Abstract
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.
Scientific Knowledge on the Subject there is a limited number of works evaluating the presence of SARS-CoV-2 RNA in the serum or plasma of patients with COVID-19, involving few patients, most of them with non-severe disease. In consequence, the impact that the presence of SARS-CoV-2 RNA viremia has on disease biology and severity is largely unknown.
What This Study Adds to the Field to our knowledge, this is the first study comparing the prevalence of SARS-CoV-2-RNA viremia in outpatients (n=50), patients admitted to the ward (n=100), and critically ill patients (n=100) with COVID-19. Multivariate analysis demonstrates that the presence of SARS-CoV-2-RNA viremia in those COVID-19 patients needing hospitalization translates into an 8-fold increase in the risk of presenting critical illness. Presence of viremia in COVID-19 patients is associated with high levels of ferritin and LDH, hypercytokinemia (increased levels of CXCL10, CCL2, IL-10, IL-1ra, G-CSF & IL-15), lymphopenia and low monocyte and platelet counts. These data indicate that SARS-CoV-2-RNA viremia could be a driver of immunological dysregulation and severe disease in COVID-19
This article has an online data supplement, which is accessible from this issue’s table of content online at www.atsjournals.org
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
NCT04457505
Funding Statement
This work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 170357), Research Nova Scotia (DJK), Atlantic Genome/Genome Canada (DJK), Li-Ka Shing Foundation (DJK), Dalhousie Medical Research Foundation (DJK), the Subvenciones de concesion directa para proyectos y programas de investigacion del virus SARS-CoV2, causante del COVID-19, FONDO - COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and finally by the Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y Leon, para la financiacion de proyectos de investigacion en enfermedad COVID-19 (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Inflammation.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Comite de Etica de la Investigacion con Medicamentos del Area de Salud de Salamanca, code PI 2020 03 452
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Data Availability
Data are available upon reasonable request