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Id Subject Object Predicate Lexical cue
T1 0-74 Sentence denotes Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea
T2 76-84 Sentence denotes Abstract
T3 85-260 Sentence denotes As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world.
T4 261-409 Sentence denotes With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated.
T5 410-478 Sentence denotes However, data on viral load kinetics in confirmed cases are lacking.
T6 479-644 Sentence denotes Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown.
T7 645-801 Sentence denotes This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.
T8 803-1156 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 1157-1473 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 1474-1599 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 1600-1847 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 1848-2077 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 2078-2300 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 2301-2370 Sentence denotes The detection limit of quantitative PCR reaction was 2,690 copies/mL.
T15 2371-2487 Sentence denotes Detailed methods and values for the tests are presented in the Supplementary Data 1 and Supplementary Tables 1 to 3.
T16 2488-2594 Sentence denotes A 35-year-old Chinese woman from Wuhan, China was confirmed to be first SARS-CoV-2 infected case in Korea.
T17 2595-2813 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 2814-2924 Sentence denotes Briefly, she was quarantined at the airport due to fever (38.3°C) at the entry inspection on January 19, 2020.
T19 2925-3083 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 3084-3152 Sentence denotes The virus was detected from URT specimens on day 2 of symptom onset.
T21 3153-3310 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 3311-3436 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 3437-3708 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 3709-3805 Sentence denotes She eventually developed cough on day 7, and infiltration was observed on CXR from the next day.
T25 3806-4023 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 4024-4176 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 4177-4338 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 4339-4460 Sentence denotes From day 14 (LRT specimen) and day 15 (URT specimen), rRT-PCR became undetectable for two consecutive days, respectively.
T29 4461-4507 Sentence denotes She had mild loose stool from day 4 to day 19.
T30 4508-4675 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 4676-4815 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 4816-4971 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 4972-5100 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 5101-5206 Sentence denotes The detailed exposure history and a clinical course of this patient is described in Supplementary Data 1.
T35 5207-5394 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 5395-5508 Sentence denotes He was tested on January 23, 2020, confirmed with SARS-CoV-2 infection next day and hospitalized on the same day.
T37 5509-5600 Sentence denotes Therefore, his admission day (January 24) was considered to be the day 15 of symptom onset.
T38 5601-5726 Sentence denotes His CXR on day 15 showed infiltration and chest HRCT on day 16 showed bilateral ground-glass opacity (Supplementary Fig. 3A).
T39 5727-5835 Sentence denotes The viral load kinetics are shown in Fig. 1B (viral RNA copies) and Supplementary Fig. 2 (reverse Ct value).
T40 5836-5969 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 5970-6226 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 6227-6337 Sentence denotes SARS-CoV-2 was detected a few more times during hospitalization from both URT and LRT specimens at low levels.
T43 6338-6436 Sentence denotes As he had just mild cough with little or no sputum, LRT specimens were available only a few times.
T44 6437-6552 Sentence denotes From D18 (URT specimen) and D20 (LRT specimen), rRT-PCR became undetectable for two consecutive days, respectively.
T45 6553-6736 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 6737-6863 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 6864-6944 Sentence denotes His CXR improved from day 19 and he was discharged on day 27 (February 5, 2020).
T48 6945-7081 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 7082-7330 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 7331-7504 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 7505-7637 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 7638-7701 Sentence denotes There are several important implications from this observation.
T53 7702-7962 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 7963-8147 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 8148-8305 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 8306-8484 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 8485-8691 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 8692-8815 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 8816-8956 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 8957-9134 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 9135-9212 Sentence denotes However, rRT-PCR results did not meet the criteria for SARS-CoV-2 positivity.
T62 9213-9311 Sentence denotes Further studies need to be performed in non-respiratory specimens such as urine and stool samples.
T63 9312-9421 Sentence denotes In Patient 2, we observed one example of mild disease with corresponding radiograph findings and viral loads.
T64 9422-9533 Sentence denotes This may represent many real-world mild cases who may present to medical facility late in their disease course.
T65 9534-9609 Sentence denotes Therefore, this patient's information has also some important implications.
T66 9610-9740 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 9741-9935 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 9936-10073 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 10074-10222 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 10223-10264 Sentence denotes There are also limitations in our report.
T71 10265-10429 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 10430-10606 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 10607-10788 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 10789-10946 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 10947-11076 Sentence denotes These data are also urgently needed to understand this virus better and to implement the control strategies as early as possible.
T76 11077-11182 Sentence denotes Finally, the virus has not been readily cultured from these specimens, yet, although we are still trying.
T77 11183-11338 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 11339-11440 Sentence denotes Therefore, knowing the virus load that can give a positive culture result is important in the future.
T79 11441-11547 Sentence denotes There is scarce information on viral load kinetics in SARS-CoV-2 infected patients throughout the illness.
T80 11548-11701 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 11702-11841 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 11842-11972 Sentence denotes While two cases were different in disease course, these data will provide valuable insight to understand the nature of this virus.
T83 11974-11990 Sentence denotes Ethics statement
T84 11991-12066 Sentence denotes The clinical data and images are presented under agreement of the patients.
