CORD-19:4977a01aec602236d923e970569adab5bdc5865e JSONTXT 7 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-91 Sentence denotes Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS-coronavirus-2
TextSentencer_T2 93-101 Sentence denotes Abstract
TextSentencer_T3 102-262 Sentence denotes Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19, which was first reported in Wuhan, China in December, 2019.
TextSentencer_T4 263-393 Sentence denotes Despite the tremendous efforts to control the disease, COVID-19 has now spread to over 100 countries and caused a global pandemic.
TextSentencer_T5 394-521 Sentence denotes SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are completely unknown.
TextSentencer_T6 522-629 Sentence denotes Here, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2.
TextSentencer_T7 630-745 Sentence denotes We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but efficiently in ferrets and cats.
TextSentencer_T8 746-813 Sentence denotes We found that the virus transmits in cats via respiratory droplets.
TextSentencer_T9 814-936 Sentence denotes Our study provides important insights into the animal reservoirs of SARS-CoV-2 and animal management for COVID-19 control.
TextSentencer_T10 938-993 Sentence denotes isolated from a human patient] were used in this study.
TextSentencer_T11 994-1135 Sentence denotes Pairs of ferrets were inoculated intranasally with 10 5 pfu of F13-E or CTan-H, respectively, and euthanized on day 4 postinoculation (p.i.).
TextSentencer_T12 1136-1368 Sentence denotes The nasal turbinate, soft palate, tonsils, trachea, lung, heart, spleen, kidneys, pancreas, small intestine, brain, and liver from each ferret were collected for viral RNA quantification by qPCR and virus titration in Vero E6 cells.
TextSentencer_T13 1369-1593 Sentence denotes Viral RNA (Fig. 1A, B) and infectious virus were detected in the nasal turbinate, soft palate, and tonsils of all four ferrets inoculated with these two viruses, but was not detected in any other organs tested (Fig. 1C, D) .
TextSentencer_T14 1594-1742 Sentence denotes These results indicate that SARS-CoV-2 can replicate in the upper respiratory tract of ferrets, but its replication in other organs is undetectable.
TextSentencer_T15 1743-1958 Sentence denotes To investigate the replication dynamics of these viruses in ferrets, groups of three animals were inoculated intranasally with 10 5 pfu of F13-E or CTan-H, and then placed in three separate cages within an isolator.
TextSentencer_T16 1959-2097 Sentence denotes Nasal washes and rectal swabs were collected on days 2, 4, 6, 8, and 10 p.i. from the ferrets for viral RNA detection and virus titration.
TextSentencer_T17 2098-2166 Sentence denotes Body temperatures and signs of disease were monitored for two weeks.
TextSentencer_T18 2167-2324 Sentence denotes As shown in Fig. 1 , viral RNA was detected in the nasal washes on days 2, 4, 6, and 8 p.i. in all six ferrets inoculated with the two viruses (Fig. 1E, F) .
TextSentencer_T19 2325-2512 Sentence denotes Viral RNA was also detected in some of the rectal swabs of the virus-inoculated ferrets although the copy numbers were notably lower than those in the nasal washes of these ferrets ( fig.
TextSentencer_T20 2513-2522 Sentence denotes S1A, B) .
TextSentencer_T21 2523-2655 Sentence denotes Infectious virus was detected from the nasal washes of all ferrets (Fig. 1G, H) , but not from the rectal swabs of any ferrets (fig.
TextSentencer_T22 2656-2664 Sentence denotes S1C, D).
TextSentencer_T23 2665-2783 Sentence denotes One ferret from each virus-inoculated group developed fever and loss of appetite on days 10 and 12 p.i., respectively.
TextSentencer_T24 2784-2984 Sentence denotes To investigate whether these symptoms were caused by virus replication in the lower respiratory tract, we euthanized the two ferrets on day 13 p.i., and collected their organs for viral RNA detection.
TextSentencer_T25 2985-3184 Sentence denotes However, viral RNA was not detected in any other tissues or organs of either ferret, except for a low copy number (10 5.4 copies/g) in the turbinate of the ferret inoculated with CTan-H ( fig S2) .
