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Id Subject Object Predicate Lexical cue
T1 0-95 Sentence denotes Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity
T2 96-126 Sentence denotes Emerging Microbes & Infections
T3 127-129 Sentence denotes W.
T4 130-141 Sentence denotes Chen et al.
T5 143-151 Sentence denotes Abstract
T6 152-160 Sentence denotes ABSTRACT
T7 161-365 Sentence denotes The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab.
T8 366-490 Sentence denotes Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients).
T9 491-704 Sentence denotes Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001).
T10 705-797 Sentence denotes Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage.
T11 798-1007 Sentence denotes However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract.
T12 1008-1093 Sentence denotes Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.
T13 1095-1325 Sentence denotes The 2019 novel coronavirus (2019-nCoV), originally outbreaking from Wuhan China, has transmitted in an extremely short period to 25 countries and infected over 31 000 individuals as of Feb 06, 2020, causing an international alarm.
T14 1326-1593 Sentence denotes Basic scientific research has achieved significantly in the investigation of viral origination [1,2], transmission and evolution [3], and unprecedented public health control actions in China have been activated and effectively prevented the otherwise dramatic spread.
T15 1594-1782 Sentence denotes The 2019-nCoV virus seems more infectious in its public transmission capacity compared to the well-known 2003 SARS virus in spite of the unavailability of convincingly scientific evidence.
T16 1783-1858 Sentence denotes The mechanism of viral transmission is still worthy of further exploration.
T17 1859-1955 Sentence denotes Currently, one urgent and critical challenge is to treat infected patients and save their lives.
T18 1956-2053 Sentence denotes Several studies have roughly described the overall clinical features of 2019-nCoV patients [4,5].
T19 2054-2356 Sentence denotes However, the more specific and classified clinical characteristics of the infected patients still require further investigation, particularly for those with severe symptoms, which is roughly estimated to be approximately 15–20 percent of totally confirmed cases based on the local data in our hospital.
T20 2357-2565 Sentence denotes Clinically, for those severe patients, the main symptoms of 2019-nCoV pneumonia are fever, decreased white blood cell and lymphocyte count, increased C reaction protein and abnormally expressed cytokines [6].
T21 2566-2739 Sentence denotes One remaining question to be resolved is whether the 2019-nCoV virus can replicate in extra-pulmonary sites, which might account for the deteriorated clinical manifestation.
T22 2740-2932 Sentence denotes In this study, we investigated whether the patients with severe clinical symptoms exhibited special profiles of virus replication or/and distribution compared to those only with mild symptoms.
T23 2933-3102 Sentence denotes Patients, who were confirmed to be infected by the 2019-nCoV virus, were firstly enrolled in or transferred to Guangzhou Eighth People’s Hospital for treatment purposes.
T24 3103-3199 Sentence denotes This study followed the guideline of the Ethics Committee of Guangzhou Eighth People’s Hospital.
T25 3200-3355 Sentence denotes All blood, pharyngeal swab, and anal swab samples were collected for diagnostic purposes in the laboratory and our study added no extra burden to patients.
T26 3356-3537 Sentence denotes Viral RNA was extracted with Nucleic Acid Isolation Kit (Da’an Gene Corporation, Cat: DA0630) on an automatic workstation Smart 32 (Da’an Gene Corporation) following the guidelines.
T27 3538-3702 Sentence denotes Real-time reverse transcriptional polymerase chain reaction (RT–PCR) reagent (Da’an Gene cooperation, Cat DA0930) was employed for viral detection per the protocol.
T28 3703-3855 Sentence denotes In brief, two PCR primer and probe sets, which target orf1ab (FAM reporter) and N (VIC reporter) genes separately, were added in the same reaction tube.
T29 3856-3929 Sentence denotes Positive and negative controls were included for each batch of detection.
T30 3930-4028 Sentence denotes Samples were considered to be viral positive when either or both set(s) gave a reliable signal(s).
T31 4029-4115 Sentence denotes All patients had pneumonia-based diseases but with diversified clinical manifestation.
T32 4116-4286 Sentence denotes To simplify data analysis, the patients were only classified as either mild or severe clinical symptom groups based on the guideline newly released by Chinese government.
