SARS-CoV-2-RNA viremia is associated to hypercytokinemia and critical illness in COVID-19

Bermejo-Martin, J. F.; Gonzalez-Rivera, M.; Almansa, R.; Micheloud, D.; Dominguez-Gil, M.; Resino, S.; Martin-Fernandez, M.; Ryan Murua, P.; Perez-Garcia, F.; Tamayo, L.; Lopez-Izquierdo, R.; Bustamante, E.; Aldecoa, C.; Gomez, J. M.; Rico-Feijoo, J.; Orduna, A.; Mendez, R.; Fernandez Natal, I.; Megias, G.; Gonzalez-Estecha, M.; Carriedo, D.; Doncel, C.; Jorge, N.; del Campo, F.; Fernandez-Ratero, J. A.; Trapiello, W.; Gonzalez-Jimenez, P.; Ruiz, G.; Kelvin, A. A.; Ostadgavahi, A. T.; Oneizat, R.; Ruiz, L. M.; Miguens, I.; Gargallo, E.; Munoz, I.; Pelegrin, S.; Martin, S.; Garcia-Olivares, P.

Rationale: whether systemic dissemination of SARS-CoV-2 has any impact on COVID-19 severity and also on the immunological alterations observed in this disease is largely unknown. Objectives: We determined the association of plasma SARS-CoV-2 RNA with clinical severity, laboratory findings and immunological parameters in a cohort of 250 patients with confirmed COVID-19 infection. Methods: Three groups of patients were studied: 50 outpatients, 100 hospitalised ward patients, and 100 critically ill. 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. The association between plasma SARS-CoV-2 RNA and laboratory parameters was evaluated using multivariate GLM with a gamma distribution. Measurements and Main Results: The prevalence of SARS-CoV-2-RNA viremia increased in parallel with severity of infection (22% in outpatients, 36 % in those hospitalised in wards, and 82% in those at the ICU). In hospitalised patients, the presence of SARS-CoV-2-RNA viremia was independently associated to critical illness: (adjusted OR= 8.30 [CI95%=4.21 - 16.34], p < 0.001). SARS-CoV-2-RNA viremia was an independent predictor of higher levels of ferritin, LDH and cytokines (involving CXCL10, CCL-2, IL-15, IL-10, IL-1ra and GCS-F), and lower of lymphocytes, monocytes and platelets counts Conclusions: SARS-CoV-2-RNA viremia is a robust marker of critical illness in COVID-19. Our findings support that hypercytokinemia in COVID-19 is a reactive event in response to the dissemination of viral material at the systemic level.