Prolonged Zika Virus NS1 Protein Circulation in Patient Sera Impacts Clinical Outcome Before the Rise of a Specific IgM Response

Zika virus (ZIKV) is a neurotropic virus that can be transmitted congenitally. In ZIKV-infected pregnant women, placental dysfunction is associated with the secretion of nonstructural protein 1 (NS1). In this study, the kinetics of NS1 secretion and antibody response were assessed and characterized in the serum of ZIKV-positive adult patients recruited in French Guiana. NS1 concentrations were quantified by a single molecule array (SiMoA) in 164 sequential serum samples collected from thirty patients during the first month after onset of symptoms. Serum NS1 concentrations in this cohort were unexpectedly low and ranged from 0.1 pg/mL to 380 pg/mL. The median persistence of NS1 in patients with a clinical score of 2 (6 days) was significantly lower than in patients with a clinical score of 3 (8 days). In both groups of patients, anti-NS1 IgM and IgG kinetics were similar but patients with a milder clinical score of 2 had statistically higher levels of specific IgM than those with a clinical score of 3. Herein, it was shown that NS1 circulating in patient sera is associated with clinical outcome, emphasizing the role of NS1 in ZIKV pathogenesis.