Abstract
HighlightsInnate immune activation during Covid-19 infection is associated with pernicious clinical outcome.BackgroundCoronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.MethodsWe measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.ResultsSevere and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.ConclusionWe propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.
Highlights
The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) disease (Covid-19) has rapidly spread from China to the rest of the world
SARS-CoV-2 is an RNA virus of the Coronaviridae family, which is closely related with SARS (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV)
Viral entry is facilitated through proteolytic cleavage of angiotensin converting enzyme 2 (ACE2) via the host type II transmembrane serine metalloprotease TMPRSS2 (Heurich et al, 2014) which cleaves the SARS-CoV-2 spike protein (Hoffmann et al, 2020)
Summary
The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) disease (Covid-19) has rapidly spread from China to the rest of the world. The resulting pandemic has challenged societies and their health care systems and requested unprecedented political, medical and scientific actions. The long-term societal and economic consequences of the pandemic per country start to emerge. SARS-CoV-2 is an RNA virus of the Coronaviridae family, which is closely related with SARS (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). These viruses are airborne and they all infects epithelium (primarily lung epithelium) through a high affinity interaction between the viral spike protein and cell surface expressed angiotensin converting enzyme 2 (ACE2). Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. We hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity
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