1887

Abstract

Although coronavirus disease 2019 (COVID-19) is regarded as an acute, resolving infection followed by the development of protective immunity, recent systematic literature review documents evidence for often highly prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory and faecal samples, periodic recurrence of PCR positivity in a substantial proportion of individuals and increasingly documented instances of reinfection associated with a lack of protective immunity. This pattern of infection is quite distinct from the acute/resolving nature of other human pathogenic respiratory viruses, such as influenza A virus and respiratory syncytial virus. Prolonged shedding of SARS-CoV-2 furthermore occurs irrespective of disease severity or development of virus-neutralizing antibodies. SARS-CoV-2 possesses an intensely structured RNA genome, an attribute shared with other human and veterinary coronaviruses and with other mammalian RNA viruses such as hepatitis C virus. These are capable of long-term persistence, possibly through poorly understood RNA structure-mediated effects on innate and adaptive host immune responses. The assumption that resolution of COVID-19 and the appearance of anti-SARS-CoV-2 IgG antibodies represents virus clearance and protection from reinfection, implicit for example in the susceptible–infected–recovered (SIR) model used for epidemic prediction, should be rigorously re-evaluated.

Funding
This study was supported by the:
  • Wellcome Trust (Award WT103767MA)
    • Principle Award Recipient: PeterSimmonds
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001545
2020-12-17
2024-12-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/102/3/vir001545.html?itemId=/content/journal/jgv/10.1099/jgv.0.001545&mimeType=html&fmt=ahah

References

  1. Byington CL, Ampofo K, Stockmann C, Adler FR, Herbener A et al. Community surveillance of respiratory viruses among families in the Utah better identification of Germs-Longitudinal viral epidemiology (BIG-LoVE) study. Clin Infect Dis 2015; 61:1217–1224 [View Article]
    [Google Scholar]
  2. Fontana L, Villamagna AH, Sikka MK, McGregor JC. Understanding viral shedding of SARS-CoV-2: review of current literature. Infect Control Hosp Epidemiol 20201–35
    [Google Scholar]
  3. Liu W-D, Chang S-Y, Wang J-T, Tsai M-J, Hung C-C et al. Prolonged virus shedding even after seroconversion in a patient with COVID-19. J Infect 2020; 81:318–356 [View Article]
    [Google Scholar]
  4. Zhang L, Li C, Zhou Y, Wang B, Zhang J. Persistent viral shedding lasting over 60 days in a mild COVID-19 patient with ongoing positive SARS-CoV-2. Quant Imaging Med Surg 2020; 10:1141–1144 [View Article]
    [Google Scholar]
  5. Molina LP, Chow S-K, Nickel A, Love JE. Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in an obstetric patient with antibody seroconversion. Obstet Gynecol 2020; 136:838–841 [View Article]
    [Google Scholar]
  6. Wang J, Hang X, Wei B, Li D, Chen F et al. Persistent SARS-COV-2 RNA positivity in a patient for 92 days after disease onset. Medicine 2020; 99:e21865 [View Article]
    [Google Scholar]
  7. Bagga B, Harrison L, Roddam P, DeVincenzo JP. Unrecognized prolonged viral replication in the pathogenesis of human RSV infection. J Clin Virol 2018; 106:1–6 [View Article]
    [Google Scholar]
  8. Warren CJ, Xu T, Guo K, Griffin LM, Westrich JA et al. Apobec3A functions as a restriction factor of human papillomavirus. J Virol 2015; 89:688–702 [View Article]
    [Google Scholar]
