Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Clinical Samples Collection
2.2. Ethical Committee
2.3. SARS-CoV-2 RNA Quantification
2.3.1. Real Time-PCR
2.3.2. ddPCR
3. Results
3.1. Patient
3.1.1. Clinical and Surgical History
3.1.2. Virological Characterization
3.2. Patient 2
3.2.1. Clinical and Surgical History
3.2.2. Virological Characterization
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020. [Google Scholar] [CrossRef]
- Andersen, K.G.; Rambaut, A.; Lipkin, W.I.; Holmes, E.C.; Garry, R.F. The proximal origin of SARS-CoV-2. Nat. Med. 2020, 2–4. [Google Scholar] [CrossRef] [Green Version]
- Bassetti, M.; Vena, A.; Giacobbe, D.R. The novel Chinese coronavirus (2019-nCoV) infections: Challenges for fighting the storm. Eur. J. Clin. Investig. 2020, 50. [Google Scholar] [CrossRef] [Green Version]
- Khailany, R.A.; Safdar, M.; Ozaslan, M. Genomic characterization of a novel SARS-CoV-2. Gene Rep. 2020. [Google Scholar] [CrossRef]
- Tabata, S.; Imai, K.; Kawano, S.; Ikeda, M.; Kodama, T.; Miyoshi, K.; Obinata, H.; Mimura, S.; Kodera, T.; Kitagaki, M.; et al. Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: A retrospective analysis. Lancet Infect. Dis. 2020. [Google Scholar] [CrossRef]
- Chen, W.; Lan, Y.; Yuan, X.; Deng, X.; Li, Y.; Cai, X.; Li, L.; He, R.; Tan, Y.; Deng, X.; et al. Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerg. Microbes Infect. 2020, 9, 469–473. [Google Scholar]
- Han, D.; Fang, Q.; Wang, X. SARS-CoV-2 was found in the bile juice from a patient with severe COVID-19. J. Med. Virol. 2020. [Google Scholar] [CrossRef]
- Novazzi, F.; Cassaniti, I.; Piralla, A.; Di Sabatino, A.; Bruno, R.; Baldanti, F. SARS-CoV-2 positivity in rectal swabs implication for possible transmission. J. Glob. Antimicrob. Resist. 2020. [Google Scholar] [CrossRef]
- Xiao, F.; Tang, M.; Zheng, X.; Liu, Y.; Li, X.; Shan, H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology 2020, 158, 1831–1833. [Google Scholar] [CrossRef]
- Pennisi, M.; Lanza, G.; Falzone, L.; Fisicaro, F.; Ferri, R.; Bella, R. SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms. Int. J. Mol. Sci. 2020, 21, 5475. [Google Scholar] [CrossRef]
- Wang, W.; Xu, Y.; Gao, R.; Lu, R.; Han, K.; Wu, G.; Tan, W. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Kang, Z.; Gong, H.; Xu, D.; Wang, J.; Li, Z.; Cui, X.; Xiao, J.; Meng, T.; Zhou, W.; et al. The digestive system is a potential route of 2019-nCov infection: A bioinformatics analysis based on single-cell transcriptomes. bioRxiv 2020. [Google Scholar] [CrossRef]
- Suo, T.; Liu, X.; Guo, M.; Feng, J.; Hu, W.; Yang, Y.; Zhang, Q.; Wang, X.; Sajid, M.; Guo, D.; et al. Highly accurate and sensitive diagnostic detection of SARS-CoV-2 by digital PCR. medRxiv 2020. [Google Scholar] [CrossRef] [Green Version]
- Yu, F.; Yan, L.; Wang, N.; Yang, S.; Wang, L.; Tang, Y.; Gao, G.; Wang, S.; Ma, C.; Xie, R.; et al. Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients. Clin. Infect. Dis. 2020. [Google Scholar] [CrossRef] [Green Version]
- Falzone, L.; Musso, N.; Gattuso, G.; Bongiorno, D.; Palermo, C.; Scalia, G.; Libra, M.; Stefani, S. Sensitivity assessment of droplet digital PCR for SARS-CoV-2 detection. Int. J. Mol. Med. 2020, 46, 957–964. [Google Scholar] [CrossRef]
- Suo, T.; Liu, X.; Feng, J.; Guo, M.; Hu, W.; Guo, D.; Ullah, H.; Yang, Y.; Zhang, Q.; Wang, X.; et al. ddPCR: A more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens. Emerg. Microbes Infect. 2020, 9, 1259–1268. [Google Scholar] [CrossRef] [Green Version]
- Park, S.; Lee, C.-W.; Park, D.-I.; Woo, H.-Y.; Cheong, H.S.; Shin, H.C.; Ahn, K.; Kwon, M.-J.; Joo, E.-J. Detection of SARS-CoV-2 in Fecal Samples from Patients with Asymptomatic and Mild COVID-19 in Korea. Clin. Gastroenterol. Hepatol. 2020. [Google Scholar] [CrossRef]
- Cento, V.; Colagrossi, L.; Nava, A.; Lamberti, A.; Senatore, S.; Travi, G.; Rossotti, R.; Vecchi, M.; Casati, O.; Matarazzo, E.; et al. Persistent positivity and fluctuations of SARS-CoV-2 RNA in clinically-recovered COVID-19 patients. J. Infect. 2020, 81, e90–e92. [Google Scholar]
