SARS-CoV-2 N-ANTIGEN SERA LEVELS ARE ASSOCIATED with COVID-19 PROGNOSTIC VALUE

ABSTRACT

Background: Small studies have reported that high levels of free SARS-CoV-2 nucleocapsid-antigen in sera (N-antigenemia) was associated with prognostic. Here, we assessed the association between N-antigenemia levels and patient's outcome in a large cohort of hospitalized patients. Methods: We analysed data from patients with at least one sera sample that were included in the French COVID cohort between January, 25 2020 and September, 2 2020. N-antigenemia levels were determined with the COV-Quanto® assay (AAZ) with a limit of detection of 2.98 pg/mL. IgG (anti-N, anti-S and anti-RBD) levels were assessed using the V-PLEX panel assay (MSD). Patient's outcome was classified in three groups death, recovery with ICU transfer (ICU) and recovery without ICU transfer (Hospital). Results: We included 1166 samples from 357 patients, with 66% of male and a median age at 63 years [IQR 52-71]. A total of 82, 96 and 142 patients were in the Death, ICU and Hospital groups, respectively. The sensitivity of N-antigenemia was 79% (131/165) within the first 10 days SSO (since symptoms onset) and 62% (365/589) from 11 to 30 days SSO. Positivity rates were significantly different across severity groups from 0 to 15 days SSO 95% (95/100), 64% (118/183), 79% (83/105) (p<0.001) for Death, ICU and Hospital groups, respectively. Among positive patients, a significant gradient was found in the levels of N-antigenemia according to disease severity, with median levels of 302, 134 and 89 in Death, ICU and hospital groups, respectively. Similar relationships were found when stratifying on the time SSO (see figure). Overall, 95, 80, 43 and 22% of N-antigenemia >10,000, >5,000, >1,000 and <1,000 pg/mL corresponded to patients who died. IgG antibodies titers were not correlated to severity and the presence of both sera N-antigen and anti-N IgG was observed for 42% (490/1166) samples. Conclusion: We observed, on a large prospective cohort, a strong relationship between N-antigenemia and COVID-19 severity. This new diagnostic tool should help to prognostic evaluation of COVID-19 patients. To our knowledge, COVID-19 is the first demonstration of the presence of free antigenemia in a viral pneumonia, and its association with prognostic.