkle, Jan Bressler, Joanne E. Curran, Lifang Hou, Timothy J. Hughes, Sharon L. R. Kardia, Lenore J. Launer, Daniel Levy, Thomas H. Mosley, Ilya M. Nasrallah, Stephen S. Rich, Jerome Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A. Gonzalez, Vasan Ramachandran, Kristine Yaffe, Paul A. Nyquist, Bruce M. Psaty, Charles C. DeCarli, Jennifer M. Smith, David C. Glahn, Hector M. Gonzalez, Joshua R. Bis, Myriam L. Fornage, Susan Heckbert, Annette L. Fitzpatrick, Chunyu Liu, Claudia L. Satizabal
Summary: This study found that higher mitochondrial DNA copy number (CN) in blood is associated with better cognitive function in both current and future settings, but is not causally related to cognition. This suggests that circulating mtDNA CN could serve as a biomarker of cognitive function in the community.
Correction
Multidisciplinary Sciences
Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernandez, Laura Montrreal, Carmen Antunez, Anna Antonell, Rick M. Tankard, Joshua Bis, Rebecca Sims, Celine Bellenguez, Ines Quintela, Antonio Gonzalez-Perez, Miguel Calero, Emilio Franco-Macias, Juan Macias, Rafael Blesa, Laura Cervera-Carles, Manuel Menendez-Gonzalez, Ana C. Frank-Garcia, Jose Luis W. Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Monica Diez-Fairen, Carmen Lage, Sebastian Garcia-Madrona, Pablo Garcia-Gonzalez, Emilio Alarcon-Martin, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Perez-Cordon, Alberto L. Benussi, Alberto Rabano, Alessandro Padovani, Alessio Squassina, Alexandre de Mendonca, Alfonso M. Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belen Pastor, Ana Espinosa, Anais Corma-Gomez, Angel Martin Montes, Angela Sanabria, Anita W. DeStefano, Anja Schneider, Annakaisa Haapasalo, Anne Kinhult Stahlbom, Anne Tybjaerg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbaton-Anchuelo, Arvid B. Rongve, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Borge G. Nordestgaard, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martinez Rodriguez, Carmen Munoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina Ferreira, Caterina Chillotti, Chandra A. Reynolds, Chiara Fenoglio, Christine Van Broeckhoven, Christopher Clark, Claudia Pisanu, Claudia L. Satizabal, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland, Dan Rujescu, Daniel Alcolea, Daniela Galimberti, David Wallon, Davide Seripa, Edna Grunblatt, Efthimios Dardiotis, Emrah Duezel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Kuecuekali, Florence Pasquier, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gael Nicolas, Geir Selbaek, Gemma K. Ortega, Genevieve Chene, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg, Hilkka Soininen, Ida Karlsson, Ignacio Alvarez, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen, Jean-Sebastien Vidal, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber, Jonathan A. Haines, Jonathan Vogelgsang, Juan Pineda, Juan Fortea, Julius Popp, Juergen Deckert, Katharina Buerger, Kevin Morgan, Klaus Fliessbach, Kristel Sleegers, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay Farrer, Li-San Wang, Luca Kleineidam, Lucia A. Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram, M. Candida Deniz-Naranjo, Magda Tsolaki, Maitee Rosende-Roca, Malin Lowenmark, Marc Hulsman, Marco Spallazzi, Margaret H. Pericak-Vance, Margaret Esiri, Maria Bernal Sanchez-Arjona, Maria Carolina Dalmasso, Maria Teresa T. Martinez-Larrad, Marina Arcaro, Markus Noethen, Marta Fernandez-Fuertes, Martin Dichgans, Martin Ingelsson, Martin Herrmann, Martin Scherer, Martin Vyhnalek, Mary M. Kosmidis, Mary M. Yannakoulia, Matthias Schmid, Michael J. Ewers, Michael T. Heneka, Michael Wagner, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja van Schoor, Nazib Seidu, Nerisa Banaj, Nicola Armstrong, Nikolaos Scarmeas, Norbert A. Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez, Ondrej Lerch, Paola Bossu, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Patrizia Mecocci, Per Hoffmann, Peter Holmans, Peter A. Fischer, Peter Riederer, Qiong Yang, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Haegg, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi, Valentina Escott-Price, Vilmantas Giedraitis, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian, Yolande A. L. Pijnenburg, Patrick Gavin Kehoe, Guillermo Garcia-Ribas, Pascual Sanchez-Juan, Pau Pastor, Jordi Perez-Tur, Gerard Pinol-Ripoll, Adolfo Lopez De Munain, Jose Maria Garcia-Alberca, Maria J. Bullido, Victoria Alvarez, Alberto Lleo, Luis M. Real, Pablo Mir Miguel Medina, Philip Scheltens, Henne Holstege, Marta Marquie, Maria Eugenia Saez, Angel Carracedo, Philippe Amouyel, Gerard D. Schellenberg, Julie Williams, Sudha Seshadri, CorneliaM. Van Duijn, Karen A. Mather, Raquel Sanchez-Valle, Manuel Serrano-Rios, Adelina Orellana, Lluis Tarraga, Kaj Blennow, Ole A. Andreassen, Danielle Posthuma, Jordi Clarimon, Merce Boada, Wiesje M. Van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. Van der Lee, Agustin Ruiz