T33 4287-4597 Sentence denotes Patients who were with at least one of the following symptom should be diagnosed to be severe case, 1) distress of respiratory with respiratory rate > = 30/min; 2) Oxygen saturation < = 93% in the rest state, and 3) arterial oxygen tension (PaO₂) over inspiratory oxygen fraction (FIO₂) of less than 300 mm Hg.
T34 4598-4731 Sentence denotes In the blood detection cohort (Figure 1(A)), patients who had at less one serum sample measurement with the PCR method were included.
T35 4732-4983 Sentence denotes In the 57, 6 cases were detected to be blood positive, all of them (100%) were severe in symptom requiring special care attention, and the blood of the rest 51 cases was without detectable virus in the blood, only 12 of them (23.5%) were severe cases.
T36 4984-5085 Sentence denotes The ratio of severe symptoms between these two groups was significantly different (p value = 0.0001).
T37 5086-5348 Sentence denotes In the anal swab cohort (Figure 1(B)), 11 of 28 cases were detected to be anal swab positive, 8 of them (72.7%) were with severe symptoms, which was significantly higher than that 4 (23.5%) of the rest 17 cases without detectable virus in anal were severe cases.
T38 5349-5358 Sentence denotes Figure 1.
T39 5359-5435 Sentence denotes Results of 2019-nCoV viral RNA detection in the blood (A) and anal swab (B).
T40 5436-5567 Sentence denotes Blood or anal swab positive represents viral RNA positive in at least one test of blood or anal swab samples from the same patient.
T41 5568-5691 Sentence denotes Blood or anal swab negative represents viral RNA negative in all tests of blood or anal swab samples from the same patient.
T42 5692-5833 Sentence denotes Severe represents that the patient is diagnosed as a severe symptom after expert consultation while mild represents the rest of the patients.
T43 5834-5882 Sentence denotes P values are shown (chi-square test, two sides).
T44 5883-5977 Sentence denotes Fortunately, two cases with detectable virus both in blood and anal swab cohort were recorded.
T45 5978-6248 Sentence denotes Patient 1 (Figure 2(A)) was admitted to ICU after enrollment evaluation and was highly suspected infection with 2019-nCoV because of his recent travelling from Wuhan and of confirmed pneumonia by radiographic diagnosis with 5-day fever and 1-day continuous dry coughing.
T46 6249-6333 Sentence denotes He was then confirmed to be infected by the 2019-nCoV virus on illness day 6 by CDC.
T47 6334-6486 Sentence denotes High concentrations of the viral RNA were detected in the pharyngeal swabs on illness days 5 (Ct = 17 + 25), 7, 8 (Ct = 25 + 26), and 11 (Ct = 15 + 25).
T48 6487-6647 Sentence denotes In the blood, no viral RNA was detected on day 5 but the sample on day 6 gave a weak positive signal (Ct = Neg+39), and then the signal was gone again on day 8.
T49 6648-6730 Sentence denotes On day 9, a low level of viral RNA (Ct = 36 + 41) was detected again in the blood.
T50 6731-6770 Sentence denotes On day 12, the blood lost signal again.
T51 6771-6934 Sentence denotes A high concentration of virus RNA (Ct = 23 + 27) was detected in the anal sample on day 13, on the day the 2019-nCoV virus was not detected in the pharyngeal swab.
T52 6935-7032 Sentence denotes Unfortunately, he was transferred out to another hospital after an emergency expert consultation.
T53 7033-7042 Sentence denotes Figure 2.
T54 7043-7151 Sentence denotes Diagram of viral detection in patient 1 (A) and 2 (B) with both detectable virus RNA in blood and anal swab.
T55 7152-7277 Sentence denotes Illness day represents the patients with clear clinical symptoms such as fever, dry-coughing is labelled over the first line.
T56 7278-7512 Sentence denotes ICU, CDC confirmed, and transfer indicates that the patient is in the ICU ward, CDC confirmation of viral positive, and transfer of patient out from ICU ward to another hospital to receive a higher level of medical care, respectively.
T57 7513-7576 Sentence denotes Ct value from the pharyngeal, blood and the anal swab is shown.
T58 7577-7861 Sentence denotes Patient 2 (Figure 2(B)), who had a clear infection history and started fever 5-day ago and dry coughing 2-day ago, was admitted with clinically highly suspect of 2019-nCoV infection, considering the radiographical diagnosis which indicated clear pneumonia in the bilateral lung lobes.
