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A new coronavirus associated with human respiratory disease in China
Abstract
object_of_studyphenomenonconcepts↗concepts↗concepts↗sensescontent_tagscontent_tags↗content_tagsEmerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1 – 3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae , which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
Main
mechanisms↗content_tagscontent_tagscontent_tags↗content_tagsThe patient studied was a 41-year-old man with no history of hepatitis, tuberculosis or diabetes. He was admitted to and hospitalized in the Central Hospital of Wuhan on 26 December 2019, 6 days after the onset of disease. The patient reported fever, chest tightness, unproductive cough, pain and weakness for 1 week on presentation (Table 1 ). Physical examination of cardiovascular, abdominal and neurological characteristics was that these were normal. Mild lymphopoenia (defined as less than 9 × 10 5 cells per ml) was observed, but white blood cell and blood platelet counts were normal in a complete blood count test. Elevated levels of C-reactive protein (41.4 mg l −1 of blood; reference range, 0–6 mg l −1 ) were observed and the levels of aspartate aminotransferase, lactic dehydrogenase and creatine kinase were slightly elevated in blood chemistry tests. The patient had mild hypoxaemia with oxygen levels of 67 mm Hg as determined by an arterial blood gas test. On the first day of admission (day 6 after the onset of disease), chest radiographs were abnormal with air-space shadowing such as ground-glass opacities, focal consolidation and patchy consolidation in both lungs (Extended Data Fig. 1 ). Computed-tomography scans of the chest revealed bilateral focal consolidation, lobar consolidation and patchy consolidation, especially in the lower lung (Extended Data Fig. 1a–d ). A chest radiograph revealed a bilateral diffuse patchy and fuzzy shadow on day 5 after admission (day 11 after the onset of disease) (Extended Data Fig. 1e ). Preliminary aetiological investigations excluded the presence of influenza virus, Chlamydia pneumoniae and Mycoplasma pneumoniae using commercial pathogen antigen-detection kits, and this was confirmed by PCR. Other common respiratory pathogens, including human adenoviruses, also tested negative by quantitative PCR (qPCR) (Extended Data Fig. 2 ). Although a combination of antibiotic, antiviral and glucocorticoid therapy was administered, the patient exhibited respiratory failure and was given high-flow non-invasive ventilation. The condition of the patient did not improve after 3 days of treatment and he was admitted to the intensive care unit. The patient was transferred to another hospital in Wuhan for further treatment 6 days after admission. Table 1 Clinical symptoms and patient data Characteristic Patient Age (years) 41 Sex Male Date of illness onset 20 December 2019 Date of admission 26 December 2019 Signs and symptoms Fever Yes Body temperature (°C) 38.4 Cough Yes Sputum production Yes Dizzy Yes Weakness Yes Chest tightness Yes Dyspnoea Yes Bacterial culture Negative Glucocorticoid therapy Yes Antibiotic therapy Cefoselis Antiviral therapy Oseltamivir Oxygen therapy Mechanical ventilation
unhoused_relationscontent_tagsEpidemiological investigations by the Wuhan Center for Disease Control and Prevention revealed that the patient worked at a local indoor seafood market. Notably, in addition to fish and shellfish, a variety of live wild animals—including hedgehogs, badgers, snakes and birds (turtledoves)—were available for sale in the market before the outbreak began, as well as animal carcasses and animal meat. No bats were available for sale. While the patient might have had contact with wild animals at the market, he recalled no exposure to live poultry.
research_questioncontributionmethod↗mechanisms↗mechanisms↗mechanisms↗concepts↗concepts↗concepts↗concepts↗concepts↗concepts↗concepts↗concepts↗concepts↗claim_relationsclaim_relationsconcept_edgescontent_tagscontent_tagscontent_tagscontent_tags↗content_tags↗content_tagscontent_tags↗content_tags↗content_tags↗To investigate the possible aetiological agents associated with this disease, we collected bronchoalveolar lavage fluid (BALF) and performed deep meta-transcriptomic sequencing. The clinical specimen was handled in a biosafety level 3 laboratory at Shanghai Public Health Clinical Center. Total RNA was extracted from 200 μl of BALF and a meta-transcriptomic library was constructed for pair-end (150-bp reads) sequencing using an Illumina MiniSeq as previously described 4 , 6 – 8 . In total, we generated 56,565,928 sequence reads that were de novo-assembled and screened for potential aetiological agents. Of the 384,096 contigs assembled by Megahit 9 , the longest (30,474 nucleotides (nt)) had a high abundance and was closely related to a bat SARS-like coronavirus (CoV) isolate—bat SL-CoVZC45 (GenBank accession number MG772933 )—that had previously been sampled in China, with a nucleotide identity of 89.1% (Supplementary Tables 1 , 2 ). The genome sequence of this virus, as well as its termini, were determined and confirmed by reverse-transcription PCR (RT–PCR) 10 and 5′/3′ rapid amplification of cDNA ends (RACE), respectively. This virus strain was designated as WH-Human 1 coronavirus (WHCV) (and has also been referred to as ‘2019-nCoV’) and its whole genome sequence (29,903 nt) has been assigned GenBank accession number MN908947 . Remapping the RNA-sequencing data to the complete genome of WHCV resulted in an assembly of 123,613 reads, providing 99.99% genome coverage at a mean depth of 6.04× (range, 0.01–78.84×) (Extended Data Fig. 3 ). The viral load in the BALF sample was estimated by qPCR to be 3.95 × 10 8 copies per ml (Extended Data Fig. 4 ).