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Judith S. Currier, Carlee Moser, Joseph J. Eron, Kara W. Chew, Davey M. Smith, Arzhang Cyrus Javan, David Alain Wohl, Eric S. Daar, Michael D. Hughes
Summary: The clinical trial is registered with identifier NCT04518410.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Yijia Li, Carlee Moser, Evgenia Aga, Judith S. Currier, David A. Wohl, Eric S. Daar, Justin Ritz, Alexander L. Greninger, Scott Sieg, Urvi M. Parikh, Robert W. Coombs, Michael D. Hughes, Joseph J. Eron, Davey M. Smith, Kara W. Chew, Jonathan Z. Li
Summary: Immunocompromised individuals with moderate/severe immunosuppression have higher nasal viral load and might have higher cumulative nasal RNA levels and plasma viremia. Immunosuppression leads to greater viral shedding and altered viral decay kinetics.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Mark J. Giganti, Kara W. Chew, Joseph J. Eron, Jonathan Z. Li, Mauricio Pinilla, Carlee Moser, Arzhang Cyrus Javan, William A. Fischer, Paul Klekotka, David Margolis, David Alain Wohl, Robert W. Coombs, Eric S. Daar, Davey M. Smith, Judith S. Currier, Michael D. Hughes
Summary: The level of SARS-CoV-2 RNA is predictive of hospitalization/death, but the level of anterior nasal (AN) RNA may not be a reliable marker for the efficacy of monoclonal antibody (mAb) treatment in COVID-19 trials.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Ruy M. Ribeiro, Manish C. Choudhary, Rinki Deo, Mark J. Giganti, Carlee Moser, Justin Ritz, Alexander L. Greninger, James Regan, James P. Flynn, David A. Wohl, Judith S. Currier, Joseph J. Eron, Michael D. Hughes, Davey M. Smith, Kara W. Chew, Eric S. Daar, Alan S. Perelson, Jonathan Z. Li
Summary: Understanding variant-specific differences in SARS-CoV-2 viral kinetics is important for explaining transmission efficiency and gaining insights on pathogenesis and prevention. In this study, we found that the Delta variant had the highest viral load and the shortest time to peak viral load among multiple variants. There were no significant differences in time to viral clearance across the variants, but differences were observed in the second phase of viral decay. These results indicate that while variant-specific differences exist, all variants appear to be efficiently cleared by the host after reaching peak viral load.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Carlee B. Moser, Kara W. Chew, Justin Ritz, Matthew Newell, Arzhang Cyrus Javan, Joseph J. Eron, Eric S. Daar, David A. Wohl, Judith S. Currier, Davey M. Smith, Michael D. Hughes
Summary: During the COVID-19 pandemic, adaptive platform trials were used to quickly assess therapeutics, such as the ACTIV-2 trial, which evaluated 7 investigational agents with different administration routes. The trial compared safety and efficacy outcomes of each agent to a pooled placebo control group. The implementation of a pooled placebo design resulted in a 6% reduction in sample size compared to a trial with separate placebo control groups, and a 26% reduction during the phase 2 evaluation of multiple agents. This study discusses the complexities and provides insights for the design of future platform trials.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Kara W. Chew, Carlee Moser, Eunice Yeh, David A. Wohl, Eric S. Daar, Justin Ritz, Arzhang Cyrus Javan, Joseph J. Eron, Judith S. Currier, Davey M. Smith, Michael D. Hughes, ACTIV-A Study Team
Summary: This study evaluated the time to symptom resolution in COVID-19 patients and found that sustained resolution of targeted symptoms for 2 days was consistent with overall symptom improvement and return to health. Requiring >2 days of symptom resolution reduced the frequency of recurrences for both high-risk and standard-risk patients.
JOURNAL OF INFECTIOUS DISEASES
(2023)