PMC:7036338 / 803-12066 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T8 0-353 Sentence denotes As of February 2020, the novel coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in China in December 2019 has been spreading in many countries over the world.123 The numbers of confirmed cases are increasing over 70,000 including 31 Korean patients as of third week of February 2020.
T9 354-670 Sentence denotes The World Health Organization declared the SARS-CoV-2 outbreak a public health emergency of international concern on January 30, 2020.4 While the information on epidemiologic investigation and clinical manifestation are being accumulated, viral kinetics of the novel virus have not been systematically evaluated yet.
T10 671-796 Sentence denotes To understand the behavior of the virus in human body, we present the viral load kinetics of the first two patients in Korea.
T11 797-1044 Sentence denotes Upper respiratory tract (URT) and lower respiratory specimen (LRT) specimens were collected from confirmed patients every day after the diagnosis of SARS-CoV-2 infection and sent to Korea Center for Disease Control for follow-up tests and culture.
T12 1045-1274 Sentence denotes Nasopharyngeal and oropharyngeal swabs were collected and placed in the same tube as URT specimen, and sputum was used as LRT specimen.5 Serum, plasma, urine, and stool samples were also collected sequentially during the illness.
T13 1275-1497 Sentence denotes Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2 using the published sequences.6 The cycle threshold (Ct) values of rRT-PCR was converted into RNA copy number of SARS-CoV-2.
T14 1498-1567 Sentence denotes The detection limit of quantitative PCR reaction was 2,690 copies/mL.
T15 1568-1684 Sentence denotes Detailed methods and values for the tests are presented in the Supplementary Data 1 and Supplementary Tables 1 to 3.
T16 1685-1791 Sentence denotes A 35-year-old Chinese woman from Wuhan, China was confirmed to be first SARS-CoV-2 infected case in Korea.
T17 1792-2010 Sentence denotes The detailed exposure history and a clinical course of this patient is described in previous report.7 Viral load kinetics of Patient 1 is shown in Fig. 1A (viral RNA copies) and Supplementary Fig. 1 (reverse Ct value).
T18 2011-2121 Sentence denotes Briefly, she was quarantined at the airport due to fever (38.3°C) at the entry inspection on January 19, 2020.
T19 2122-2280 Sentence denotes She had no significant exposure history and developed fever, chills, and myalgia one day before the entry to Korea (January 18, 2020, day 1 of symptom onset).
T20 2281-2349 Sentence denotes The virus was detected from URT specimens on day 2 of symptom onset.
T21 2350-2507 Sentence denotes As she did not have significant respiratory symptoms, LRT specimen (spontaneous sputum) was obtained with airway clearance techniques of percussion on day 3.
T22 2508-2633 Sentence denotes Although any infiltration was not noticed on her chest X-ray (CXR) on the same day, LRT specimen was positive for SARS-CoV-2.
T23 2634-2905 Sentence denotes On day 4, high resolution computed tomography (HRCT) was taken and multiple ground-glass opacities were observed in both sub-pleural spaces.7 On day 5, the viral load was increased from day 3 in LRT specimen and she required oxygen supplement via nasal cannula (3 L/min).
T24 2906-3002 Sentence denotes She eventually developed cough on day 7, and infiltration was observed on CXR from the next day.
T25 3003-3220 Sentence denotes However, it appeared that the viral loads already started to decrease from around day 7 in both URT and LRT specimens. rRT-PCR continued to be positive at low level until day 13 (LRT specimens) and 14 (URT specimens).
T26 3221-3373 Sentence denotes On day 12, her CXR was worsened with increase in oxygen requirement up to 10 L/min, while the viral loads dropped significantly from the initial values.
T27 3374-3535 Sentence denotes Therefore, by the time when the significant infiltration was visible on a plain chest radiography, the viral load might be already on its lower end of detection.
T28 3536-3657 Sentence denotes From day 14 (LRT specimen) and day 15 (URT specimen), rRT-PCR became undetectable for two consecutive days, respectively.
T29 3658-3704 Sentence denotes She had mild loose stool from day 4 to day 19.
T30 3705-3872 Sentence denotes Although RdRp and/or E gene were detected occasionally from urine and stool specimens collected from day 5 to 12, none of specimen satisfied conditions for positivity.