T85 12068-12083 Sentence denotes ACKNOWLEDGMENTS
T86 12084-12274 Sentence denotes We greatly appreciate the efforts of all the hospital employees and their families at the Incheon Medical Center and National Medical Center, who are working tirelessly during this outbreak.
T87 12275-12420 Sentence denotes We thank to Yoonju Oh, Sung Hee Kim, Yoon Soog Kang, and Kwang Sil Kim (Incheon Medical Center) for collecting and preserving clinical specimens.
T88 12421-12558 Sentence denotes We thank Hyun Mee Park (Department of Radiology, National Medical Center) for the obtainment of excellent radiologic study result safely.
T89 12559-12703 Sentence denotes We also thank to Yunyoung Jang, and Eunhee Kim for the dedication to protect healthcare workers of National Medical Center by infection control.
T90 12704-12838 Sentence denotes We sincerely appreciate the discussion and critical feedback from Dr. Janet A Englund (Seattle Children’s Hospital, Seattle, WA, USA).
T91 12839-13132 Sentence denotes Lastly, we thank all the members of the Korean Society of Infectious Diseases (KSID), the groups of Korean Emerging Infectious Diseases (KoEID) application, and Korea National Clinical Management Network (KNCMN) for COVID-19, who are coping with the current global outbreak situation together.
T92 13133-13144 Sentence denotes Disclosure:
T93 13145-13209 Sentence denotes The authors have no potential conflicts of interest to disclose.
T94 13210-13231 Sentence denotes Author Contributions:
T95 13232-13250 Sentence denotes Conceptualization:
T96 13251-13275 Sentence denotes Kim JY, Chin BS, Kim YJ.
T97 13276-13290 Sentence denotes Data curation:
T98 13291-13330 Sentence denotes Kim JY, Chin BS, Han MG, Kim SY, Ko JH.
T99 13331-13347 Sentence denotes Formal analysis:
T100 13348-13387 Sentence denotes Kim JY, Chin BS, Han MG, Kim SY, Ko JH.
T101 13388-13400 Sentence denotes Methodology:
T102 13401-13442 Sentence denotes Kim JM, Chung YS, Kim HM, Kim SY, Han MG.
T103 13443-13468 Sentence denotes Writing - original draft:
T104 13469-13508 Sentence denotes Kim YJ, Kim JY, Chin BS, Han MG, Ko JH.
T105 13509-13536 Sentence denotes Writing - review & editing:
T106 13537-13617 Sentence denotes Kim JY, Ko JH, Kim Y, Kim YJ, Kim JM, Chung YS, Kim HM, Han MG, Kim SY, Chin BS.
T107 13619-13642 Sentence denotes SUPPLEMENTARY MATERIALS
T108 13643-13663 Sentence denotes Supplementary Data 1
T109 13664-13727 Sentence denotes Laboratory procedures and detailed clinical course of Patient 2
T110 13728-13749 Sentence denotes Supplementary Table 1
T111 13750-13839 Sentence denotes Clinical course and viral loads of Patient 1 according to the timeline from symptom onset
T112 13840-13861 Sentence denotes Supplementary Table 2
T113 13862-13951 Sentence denotes Clinical course and viral loads of Patient 2 according to the timeline from symptom onset
T114 13952-13973 Sentence denotes Supplementary Table 3
T115 13974-14029 Sentence denotes Estimated number of viral copy of respiratory specimens
T116 14030-14050 Sentence denotes Supplementary Fig. 1
T117 14051-14293 Sentence denotes Viral load kinetics according to the clinical course of Patient 1, presented by reverse Ct value. (A) Viral load kinetics of respiratory specimen, (B) Viral load kinetics of blood specimen, (C) Viral load kinetics of urine and stool specimen.
T118 14294-14314 Sentence denotes Supplementary Fig. 2
T119 14315-14557 Sentence denotes Viral load kinetics according to the clinical course of Patient 2, presented by reverse Ct value. (A) Viral load kinetics of respiratory specimen, (B) Viral load kinetics of blood specimen, (C) Viral load kinetics of urine and stool specimen.
T120 14558-14578 Sentence denotes Supplementary Fig. 3
T121 14579-14776 Sentence denotes Images of Patient 2. (A) Chest X-ray taken on admission, January 24, 2010 (day 15 from symptom onset). (B) High resolution computed tomography taken on January 25, 2010 (day 16 from symptom onset).
T122 14778-15010 Sentence denotes Fig. 1 Viral load kinetics according to the clinical course of the first two SARS-CoV-2 infected patients in Korea. (A) Viral load kinetics and clinical course of Patient 1. (B) Viral load kinetics and clinical course of Patient 2.
T123 15011-15226 Sentence denotes URT = upper respiratory tract, LRT = lower respiratory tract, ND = not detected, CXR = chest X-ray, GGO = ground glass opacity, CT = computed tomography, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
T124 15227-15412 Sentence denotes a)In Patient 2, the exact fever duration could not be estimated because he had taken non-steroidal anti-inflammatory agent to control his myalgia and sore throat before hospitalization.
T125 15413-15554 Sentence denotes When his physician discontinued the medication, the fever was observed; b)Patient 2 experienced loose stool after taking Lopinavir/ritonavir.