Evaluation of the Detection Performance of the N Antigenemia of SARS-CoV-2 in the General Population for the Diagnosis and Screening of COVID-19 (CoviBlood)

SARS-CoV-2 is responsible for the COVID-19 pathology. Since the emergence of the virus in China at the end of 2019, the virus has become pandemic and responsible for constant epidemic waves since 2020. France was hit by a first epidemic wave from February to April 2020. This epidemic wave could only be stopped by the implementation of national containment. The virus continues to circulate in France and has been accelerating since the end of August in the general population. The fight against this expansion and new waves aims to slow the viral expansion, to allow the development of new knowledge, treatments and vaccine approaches, as well as to limit the use of intensive care units, so as not to exceed their reception capacities. This fight involves in particular the use of broad and rapid screening practices in the general population in the event of symptoms, events inducing at risk contacts or travel. Today, gold standard assays are the reference methods of RT-PCR on nasopharyngeal swabs. The general population still has great difficulties in finding an available screening center and obtaining a result in a short time, allowing effective isolation and investigation of cases. Alternatives are being used to increase testing capabilities: (i) detection of the N antigen on a nasopharyngeal sample, however with less sensitivity than RT-PCR (ii) saliva sampling but mostly limited, in France, to children population as less sensitive than nasopharyngeal sampling.

Today, only RT-PCR performed on a nasopharyngeal sample therefore remains the reference technique for diagnosing SARS-CoV-2 infection. This method has several flaws, in particular for mass screening. Thus, (i) RT-PCR can only be carried out in laboratories suitable for molecular biology approaches, limiting the number of centers and sometimes imposing significant transport delays; (ii) RT-PCR is a technique requiring long turn around times, rarely compatible with rapid screening strategies; (iii) RT-PCR is relatively expensive; (iv) the nasopharyngeal sample is a sample that is often poorly tolerated by patients and associated with a non-negligible risk of infection for the medical staff performing the sampling. Several other approaches have been evaluated to overcome these difficulties. Antigenic detection of SARS-CoV-2 on nasopharyngeal swab: these approaches were authorized by the French HAS authorities for symptomatic patients. The sensitivity is more limited than with RT-PCR approaches and still potentially infectious viral loads (between 25 and 33 Ct) may not be detected. PCR detection of SARS-CoV-2 on saliva sample allow to avoid the constraints of nasopharyngeal samples but present a sensitivity issue, especially in patients with little or no symptoms. Recently, a new approach, based on the detection of the N antigen of the virus in a blood sample, has been described. The first commercially available method was evaluated at the Virology laboratory at Bichat Hospital in the case of a retrospective study on frozen serum samples. This innovative approach shows satisfactory sensitivity in hospitalized patients. Sensitivity was estimated to be 93.0% (95% CI: 84.7-100) within the first 14 days after symptom onset among 165 patients tested with PCR positive for SARS-CoV-2. The sensitivity was better for high viral loads (49 positives out of 50 with a viral load <30 Ct obtained in the same 24 hours as the serum sample). The specificity, estimated on 63 non-COVID patients, was 98.4% (95% CI: 85.3 to 100). This first study included few outpatients