TextSentencer_T26 3185-3476 Sentence denotes Pathological studies revealed severe lymphoplasmacytic perivasculitis and vasculitis, increased numbers of type II pneumocytes, macrophages, and neutrophils in the alveolar septa and alveolar lumen, and mild peribronchitis in the lungs of the two ferrets euthanized on day 13 p.i. (fig.S3 ).
TextSentencer_T27 3477-3751 Sentence denotes Antibodies against SARS-CoV-2 were detected in all of the ferrets by an ELISA and a neutralization assay, although the antibody titers of the two ferrets that were euthanized on day 13 p.i. were notably lower than those of the ferrets euthanized on day 20 p.i. (Fig. 1I-L) .
TextSentencer_T28 3752-3850 Sentence denotes To further investigate whether SARS-CoV-2 replicates in the lungs of ferrets, we intratracheally .
TextSentencer_T29 3851-3903 Sentence denotes CC-BY-NC-ND 4.0 International license author/funder.
TextSentencer_T30 3904-4234 Sentence denotes It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint inoculated eight ferrets with 10 5 pfu of CTan-H, and euthanized two animals each on days 2, 4, 8, and 14 p.i. to look for viral RNA in the tissues and organs.
TextSentencer_T31 4235-4612 Sentence denotes Viral RNA was only detected in the nasal turbinate and soft palate of one of the two ferrets that were euthanized on days 2 and 4 p.i.; in the soft palate of one ferret and in the nasal turbinate, soft palate, tonsil, and trachea of the other ferret that were euthanized on day 8 p.i.; and was not detected in either of the two ferrets that were euthanized on day 14 p.i. (fig.
TextSentencer_T32 4613-4618 Sentence denotes S4 ).
TextSentencer_T33 4619-4776 Sentence denotes These results indicate that SARS-CoV-2 can replicate in the upper respiratory tract of ferrets for up to eight days, without causing severe disease or death.
TextSentencer_T34 4777-4925 Sentence denotes Cats and dogs are in close contact with humans, and therefore it is important to understand their susceptibility to SARS-CoV-2 for COVID-19 control.
TextSentencer_T35 4926-4986 Sentence denotes We first investigated the replication of SARS-CoV-2 in cats.
TextSentencer_T36 4987-5117 Sentence denotes Five 8-month-old outbred domestic cats (referred to here as "subadult cats") were intranasally inoculated with 10 5 pfu of CTan-H.
TextSentencer_T37 5118-5235 Sentence denotes Two of the subadult cats were scheduled to be euthanized on day 6 p.i. to evaluate viral replication in their organs.
TextSentencer_T38 5236-5305 Sentence denotes Three subadult cats were placed in separate cages within an isolator.
TextSentencer_T39 5306-5428 Sentence denotes To monitor respiratory droplet transmission, an uninfected cat was placed in a cage adjacent to each of the infected cats.
TextSentencer_T40 5429-5537 Sentence denotes It was difficult to perform regular nasal wash collection on the subadult cats because they were aggressive.
TextSentencer_T41 5538-5663 Sentence denotes To avoid possible injury, we only collected feces from these cats and checked for viral RNA in their organs after euthanasia.
TextSentencer_T42 5664-6005 Sentence denotes From the two subadult cats that were euthanized on day 6 p.i. with CTan-H, viral RNA was detected in the nasal turbinates, soft palates, and tonsils of both animals, in the trachea of one animal, and in the small intestine of the other; however, viral RNA was not detected in any of the lung samples from either of these animals ( Fig. 2A) .
TextSentencer_T43 6006-6206 Sentence denotes Infectious virus was detected in the viral RNA-positive nasal turbinates, soft palates, tonsils, and trachea of these cats, but was not recovered from the viral RNApositive small intestine (Fig. 2B ).
TextSentencer_T44 6207-6396 Sentence denotes In the transmission study, viral RNA was detected in the feces of two virus-inoculated subadult cats on day 3 p.i., and in all three virus-inoculated subadult cats on day 5 p.i. (Fig. 3A ).
TextSentencer_T45 6397-6477 Sentence denotes Viral RNA was detected in the feces of one exposed cat on day 3 p.i. (Fig. 3A) .
