Discussion
The present study investigated the role of circulating SARS-CoV-2 NCP in
COVID-19 with relation to antibody status, disease severity, time post
diagnosis and inflammation markers. We show that high systemic
concentrations of NCP antigen are a consistent feature of the early
phase of hospitalized COVID-19 patients, independent of disease
severity. Remarkably, NCP antigen clearance to levels below the
detection threshold was impaired after the 8th day of
disease in COVID-19 patients needing intensive care compared to non-ICU
patients, suggesting a reduced systemic antigen clearance in severe
disease.
Circulating NCP antigen is detected at higher concentrations in severely
ill COVID19 patients [7, 9-11]. Our study identified a moderate but
significant correlation between NCP antigenemia and CRP / IL-6 in ICU
patients. Earlier investigations had observed an association of higher
NCP antigenemia with CRP [6], IL-10, IP-10 and RAGE [10]. As a
prognostic marker, NCP concentrations of >1000 pg/mL upon
hospitalization were associated with later ICU admission and delayed
hospital discharge [10, 12]. Our study now adds that clearance of
NCP antigenemia is delayed in >40% of severely ill COVID19
patients who required intensive care. Thus, if NCP is detectable after 1
week of illness, a potentially severe course of disease is likely,
emphasizing its role as a prognostic biomarker.
The biological basis of NCP antigenemia is still ill-defined. Plasma NCP
antigenemia was found not to correlate with mucosal Ct values [8].
However, it is unresolved whether NCP antigen in plasma reflects ongoing
systemic viral replication [12], or rather dissemination from the
respiratory tract [10]. Our study is the first to show that
prolonged antigenemia in ICU patients is associated with lower S1- but
not NCP-specific IgG after 8 days post diagnosis. Reduced S1-specific
antibodies could thus result in less efficient neutralization and permit
systemic dissemination of virions.
Of note, the present study found that PCR results from nasopharyngeal
swabs did not differ significantly between ICU and non-ICU patients, as
also described by Yilmaz et al. [13]. In contrast, systemic NCP
antigenemia could differentiate both groups, suggesting independent
regulation of viral clearance from the mucosa and systemic clearance of
viral antigen. Consequently, detection of systemic NCP antigen after 8
days post COVID-19 diagnosis identifies patients that progress to
clinical deterioration requiring intensive care, while those who clear
antigenemia after this time are likely to recover. Thus, prolonged
antigenemia can serve as a novel biomarker to recognize severe courses
of COVID-19 infection.