The DOI matches its Crossref record; 34 of the 37 references it cites were found in a registry or an index.
Virological assessment of hospitalized patients with COVID-2019
Open accessPublished version of a preprint
Abstract
Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019 1,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses 3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung 2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 2003 5. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission 6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 10 8 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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“It appears that peak viral loads can vary >100,000-fold between cases (Magleby et al., 2020; Wölfel et al., 2020)”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Wölfel et al., 2020
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“Clinical reports suggest that infection with CoV-2 is associated with high rates of disturbances in smell and taste perception, including anosmia (8-13).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [10]
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A novel coronavirus from patients with pneumonia in China, 2019
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001017 · Cited by 28,244
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Self-citationGorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0695-z · Cited by 8,745
Self-citationDetection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR
Corman, V. M., Landt, O., Kaiser, M., Molenkamp, R., Meijer, A., Chu, D. K. W., Bleicker, T., Brünink, S., Schneider, J. A., Schmidt, M. L., et al. (2020) · Eurosurveillance · doi:10.2807/1560-7917.es.2020.25.3.2000045 · Cited by 7,266
Self-citationFirst case of 2019 novel coronavirus in the United States
Holshue, M. L., DeBolt, C., Lindquist, S., Lofy, K. H., Wiesman, J., Bruce, H., Spitters, C., Ericson, K., Wilkerson, S., Tural, A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001191 · Cited by 6,030
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients
Zou, L., Ruan, F., Huang, M.-X., Liang, L.-J., Huang, H., Hong, Z.-S., Yu, J.-X., Kang, M., Song, Y.-C., Xia, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2001737 · Cited by 4,590
Identification of a novel coronavirus in patients with severe acute respiratory syndrome
Drosten, C., Günther, S., Preiser, W., van der Werf, S., Brodt, H.-R., Becker, S., Rabenau, H., Panning, M., Kolesnikova, L., Fouchier, R. A. M., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030747 · Cited by 4,574
Self-citationA Novel Coronavirus Associated with Severe Acute Respiratory Syndrome
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Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany
Rothe, C., Schunk, M., Sothmann, P., Bretzel, G., Froeschl, G., Wallrauch, C., Zimmer, T., Thiel, V., Jänke, C., Guggemos, W., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2001468 · Cited by 4,211
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Indoor Aerosol Science Aspects of SARS-CoV-2 Transmission
Nazaroff, W. W. (2022) · Indoor Air · doi:10.1111/ina.12970 · Cited by 70
Wyllie, D., Jones, H. E., Mulchandani, R., Trickey, A., Taylor-Phillips, S., Brooks, T., Charlett, A., Ades, A., EDSAB-HOME investigators, Moore, P., et al. (2020) · doi:10.1101/2020.11.02.20222778 · Cited by 96
Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques
He, X., Chandrashekar, A., Zahn, R., Wegmann, F., Yu, J., Mercado, N. B., McMahan, K., Martinot, A. J., Piedra-Mora, C., Beecy, S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.05.040 · Cited by 65
“We assessed viral loads in bronchoalveolar lavage (BAL) and nasal swabs (NSs) by RT-PCR specific for subgenomic mRNA (sgRNA), which is believed to measure replicating virus (Chandrashekar et al., 2020; Wolfel et al., 2020).”
Molecular mechanisms and epidemiology of COVID-19 from an allergist’s perspective
Hosoki, K., Chakraborty, A., & Sur, S. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.05.033 · Cited by 63
Zhao, H., Wang, T.-C., Li, X.-F., Zhang, N.-N., Li, L., Zhou, C., Deng, Y.-Q., Cao, T.-S., Yang, G., Li, R.-T., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00861-4 · Cited by 60
“As previously mentioned, subgenomic RNA (sgRNA) was used to quantify RNA replication in nasal swabs, lung, and trachea specimens.(17) The limit of detection was the lowest level at which viral RNA can be specifically amplified in this assay (Ct value of 38).”