  9. Takeyama A, Hashimoto K, Sato M, Kawashima R, Kawasaki Y et al. Respiratory syncytial virus shedding by children hospitalized with lower respiratory tract infection. J Med Virol 2016; 88:938–946 [View Article]
    [Google Scholar]
  10. Munywoki PK, Koech DC, Agoti CN, Kibirige N, Kipkoech J et al. Influence of age, severity of infection, and co-infection on the duration of respiratory syncytial virus (RSV) shedding. Epidemiol Infect 2015; 143:804–812 [View Article]
    [Google Scholar]
  11. DKM I, LLH L, Chan KH, Fang VJ, Leung GM et al. The dynamic relationship between clinical symptomatology and viral shedding in naturally acquired seasonal and pandemic influenza virus infections. Clin Infect Dis 2016; 62:431–437
    [Google Scholar]
  12. Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol 2008; 167:775–785 [View Article]
    [Google Scholar]
  13. Memoli MJ, Shaw PA, Han A, Czajkowski L, Reed S et al. Evaluation of antihemagglutinin and Antineuraminidase antibodies as correlates of protection in an influenza A/H1N1 virus healthy human challenge model. mBio 2016; 7:e00417–16 [View Article]
    [Google Scholar]
  14. Maier HE, Nachbagauer R, Kuan G, Ng S, Lopez R et al. Pre-existing antineuraminidase antibodies are associated with shortened duration of influenza A(H1N1)pdm virus shedding and illness in naturally infected adults. Clin Infect Dis 2020; 70:2290–2297 [View Article]
    [Google Scholar]
  15. Dao TL, Hoang VT, Gautret P. Recurrence of SARS-CoV-2 viral RNA in recovered COVID-19 patients: a narrative review. Eur J Clin Microbiol Infect Dis 20201–13
    [Google Scholar]
  16. Xiao AT, Tong YX, Zhang S. False negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: rather than recurrence. J Med Virol. 2020
    [Google Scholar]
  17. Miyamae Y, Hayashi T, Yonezawa H, Fujihara J, Matsumoto Y et al. Duration of viral shedding in asymptomatic or mild cases of novel coronavirus disease 2019 (COVID-19) from a cruise ship: A single-hospital experience in Tokyo, Japan. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases; 2020; 97293–295
  18. Lee PH, Tay WC, Sutjipto S, Fong Siew‐Wai, Ong SWX et al. Associations of viral ribonucleic acid (RNA) shedding patterns with clinical illness and immune responses in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Clin Transl Immunol 2020; 9:e1160 [View Article]
    [Google Scholar]
  19. Huang J, Zheng L, Li Z, Hao S, Ye F et al. Kinetics of SARS-CoV-2 positivity of infected and recovered patients from a single center. Sci Rep 2020; 10:18629 [View Article]
    [Google Scholar]
  20. Yang C, Jiang M, Wang X, Tang X, Fang S et al. Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study. Emerg Microbes Infect 2020; 9:2368–2378 [View Article]
    [Google Scholar]
  21. Goldman JD, Wang K, Roltgen K, Nielsen SCA, Roach JC et al. Reinfection with SARS-CoV-2 and failure of humoral immunity: a case report. medRxiv 2020; 2020.09.22.20192443:
    [Google Scholar]
  22. Tillett RL, Sevinsky JR, Hartley PD, Kerwin H, Crawford N et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis 2020 [View Article]
    [Google Scholar]
  23. KK T, Hung IF, JD I, Chu AW, Chan WM et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis 2020
    [Google Scholar]
  24. Van Elslande J, Vermeersch P, Vandervoort K, Wawina-Bokalanga T, Vanmechelen B et al. Symptomatic SARS-CoV-2 reinfection by a phylogenetically distinct strain. Clin Infect Dis 2020 [View Article]
    [Google Scholar]
  25. Gupta V, Bhoyar RC, Jain A, Srivastava S, Upadhayay R et al. Asymptomatic reinfection in two healthcare workers from India with genetically distinct SARS-CoV-2. Clin Infect Dis 2020
    [Google Scholar]