concepts↗concepts↗concepts↗concepts↗content_tagscontent_tagscontent_tagscontent_tags↗content_tagscontent_tagscontent_tagsThe viral genome organization of WHCV was determined by sequence alignment to two representative members of the genus Betacoronavirus: a coronavirus associated with humans (SARS-CoV Tor2, GenBank accession number AY274119 ) and a coronavirus associated with bats (bat SL-CoVZC45, GenBank accession number MG772933 ). The un-translational regions and open-reading frame (ORF) of WHCV were mapped on the basis of this sequence alignment and ORF prediction. The WHCV viral genome was similar to these two coronaviruses (Fig. 1 and Supplementary Table 3 ). The order of genes (5′ to 3′) was as follows: replicase ORF1ab , spike ( S ), envelope ( E ), membrane ( M ) and nucleocapsid ( N ). WHCV has 5′ and 3′ terminal sequences that are typical of betacoronaviruses, with 265 nt at the 5′ terminal end and 229 nt at the 3′ terminal end. The predicted replicase ORF1ab gene of WHCV is 21,291 nt in length and contained 16 predicted non-structural proteins (Supplementary Table 4 ), followed by (at least) 13 downstream ORFs. Additionally, WHCV shares a highly conserved domain (LLRKNGNKG: amino acids 122–130) in nsp1 with SARS-CoV. The predicted S , ORF3a , E , M and N genes of WHCV are 3,822, 828, 228, 669 and 1,260 nt in length, respectively. In addition to these ORF regions, which are shared by all members of the subgenus Sarbecovirus, WHCV is similar to SARS-CoV in that it carries a predicted ORF8 gene (with a length of 366 nt) that is located between the M and N ORF genes. The functions of WHCV ORFs were predicted on the basis of those of known coronaviruses and are described in Supplementary Table 5 . In a manner similar to SARS-CoV Tor2, a leader transcription regulatory sequence (TRS) and nine putative body TRSs could be readily identified upstream of the 5′ end of the ORF in WHCV, and the putative conserved TRS core sequence appeared in two forms—ACGAAC or CUAAAC (Supplementary Table 6 ). Fig. 1 Genome organization of SARS and SARS-like CoVs. The organization of genes for WHCV, bat SL-CoVZC45 and SARS-CoV Tor2.
mechanisms↗concepts↗concepts↗content_tagscontent_tagsTo determine the evolutionary relationships between WHCV and previously identified coronaviruses, we estimated phylogenetic trees on the basis of the nucleotide sequences of the whole-genome sequence, the non-structural protein genes ORF1a and ORF1b , and the main structural proteins encoded by the S , E , M and N genes (Fig. 2 and Extended Data Fig. 5 ). In all phylogenies, WHCV clustered with members of the subgenus Sarbecovirus, including the SARS-CoV that was responsible for the global SARS pandemic 1 , 2 of 2002–2003, as well as a number of SARS-like coronaviruses that have been obtained from bats 5 , 11 – 13 . However, WHCV changed topological position within the subgenus Sarbecovirus depending on which gene was used, which suggests that recombination has occurred in this group of viruses in the past (Fig. 2 and Extended Data Fig. 5 ). Specifically, in the S gene tree (Extended Data Fig. 5 ), WHCV was most closely related to the bat coronavirus SL-CoVZC45 with 82.3% amino acid identity (and around 77.2% amino acid identity to SARS-CoV; Supplementary Table 3 ) whereas in the ORF1b phylogeny, WHCV fell in a basal position within the subgenus Sarbecovirus (Fig. 2 ). This topological division, which probably reflects recombination among the bat sarbecoviruses, was also observed in the phylogenetic trees estimated for conserved domains in the replicase polyprotein pp1ab (Extended Data Fig. 6 ). Fig. 2 Maximum likelihood phylogenetic trees of nucleotide sequences of the ORF1a , ORF1b , E and M genes of WHCV and related coronaviruses. a , Phylogenetic trees of ORF1a . b , Phylogenetic trees of ORF1b . c , Phylogenetic trees of E . d , Phylogenetic trees of M . EriCoV, Erinaceus coronavirus. Numbers (>70) above or below the branches indicate percentage bootstrap values for the associated nodes. The trees were mid-point rooted for clarity only. The scale bar represents the number of substitutions per site.
mechanisms↗mechanisms↗limitationsconcepts↗concepts↗concepts↗concepts↗concepts↗unhoused_relationsclaim_relationscontent_tagscontent_tags↗content_tags↗To better understand the potential of WHCV to infect humans, the receptor-binding domain (RBD) of its spike protein was compared with those of SARS-CoVs and bat SARS-like CoVs. The RBD sequences of WHCV were more closely related to those of SARS-CoVs (73.8–74.9% amino acid identity) and SARS-like CoVs, including strains Rs4874, Rs7327 and Rs4231 (75.9–76.9% amino acid identity), that are able to use the human ACE2 receptor for cell entry 11 (Supplementary Table 7 ). In addition, the RBD of the spike protein from WHCV was only one amino acid longer than the RBD of the spike protein from SARS-CoV (Extended Data Fig. 7a ). By contrast, other bat SARS-like CoVs—including the Rp3 strain that cannot bind to human ACE2 14 —had amino acid deletions at positions 433–437 and 460–472 compared with the sequence in SARS-CoVs (Extended Data Fig. 7a ). The previously determined 15 crystal structure of the RBD of the spike protein of SARS-CoV complexed with human ACE2 (Protein Data Bank (PDB) 2AJF) revealed that regions 433–437 and 460–472 directly interact with human ACE2 and hence may be important in determining species specificity (Extended Data Fig. 7b ). We predicted the three-dimensional protein structures of the RBD domains of the spike protein of WHCV, Rs4874 and Rp3 by protein homology modelling using the SWISS-MODEL server and compared them to the crystal structure of RBD domain of the spike protein of SARS-CoV (PDB 2GHV) (Extended Data Fig. 7c–f ). In accordance with the sequence alignment, the predicted protein structures of the RBD domains of WHCV and Rs4874 were closely related to that of SARS-CoV and different from the predicted structure of the RBD domain from Rp3. In addition, the N terminus of the spike protein of WHCV is more similar to that of SARS-CoV than other human coronaviruses (HKU1 and OC43) (Extended Data Fig. 8 ) that can bind to sialic acid 16 . In summary, the high similarities of the amino acid sequences and predicted protein structures of the RBD domains of WHCV and SARS-CoV suggest that WHCV may efficiently use human ACE2 as a receptor for cellular entry, which could potentially facilitate human-to-human transmission 11 , 17 , 18 .
