SARS-CoV-2 RNA viremia is associated with a sepsis-like host response and critical illness in COVID-19
Authors: Bermejo-Martin Jesús F , González-Rivera Milagros , Almansa Raquel , Micheloud Dariela , Domínguez-Gil Marta , Resino Salvador , Martín-Fernández Marta , Murua Pablo Ryan , Pérez-García Felipe , Tamayo Luis , Lopez-Izquierdo Raúl , Bustamante Elena , Aldecoa César , Gómez José Manuel , Rico-Feijoo Jesús , Orduña Antonio , Méndez Raúl , Natal Isabel Fernández , Megías Gregoria , González-Estecha Montserrat , Carriedo Demetrio , Doncel Cristina , Jorge Noelia , del Campo Félix , Fernández-Ratero José Antonio , Trapiello Wysali , González-Jiménez Paula , Ruiz Guadalupe , Kelvin Alyson A. , Ostadgavahi Ali Toloue , Oneizat Ruth , Ruiz Luz María , Miguéns Iria , Gargallo Esther , Muñoz Ioana , Pelegrin Sara , Martín Silvia , Olivares Pablo García , Cedeño Jamil Antonio , Albi Tomás Ruiz , Puertas Carolina , Berezo Jose Ángel , Renedo Gloria , Herrán Rubén , Bustamante-Munguira Juan , Enríquez Pedro , Cicuendez Ramón , Blanco Jesús , Abadia Jesica , Barquero Julia Gómez , Mamolar Nuria , Blanca-López Natalia , Valdivia Luis Jorge , Caso Belén Fernández , Mantecón María Ángeles , Motos Anna , Fernandez-Barat Laia , Ferrer Ricard , Barbé Ferrán , Torres Antoni , Menéndez Rosario , Eiros José María , Kelvin David J 
Published: August 2020

Background

Severe COVID-19 is characterized by clinical and biological manifestations typically observed in sepsis. SARS-CoV-2 RNA is commonly detected in nasopharyngeal swabs, however viral RNA can be found also in peripheral blood and other tissues.

Whether systemic spreading of the virus or viral components plays a role in the pathogenesis of the sepsis-like disease observed in severe COVID-19 is currently unknown.

Methods

We determined the association of plasma SARS-CoV-2 RNA with the biological responses and the clinical severity of patients with COVID-19. 250 patients with confirmed COVID-19 infection were recruited (50 outpatients, 100 hospitalised ward patients, and 100 critically ill). The association between plasma SARS-CoV-2 RNA and laboratory parameters was evaluated using multivariate GLM with a gamma distribution. The association between plasma SARS-CoV-2 RNA and severity was evaluated using multivariate ordinal logistic regression analysis and Generalized Linear Model (GLM) analysis with a binomial distribution.

Results

The presence of SARS-CoV-2-RNA viremia was independently associated with a number of features consistently identified in sepsis: 1) high levels of cytokines (including CXCL10, CCL-2, IL-10, IL-1ra, IL-15, and G-CSF); 2) higher levels of ferritin and LDH; 3) low lymphocyte and monocyte counts 4) and low platelet counts. In hospitalised patients, the presence of SARS-CoV-2-RNA viremia was independently associated with critical illness: (adjusted OR= 8.30 [CI95%=4.21 - 16.34], p < 0.001). CXCL10 was the most accurate identifier of SARS-CoV-2-RNA viremia in plasma (area under the curve (AUC), [CI95%], p) = 0.85 [0.80 - 0.89), <0.001]), suggesting its potential role as a surrogate biomarker of viremia. The cytokine IL-15 most accurately differentiated clinical ward patients from ICU patients (AUC: 0.82 [0.76 - 0.88], <0.001).

Conclusions

systemic dissemination of genomic material of SARS-CoV-2 is associated with a sepsis-like biological response and critical illness in patients with COVID-19. RNA viremia could represent an important link between SARS-CoV-2 infection, host response dysfunction and the transition from moderate illness to severe, sepsis-like COVID-19 disease.