  26. Selhorst P, Van Ierssel S, Michiels J, Mariën J, Bartholomeeusen K et al. Symptomatic SARS-CoV-2 re-infection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response. medRxiv. 2020; 2020.11.05.20225052:
    [Google Scholar]
  27. Gaebler C, Wang Z, Lorenzi JCC, Muecksch F, Finkin S et al. Evolution of antibody immunity to SARS-CoV-2. bioRxiv 2020; 2020.11.03.367391:
    [Google Scholar]
  28. Simmonds P. Pervasive RNA secondary structure in the genomes of SARS-CoV-2 and other coronaviruses. mBio 2020; 11:e01661–20 [View Article]
    [Google Scholar]
  29. Tang S, Sun R, Xiao Q, Mao T, Ge W et al. Proteomics uncovers immunosuppression in COVID-19 patients with long disease course. medRxiv 2020; 2020.06.14.20131078:
    [Google Scholar]
  30. Liu B, Han J, Cheng X, Yu L, Zhang L et al. Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients. medRxiv 2020; 2020.03.26.20044768:
    [Google Scholar]
  31. Mallett S, Allen AJ, Graziadio S, Taylor SA, Sakai NS et al. At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data. BMC Med 2020; 18:346 [View Article]
    [Google Scholar]
  32. Gupta S, Parker J, Smits S, Underwood J, Dolwani S. Persistent viral shedding of SARS‐CoV‐2 in faeces – a rapid review. Colorectal Dis 2020; 22:611–620 [View Article]
    [Google Scholar]
  33. Wu F, Xiao A, Zhang J, Moniz K, Endo N et al. SARS-CoV-2 titers in wastewater foreshadow dynamics and clinical presentation of new COVID-19 cases. medRxiv. 2020; 2020.06.15.20117747.:
    [Google Scholar]
  34. Peccia J, Zulli A, Brackney DE, Grubaugh ND, Kaplan EH et al. SARS-CoV-2 RNA concentrations in primary municipal sewage sludge as a leading indicator of COVID-19 outbreak dynamics. Nat Biotechnol 2020; 38:1164–1167
    [Google Scholar]
  35. Trottier J, Darques R, Ait Mouheb N, Partiot E, Bakhache W et al. Post-lockdown detection of SARS-CoV-2 RNA in the wastewater of Montpellier, France. One Health 2020; 10:100157 [View Article]
    [Google Scholar]
  36. Wurtzer S, Marechal V, Mouchel J-M, Maday Y, Teyssou R et al. Evaluation of lockdown impact on SARS-CoV-2 dynamics through viral genome quantification in Paris wastewaters. medRxiv. 2020; 2020.04.12.20062679:
    [Google Scholar]
  37. Cevik M, Tate M, Lloyd O, Maraolo AE, Schafers J et al. SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness: a living systematic review and meta-analysis. SSRN Journal 2020; 2020.07.25.20162107: [View Article]
    [Google Scholar]
  38. Bullard J, Dust K, Funk D, Strong JE, Alexander D et al. Predicting infectious SARS-CoV-2 from diagnostic samples. Clin Infect Dis. 2020
    [Google Scholar]
  39. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581:465–469 [View Article]
    [Google Scholar]
  40. La Scola B, Le Bideau M, Andreani J, Hoang VT, Grimaldier C et al. Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards. Eur J Clin Microbio Infect Dis 2020; 39:1059–1061 [View Article]
    [Google Scholar]
  41. Gniazdowski V, Morris CP, Wohl S, Mehoke T, Ramakrishnan S et al. Repeat COVID-19 molecular testing: correlation of SARS-CoV-2 culture with molecular assays and cycle thresholds. Clin Infect Dis 2020 [View Article]
    [Google Scholar]
  42. van Kampen JJA, van de Vijver D, Fraaij PLA, Haagmans BL, Lamers MM et al. Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants. medRxiv 2020; 2020.06.08.20125310.:
    [Google Scholar]
  43. Trypsteen W, Van Cleemput J, Snippenberg Wvan, Gerlo S, Vandekerckhove L. On the whereabouts of SARS-CoV-2 in the human body: a systematic review. PLoS Pathog 2020; 16:e1009037 [View Article]
    [Google Scholar]