TextSentencer_T46 6478-6828 Sentence denotes The subadult cats with viral RNA-positive feces were euthanized on day 11 p.i., and viral RNA was detected in the soft palate and tonsils of the virusinoculated animal and in the nasal turbinate, soft palate, tonsils, and trachea of the exposed animal ( Fig. 3B ), indicating that respiratory droplet transmission had occurred in this pair of cats.
TextSentencer_T47 6829-7055 Sentence denotes We euthanized the other pairs of animals on day 12 p.i., and viral RNA was detected in the tonsils of one virus-inoculated subadult cat, in the nasal turbinate, soft palate, tonsils, and trachea of the other virus-inoculated .
TextSentencer_T48 7056-7108 Sentence denotes CC-BY-NC-ND 4.0 International license author/funder.
TextSentencer_T49 7109-7384 Sentence denotes It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint subadult cat, but was not detected in any organs or tissues of the two exposed subadult cats (Fig. 3B ).
TextSentencer_T50 7385-7551 Sentence denotes Antibodies against SARS-CoV-2 were detected in all three virus-inoculated subadult cats and one exposed cat by use of an ELISA and neutralization assay (Fig. 3C, D) .
TextSentencer_T51 7552-7664 Sentence denotes We replicated the replication and transmission studies in juvenile cats (aged 70-100 days) ( (Table 1, fig S7) .
TextSentencer_T52 7665-7730 Sentence denotes These results indicate that dogs have low susceptibility to SARS-
TextSentencer_T53 7731-8140 Sentence denotes We also investigated the susceptibility of pigs, chickens, and ducks to SARS-CoV-2 by using the same strategy as that used to assess dogs; however, viral RNA was not detected in any swabs collected from these virus-inoculated animals or from naïve contact animals (Table 1) , and all of the animals were seronegative for SARS-CoV-2 when tested by using the ELISA with sera collected on day 14 p.i. (Table 1 ).
TextSentencer_T54 8141-8229 Sentence denotes These results indicate that pigs, chickens, and ducks are not susceptible to SARS-CoV-2.
TextSentencer_T55 8230-8424 Sentence denotes In summary, we found that ferrets and cats are highly susceptible to SARS-CoV-2, dogs have low susceptibility, and livestock including pigs, chickens, and ducks are not susceptible to the virus.
TextSentencer_T56 8425-8557 Sentence denotes Ferrets have frequently been used as an animal model for the study of human respiratory viruses (20) (21) (22) (23) (24) (25) (26) .
TextSentencer_T57 8558-8652 Sentence denotes Unlike influenza viruses and other human SARS-coronavirus, which replicate in both the upper .
TextSentencer_T58 8653-8705 Sentence denotes CC-BY-NC-ND 4.0 International license author/funder.
TextSentencer_T59 8706-9034 Sentence denotes It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint and lower respiratory tract of ferrets (20, 22-24, 26, 27) , we found SARS-CoV-2 only replicates in the nasal turbinate, soft palate, and tonsils of ferrets.
TextSentencer_T60 9035-9270 Sentence denotes It may also replicate in the digestive tract, as viral RNA was detected in the rectal swabs of the virus-infected ferrets, but virus was not detected in lung lobes, even after the ferrets were intratracheally inoculated with the virus.
TextSentencer_T61 9271-9412 Sentence denotes Several studies have reported that SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as its receptor to enter cells (3, (28) (29) (30) .
TextSentencer_T62 9413-9695 Sentence denotes ACE2 is mainly expressed in type II pneumocytes and serous epithelial cells of tracheo-bronchial submucosal glands in ferrets (25) ; therefore, the underlying mechanism that prevents the replication of SARS-CoV-2 in the lower respiratory tract of ferrets remains to be investigated.
TextSentencer_T63 9696-9892 Sentence denotes The fact that SARS-CoV-2 replicates efficiently in the upper respiratory tract of ferrets makes them a candidate animal model for evaluating antiviral drugs or vaccine candidates against COVID-19.
TextSentencer_T64 9893-10040 Sentence denotes The cats we used in this study were outbred, and were highly susceptible to SARS-CoV-2, which replicated efficiently and transmitted to naïve cats.
TextSentencer_T65 10041-10152 Sentence denotes Surveillance for SARS-CoV-2 in cats should be considered as an adjunct to elimination of of COVID-19 in humans.
