Nasopharyngeal SARS-CoV-2 Load at Hospital Admission as a Predictor of Mortality

Vecchi, Marta; Alteri, Claudia; Antonello, Maria; Baiguera, Chiara; Bielli, Alessandra; Bottiroli, Maurizio; Brioschi, Paolo; Campisi, Daniela; Carta, Stefania; Casalicchio, G.; Cento, Valeria; Chieregato, Arturo; Colagrossi, Luna; Costabile, Valentino; Colombo, Jacopo; Ruscio, Federica Di; Epis, Oscar Massimiliano; Fanti, Diana; Länger, Thomas; Matarazzo, E.; Merli, Marco; Nava, Alice; Molteni, Silvia Nerini; Perno, Carlo Federico; Puoti, Massimo; Renica, Silvia; Tartaglione, Livia; Ughi, Nicola; Vismara, Chiara

doi:10.1093/cid/ciaa956

Cited by 13 publications

(12 citation statements)

References 7 publications

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“…However, the quite low Ct values observed in our population (median, IQR: 18.8, 16.8-20.1) could be in line with the association of D614G variant with lower Ct values, indicative of potentially higher in vivo viral loads 23 , and thus related to severe outcome in COVID-19 (refs. [24][25][26] ).…”

Section: Discussionmentioning

confidence: 99%

Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy

et al. 2021

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From February to April 2020, Lombardy (Italy) reported the highest numbers of SARS-CoV-2 cases worldwide. By analyzing 346 whole SARS-CoV-2 genomes, we demonstrate the presence of seven viral lineages in Lombardy, frequently sustained by local transmission chains and at least two likely to have originated in Italy. Six single nucleotide polymorphisms (five of them non-synonymous) characterized the SARS-CoV-2 sequences, none of them affecting N-glycosylation sites. The seven lineages, and the presence of local transmission clusters within three of them, revealed that sustained community transmission was underway before the first COVID-19 case had been detected in Lombardy.

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Section: Discussionmentioning

confidence: 99%

Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy

et al. 2021

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“…The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.09.20246520 doi: medRxiv preprint SARS-CoV-2 Ct values have shown promise as a means to roughly quantify viral burden and so to guide infection control and public health interventions (1,2,(4)(5)(6)(7)(8). However, variability in NP specimen collection may exert large effects on observed SARS-CoV-2 Ct values, limiting these useful applications.…”

Section: Discussionmentioning

confidence: 99%

“…As the COVID-19 pandemic continues to drive morbidity and mortality around the world, interest has grown in using SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) cycle of threshold (Ct) values as a means of quantifying viral load (1,2). It has been proposed that SARS-CoV-2 Ct values may correspond with viral burden and infectivity, and that SARS-CoV-2 values may be used to predict disease severity and guide isolation precautions for individuals with COVID-19 (3)(4)(5)(6)(7). SARS-CoV-2 Ct values have been shown to correspond with community COVID-19 burden, and it has also been proposed that community Ct values may help to guide non-pharmaceutical interventions to control COVID-19 (8).…”

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confidence: 99%

Impact of Nasopharyngeal Specimen Quality on SARS-CoV-2 Test Sensitivity

Richard-Greenblatt

Ziegler

Bromberg

et al. 2020

Preprint

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BackgroundThe SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) cycle of threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with COVID-19 and guiding public health interventions. However, variability in specimen quality can alter the Ct values obtained from SARS-CoV-2 clinical assays. We sought to define how variable nasopharyngeal (NP) swab quality impacts clinical SARS-CoV-2 test sensitivity.MethodsWe performed amplification of a human gene target (β-actin) in parallel with a clinical RT-PCR targeting the SARS-CoV-2 ORF1ab gene for 1311 NP specimens collected from patients with clinical concern for COVID-19. We evaluated the relationship between NP specimen quality, characterized by high Ct values for the human gene target β-actin Ct, and the probability of SARS-CoV-2 detection via logistic regression, as well as the linear relationship between SARS-CoV-2 and β-actin Ct.ResultsLow quality NP swabs are less likely to detect SARS-CoV-2 (odds ratio 0.654, 95%CI 0.523 to 0.802). We observed a positive linear relationship between SARS-CoV-2 and β-actin Ct values (slope 0.169, 95%CI 0.092 to 0.247). COVID-19 disease severity was not associated with β-actin Ct values.ConclusionsVariability in NP specimen quality accounts for significant differences in the sensitivity of clinical SARS-CoV-2 assays. If unrecognized, low quality NP specimens, which are characterized by a low level of amplifiable human DNA target, may limit the application of SARS-CoV-2 Ct values to direct infection control and public health interventions.

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“…In our view, our data fit better with a pathogenetic model, in which SARS-CoV-2 replication in the LRT or its presence in the blood compartment at a certain point over the course of ICU stay might not be a major driver of systemic inflammation, lymphopenia, lung dysfunction, multisystemic organ failure and death. This does not invalidate the importance of virus replication rate in the URT in the early stage after infection in determining the clinical course of COVID-19 [6][7][8]. Further studies are needed to resolve this issue.…”

Section: Virological Parameters and Mortalitymentioning

confidence: 99%

SARS-CoV-2 RNA load in the lower respiratory tract, viral RNAemia and N-antigenemia in critically ill adult COVID-19 patients: relationship with biomarkers of disease severity

Olea

Albert

Torres

et al. 2021

Preprint

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Background: Little is known about the comparative kinetics of SARS-CoV-RNA load in the lower respiratory tract and in blood compartment in patients admitted to the intensive care unit, and how these relate to biomarkers of COVID-19 severity. Methods: Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial lower respiratory tract (n=165) and plasma (n=340) specimens were collected. RT-PCR and lateral flow immunochromatography assay were used for SARS-CoV-2 RNA quantitation and N protein detection in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were analyzed. Results: SARS-CoV-RNA was detected in the lower respiratory tract of most patients (92%). Viral RNAemia and N-antigenemia were documented in 35.6% and 40.1% of patients, respectively. Viral RNAemia and N-antigenemia cleared at a faster rate than SARS-CoV-2 RNA in tracheal aspirates (TA). SARS-CoV-2 RNA load was higher (P<0.001) in TA than in plasma, and correlated significantly (Rho, 0.41; P<0.001). A modest correlation was found between SARS-CoV-2 RNA load in TA and plasma and levels of ferritin and lactose dehydrogenase (Rho≤0.3; P≤0.008) in paired serum specimens. Neither the dynamics of SARS-CoV-2 RNA load in TA and plasma, nor N-antigenemia detection rate differed between surviving and deceased patients. Yet, a trend towards a higher mortality was seen in patients with viral RNAemia (OR; 2.82; 95% CI, 0.94-8.47; P=0.06).

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Nasopharyngeal SARS-CoV-2 Load at Hospital Admission as a Predictor of Mortality

Cited by 13 publications

References 7 publications

Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy

Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy

Impact of Nasopharyngeal Specimen Quality on SARS-CoV-2 Test Sensitivity

SARS-CoV-2 RNA load in the lower respiratory tract, viral RNAemia and N-antigenemia in critically ill adult COVID-19 patients: relationship with biomarkers of disease severity

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