  44. Maiese A, Manetti AC, La Russa R, Di Paolo M, Turillazzi E et al. Autopsy findings in COVID-19-related deaths: a literature review. Forensic Sci Med Pathol 20201–18
    [Google Scholar]
  45. Vasquez-Bonilla WO, Orozco R, Argueta V, Sierra M, Zambrano LI et al. A review of the main histopathological findings in coronavirus disease 2019. Hum Pathol. 2020
    [Google Scholar]
  46. De Melo GD, Lazarini F, Levallois S, Hautefort C, Michel V et al. COVID-19-associated olfactory dysfunction reveals SARS-CoV-2 neuroinvasion and persistence in the olfactory system. bioRxiv. 2020; 2020.11.18.388819:
    [Google Scholar]
  47. Xiao F, Tang M, Zheng X, Liu Y, Li X et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020; 158:1831–1833 [View Article]
    [Google Scholar]
  48. Wang W, Xu Y, Gao R, Lu R, Han K et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020; 323:1843–1844 [View Article]
    [Google Scholar]
  49. Sun J, Zhu A, Li H, Zheng K, Zhuang Z et al. Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient. Emerg Microbes Infect 2020; 9:991–993 [View Article]
    [Google Scholar]
  50. Wege H, Siddell S, Meulen ter V. The biology and pathogenesis of coronaviruses. Curr Top Microbiol Immunol 1982; 99:165–200
    [Google Scholar]
  51. Workman AM, Kuehn LA, McDaneld TG, Clawson ML, Loy JD. Longitudinal study of humoral immunity to bovine coronavirus, virus shedding, and treatment for bovine respiratory disease in pre-weaned beef calves. BMC Vet Res 2019; 15:161 [View Article]
    [Google Scholar]
  52. Kanno T, Ishihara R, Hatama S, UCHIDA I. A long-term animal experiment indicating persistent infection of bovine coronavirus in cattle. J Vet Med Sci 2018; 80:1134–1137 [View Article]
    [Google Scholar]
  53. Legnardi M, Franzo G, Koutoulis KC, Wiśniewski M, Catelli E et al. Vaccine or field strains: the jigsaw pattern of infectious bronchitis virus molecular epidemiology in Poland. Poult Sci 2019; 98:6388–6392 [View Article]
    [Google Scholar]
  54. Santos Fernando F, Coelho Kasmanas T, Diniz Lopes P, da Silva Montassier MdeF, Zanella Mores MA et al. Assessment of molecular and genetic evolution, antigenicity and virulence properties during the persistence of the infectious bronchitis virus in broiler breeders. J Gen Virol 2017; 98:2470–2481 [View Article]
    [Google Scholar]
  55. Pensaert MB, Martelli P. Porcine epidemic diarrhea: a retrospect from Europe and matters of debate. Virus Res 2016; 226:1–6 [View Article]
    [Google Scholar]
  56. Pensaert M, Cox E, van Deun K, Callebaut P. A sero‐epizootiological study of porcine respiratory coronavirus in Belgian swine. Vet Q 1993; 15:16–20 [View Article]
    [Google Scholar]
  57. Pijpers A, van Nieuwstadt A, Terpstra C, Verheijden J. Porcine epidemic diarrhoea virus as a cause of persistent diarrhoea in a herd of breeding and finishing pigs. Vet Rec 1993; 132:129–131 [View Article]
    [Google Scholar]
  58. Laude H, Van Reeth K, Pensaert M. Porcine respiratory coronavirus: molecular features and virus-host interactions. Vet Res 1993; 24:125–150
    [Google Scholar]
  59. Addie DD, Schaap IAT, Nicolson L, Jarrett O. Persistence and transmission of natural type I feline coronavirus infection. J Gen Virol 2003; 84:2735–2744 [View Article]
    [Google Scholar]
  60. Herrewegh AAPM, Mähler M, Hedrich HJ, Haagmans BL, Egberink HF et al. Persistence and evolution of feline coronavirus in a closed cat-breeding colony. Virology 1997; 234:349–363 [View Article]
    [Google Scholar]
  61. Addie DD, Jarrett O. Use of a reverse-transcriptase polymerase chain reaction for monitoring the shedding of feline coronavirus by healthy cats. Veterinary Record 2001; 148:649–653 [View Article]