TextSentencer_T66 10153-10859 Sentence denotes The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint inoculated with or exposed to CTan-H at the indicated timepoints. (B) Viral RNA in tissues or organs of subadult cats that were inoculated with or exposed to CTan-H, the pair one cats (red bars) were euthanized on day 11 p.i. and the other two pairs were euthanized on day 12 p.i.
TextSentencer_T67 10860-11075 Sentence denotes Antibodies against SARS-CoV-2 of these euthanized cats were detected by using an ELISA (C) and neutralization assay (D). (E) Viral RNA in nasal washes of juvenile cats that were inoculated with or exposed to CTan-H.
TextSentencer_T68 11076-11238 Sentence denotes Sera of the juvenile cats were collected on day 20 p.i., and their antibodies against SARS-CoV-2 were detected by using an ELISA (F) and neutralization assay (G).
TextSentencer_T69 11239-11397 Sentence denotes One virus inoculated cat died on day 13 p.i. and the antibody values of this cat (indicated by asterisks) were detected from the sera collected on day 10 p.i.
TextSentencer_T70 11398-11460 Sentence denotes Each color bar represents the value from an individual animal.
TextSentencer_T71 11461-11527 Sentence denotes The horizontal dashed lines indicate the lower limit of detection.
TextSentencer_T72 11528-11529 Sentence denotes .
TextSentencer_T73 11530-11582 Sentence denotes CC-BY-NC-ND 4.0 International license author/funder.
TextSentencer_T74 11583-11756 Sentence denotes It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint b.
TextSentencer_T75 11757-12057 Sentence denotes One virus-inoculated beagle was euthanized on day 4 p.i., but viral RNA was not detected in any of its collected organs, which included lung, trachea, nasal turbinate, soft palate, brain, heart, submaxillary lymph nodes, tonsil, kidneys, spleen, liver, pancreas, and small intestine (data not shown).
TextSentencer_T76 12058-12060 Sentence denotes c.
TextSentencer_T77 12061-12234 Sentence denotes Sera were collected from all animals on day 14 p.i., and antibodies against SARS-Cov-2 were detected by using a Double Antigen Sandwich ELISA kit (ProtTech, Luoyang, China).
TextSentencer_T78 12236-12335 Sentence denotes Three-to four-month-old female ferrets (Wuxi Cay Ferret Farm, Wuxi, China) were used in this study.
TextSentencer_T79 12336-12575 Sentence denotes Groups of five ferrets were anesthetized with Zoletil 50 (Virbac, Carros, France) and inoculated intranasally with 10 5 PFU of SARS-CoV-2 CTan-H or F13-E in a volume of 1 mL and each ferret was housed in a separate cage inside an isolator.
TextSentencer_T80 12576-12900 Sentence denotes Two ferrets from each group were euthanized on day 4 post-inoculation (p.i.) and their organs and tissues, including lungs, tracheas, nasal turbinates, soft palates, brains, hearts, submaxillary lymph nodes, tonsils, kidneys, spleens, livers, pancreas, and small intestines, were collected for viral RNA and virus detection.
TextSentencer_T81 12901-13041 Sentence denotes Nasal washes and rectal swabs were collected from the other three ferrets on days 2, 4, 6, 8, and 10 p.i. for viral RNA and virus detection.
TextSentencer_T82 13042-13107 Sentence denotes Body weights and body temperature were monitored every other day.
TextSentencer_T83 13108-13139 Sentence denotes The ferrets were scheduled to .
TextSentencer_T84 13140-13192 Sentence denotes CC-BY-NC-ND 4.0 International license author/funder.
TextSentencer_T85 13193-13553 Sentence denotes It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint be euthanized on day 20 p.i. to assess them for antibodies against SARS-CoV-2 by using the Double Antigen Sandwich ELISA kit (ProtTech, Luoyang, China) and by use of a neutralization assay.
TextSentencer_T86 13554-13629 Sentence denotes Eight ferrets were also inoculated intratracheally with 10 5 PFU of CTan-H.
TextSentencer_T87 13630-13746 Sentence denotes On days 2, 4, 8, and 14 p.i., two ferrets were each euthanized, and their organs were collected for virus detection.
