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

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.

Costa R ，Alberola J ，Olea B ，Gozalbo-Rovira R ，Giménez E ，Cuevas-Ferrando E ，Torres I ，Albert E ，Carbonell N ，Ferreres J ，Sánchez G ，Rodríguez-Díaz J ，Blasco ML ，Navarro D ... -  《Scientific Reports》

SARS-CoV-2 N-antigenemia in critically ill adult COVID-19 patients: Frequency and association with inflammatory and tissue-damage biomarkers.

The current study aimed at characterizing the dynamics of SARS-CoV-2 nucleocapsid (N) antigenemia in a cohort of critically ill adult COVID-19 patients and assessing its potential association with plasma levels of biomarkers of clinical severity and mortality. Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial plasma (n = 340) specimens were collected. A lateral flow immunochromatography assay and reverse-transcription polymerase chain reaction (RT-PCR) were used for SARS-CoV-2 N protein detection and RNA quantitation and in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were measured. SARS-CoV-RNA N-antigenemia and viral RNAemia were documented in 40.1% and 35.6% of patients, respectively at a median of 9 days since symptoms onset. The level of agreement between the qualitative results returned by the N-antigenemia assay and plasma RT-PCR was moderate (k = 0.57; p < 0.0001). A trend towards higher SARS-CoV-2 RNA loads was seen in plasma specimens testing positive for N-antigenemia assay than in those yielding negative results (p = 0.083). SARS-CoV-2 RNA load in tracheal aspirates was significantly higher (p < 0.001) in the presence of concomitant N-antigenemia than in its absence. Significantly higher serum levels of ferritin, lactose dehydrogenase, C-reactive protein, and D-dimer were quantified in paired plasma SARS-CoV-2 N-positive specimens than in those testing negative. Occurrence of SARS-CoV-2 N-antigenemia was not associated with increased mortality in univariate logistic regression analysis (odds ratio, 1.29; 95% confidence interval, 0.49-3.34; p = 0.59). In conclusion, SARS-CoV-2 N-antigenemia detection is relatively common in ICU patients and appears to associate with increased serum levels of inflammation and tissue-damage markers. Whether this virological parameter may behave as a biomarker of poor clinical outcome awaits further investigations.

Olea B ，Albert E ，Torres I ，Gozalbo-Rovira R ，Carbonell N ，Ferreres J ，Poujois S ，Costa R ，Colomina J ，Rodríguez-Díaz J ，Blasco ML ，Navarro D ... -  《-》

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.

Bermejo-Martin JF ，González-Rivera M ，Almansa R ，Micheloud D ，Tedim AP ，Domínguez-Gil M ，Resino S ，Martín-Fernández M ，Ryan Murua P ，Pérez-García F ，Tamayo L ，Lopez-Izquierdo R ，Bustamante E ，Aldecoa C ，Gómez JM ，Rico-Feijoo J ，Orduña A ，Méndez R ，Fernández Natal I ，Megías G ，González-Estecha M ，Carriedo D ，Doncel C ，Jorge N ，Ortega A ，de la Fuente A ，Del Campo F ，Fernández-Ratero JA ，Trapiello W ，González-Jiménez P ，Ruiz G ，Kelvin AA ，Ostadgavahi AT ，Oneizat R ，Ruiz LM ，Miguéns I ，Gargallo E ，Muñoz I ，Pelegrin S ，Martín S ，García Olivares P ，Cedeño JA ，Ruiz Albi T ，Puertas C ，Berezo JÁ ，Renedo G ，Herrán R ，Bustamante-Munguira J ，Enríquez P ，Cicuendez R ，Blanco J ，Abadia J ，Gómez Barquero J ，Mamolar N ，Blanca-López N ，Valdivia LJ ，Fernández Caso B ，Mantecón MÁ ，Motos A ，Fernandez-Barat L ，Ferrer R ，Barbé F ，Torres A ，Menéndez R ，Eiros JM ，Kelvin DJ ... -  《CRITICAL CARE》

SARS-CoV-2 antigenemia and RNAemia in association with disease severity in patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0-79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan-Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.

Kim DM ，Lawrence Panchali MJ ，Kim CM ，Lee DY ，Seo JW ，Kim DY ，Yun NR ... -  《Scientific Reports》

Highly Sensitive Quantification of Plasma Severe Acute Respiratory Syndrome Coronavirus 2 RNA Sheds Light on its Potential Clinical Value.

Coronavirus disease 2019 (COVID-19) is a global public health problem that has already caused more than 662 000 deaths worldwide. Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, some patients present other severe damage such as cardiovascular, renal and liver injury, and/or multiple organ failure, suggesting a spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in blood. Recent ultrasensitive polymerase chain reaction (PCR) technology now allows absolute quantification of nucleic acids in plasma. We intend to use the droplet-based digital PCR technology to obtain sensitive detection and precise quantification of plasma SARS-CoV-2 viral load (SARS-CoV-2 RNAemia) in hospitalized COVID-19 patients. Fifty-eight consecutive COVID-19 patients with pneumonia 8 to 12 days after onset of symptoms and 12 healthy controls were analyzed. Disease severity was categorized as mild to moderate in 17 patients, severe in 16, and critical in 26. Plasma SARS-CoV-2 RNAemia was quantified by droplet digital Crystal Digital PCR next-generation technology (Stilla Technologies, Villejuif, France). Overall, SARS-CoV-2 RNAemia was detected in 43 (74.1%) patients. Prevalence of positive SARS-CoV-2 RNAemia correlated with disease severity, ranging from 53% in mild-to-moderate patients to 88% in critically ill patients (P = .036). Levels of SARS-CoV-2 RNAemia were associated with severity (P = .035). Among 9 patients who experienced clinical deterioration during follow-up, 8 had positive SARS-CoV-2 RNAemia at baseline, whereas only 1 critical patient with undetectable SARS-CoV-2 RNAemia at the time of analysis died at day 27. SARS-CoV-2 RNAemia measured by droplet-based digital PCR constitutes a promising prognosis biomarker in COVID-19 patients.

Veyer D ，Kernéis S ，Poulet G ，Wack M ，Robillard N ，Taly V ，L'Honneur AS ，Rozenberg F ，Laurent-Puig P ，Bélec L ，Hadjadj J ，Terrier B ，Péré H ... -  《-》