Combined kinetic analysis of SARS-CoV-2 RNAemia, N-antigenemia and virus-specific antibodies in critically ill adult COVID-19 patients

Abstract

Combined kinetic analysis of plasma SARS-CoV-2 RNAemia, Nucleocapsid (N)-antigenemia and virus-specific antibodies may help ascertain the role of antibodies in preventing virus dissemination in COVID-19 patients. We performed this analysis in a cohort of 71 consecutive critically ill COVID-19 patients (49 male; median age, 65 years) using RT-PCR assay, lateral flow immunochromatography method and receptor binding domain (RBD) and N-based immunoassays. A total of 338 plasma specimens collected at a median of 12 days after symptoms onset were available for analyses. SARS-CoV-2 RNAemia and N-antigenemia were detected in 37 and 43 specimens from 26 (36.5%) and 30 (42.2%) patients, respectively. Free RNA was the main biological form of SARS-CoV-2 found in plasma. The detection rate for both viral components was associated with viral load at the upper respiratory tract. Median time to SARS-CoV-2-RBD antibody detection was 14 days (range, 4–38) from onset of symptoms. Decreasing antibody levels were observed in parallel to increasing levels of both RNAemia and N-antigenemia, yet overall a fairly modest inverse correlation (Rho = −0.35; P < 0.001) was seen between virus RNAemia and SARS-CoV-2-RBD antibody levels. The data cast doubts on a major involvement of antibodies in virus clearance from the bloodstream within the timeframe examined.

Nucleocapsid Antigenemia in Patients Receiving Anti-CD20 Therapy With Protracted COVID-19

“…Although mechanisms have not been determined, antigenemia is likely protein shed into circulation from cells containing replicating virus that resolves in a short period following immune clearance of active virus [ 14 ]. Serial measurements in Cases 1 and 2 demonstrated a decline in antigenemia that correlated with antiviral therapy and symptomatic improvement.…”

SARS-CoV-2-reactive IFN-γ-producing CD4+ and CD8+ T cells in blood do not correlate with clinical severity in unvaccinated critically ill COVID-19 patients

“…Undiluted tracheal aspirates (TA) were obtained through a Halyard Turbo-cleaning closed suction system, which was connected to an orotracheal tube as a standard of care during the pandemic. SARS-CoV-2 RNA quantitation in TA was carried out by the Abbott RealTime SARS-CoV-2 assay Abbott Molecular (Des Plaines, IL, USA) 29 , 30 . SARS-CoV-2 viral loads (in copies/mL) were estimated using the AmpliRun Total SARS-CoV-2 RNA Control (Vircell SA, Granada, Spain).…”

“…This observational, prospective and longitudinal study included a total of 71 non-consecutive critically ill patients, (49 male and 22 female; median age, 65 years; range, 21-80 years, as previously defined 27 ) with COVID-19 microbiologically documented by RT-PCR in nasopharyngeal specimens collected prior to recruitment at the intensive care unit (ICU) between October 2020 and February 2021. These patients were included in previous studies [28][29][30] assessing the rate and kinetics of SARS-CoV-2 RNAemia and Nucleocapsid (N) antigenemia, as well as the potential role of SARS-CoV-2-Spike-targeting antibodies in mediating SARS-CoV-2 RNAemia and N-antigenemia clearance. No data on SARS-CoV-2 T-cell responses were included in these studies.…”

SARS-CoV-2-reactive IFN-γ CD4 + and CD8 + T cells, clinical severity biomarkers and mortality in unvaccinated critically ill COVID-19 patients

“…In this observational prospective and longitudinal study, a total of 71 non-consecutive critically ill patients [21] (49 male and 22 female; median age, 65 years; range, 21 to 80 years) with COVID-19 microbiologically documented by RT-PCR in nasopharyngeal specimens were recruited at the intensive care unit (ICU) between October 2020 and February 2021. These patients have been included in previous studies [22][23][24]. The only patient inclusion criterion was availability of whole blood specimens for T-cell immunity analyses, which were scheduled for once-weekly collection during ICU stay.…”