mechanisms↗limitationsconcepts↗unhoused_relationsclaim_relationscontent_tagscontent_tagsTo further characterize the putative recombination events in the evolutionary history of the sarbecoviruses, the whole-genome sequence of WHCV and four representative coronaviruses—bat SARS-like CoV Rp3, CoVZC45, CoVZXC21 and SARS-CoV Tor2—were analysed using the Recombination Detection Program v.4 (RDP4) 19 . Although the similarity plots suggested that possible recombination events had occurred between WHCV and SARS-CoVs or SARS-like CoVs (Extended Data Fig. 9 ), there was no significant evidence for recombination across the genome as a whole. However, some evidence for past recombination was detected in the S gene of WHCV, SARS-CoV and bat SARS-like CoVs (WIV1 and RsSHC014) ( P < 3.147 × 10 −3 to P < 9.198 × 10 −9 ), for which the similarity plots suggested the presence of recombination breakpoints at nucleotides 1,029 and 1,652, which separate the S gene of WHCV into three regions (Fig. 3 ). In phylogenies of the nucleotide fragments from 1 to 1,029 and from 1,652 to the end of the sequence, WHCV was most closely related to bat SL-CoVZC45 and bat SL-CoVZXC21, whereas in the region of nucleotides 1,030 to 1,651 (the RBD region) WHCV grouped with SARS-CoV and bat SARS-like CoVs (WIV1 and RsSHC014) that are capable of direct human transmission 17 , 20 . Despite these recombination events, which seem relatively common among sarbecoviruses, there is no evidence that recombination has facilitated the emergence of WHCV. Fig. 3 Possible recombination events in the S gene of sarbecoviruses. a , The sequence similarity plot reveals two putative recombination breakpoints (black dashed lines), with their locations indicated at the bottom. The plot shows similarity comparisons of the S gene of WHCV (query) compared with the sequences of SARS-CoV Tor2 and bat SARS-like CoVs WIV1, Rf1 and CoVZC45. b , Phylogenies of the major parental region (1–1,028 and 1,653–3,804) and minor parental region (1,029–1,652). Phylogenies were estimated using a maximum likelihood method and were mid-point rooted for clarity only. Numbers above or below the branches indicate percentage bootstrap values. The scale bar represents the number of substitutions per site.
claim_typelimitationslimitationsconcepts↗unhoused_relationssensesclaim_relationsclaim_relationsconcept_edgescontent_tagsCoronaviruses are associated with a number of infectious disease outbreaks in humans, including SARS in 2002–2003 and Middle East respiratory syndrome (MERS) in 2012 1 , 21 . Four other coronaviruses—human coronaviruses HKU1, OC43, NL63 and 229E—are also associated with respiratory disease 22 – 25 . Although SARS-like coronaviruses have been widely identified in mammals including bats since 2005 in China 10 , 26 – 28 , the exact origin of human-infected coronaviruses remains unclear. Here we describe a new coronavirus—WHCV—in the BALF from a patient who experienced severe respiratory disease in Wuhan, China. Phylogenetic analysis suggests that WHCV is a member of the genus Betacoronavirus (subgenus Sarbecovirus) that has some genomic and phylogenetic similarities to SARS-CoV 1 , particularly in the RBD of the spike protein. These genomic and clinical similarities to SARS, as well as its high abundance in clinical samples, provides evidence for an association between WHCV and the ongoing outbreak of respiratory disease in Wuhan and across the world. Although the isolation of the virus from only a single patient is not sufficient to conclude that it caused these respiratory symptoms, our findings have been independently corroborated in further patients in a separate study 29 .
limitationslimitationsconcepts↗concepts↗unhoused_relationssensescontent_tagsThe identification of multiple SARS-like CoVs in bats have led to the idea that these animals act as hosts of a natural reservoir of these viruses 22 , 23 . Although SARS-like viruses have been identified widely in bats in China, viruses identical to SARS-CoV have not yet been documented. Notably, WHCV is most closely related to bat coronaviruses, and shows 100% amino acid similarity to bat SL-CoVZC45 in the nsp7 and E proteins (Supplementary Table 3 ). Thus, these data suggest that bats are a possible host for the viral reservoir of WHCV. However, as a variety of animal species were for sale in the market when the disease was first reported, further studies are needed to determine the natural reservoir and any intermediate hosts of WHCV.
concepts↗concepts↗unhoused_relationssensescontent_tags↗content_tags↗Note added in proof: Since this paper was accepted, the ICTV has designated the virus as SARS-CoV-2 30 ; in addition, the WHO has released the official name of the disease caused by this virus, which is COVID-19 31 .
Methods
Data reporting
limitationsNo statistical methods were used to predetermine sample size. The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment.
Patient information and collection of clinical data and sample
concepts↗sensescontent_tags↗A patient presenting with acute onset of fever (temperature over 37.5 °C), cough and chest tightness, who was admitted to the Central Hospital of Wuhan, in Wuhan, China, was considered to be a suspected case. During admission, BALF was collected and stored at −80 °C until further processing. Demographic, clinical and laboratory data were retrieved from the clinical records of the patient. The study was reviewed and approved by the ethics committee of the National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention. Signed written informed consent was obtained from the patient.
RNA library construction and sequencing
Total RNA was extracted from the BALF sample using the RNeasy Plus Universal Mini kit (Qiagen) following the manufacturer’s instructions. The quantity and quality of the RNA solution was assessed using a Qbit machine and an Agilent 2100 Bioanalyzer (Agilent Technologies) before library construction and sequencing. An RNA library was then constructed using the SMARTer Stranded Total RNA-Seq kit v.2 (TaKaRa). Ribosomal RNA depletion was performed during library construction following the manufacturer’s instructions. Paired-end (150-bp reads) sequencing of the RNA library was performed on the MiniSeq platform (Illumina). Library preparation and sequencing were carried out at the Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Data processing and identification of the viral agent
content_tags↗content_tagscontent_tagsSequencing reads were first adaptor and quality trimmed using the Trimmomatic program 32 . The remaining 56,565,928 reads were assembled de novo using both Megahit (v.1.1.3) 9 and Trinity (v.2.5.1) 33 with default parameter settings. Megahit generated a total of 384,096 assembled contigs (size range of 200–30,474 nt), whereas Trinity generated 1,329,960 contigs with a size range of 201–11,760 nt. All of these assembled contigs were compared (using BLASTn and Diamond BLASTx) against the entire non-redundant (nr) nucleotide and protein databases, with e values set to 1 × 10 −10 and 1 × 10 −5 , respectively. To identify possible aetiological agents present in the sequencing data, the abundance of the assembled contigs was first evaluated as the expected counts using the RSEM program 34 implemented in Trinity. Non-human reads (23,712,657 reads), generated by filtering host reads using the human genome (human release 32, GRCh38.p13, downloaded from Gencode) by Bowtie2 35 , were used for the RSEM abundance assessment.