T59 7862-7951 Sentence denotes The virus was detected in his blood on illness day 7 (Ct = 34 + 36) and 8 (Ct = 38 + 38).
T60 7952-8004 Sentence denotes His infection was also informed by the CDC on day 8.
T61 8005-8216 Sentence denotes Because his disease advanced very fast, he was transferred to the ICU ward for special medical care requirements on day 9, on which day high titers of virus (Ct = 25 + 36) were detected in the pharyngeal sample.
T62 8217-8350 Sentence denotes Importantly, virus RNA was detected in all pharyngeal (Ct = 23 + 24), blood (Ct = 34 + 39) and anal (Ct = 24 + 29) samples on day 10.
T63 8351-8433 Sentence denotes He was transferred out to another hospital after an emergency expert consultation.
T64 8434-8511 Sentence denotes Finally, we described here the four patients with detectable serum viral RNA.
T65 8512-8794 Sentence denotes Patient 3 (Figure 3(A)) was transferred to the ICU directly on illness day 11 because of his severe condition, the 2019-nCoV virus was laboratory detected both in pharyngeal (Ct = 30 + 30) and blood samples (Ct = 37 + 39) on day 12, And his infection was confirmed by CDC on day 13.
T66 8795-8880 Sentence denotes Pharyngeal samples were PCR positive on days 14 and 17 and became negative on day 22.
T67 8881-8982 Sentence denotes Patient 4 (Figure 3(B)) was transferred to the ICU ward on the illness day 6 with a CDC confirmation.
T68 8983-9145 Sentence denotes His disease advanced pretty fast and became severe on day 7 and he was transferred to ICU after his blood sample was detected to be virus-positive (Ct = 32 + 37).
T69 9146-9179 Sentence denotes On day 9, he was transferred out.
T70 9180-9299 Sentence denotes Patient 5 (Figure 3(C)) was admitted on illness day 4 and his blood sample was virus-positive (Ct = 38 + Neg) on day 6.
T71 9300-9372 Sentence denotes Her disease progressed rapidly to a severe stage within the next 3 days.
T72 9373-9485 Sentence denotes Patient 6 (Figure 3(D)) with a clear history of virus infection was confirmed to be infected on infection day 7.
T73 9486-9578 Sentence denotes Viral RNA was detected in his blood sample on day 9, one day ahead of his transfer into ICU.
T74 9579-9638 Sentence denotes As his condition worsens, he was transferred out on day 13.
T75 9639-9648 Sentence denotes Figure 3.
T76 9649-9757 Sentence denotes Diagram of viral detection in Patient 3 (A), 4 (B), 5 (C) and 6 (D) with both detectable virus RNA in blood.
T77 9758-9800 Sentence denotes Labels are identical to those in Figure 2.
T78 9801-9875 Sentence denotes Severe represents that the patient is diagnosed to be severe symptoms (B).
T79 9876-9948 Sentence denotes Infection day represents the patient with a clear time of infection (D).
T80 9949-10061 Sentence denotes In this retrospective study, we analyzed the PCR data of virus detection in different tissues in our laboratory.
T81 10062-10244 Sentence denotes Firstly, our observation indicated that the presence of viral RNA outside of the respiratory tract might herald the severity of the disease and alarm the requirement of special care.
T82 10245-10481 Sentence denotes In the blood test cohort, all the 6 infected patients were in (or later progressed to) severe disease stage when serum viral RNA became detectable, which showed a significant difference compared to the blood negative group (p = 0.0001).
T83 10482-10645 Sentence denotes Patient 2 (Figure 2(B)), 5 (Figure 3(C)) and 6 (Figure 3(D)) all had detectable viral RNA in the serum before they progressed to the clinical severe symptom stage.
T84 10646-10936 Sentence denotes Unfortunately, we missed the earlier time points of patient 1 (Figure 2(A)) and 3 (Figure 3(A)) who were directly admitted to ICU on transfer to our hospital because of severe condition, of patient 4 (Figure 3(B)) who had serum sample collected one day post the diagnosis of severe illness.
T85 10937-11028 Sentence denotes We, fortunately, observed high serum viral load in serum within their severe illness stage.
