An Address on the Pathology of Syphilis: Being an Introduction to a Debate at the Pathological Society of London
Authors: J. Hutchinson
Journal: BMJ (1876)

<h3>Abstract</h3> <h3>Rationale</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Measurements and Main Results</h3> 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], <i>p</i> &lt; 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 <h3>Conclusions</h3> 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. <h3>“At a Glance Commentary”</h3> <h3>Scientific Knowledge on the Subject</h3> 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. <h3>What This Study Adds to the Field</h3> 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 &amp; 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