As the longest contigs generated by Megahit (30,474 nt) and Trinity (11,760 nt) both showed high similarity to the bat SARS-like coronavirus isolate bat SL-CoVZC45 and were found at a high abundance (Supplementary Tables 1 , 2 ), the longer sequence (30,474 nt)—which covered almost the whole virus genome—was used for primer design for PCR confirmation and determination of the genome termini. Primers used for PCR, qPCR and RACE experiments are listed in Supplementary Table 8 . The PCR assay was conducted as previously described 10 and the complete genome termini was determined using the Takara SMARTer RACE 5′/3′ kit (TaKaRa) following the manufacturer’s instructions. Subsequently, the genome coverage and sequencing depth were determined by remapping all of the adaptor- and quality-trimmed reads to the whole genome of WHCV using Bowtie2 35 and Samtools 36 .
concepts↗content_tags↗The viral loads of WHCV in BALF were determined by quantitative real-time RT–PCR using the Takara One Step PrimeScript RT–PCR kit (Takara RR064A) following the manufacturer’s instructions. Real-time RT–PCR was performed using 2.5 μl RNA with 8 pmol of each primer and 4 pmol probe under the following conditions: reverse transcription at 42 °C for 10 min, 95 °C for 1 min, followed by 40 cycles of 95 °C for 15 s and 60 °C for 1 min. The reactions were performed and detected by ABI 7500 Real-Time PCR Systems. The PCR product covering the Taqman primers and probe region was cloned into pLB vector using the Lethal Based Simple Fast Cloning Kit (TianGen) as standards for quantitative viral load test.
Virus genome characterization and phylogenetic analysis
For the newly identified virus genome, the potential ORFs were predicted and annotated using the conserved signatures of the cleavage sites recognized by coronavirus proteinases, and were processed in the Lasergene software package (v.7.1, DNAstar). The viral genes were aligned using the L-INS-i algorithm implemented in MAFFT (v.7.407) 37 .
concepts↗Phylogenetic analyses were then performed using the nucleotide sequences of various CoV gene datasets: (1) whole genome, (2) ORF1a, (3) ORF1b, (4) nsp5 (3CLpro), (5) RdRp (nsp12), (6) nsp13 (Hel), (7) nsp14 (ExoN), (8) nsp15 (NendoU), (9) nsp16 (O-MT), (10) spike (S) and (11) nucleocapsid (N). Phylogenetic trees were inferred using the maximum likelihood method implemented in the PhyML program (v.3.0) 38 , using the generalized time reversible substitution model and subtree pruning and regrafting branch swapping. Bootstrap support values were calculated from 1,000 pseudo-replicate trees. The best-fitting model of nucleotide substitution was determined using MEGA (v.5) 39 . Amino acid identities among sequences were calculated using the MegAlign program implemented in the Lasergene software package (v.7.1, DNAstar).
Genome recombination analysis
Potential recombination events in the history of the sarbecoviruses were assessed using both the RDP4 19 and Simplot (v.3.5.1) 40 . The RDP4 analysis was conducted based on the complete genome (nucleotide) sequence, using RDP, GENECONV, BootScan, maximum chi square, Chimera, SISCAN and 3SEQ methods. Putative recombination events were identified with a Bonferroni corrected P -value cut-off of 0.01. Similarity plots were inferred using Simplot to further characterize potential recombination events, including the location of possible breakpoints.
Analysis of the RBD domain of the spike protein of WHCV
concepts↗claim_relationsAn amino acid sequence alignment of RBD sequences from WHCV, SARS-CoVs and bat SARS-like CoVs was performed using MUSCLE 41 . The predicted protein structures of the RBD of the spike protein were estimated based on target–template alignment using ProMod3 on SWISS-MODEL server ( https://swissmodel.expasy.org/ ). The sequences of the RBD domains spike of WHCV, Rs4874 and Rp3 were searched by BLAST against the primary amino acid sequence contained in the SWISS-MODEL template library (last update, 9 January 2020; last included PDB release, 3 January 2020). Models were built based on the target–template alignment using ProMod3. The global and per-residue model quality was assessed using the QMEAN scoring function 42 . The PDB files of the predicted protein structures were displayed and compared with the crystal structures of the spike RBD of SARS-CoV (PDB 2GHV) 43 and the crystal of structure of the spike RBD of SARS-CoV complexed with human ACE2 (PDB 2AJF) 15 .
Reporting summary
Further information on research design is available in the Nature Research Reporting Summary linked to this paper.
Online content
Any methods, additional references, Nature Research reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41586-020-2008-3.
Supplementary information
This file contains Supplementary Tables 1-8.
Reporting Summary
Relations on this page carry a quotation for the claim. Where a relation was separately evidenced — and so tested against the vocabulary for its type — the row says so; 2 of 2 relations here carry that mark. The rest are the tagger’s reading of the sentence quoted beside them.