TextSentencer_T88 13747-14116 Sentence denotes Ten outbred domestic juvenile cats (aged between 70 days and three months) and eight outbred subadult cats (aged 6-9 months) obtained from the National Engineering Research Center of To investigate the transmissibility of SARS-CoV-2 in cats, six cats were inoculated intranasally with 10 5 PFU of CTan-H and each animal was placed in a separate cage within an isolator.
TextSentencer_T89 14117-14226 Sentence denotes A similar-aged naive cat was then placed in each cage adjacent to the one that held the virus-inoculated cat.
TextSentencer_T90 14227-14393 Sentence denotes Feces were collected on days 3, 5, 7, and 9 p.i. from the big cats, and nasal washes were collected from the juvenile cats for viral RNA detection or virus titration.
TextSentencer_T91 14394-14737 Sentence denotes One pair and two pairs of the subadult cats were euthanized on days 11 and 12 p.i., respectively, and their organs, including lungs, tracheas, nasal turbinates, soft palates, brains, hearts, submaxillary lymph nodes, tonsils, kidneys, spleens, livers, pancreas, and small intestines, were collected for viral RNA detection and virus titration.
TextSentencer_T92 14738-14907 Sentence denotes Sera were collected and antibodies against SARS-CoV-2 were detected by using the Double Antigen Sandwich ELISA kit (ProtTech, Luoyang, China) and a neutralization assay.
TextSentencer_T93 14908-15338 Sentence denotes To access the susceptibility of dogs, pigs, chickens, and ducks to SARS-CoV-2, three-month-old beagles The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint ducks) of CTan-H, and two (dogs) or three (pigs, chickens, ducks) uninfected animals were housed in the same room with their infected counterparts to monitor the transmission of CTan-H.
TextSentencer_T94 15339-15442 Sentence denotes Oropharyngeal and rectal swabs from all animals were collected every other day for viral RNA detection.
TextSentencer_T95 15443-15745 Sentence denotes One beagle was viral RNA positive by its rectal swab on day 2 p.i. and was euthanized on day 4 p.i.; its organs, including nasal turbinates, soft palates, tonsils, tracheas, lungs, brains, hearts, kidneys, spleens, livers, pancreas, and small intestines, were collected for viral RNA detection by qPCR.
TextSentencer_T96 15746-15929 Sentence denotes Sera were collected from all remaining animals on day 14 p.i., and antibodies against SARS-CoV-2 were detected by using a Double Antigen Sandwich ELISA kit (ProtTech, Luoyang, China).
TextSentencer_T97 15930-16032 Sentence denotes SARS-CoV-2 CTan strain (100 PFU) was incubated with two-fold serial dilutions of sera for 1 h at 37°C.
TextSentencer_T98 16033-16117 Sentence denotes A plaque assay was then performed in Vero E6 cells with the neutralization mixtures.
TextSentencer_T99 16118-16302 Sentence denotes Neutralizing antibody titers were calculated as the maximum serum dilution yielding a 50% reduction in the number of plaques relative to control serum prepared from uninfected animals.
TextSentencer_T100 16303-16415 Sentence denotes Tissues of animals were fixed in 10% neutral-buffered formalin, embedded in paraffin, and cut into 4µm sections.
TextSentencer_T101 16416-16515 Sentence denotes The sections were stained with hematoxylin-eosin (H&E) or used in immunohistochemical (IHC) assays.
TextSentencer_T102 16516-16661 Sentence denotes The sections used for immunohistochemistry were dewaxed in xylene and hydrated through a series of descending concentrations of alcohol to water.
TextSentencer_T103 16662-16778 Sentence denotes For viral antigen retrieval, sections were immersed in citric acid/sodium citrate solution at 121 °C for 15 minutes.
TextSentencer_T104 16779-16962 Sentence denotes After cooling, the sections were treated with 3% hydrogen peroxide for 30 minutes to remove endogenous peroxidase activity and blocked with 8% skim milk to reduce nonspecific binding.
TextSentencer_T105 16963-17230 Sentence denotes After three 5-minute washes in TBS, the sections were incubated with rabbit anti-SARS-CoV-2 nucleoprotein monoclonal antibody The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015347 doi: bioRxiv preprint