High Frequency of SARS-CoV-2 RNAemia and Association With Severe Disease.

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in blood, also known as RNAemia, has been reported, but its prognostic implications are poorly understood. This study aimed to determine the frequency of SARS-CoV-2 RNA in plasma and its association with coronavirus disease 2019 (COVID-19) clinical severity. An analytical cross-sectional study was performed in a single-center tertiary care institution and included consecutive inpatients and outpatients with confirmed COVID-19. The prevalence of SARS CoV-2 RNAemia and the strength of its association with clinical severity variables were examined and included intensive care unit (ICU) admission, invasive mechanical ventilation, and 30-day all-cause mortality. Paired nasopharyngeal and plasma samples were included from 85 patients. The median age was 55 years, and individuals with RNAemia were older than those with undetectable SARS-CoV-2 RNA in plasma (63 vs 50 years; P = .04). Comorbidities were frequent including obesity (37.6%), hypertension (30.6%), and diabetes mellitus (22.4%). RNAemia was detected in 28/85 (32.9%) of patients, including 22/28 (78.6%) who required hospitalization. In models adjusted for age, RNAemia was detected more frequently in individuals who developed severe disease including ICU admission (32.1 vs 14.0%; P = .04) and invasive mechanical ventilation (21.4% vs 3.5%; P = .02). All 4 deaths occurred in individuals with detectable RNAemia. An additional 121 plasma samples from 28 individuals with RNAemia were assessed longitudinally, and RNA was detected for a maximum duration of 10 days. This study demonstrated a high proportion of SARS-CoV-2 RNAemia, and an association between RNAemia and clinical severity suggesting the potential utility of plasma viral testing as a prognostic indicator for COVID-19.

Hogan CA ，Stevens BA ，Sahoo MK ，Huang C ，Garamani N ，Gombar S ，Yamamoto F ，Murugesan K ，Kurzer J ，Zehnder J ，Pinsky BA ... -  《-》

SARS-CoV-2 RNAemia with a higher nasopharyngeal viral load is strongly associated with disease severity and mortality in patients with COVID-19.

This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/μl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/μl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/μl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/μl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.

Kawasuji H ，Morinaga Y ，Tani H ，Yoshida Y ，Takegoshi Y ，Kaneda M ，Murai Y ，Kimoto K ，Ueno A ，Miyajima Y ，Fukui Y ，Kimura M ，Yamada H ，Sakamaki I ，Yamamoto Y ... -  《-》

Quantitative assessment of SARS-CoV-2 RNAemia and outcome in patients with coronavirus disease 2019.

The disease spectrum of coronavirus disease 2019 (COVID-19) varies from asymptomatic infection to critical illness and death. Identification of prognostic markers is vital for predicting progression and clinical practice. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, known as RNAemia, has been detected in the blood. However, the potential clinical value of SARS-CoV-2 RNAemia remains unknown. We, therefore, conducted a meta-analysis using a random-effects model to estimate the pooled prevalence of SARS-CoV-2 RNAemia as well as summary strength of RNAemia in association with disease severity and unfavorable clinical outcomes. A total of 21 studies involving 2181 patients were included. SARS-CoV-2 RNAemia in COVID-19 patients varied from 9.4% to 74.1%, with a pooled estimate of 34% (95% confidene interval [CI]: 26%-43%). Overall, SARS-CoV-2 RNAemia was associated with COVID-19 severity with odds ratio (OR) of 5.43 (95% CI: 3.46-8.53). In addition, SARS-CoV-2 RNAemia was a significant risk factor for unfavorable clinical outcomes (OR = 6.54, 95% CI: 3.82-11.21). The summary OR was 4.28 (95% CI: 2.20-8.33) for intensive care unit (ICU) admission, 11.07 (95% CI: 5.60-21.88) for mortality. Furthermore, RNAemia was also a significant risk factor for invasive mechanical ventilation and multiple organ failure. SARS-CoV-2 RNAemia is associated with disease severity, ICU admission, death in COVID-19, and may serve as a clinical predictor. More prospective trials in evaluating the potential of SARS-CoV-2 RNAemia as a prognostic indicator are necessary.

Tang K ，Wu L ，Luo Y ，Gong B ... -  《-》

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 ... -  《-》

Relationship Between Serum Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid and Organ Damage in Coronavirus 2019 Patients: A Cohort Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.

Xu D ，Zhou F ，Sun W ，Chen L ，Lan L ，Li H ，Xiao F ，Li Y ，Kolachalama VB ，Li Y ，Wang X ，Xu H ... -  《-》