T31 3873-4012 Sentence denotes Only one serum sample collected on day 8 showed positive rRT-PCR result, but the Ct value was adjacent to the cut-off value for positivity.
T32 4013-4168 Sentence denotes Her symptoms, oxygen requirement, and CXR findings significantly improved from day 17 and she was discharged on day 20 of symptom onset (February 6, 2019).
T33 4169-4297 Sentence denotes Patient 2 was a 55-year-old Korean man, who had been working at Wuhan, China, arrived in Korea via Shanghai on January 22, 2020.
T34 4298-4403 Sentence denotes The detailed exposure history and a clinical course of this patient is described in Supplementary Data 1.
T35 4404-4591 Sentence denotes Briefly, he did not have any significant exposure history and developed sore throat and intermittent myalgia since January 10 which was controlled by nonsteroidal anti-inflammatory agent.
T36 4592-4705 Sentence denotes He was tested on January 23, 2020, confirmed with SARS-CoV-2 infection next day and hospitalized on the same day.
T37 4706-4797 Sentence denotes Therefore, his admission day (January 24) was considered to be the day 15 of symptom onset.
T38 4798-4923 Sentence denotes His CXR on day 15 showed infiltration and chest HRCT on day 16 showed bilateral ground-glass opacity (Supplementary Fig. 3A).
T39 4924-5032 Sentence denotes The viral load kinetics are shown in Fig. 1B (viral RNA copies) and Supplementary Fig. 2 (reverse Ct value).
T40 5033-5166 Sentence denotes In this patient, the initial test was performed on day 14 of symptom onset and SARS-CoV-2 was detected in both URT and LRT specimens.
T41 5167-5423 Sentence denotes However, the initial viral loads were relatively lower (49,047 copies/mL for URT and 391,243 copies/mL for LRT) than those of Patient 1 (46,971,053 copies/mL for URT and 9,171,220 copies/mL for LRT) in whom the test was performed on day 2 of symptom onset.
T42 5424-5534 Sentence denotes SARS-CoV-2 was detected a few more times during hospitalization from both URT and LRT specimens at low levels.
T43 5535-5633 Sentence denotes As he had just mild cough with little or no sputum, LRT specimens were available only a few times.
T44 5634-5749 Sentence denotes From D18 (URT specimen) and D20 (LRT specimen), rRT-PCR became undetectable for two consecutive days, respectively.
T45 5750-5933 Sentence denotes On day 25, RdRp (Ct value of 36.69) and E (Ct value of 33.18) genes was detected again from the URT sample of day 25, it was interpreted as negative due to high Ct value of RdRp gene.
T46 5934-6060 Sentence denotes From his plasma and stool specimens, only E genes were once detected on day 17 and it was also interpreted as negative result.
T47 6061-6141 Sentence denotes His CXR improved from day 19 and he was discharged on day 27 (February 5, 2020).
T48 6142-6278 Sentence denotes This study presents the viral load kinetics of the first two confirmed patients in Korea in whom distinct viral load kinetics are shown.
T49 6279-6527 Sentence denotes Although the viral load and CXR findings in these two patients may not represent the whole spectrum of SARS-CoV-2 illness, our report will provide many important findings and opportunity to understand this newly discovered virus infection in human.
T50 6528-6701 Sentence denotes In Patient 1, we observed one example of moderate disease (shortness of breath and oxygen requirement up to 10 L/min) with corresponding radiograph findings and viral loads.
T51 6702-6834 Sentence denotes We could observe her clinical presentation from day 2 of symptom onset and the whole clinical picture was captured with viral loads.
T52 6835-6898 Sentence denotes There are several important implications from this observation.
T53 6899-7159 Sentence denotes First, unlike SARS-CoV infection,8 we found that viral load was highest during the early phase of the illness (3–5 days from first symptom onset, fever and myalgia were the only symptoms in Patient 1) and continued to decrease until the end of the second week.
T54 7160-7344 Sentence denotes While she developed cough as well as shortness of breath and infiltration appeared on CXR at the end of first week of illness, the viral load already started to decrease at this phase.