- Hartman, W.R.; Hess, A.S.; Connor, J.P. Persistent viral RNA shedding after COVID -19 symptom resolution in older convalescent plasma donors. Transfusion 2020. [Google Scholar] [CrossRef]
- Zheng, S.; Fan, J.; Yu, F.; Feng, B.; Lou, B.; Zou, Q.; Xie, G.; Lin, S.; Wang, R.; Yang, X.; et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: Retrospective cohort study. BMJ 2020. [Google Scholar] [CrossRef] [Green Version]
- Gupta, A.; Madhavan, M.V.; Sehgal, K.; Nair, N.; Mahajan, S.; Sehrawat, T.S.; Bikdeli, B.; Ahluwalia, N.; Ausiello, J.C.; Wan, E.Y.; et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 2020, 26, 1017–1032. [Google Scholar] [CrossRef] [PubMed]
- Lax, S.F.; Skok, K.; Zechner, P.; Kessler, H.H.; Kaufmann, N.; Koelblinger, C.; Vander, K.; Bargfrieder, U.; Trauner, M. Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series. Ann. Intern. Med. 2020. [Google Scholar] [CrossRef]
- Balaphas, A.; Gkoufa, K.; Meyer, J.; Peloso, A.; Bornand, A.; McKee, T.A.; Toso, C.; Popeskou, S.-G. COVID-19 can mimic acute cholecystitis and is associated with the presence of viral RNA in the gallbladder wall. J. Hepatol. 2020. [Google Scholar] [CrossRef]
Date of Sample Withdrawal | 12 May | 13 May | 19 May | 26 May | 10 June | 2 July | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Days after respiratory symptoms start | 46 | 47 | 53 | 60 | 75 | 97 | ||||||||||||
Gene targeted by assays for RNA quantification | N | RdRp | E | N | RdRp | E | N | RdRp | E | N | RdRp | E | N | RdRp | E | N | RdRp | E |
Results by ddPCR a | ||||||||||||||||||
Nasopharyngeal swab, copies/mL | 594 | 266 | n.a. | 247 | 94 | n.a. | 46 | TND | n.a. | 8 | 10 | n.a. | 10 | 17 | n.a. | TND | TND | n.a. |
Plasma, copies/mL b | 84 | 176 | n.a. | - | - | - | TND | 30 | n.a. | 6 | 11 | n.a. | 6 | 11 | n.a. | TND | TND | n.a. |
Bile, copies/mL b | 100 * | 86 * | n.a. | 6 | 29 | n.a. | 18 | 27 | n.a. | - | - | - | TND | TND | n.a. | TND | TND | n.a. |
Rectal swab, copies/mL b | 22 | 52 | n.a. | - | - | - | 6 | 10 | n.a. | TND | 12 | n.a. | TND | TND | n.a. | TND | TND | n.a. |
Urine, copies/mL b | TND | TND | n.a. | - | - | - | TND | TND | n.a. | TND | TND | n.a. | TND | TND | n.a. | - | - | - |
Ct obtained by Real-time PCR a | ||||||||||||||||||
Nasopharyngeal swab b | - | - | - | 38.5 | Neg | Neg | Neg | Neg | Neg | Neg | Neg | Neg | Neg | Neg | Neg | - | - | - |
Date of Sample Withdrawal | 28 May | 4 June | 10 June | ||||||
---|---|---|---|---|---|---|---|---|---|
Days after respiratory symptoms start | 63 | 70 | 75 | ||||||
Gene targeted by assays for viral RNA quantification | N | RdRp | E | N | RdRp | E | N | RdRp | E |
Results by ddPCR a | |||||||||
Nasopharyngeal swab, copies/mL | 574 | 214 | n.a. | 818 | 244 | n.a. | 16 | 17 | n.a. |
Plasma, copies/mL | 11 | 27 | n.a. | 12 | 11 | n.a. | 6 | 11 | n.a. |
Bile, copies/mL | 12 * | 20 * | n.a. | 12 | 11 | n.a. | 19 | 29 | n.a. |
Rectal swab, copies/mL | 220 | 43 | n.a. | 14 | 14 | n.a. | 5 | 23 | n.a. |
Urine, copies/mL | 12 | 31 | n.a. | TND | TND | n.a. | TND | TND | n.a. |
Ct obtained by Real-time PCR a | |||||||||
Nasopharyngeal swab | 25.8 | 28.5 | 26.9 | 31.2 | 31.1 | 29.6 | 38.3 | 29.7 | Neg |
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Scutari, R.; Piermatteo, L.; Manuelli, M.C.; Iannetta, M.; Salpini, R.; Bertoli, A.; Alteri, C.; Saccomandi, P.; Bellocchi, M.C.; Malagnino, V.; et al. Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis. Life 2020, 10, 302. https://doi.org/10.3390/life10110302
Scutari R, Piermatteo L, Manuelli MC, Iannetta M, Salpini R, Bertoli A, Alteri C, Saccomandi P, Bellocchi MC, Malagnino V, et al. Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis. Life. 2020; 10(11):302. https://doi.org/10.3390/life10110302
Chicago/Turabian StyleScutari, Rossana, Lorenzo Piermatteo, Matteo Ciancio Manuelli, Marco Iannetta, Romina Salpini, Ada Bertoli, Claudia Alteri, Patrizia Saccomandi, Maria Concetta Bellocchi, Vincenzo Malagnino, and et al. 2020. "Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis" Life 10, no. 11: 302. https://doi.org/10.3390/life10110302