T86 11029-11188 Sentence denotes In the anal swab cohort, we found that the presence of virus RNA in the anal digestive tract was also positively correlated with disease severity (p = 0.0102).
T87 11189-11318 Sentence denotes The 3 patients detected with anal virus RNA but in mild stage should be monitored whether they will progress to the severe stage.
T88 11319-11483 Sentence denotes We have summarized the information of approximately 70 percent of the patients in Guangzhou city, and the study represented nearly the whole picture of this region.
T89 11484-11613 Sentence denotes However, the virus outbroke in such an emergence, allowing no delay in waiting for more patients to further confirm the findings.
T90 11614-11758 Sentence denotes Secondly, a high concentration of viral RNA in anal swabs suggested the digestive tract might be one extra-pulmonary site for virus replication.
T91 11759-11919 Sentence denotes For patient 1, a high concentration of viral RNA (Ct = 23 + 27, on day 13) was detected in anal swab but not in pharyngeal (the same day) and blood (1 d ahead).
T92 11920-12097 Sentence denotes For patient 2, higher concentrations of viral RNAs were detected in anal swab (Ct = 24 + 39) and pharyngeal swab (Ct = 23 + 24) than in the blood (Ct = 34 + 39) on the same day.
T93 12098-12206 Sentence denotes Angiotensin-converting enzyme 2 (ACE2) still is one of the receptors for 2019-nCoV attachment and entry [2].
T94 12207-12417 Sentence denotes Intensive structural analysis of the S protein of 2019-nCoV with the SARS-Coronavirus suggested that several critical residues in the viral spike protein might confer favourable interaction with human ACE2 [7].
T95 12418-12716 Sentence denotes Of note, ACE2 is also abundantly present in humans in the epithelia of the small intestine besides the respiratory tract and is ubiquitously present in endothelial cells [8], which might provide possible routes of transmission, and might account for the high transmission capacity of the new virus.
T96 12717-12951 Sentence denotes We propose that rampant coronavirus replication in pulmonary alveolus results in the breakdown of the alveolar vessel and the subsequent virus leakage into the blood flow, through which the virus is disseminated across the whole body.
T97 12952-13113 Sentence denotes Then the virus succeeds in establishing reinfection in the digestive tract by using the highly expressed ACE2 receptor, which exacerbated the disease vice versa.
T98 13114-13290 Sentence denotes Bat originated coronavirus was found to replicate in the swine digestive tract recently, also suggesting the potential replication possibility in the human digestive tract [9].
T99 13291-13445 Sentence denotes Nevertheless, confirmation of virus transmission through the digestive tract warrants further virus isolation from the anal swab in high safety level lab.
T100 13446-13564 Sentence denotes Unfortunately, in our study, we did not collect stool samples from patients and did not pursue viral RNA in the stool.
T101 13565-13805 Sentence denotes But we believe the existence of virus RNA in the stool samples from these patients because that a large amount of viral RNA was detected in anal swabs and that viral RNA had also been detected in a case reported from the United States [10].
T102 13806-14210 Sentence denotes Also, we didn’t collect sputum and bronchoalveolar lavage fluid for virus detection because that the dry coughing characteristic of patients infected with 2019-nCoV prevents producing enough amount of sputum and that bronchoalveolar lavage fluid collection requires a sophisticated operation which increases virus exposure possibility of care providers to high concentrations of virus-containing aerosol.
T103 14211-14485 Sentence denotes In summary, we find that the presence of viral RNA in the blood and anal swab is positively correlated with the severe disease stage and that early monitoring of virus RNA in blood and the digestive tract on top of the respiratory tract might benefit the disease prediction.
T104 14487-14502 Sentence denotes Acknowledgement
T105 14503-14536 Sentence denotes We declare no competing interest.
T106 14537-14601 Sentence denotes We thank all the physicians and nurses who cared these patients.
T107 14602-14684 Sentence denotes This work was supported by National Natural Science Foundation of China Grant (No.
T108 14685-14801 Sentence denotes 81670536 and 81770593) and by the National Grand Program on Key Infectious Disease Control (2017ZX10202203-004-002).
T109 14803-14823 Sentence denotes Disclosure statement
T110 14824-14888 Sentence denotes No potential conflict of interest was reported by the author(s).