This record holds no controls. A layer is empty when the tagger recorded nothing in it — which is not the same as the paper having nothing to record.
| facet | tag | field | conf. | whose words |
|---|---|---|---|---|
| object_of_study | the aetiological agent of a severe respiratory disease outbreak in Wuhan, studied through one hospitalised seafood-market worker whose bronchoalveolar lavage fluid was sequenced, and the new coronavirus's genome, phylogenetic relatives, recombination history and likely cell-entry receptor | object_of_study | the paper's words | |
| research_question | what agent is associated with the Wuhan respiratory outbreak, how that agent is related to known coronaviruses, and whether it could use the human receptor that SARS-CoV uses | research_question | the paper's words | |
| contribution | identification and complete 29,903-nucleotide genome of a new coronavirus, WH-Human 1 (WHCV, also called 2019-nCoV), recovered by metagenomic RNA sequencing from a single patient's lavage fluid, placed within the subgenus Sarbecovirus and shown by receptor-binding-domain comparison to be a plausible user of human ACE2 | contribution | the paper's words | |
| claim_type | existence | claim_type | the paper's words | |
| phenomenon | a severe respiratory disease appearing in Wuhan from December 2019, epidemiologically tied to a seafood market and with no aetiological agent identified by routine pathogen testing | phenomenon | the paper's words | |
| method | omics-profiling also in: omics-profiling | method | the paper's words | |
| mechanisms | Total RNA from the clinical sample is sequenced and assembled de novo, then every contig is screened against nucleotide and protein databases, so an unknown agent can be found without being suspected first. | mechanisms[0] | 0.95 | the tagger's words |
| mechanisms | The candidate is picked out by being simultaneously the longest contig, present at high abundance, and closely related to a known bat SARS-like coronavirus. | mechanisms[1] | 0.94 | the tagger's words |
| mechanisms | Influenza virus, Chlamydia pneumoniae, Mycoplasma pneumoniae and other common respiratory pathogens were ruled out by antigen kits and PCR before the metagenomic search, which is what makes the unknown agent the residual explanation. about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 2311: 'Table 1 Clinical symptoms and patient data Characteristic Patient Age …'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. also in: exclusion of known pathogens first | mechanisms[2] | 0.93 | the tagger's words |
| mechanisms | Because the spike receptor-binding domain determines which receptor a sarbecovirus can use, its sequence and predicted structure are compared with those of viruses known to use or not use human ACE2, and the resemblance is read as potential for human infection. | mechanisms[3] | 0.93 | the tagger's words |
| mechanisms | Bat SARS-like coronaviruses that cannot bind human ACE2 carry deletions in the two regions that the SARS-CoV crystal structure shows contacting the receptor; WHCV has no such deletions. | mechanisms[4] | 0.93 | the tagger's words |
| mechanisms | The virus takes different topological positions inside the subgenus depending on which gene the tree is built from, which is read as a signature of past recombination rather than of one descent. about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 1419: 'Fig. 2 Maximum likelihood phylogenetic trees of nucleotide sequences o…'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. | mechanisms[5] | 0.94 | the tagger's words |
| mechanisms | Similarity plots and recombination tests place two breakpoints inside the spike gene, splitting it into three regions whose phylogenies have different closest relatives. about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 1441: 'Fig. 3 Possible recombination events in the S gene of sarbecoviruses. …'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. also in: breakpoint mapping inside one gene | mechanisms[6] | 0.93 | the tagger's words |
| mechanisms | All trimmed reads are mapped back onto the assembled genome, and the resulting coverage and depth report how well the sample supports the sequence. | mechanisms[7] | 0.92 | the tagger's words |
| limitations | The virus was recovered from a single patient, which the authors state is not sufficient to conclude that it caused the respiratory symptoms. | limitations[0] | 0.96 | the tagger's words |
| limitations | The origin of human-infecting coronaviruses remains unclear despite years of SARS-like coronavirus sampling in mammals. | limitations[1] | 0.93 | the tagger's words |
| limitations | The natural reservoir and any intermediate hosts of the virus are undetermined, and a variety of animal species were on sale at the implicated market. | limitations[2] | 0.94 | the tagger's words |
| limitations | Bats are only a possible reservoir host: SARS-like viruses are widespread in bats in China, but viruses identical to SARS-CoV have never been documented there. | limitations[3] | 0.93 | the tagger's words |
| limitations | Use of human ACE2 is inferred from sequence identity and homology-modelled structures, not measured by a binding or entry experiment. | limitations[4] | 0.93 | the tagger's words |
| limitations | No statistical methods were used to determine sample size; the work was not randomised and the investigators were not blinded. | limitations[5] | 0.92 | the tagger's words |
| limitations | Although similarity plots suggested recombination between this virus and SARS-CoV or SARS-like coronaviruses, there was no significant evidence for recombination across the genome as a whole. | limitations[6] | 0.92 | the tagger's words |
| concepts | WH-Human 1 coronavirus also in: WH-Human 1 coronavirus | concepts[0] | 0.96 | the paper's words |
| concepts | 2019-nCoV also in: 2019-nCoV | concepts[1] | 0.93 | the paper's words |
| concepts | SARS-CoV-2 also in: SARS-CoV-2 | concepts[2] | 0.94 | the paper's words |
| concepts | COVID-19 also in: COVID-19 | concepts[3] | 0.93 | the paper's words |
| concepts | Betacoronavirus also in: Betacoronavirus | concepts[4] | 0.94 | the paper's words |
| concepts | Sarbecovirus also in: Sarbecovirus | concepts[5] | 0.93 | the paper's words |
| concepts | SARS-CoV also in: SARS-CoV | concepts[6] | 0.94 | the paper's words |
| concepts | bat SL-CoVZC45 also in: bat SL-CoVZC45 | concepts[7] | 0.94 | the paper's words |
| concepts | human ACE2 also in: human ACE2 | concepts[8] | 0.94 | the paper's words |
| concepts | spike protein also in: spike protein | concepts[9] | 0.94 | the paper's words |
