Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19

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RESEARCH

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19 Jesús F. Bermejo‑Martin1,2,3†, Milagros González‑Rivera4,5†, Raquel Almansa1,2,3†, Dariela Micheloud6†, Ana P. Tedim1,2, Marta Domínguez‑Gil7†, Salvador Resino8†, Marta Martín‑Fernández1,2, Pablo Ryan Murua9, Felipe Pérez‑García10, Luis Tamayo1,11, Raúl Lopez‑Izquierdo12, Elena Bustamante13, César Aldecoa1,14,15, José Manuel Gómez16, Jesús Rico‑Feijoo1,15, Antonio Orduña17, Raúl Méndez18, Isabel Fernández Natal19, Gregoria Megías20, Montserrat González‑Estecha4,5, Demetrio Carriedo21, Cristina Doncel1,2,3, Noelia Jorge1,2,3, Alicia Ortega1,2,3, Amanda de la Fuente1,2,3, Félix del Campo22, José Antonio Fernández‑Ratero23, Wysali Trapiello24, Paula González‑Jiménez18, Guadalupe Ruiz24, Alyson A. Kelvin25,26, Ali Toloue Ostadgavahi25,26, Ruth Oneizat7, Luz María Ruiz7, Iria Miguéns6, Esther Gargallo6, Ioana Muñoz6, Sara Pelegrin15, Silvia Martín1,15, Pablo García Olivares16, Jamil Antonio Cedeño16, Tomás Ruiz Albi22, Carolina Puertas4, Jose Ángel Berezo1,11, Gloria Renedo13, Rubén Herrán1,11, Juan Bustamante‑Munguira27, Pedro Enríquez11, Ramón Cicuendez13, Jesús Blanco11, Jesica Abadia28, Julia Gómez Barquero28, Nuria Mamolar13, Natalia Blanca‑López9, Luis Jorge Valdivia21, Belén Fernández Caso19, María Ángeles Mantecón20, Anna Motos3,29, Laia Fernandez‑Barat3,29, Ricard Ferrer3,30, Ferrán Barbé3,31, Antoni Torres3,29†, Rosario Menéndez3,18†, José María Eiros7† and David J. Kelvin25,26*†

Abstract  Background:  COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in res‑ piratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods:  A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral *Correspondence: [email protected] † Jesús F. Bermejo-Martin, Milagros González-Rivera, Raquel Almansa, Dariela Micheloud, Marta Domínguez-Gil, Salvador Resino are co-first authors and these authors contributed equally. † Antoni Torres, Rosario Menéndez, José María Eiros, David J. Kelvin are co-last authors and these authors contributed equally. 25 Department of Microbiology and Immunology, Faculty of Medicine, Canadian Center for Vaccinology CCfV, Dalhousie University, Halifax, NS B3H 4R2, Canada Full list of author information is available at the end of the article © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 Internation