Antigenemia Is Associated to Viral Sepsis and Mortality in COVID-19 (preprint)

Background: Severe COVID-19 has been proposed to represent a form of viral sepsis. The prevalence of sepsis due to this disease has not been evaluated. Some patients with severe COVID-19 present SARS-CoV-2 antigenemia. Whether antigenemia constitutes a factor associated to viral sepsis and fatal outcome in these patients is unknown. Methods: This study recruited 400 patients hospitalized with COVID-19. Prevalence of sepsis in the first 24 hours following hospitalization was determined using the SEPSIS-3 criteria. Prevalence and concentration of SARS-CoV-2 N-antigenemia was determined in plasma at hospitalization using the Panbio® COVID-19 Ag Rapid Test from Abbott and the COV-QUANTO® ELISA from AAZ. Findings: The prevalence of sepsis due to SARS-CoV-2 infection at hospitalization was of 54%, affecting mostly to the respiratory, renal and coagulation function. Antigenemia was present in the 53% of the patients, and constituted an independent risk factor of sepsis in the multivariate analysis (OR [CI95%], p): presence of N-antigenemia (Panbio®): (1·6 [1·1 - 2·5],0·023); concentration of N-antigen >575 pg/mL (COV-QUANTO®): (1·9 [1·0 - 3·5], 0·043). Antigenemia was associated with a reduction in the survival mean time of 9·42 and 9·33 days in the 90 first days following hospitalization, based on the PANBIO® and the COV-QUANTO® tests respectively. Interpretation: Half of the COVID-19 patients needing of hospitalization fulfill the criteria of sepsis. Antigenemia is strongly linked to the presence of this condition, and confers a higher risk of mortality. Monitoring the presence of antigenemia at the earlier moments of COVID-19 could help to identify those patients at risk of deterioration. Clinical Trial Registration Details: This was a sub-study of the CIBERES-UCI-COVID project, registered at Clinicaltrials.gov with the identification NCT04457505. Funding Information: Instituto de Salud Carlos III (COV20/00110; CP20/00041; FI20/00278), Fundació La Marató de TV3 (473/C/2021).Declaration of Interests: AT, JME, FB, RA and JFBM have a patent application on SARS-CoV-2 antigenemia. The remainder authors declare no conflicts of interest regarding this work.Ethics Approval Statement: Written or oral informed consent was obtained directly from all patients, or their legal representative, before enrolment. Scientific and ethical approval of the study protocol was obtained from the respective scientific committees for clinical research of the participant hospitals.

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

BackgroundSevere 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. MethodsWe 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. ResultsThe 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). Conclusionssystemic 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.