T55 7345-7502 Sentence denotes This may have a very important implication to determine the optimal time point for antiviral treatment intervention to prevent progression to severe disease.
T56 7503-7681 Sentence denotes Second, the virus was detected from LRT specimens even before the development of LRT symptoms (cough, shortness of breath, and oxygen requirement) or visible infiltration on CXR.
T57 7682-7888 Sentence denotes This may suggest that although the patient does not complain of any LRT symptoms, the virus is already there and causing insidious pathology, ultimately leading to LRT symptoms and chest infiltration later.
T58 7889-8012 Sentence denotes However, the viral load starts to decrease in both URT and LRT specimens at the same time, which may puzzle the clinicians.
T59 8013-8153 Sentence denotes Third, unlike in MERS-CoV revealing higher concentration of virus in LRT specimens,9 viral loads were similar in both URT and LRT specimens.
T60 8154-8331 Sentence denotes Fourth, low concentration of genetic materials, especially E gene, was detected in urine and stool from the end of the first week until the patient recovered from the infection.
T61 8332-8409 Sentence denotes However, rRT-PCR results did not meet the criteria for SARS-CoV-2 positivity.
T62 8410-8508 Sentence denotes Further studies need to be performed in non-respiratory specimens such as urine and stool samples.
T63 8509-8618 Sentence denotes In Patient 2, we observed one example of mild disease with corresponding radiograph findings and viral loads.
T64 8619-8730 Sentence denotes This may represent many real-world mild cases who may present to medical facility late in their disease course.
T65 8731-8806 Sentence denotes Therefore, this patient's information has also some important implications.
T66 8807-8937 Sentence denotes First, even in a patient with mild disease (sore throat only), visible infiltration on CXR was observed at the end of second week.
T67 8938-9132 Sentence denotes Second, even in a patient with mild disease, if visible infiltration on CXR is observed, virus is still detected in both URT and LRT specimens even at the end of second week after symptom onset.
T68 9133-9270 Sentence denotes Viral loads of URT were similar with and sometimes higher than LRT specimens, and virus was detectable for longer period in URT specimen.
T69 9271-9419 Sentence denotes This could be also probably because the patient did not have significant cough and had little amount of spontaneous sputum insufficient for testing.
T70 9420-9461 Sentence denotes There are also limitations in our report.
T71 9462-9626 Sentence denotes Since we only presented two patients (mild and moderate), the information from these patients may not be generalizable to many other cases, especially severe cases.
T72 9627-9803 Sentence denotes Second, Lopinavir/ritonavir was used in both patients on day 5 and day 17 from symptom onset, but its role cannot be determined in viral load reduction or clinical improvement.
T73 9804-9985 Sentence denotes In addition, since they received Lopinavir/ritonavir which can also cause diarrhea, how much of gastrointestinal tract symptom was in fact related to SARS-CoV-2 or drug side effect.
T74 9986-10143 Sentence denotes Third, we cannot estimate the time point when these patients were exposed to virus and when they started to shed the virus from their respiratory secretions.
T75 10144-10273 Sentence denotes These data are also urgently needed to understand this virus better and to implement the control strategies as early as possible.
T76 10274-10379 Sentence denotes Finally, the virus has not been readily cultured from these specimens, yet, although we are still trying.
T77 10380-10535 Sentence denotes It is not clear whether there was not viable virus (possibly infectious) or we were not successful to culture this newly discovered virus in the beginning.
T78 10536-10637 Sentence denotes Therefore, knowing the virus load that can give a positive culture result is important in the future.
T79 10638-10744 Sentence denotes There is scarce information on viral load kinetics in SARS-CoV-2 infected patients throughout the illness.
T80 10745-10898 Sentence denotes Therefore, although our report is based on observation from only two patients, this will provide valuable insight to understand the nature of this virus.
T81 10899-11038 Sentence denotes In conclusion, we report a unique pattern of SARS-CoV-2 viral kinetics in URT and LRT specimens from first two patients diagnosed in Korea.
T82 11039-11169 Sentence denotes While two cases were different in disease course, these data will provide valuable insight to understand the nature of this virus.
T83 11171-11187 Sentence denotes Ethics statement
T84 11188-11263 Sentence denotes The clinical data and images are presented under agreement of the patients.