| concepts | receptor-binding domain also in: receptor-binding domain | concepts[10] | 0.95 | the paper's words |
| concepts | open-reading frame also in: open-reading frame | concepts[11] | 0.92 | the paper's words |
| concepts | ORF8 also in: ORF8 | concepts[12] | 0.92 | the paper's words |
| concepts | transcription regulatory sequence also in: transcription regulatory sequence | concepts[13] | 0.92 | the paper's words |
| concepts | non-structural proteins also in: non-structural proteins | concepts[14] | 0.91 | the paper's words |
| concepts | meta-transcriptomic sequencing also in: meta-transcriptomic sequencing | concepts[15] | 0.95 | the paper's words |
| concepts | Megahit also in: Megahit | concepts[16] | 0.93 | the paper's words |
| concepts | contig also in: contig | concepts[17] | 0.92 | the paper's words |
| concepts | RACE also in: RACE | concepts[18] | 0.91 | the paper's words |
| concepts | quantitative PCR also in: quantitative PCR | concepts[19] | 0.92 | the paper's words |
| concepts | maximum likelihood method also in: maximum likelihood method | concepts[20] | 0.93 | the paper's words |
| concepts | homology modelling also in: homology modelling | concepts[21] | 0.92 | the paper's words |
| concepts | recombination also in: recombination | concepts[22] | 0.94 | the paper's words |
| concepts | recombination breakpoint also in: recombination breakpoint | concepts[23] | 0.92 | the paper's words |
| concepts | viral load also in: viral load | concepts[24] | 0.92 | the paper's words |
| concepts | natural reservoir also in: natural reservoir | concepts[25] | 0.93 | the paper's words |
| concepts | intermediate host also in: intermediate host | concepts[26] | 0.92 | the paper's words |
| concepts | viral spill-over also in: viral spill-over | concepts[27] | 0.93 | the paper's words |
| concepts | emerging infectious disease also in: emerging infectious disease | concepts[28] | 0.92 | the paper's words |
| concepts | human-to-human transmission also in: human-to-human transmission | concepts[29] | 0.9 | the paper's words |
| concepts | species specificity also in: species specificity | concepts[30] | 0.92 | the paper's words |
| concepts | bronchoalveolar lavage fluid also in: bronchoalveolar lavage fluid | concepts[31] | 0.93 | the paper's words |
| concepts | suspected case also in: suspected case | concepts[32] | 0.92 | the paper's words |
| unhoused_relations | WH-Human 1 coronavirus → COVID-19 The paper states an association between the virus and the outbreak and explicitly declines the causal claim, because the virus was isolated from one patient only. — the relation stated: Although the isolation of the virus from only a single patient is not sufficient to conclude that it caused these respiratory symptoms, the genomic and clinical similarities provide evidence for an association between WHCV and the outbreak. | unhoused_relations[0] | 0.95 | the tagger's words |
| unhoused_relations | WH-Human 1 coronavirus → SARS-CoV-2 After acceptance, the ICTV designated the virus SARS-CoV-2 and the WHO named the disease COVID-19, so the paper's own names were superseded by naming authorities in a note added in proof. — the relation stated: Since this paper was accepted, the ICTV has designated the virus as SARS-CoV-2; in addition, the WHO has released the official name of the disease caused by this virus, which is COVID-19. | unhoused_relations[1] | 0.94 | the tagger's words |
| unhoused_relations | receptor-binding domain → human-to-human transmission Sequence and modelled-structure similarity of the RBD to that of SARS-CoV is read as efficient use of human ACE2, which is in turn read as potentially facilitating human-to-human transmission. — the relation stated: The high similarities of the amino acid sequences and predicted protein structures of the RBD domains of WHCV and SARS-CoV suggest that WHCV may efficiently use human ACE2 as a receptor for cellular entry, which could potentially facilitate human-to-human transmission. | unhoused_relations[2] | 0.92 | the tagger's words |
| unhoused_relations | bat SL-CoVZC45 → natural reservoir Because the virus is closest to bat coronaviruses and identical to SL-CoVZC45 in two proteins, bats are offered as a possible host of its reservoir. — the relation stated: These data suggest that bats are a possible host for the viral reservoir of WHCV. | unhoused_relations[3] | 0.92 | the tagger's words |
| unhoused_relations | recombination → WH-Human 1 coronavirus Recombination is common among sarbecoviruses and detectable in the spike gene, yet there is no evidence that it brought about the emergence of this virus. — about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 1441: 'Fig. 3 Possible recombination events in the S gene of sarbecoviruses. …'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. The row's relation quote (the separate quote for the relation) repeats this quote word for word and carries the same caption at the same place. · the relation stated: Despite these recombination events, which seem relatively common among sarbecoviruses, there is no evidence that recombination has facilitated the emergence of WHCV. | unhoused_relations[4] | 0.93 | the tagger's words |
| unhoused_relations | seafood market → viral spill-over The outbreak is tied to a market selling live wild animals, the patient worked there, and yet no bats were on sale and he recalled no poultry exposure, so the market is an epidemiological association with no identified animal source. — the relation stated: A variety of live wild animals were available for sale in the market before the outbreak began, but no bats were available for sale, and while the patient might have had contact with wild animals he recalled no exposure to live poultry. | unhoused_relations[5] | 0.9 | the tagger's words |
| senses | associated with - the title, the abstract and the discussion all say the virus is associated with the disease, and the same discussion states that one patient is not enough to conclude it caused the symptoms; association is chosen over causation deliberately and the paper marks the gap | senses[0] | 0.95 | the tagger's words |
| senses | one virus, four names - WH-Human 1 coronavirus and WHCV are coined here, 2019-nCoV is the name already circulating, and SARS-CoV-2 arrives from the ICTV in a note added in proof; the paper names the same object four ways inside one text | senses[1] | 0.94 | the tagger's words |
| senses | similarity against identity - the abstract reports the same 89.1% comparison as 'nucleotide similarity' while the main text calls it 'nucleotide identity'; in sequence analysis these are not interchangeable words | senses[2] | 0.92 | the tagger's words |