MethodBolze, A., Cirulli, E. T., Luo, S., White, S., Wyman, D., Dei Rossi, A., Machado, H., Cassens, T., Jacobs, S., Schiabor Barrett, K. M., et al. (2021) · doi:10.1101/2021.06.20.21259195 · Cited by 116
Bao, C., Tao, X., Cui, W., Hao, Y., Zheng, S., Yi, B., Pan, T., Young, K. H., & Qian, W. (2021) · Experimental Hematology & Oncology · doi:10.1186/s40164-021-00199-1 · Cited by 47
Mobile Health (mHealth) Viral Diagnostics Enabled with Adaptive Adversarial Learning
Shokr, A., Pacheco, L. G. C., Thirumalaraju, P., Kanakasabapathy, M. K., Gandhi, J., Kartik, D., Silva, F. S. R., Erdogmus, E., Kandula, H., Luo, S., et al. (2021) · ACS Nano · doi:10.1021/acsnano.0c06807 · Cited by 45
“17,18 The signal was also reliably differentiated from results obtained with influenza A and B samples (Figure 2e, right panel).”
ResultCorbett, K. S., Nason, M. C., Flach, B., Gagne, M., O’ Connell, S., Johnston, T. S., Shah, S. N., Edara, V. V., Floyd, K., Lai, L., et al. (2021) · doi:10.1101/2021.04.20.440647 · Cited by 43
“In this study, a challenge dose of 8x105 PFU of a newly characterized, pathogenic 316 SARS-CoV-2 USA-WA1/2020 strain was used to achieve a level of viral replication comparable 317 to or exceeding that observed from nasal swabs of humans with symptomatic infection, measured 318 by sgRNA (33) or genomic vRNA (34-36).”
MethodAttenuation of SARS-CoV-2 infection by losartan in human kidney organoids
Rahmani, W., Chung, H., Sinha, S., Bui-Marinos, M. P., Arora, R., Jaffer, A., Corcoran, J. A., Biernaskie, J., & Chun, J. (2022) · iScience · doi:10.1016/j.isci.2022.103818 · Cited by 25
Lai, A., Chang, M. L., O'Donnell, R. P., Zhou, C., Sumner, J. A., & Hsiai, T. K. (2021) · Science of The Total Environment · doi:10.1016/j.scitotenv.2021.146464 · Cited by 25
Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., et al. (2021) · doi:10.1101/2021.08.13.456316 · Cited by 8
Metadata
- Authors
- Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., Niemeyer, D., Jones, T. C., Vollmar, P., Rothe, C., Hoelscher, M., Bleicker, T., Brünink, S., Schneider, J., Ehmann, R., Zwirglmaier, K., Drosten, C., & Wendtner, C.
- Affiliations
- Institut für Mikrobiologie der Bundeswehr (DE)
- Charité – Universitätsmedizin Berlin (DE)
- München Klinik Schwabing (DE)
- University of Cambridge (GB)
- LMU Klinikum (DE)
- Corresponding author
- Drosten, Christian
- Wendtner, Clemens
- ORCID
- Venue
- Nature
- Published
- 2020-04-01
- Volume
- 581
- Issue
- 7809
- Pages
- 465-469
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3013893137
- Cited by
- 6,661
- References
- 37
- Citations by year
- 2026: 92 · 2025: 165 · 2024: 328 · 2023: 526 · 2022: 1091 · 2021: 2228 · 2020: 2219
- FWCI
- 199.03
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-12-11)
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- European Commission (602525)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- COVID-19 pandemic, SARS-CoV-2, upper respiratory tract, viral replication, seroconversion, viral load, hospitalized patients
- MeSH terms
- Seroconversion, Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Testing, Coronavirus Envelope Proteins, Antibodies, Viral, Base Sequence, Blood, Feces, Hospitalization, Humans, Immunoglobulin G, Immunoglobulin M, Lung, Pharynx, Pneumonia, Viral, RNA, Viral, Sputum, Urine, Viral Envelope Proteins, Virus Replication, Virus Shedding, Coronavirus Infections, Clinical Laboratory Techniques, Viral Load, Polymorphism, Single Nucleotide, Pandemics
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