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medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.06.01.21257987


ABSTRACT BACKGROUND: Information is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions. METHODS: Prospective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020--April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription--polymerase-chain-reaction (RT-PCR). VE was calculated as 100%x (1-hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation . RESULTS: SARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially ([≥]14 days post-dose-1 to 13 days after dose-2) or fully ([≥]14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%--97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants. CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.

Severe Acute Respiratory Syndrome , Breakthrough Pain , COVID-19
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.12.22.422953


The Membrane Associated RING-CH (MARCH) proteins belong to a family of E3 ubiquitin ligases, whose main function is to remove transmembrane proteins from the plasma membrane. Recent work has shown that the human MARCH1, 2 and 8 are antiretroviral factors that target the Human Immunodeficiency virus-1 (HIV-1) envelope glycoproteins by reducing their incorporation in the budding virions. Nevertheless, the dearth of information regarding the antiviral mechanism of this family of proteins necessitates further examination. In this study, using both the human MARCH proteins and their mouse homologues, we provide a comprehensive analysis of the antiretroviral mechanism of this family of proteins. Moreover, we show that human MARCH proteins restrict to varying degrees the envelope glycoproteins of a diverse number of viruses. This report sheds light on the important antiviral function of MARCH proteins and their significance in cell intrinsic immunity.

Stephanie A. Kujawski; Karen K Wong; Jennifer P. Collins; Lauren Epstein; Marie E. Killerby; Claire M. Midgley; Glen R. Abedi; N. Seema Ahmed; Olivia Almendares; Francisco N. Alvarez; Kayla N. Anderson; Sharon Balter; Vaughn Barry; Karri Bartlett; Karlyn Beer; Michael A. Ben-Aderet; Isaac Benowitz; Holly Biggs; Alison M. Binder; Stephanie R. Black; Brandon Bonin; Catherine M. Brown; Hollianne Bruce; Jonathan Bryant-Genevier; Alicia Budd; Diane Buell; Rachel Bystritsky; Jordan Cates; E. Matt Charles; Kevin Chatham-Stephens; Nora Chea; Howard Chiou; Demian Christiansen; Victoria Chu; Sara Cody; Max Cohen; Erin Conners; Aaron Curns; Vishal Dasari; Patrick Dawson; Traci DeSalvo; George Diaz; Matthew Donahue; Suzanne Donovan; Lindsey M. Duca; Keith Erickson; Mathew D. Esona; Suzanne Evans; Jeremy Falk; Leora R. Feldstein; Martin Fenstersheib; Marc Fischer; Rebecca Fisher; Chelsea Foo; Marielle J. Fricchione; Oren Friedman; Alicia M. Fry; Romeo R. Galang; Melissa M. Garcia; Susa I. Gerber; Graham Gerrard; Isaac Ghinai; Prabhu Gounder; Jonathan Grein; Cheri Grigg; Jeffrey D. Gunzenhauser; Gary I. Gutkin; Meredith Haddix; Aron J. Hall; George Han; Jennifer Harcourt; Kathleen Harriman; Thomas Haupt; Amber Haynes; Michelle Holshue; Cora Hoover; Jennifer C. Hunter; Max W. Jacobs; Claire Jarashow; Michael A. Jhung; Kiran Joshi; Talar Kamali; Shifaq Kamili; Lindsay Kim; Moon Kim; Jan King; Hannah L. Kirking; Amanda Kita-Yarbro; Rachel Klos; Miwako Kobayashi; Anna Kocharian; Kenneth K. Komatsu; Ram Koppaka; Jennifer E. Layden; Yan Li; Scott Lindquist; Stephen Lindstrom; Ruth Link-Gelles; Joana Lively; Michelle Livingston; Kelly Lo; Jennifer Lo; Xiaoyan Lu; Brian Lynch; Larry Madoff; Lakshmi Malapati; Gregory Marks; Mariel Marlow; Glenn E. Mathisen; Nancy McClung; Olivia McGovern; Tristan D. McPherson; Mitali Mehta; Audrey Meier; Lynn Mello; Sung-sil Moon; Margie Morgan; Ruth N. Moro; Janna' Murray; Rekha Murthy; Shannon Novosad; Sara E. Oliver; Jennifer O'Shea; Massimo Pacilli; Clinton R. Paden; Mark A. Pallansch; Manisha Patel; Sajan Patel; Isabel Pedraza; Satish K. Pillai; Talia Pindyck; Ian Pray; Krista Queen; Nichole Quick; Heather Reese; Brian Rha; Heather Rhodes; Susan Robinson; Philip Robinson; Melissa Rolfes; Janell Routh; Rachel Rubin; Sarah L. Rudman; Senthilkumar K. Sakthivel; Sarah Scott; Christopher Shepherd; Varun Shetty; Ethan A. Smith; Shanon Smith; Bryan Stierman; William Stoecker; Rebecca Sunenshine; Regina Sy-Santos; Azaibi Tamin; Ying Tao; Dawn Terashita; Natalie J. Thornburg; Suxiang Tong; Elizabeth Traub; Ahmet Tural; Anna Uehara; Timothy M. Uyeki; Grace Vahey; Jennifer R. Verani; Elsa Villarino; Megan Wallace; Lijuan Wang; John T. Watson; Matthew Westercamp; Brett Whitaker; Sarah Wilkerson; Rebecca C. Woodruff; Jonathan M. Wortham; Tiffany Wu; Amy Xie; Anna Yousaf; Matthew Zahn; Jing Zhang.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.03.09.20032896


Introduction: More than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. Methods: We collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. Results: Among the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. Conclusions: In 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

Coronavirus Infections , Fever , Pneumonia , COVID-19
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.03.02.972935


The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures. Article SummaryScientists have isolated virus from the first US COVID-19 patient. The isolation and reagents described here will serve as the US reference strain used in research, drug discovery and vaccine testing.

Severe Acute Respiratory Syndrome , Pneumonia , COVID-19