| senses | reservoir against intermediate host - bats are named a possible host of the viral reservoir while the animal that would have carried the virus to the market is left open as an intermediate host; two host roles the paper keeps apart | senses[3] | 0.93 | the tagger's words |
| senses | suspected case - a case definition written from symptoms and admission, not from the agent, because the agent did not yet exist as a category when the sample was taken | senses[4] | 0.92 | the tagger's words |
| claim_relations | builds-on → the meta-transcriptomic sequencing protocol previously used by the same group for virus discovery note: The library and sequencing follow an already published procedure. | claim_relations[0] | 0.93 | the tagger's words |
| claim_relations | builds-on → bat SARS-like coronavirus surveillance in China, which produced the closest relative SL-CoVZC45 note: Without the earlier bat sampling the new genome would have had no close comparator. | claim_relations[1] | 0.94 | the tagger's words |
| claim_relations | builds-on → the crystal structure of the SARS-CoV spike RBD in complex with human ACE2 (PDB 2AJF) note: The contact regions that decide species specificity come from that structure. | claim_relations[2] | 0.93 | the tagger's words |
| claim_relations | builds-on → the Recombination Detection Program v.4 and Simplot for detecting recombination and breakpoints note: External tools used unchanged. | claim_relations[3] | 0.92 | the tagger's words |
| claim_relations | builds-on → SWISS-MODEL and ProMod3 homology modelling with QMEAN quality assessment note: The structural claim about the RBD rests on modelled, not solved, structures. | claim_relations[4] | 0.92 | the tagger's words |
| claim_relations | extends → the record of coronavirus outbreaks in humans - SARS in 2002-2003, MERS in 2012, and the four endemic human coronaviruses note: The new virus is placed as the next member of a known series. | claim_relations[5] | 0.93 | the tagger's words |
| claim_relations | confirms → an independent study of further patients, which reports the same virus note: Direction: the separate study corroborates this identification; recorded because the paper rests its causal caution on it. | claim_relations[6] | 0.92 | the tagger's words |
| concept_edges | WH-Human 1 coronavirus —is-a→ Betacoronavirus the relation itself is separately evidenced · strength of the relation: 0.9 · note: Literal kind cue 'is a member of the genus', stated as what the phylogenetic analysis suggests; weight held below 1.0 for that hedge. · the relation stated: WHCV is a member of the genus Betacoronavirus (subgenus Sarbecovirus).
Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but abbreviation endpoint: the span writes 'WHCV' for WH-Human 1 coronavirus; 'suggests'; hedged. also in: WH-Human 1 coronavirus · Betacoronavirus | concept_edges[0] | 0.93 | the tagger's words |
| concept_edges | WH-Human 1 coronavirus —same-as→ 2019-nCoV the relation itself is separately evidenced · strength of the relation: 1 · note: Explicit naming equivalence: 'has also been referred to as'. · the relation stated: The strain designated WH-Human 1 coronavirus (WHCV) has also been referred to as 2019-nCoV. also in: WH-Human 1 coronavirus · 2019-nCoV | concept_edges[1] | 0.94 | the tagger's words |
| content_tags | Metagenomic RNA sequencing of one lavage sample yielded a complete 29,903-nucleotide genome of a previously unknown coronavirus, deposited as GenBank MN908947. | content_tags.findings[0] | 0.96 | the tagger's words |
| content_tags | The new virus is 89.1% identical at the nucleotide level to bat SARS-like coronavirus SL-CoVZC45, previously sampled in China. | content_tags.findings[1] | 0.95 | the tagger's words |
| content_tags | Remapping gave 99.99% genome coverage at a mean depth of 6.04x, and the viral load in the lavage fluid was about 3.95 x 10^8 copies per ml. | content_tags.findings[2] | 0.94 | the tagger's words |
| content_tags | The genome organisation, terminal sequences and transcription regulatory sequences are typical of betacoronaviruses, with genes in the order ORF1ab, S, E, M and N. | content_tags.findings[3] | 0.94 | the tagger's words |
| content_tags | Like SARS-CoV and unlike other members of the subgenus, the virus carries a predicted ORF8 gene between the M and N genes. | content_tags.findings[4] | 0.93 | the tagger's words |
| content_tags | The virus shares the conserved nsp1 domain LLRKNGNKG with SARS-CoV. | content_tags.findings[5] | 0.92 | the tagger's words |
| content_tags | In every phylogeny the virus falls within the subgenus Sarbecovirus, alongside SARS-CoV and bat SARS-like coronaviruses. | content_tags.findings[6] | 0.95 | the tagger's words |
| content_tags | In the spike gene tree the virus is closest to bat SL-CoVZC45 at 82.3% amino acid identity, but in the ORF1b tree it falls in a basal position within the subgenus. | content_tags.findings[7] | 0.94 | the tagger's words |
| content_tags | The receptor-binding domain is 73.8-74.9% identical to those of SARS-CoVs and its spike RBD is only one amino acid longer than that of SARS-CoV, without the deletions carried by bat viruses that cannot bind human ACE2. | content_tags.findings[8] | 0.94 | the tagger's words |
| content_tags | Past recombination is detectable in the spike gene of this virus, SARS-CoV and bat SARS-like coronaviruses, but there is no evidence that recombination brought about the emergence of this virus. | content_tags.findings[9] | 0.93 | the tagger's words |
| content_tags | The virus shows 100% amino acid similarity to bat SL-CoVZC45 in the nsp7 and E proteins, which the authors read as evidence that bats are a possible reservoir host. | content_tags.findings[10] | 0.93 | the tagger's words |
| content_tags | The patient was a 41-year-old market worker with fever, cough and hypoxaemia whose chest imaging showed ground-glass opacities and consolidation in both lungs, who deteriorated into intensive care despite antibiotic, antiviral and glucocorticoid treatment. | content_tags.findings[11] | 0.94 | the tagger's words |
| content_tags | Common respiratory pathogens, including human adenoviruses, tested negative by quantitative PCR. | content_tags.findings[12] | 0.93 | the tagger's words |
| content_tags | Live wild animals including hedgehogs, badgers, snakes and birds were on sale at the market, but no bats were, and the patient recalled no exposure to live poultry. | content_tags.findings[13] | 0.93 | the tagger's words |
| content_tags | By 25 January 2020 at least 1,975 cases had been reported since the first patient was hospitalised on 12 December 2019. | content_tags.findings[14] | 0.94 | the tagger's words |
| content_tags | The identification was independently corroborated in further patients in a separate study. | content_tags.findings[15] | 0.94 | the tagger's words |
| content_tags | WH-Human 1 coronavirus: the name given here to the new virus strain assembled from the patient's lavage fluid, also referred to as 2019-nCoV also in: WHCV | content_tags.definitions[0] | 0.96 | the tagger's words |
| content_tags | a patient with acute onset of fever over 37.5 degrees Celsius, cough and chest tightness admitted to the Central Hospital of Wuhan - a case definition by symptom and admission, made while the agent was unknown also in: suspected case | content_tags.definitions[1] | 0.94 | the tagger's words |
| content_tags | bronchoalveolar lavage fluid, the clinical specimen from which the virus was sequenced also in: BALF | content_tags.definitions[2] | 0.94 | the tagger's words |
| content_tags | the receptor-binding domain of the spike protein, the part compared across viruses to judge which receptor a virus can use also in: RBD | content_tags.definitions[3] | 0.94 | the tagger's words |
| content_tags | a transcription regulatory sequence: one leader and nine putative body sequences upstream of the open reading frames, with the conserved core appearing as ACGAAC or CUAAAC also in: TRS | content_tags.definitions[4] | 0.93 | the tagger's words |
| content_tags | stipulated here as fewer than 9 x 10^5 cells per ml also in: mild lymphopoenia | content_tags.definitions[5] | 0.92 | the tagger's words |
| content_tags | the subgenus of Betacoronavirus containing SARS-CoV and the SARS-like coronaviruses found in bats also in: Sarbecovirus | content_tags.definitions[6] | 0.93 | the tagger's words |
| content_tags | the name the ICTV designated for this virus after the paper was accepted also in: SARS-CoV-2 | content_tags.definitions[7] | 0.95 | the tagger's words |
| content_tags | the official WHO name of the disease caused by this virus, released after the paper was accepted also in: COVID-19 | content_tags.definitions[8] | 0.95 | the tagger's words |
| content_tags | every contig is compared against the entire non-redundant nucleotide and protein databases, with e values of 1e-10 and 1e-5, before any agent is called note: Term relabelled 2026-09-12: 'false positive contig screening' was this tagger's coinage and never occurs in the paper, so the renderer could not mark it; replaced with the paper's own wording. Evidence, confidence and anchor unchanged. also in: assembled contigs | content_tags.definitions[9] | 0.9 | the tagger's words |
| content_tags | 56,565,928 reads generated from the lavage sample | content_tags.quantities[0] | 0.95 | the tagger's words |
| content_tags | 384,096 contigs assembled by Megahit, the longest 30,474 nucleotides also in: contigs | content_tags.quantities[1] | 0.94 | the tagger's words |
| content_tags | 23,712,657 reads left after filtering against the human genome, used for the abundance assessment | content_tags.quantities[2] | 0.93 | the tagger's words |
| content_tags | 29,903 nucleotides, with 265 nucleotides of 5' terminal sequence and 229 of 3' about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 1909: 'Fig. 1 Genome organization of SARS and SARS-like CoVs. The organizatio…'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. · value source note: THE DESCRIPTION DRAWS ON THE PAPER BEYOND THIS QUOTE: the genome length is stated in the paragraph before ('its whole genome sequence (29,903 nt)'). | content_tags.quantities[3] | 0.94 | the tagger's words |
| content_tags | ORF1ab is 21,291 nucleotides and contains 16 predicted non-structural proteins, followed by at least 13 downstream open reading frames about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 1909: 'Fig. 1 Genome organization of SARS and SARS-like CoVs. The organizatio…'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. | content_tags.quantities[4] | 0.94 | the tagger's words |
| content_tags | S, ORF3a, E, M and N are 3,822, 828, 228, 669 and 1,260 nucleotides about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 1909: 'Fig. 1 Genome organization of SARS and SARS-like CoVs. The organizatio…'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. | content_tags.quantities[5] | 0.93 | the tagger's words |
| content_tags | at least 1,975 cases by 25 January 2020 | content_tags.quantities[6] | 0.94 | the tagger's words |
| content_tags | 41.4 mg per litre of blood against a reference range of 0-6 | content_tags.quantities[7] | 0.92 | the tagger's words |
| content_tags | 1,329,960 contigs from 201 to 11,760 nucleotides, against Megahit's 384,096 | content_tags.quantities[8] | 0.92 | the tagger's words |
| content_tags | P < 3.147 x 10^-3 to P < 9.198 x 10^-9 for recombination in the spike gene, with a Bonferroni-corrected cut-off of 0.01 about this quote: A FIGURE/TABLE CAPTION IS JOINED INTO THE 'evidence' QUOTE, beginning at character 1441: 'Fig. 3 Possible recombination events in the S gene of sarbecoviruses. …'. The page prints the caption apart from the paragraph; read the quote as the paragraph, then the caption. | content_tags.quantities[9] | 0.9 | the tagger's words |
| content_tags | percentage identity between the new genome and reference coronavirus genomes, the measure placing it near bat SL-CoVZC45 also in: nucleotide identity | content_tags.variables[0] | 0.94 | the tagger's words |
| content_tags | the percentage identity of the receptor-binding domain, used to judge whether the virus could use human ACE2 note: Term relabelled 2026-09-12: 'amino acid identity of the RBD' was this tagger's coinage and never occurs in the paper, so the renderer could not mark it; replaced with the paper's own wording. Evidence, confidence and anchor unchanged. also in: amino acid identity | content_tags.variables[1] | 0.93 | the tagger's words |
| content_tags | the proportion of the genome covered, with the mean read depth, after remapping the reads note: Term relabelled 2026-09-12: 'genome coverage and depth' was this tagger's coinage and never occurs in the paper, so the renderer could not mark it; replaced with the paper's own wording. Evidence, confidence and anchor unchanged. also in: genome coverage | content_tags.variables[2] | 0.92 | the tagger's words |
| content_tags | genome copies per millilitre of lavage fluid measured by quantitative RT-PCR also in: viral load | content_tags.variables[3] | 0.93 | the tagger's words |
Tags that could not be placed in the text:
What was deliberately not tagged, and why, is recorded per paper by the tagger. Where a paper has no such record, this page says so rather than implying that nothing was declined.