    [Google Scholar]
  62. Foley JE, Poland A, Carlson J, Pedersen NC. Patterns of feline coronavirus infection and fecal shedding from cats in multiple-cat environments. J Am Vet Med Assoc 1997; 210:1307–1312
    [Google Scholar]
  63. Pedersen NC, Allen CE, Lyons LA. Pathogenesis of feline enteric coronavirus infection. J Feline Med Surg 2008; 10:529–541 [View Article]
    [Google Scholar]
  64. Klein-Richers U, Hartmann K, Hofmann-Lehmann R, Unterer S, Bergmann M et al. Prevalence of feline coronavirus shedding in German Catteries and associated risk factors. Viruses 2020; 12:1000 [View Article]
    [Google Scholar]
  65. Sabshin SJ, Levy JK, Tupler T, Tucker SJ, Greiner EC et al. Enteropathogens identified in cats entering a Florida animal shelter with normal feces or diarrhea. J Am Vet Med Assoc 2012; 241:331–337 [View Article]
    [Google Scholar]
  66. McKay LA, Meachem M, Snead E, Brannen T, Mutlow N et al. Prevalence and mutation analysis of the spike protein in feline enteric coronavirus and feline infectious peritonitis detected in household and shelter cats in Western Canada. Can J Vet Res 2020; 84:18–23
    [Google Scholar]
  67. Smith CS, de Jong CE, Meers J, Henning J, Wang L-F et al. Coronavirus infection and diversity in bats in the Australasian region. Ecohealth 2016; 13:72–82 [View Article]
    [Google Scholar]
  68. Suzuki J, Sato R, Kobayashi T, Aoi T, Harasawa R. Group B betacoronavirus in rhinolophid bats, Japan. J Vet Med Sci 2014; 76:1267–1269 [View Article]
    [Google Scholar]
  69. Khalafalla AI, Lu X, Al-Mubarak AIA, Dalab AHS, Al-Busadah KAS et al. Mers-Cov in upper respiratory tract and lungs of dromedary camels, Saudi Arabia, 2013–2014. Emerg Infect Dis 2015; 21:1153–1158 [View Article]
    [Google Scholar]
  70. Al-Gethamy M, Corman VM, Hussain R, Al-Tawfiq JA, Drosten C et al. A case of long-term excretion and subclinical infection with middle East respiratory syndrome coronavirus in a healthcare worker. Clin Infect Dis 2015; 60:973–974 [View Article]
    [Google Scholar]
  71. Kiyuka PK, Agoti CN, Munywoki PK, Njeru R, Bett A et al. Human coronavirus NL63 molecular epidemiology and evolutionary patterns in rural coastal Kenya. J Infect Dis 2018; 217:1728–1739 [View Article]
    [Google Scholar]
  72. Tavares RdeCA, Mahadeshwar G, Wan H, Huston NC, Pyle AM. The global and local distribution of RNA structure throughout the SARS-CoV-2 genome. J Virol 2020 02 Dec 2020 [View Article][PubMed]
    [Google Scholar]
  73. Simmonds P, Tuplin A, Evans DJ. Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: implications for virus evolution and host persistence. RNA 2004; 10:1337–1351 [View Article]
    [Google Scholar]
  74. Davis M, Sagan SM, Pezacki JP, Evans DJ, Simmonds P. Bioinformatic and physical characterizations of genome-scale ordered RNA structure in mammalian RNA viruses. J Virol 2008; 82:11824–11836 [View Article]
    [Google Scholar]
  75. Mehta SH, Cox A, Hoover DR, Wang X-H, Mao Q et al. Protection against persistence of hepatitis C. The Lancet 2002; 359:1478–1483 [View Article]
    [Google Scholar]
  76. Grebely J, Prins M, Hellard M, Cox AL, Osburn WO et al. Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine. Lancet Infect Dis 2012; 12:408–414 [View Article]
    [Google Scholar]
  77. Saichi M, Ladjemi MZ, Korniotis S, Rousseau C, Ait-Hamou Z et al. Single cell RNA sequencing of blood antigen-presenting cells in severe Covid-19 reveals multi-process defects in antiviral immunity. bioRxiv 2020; 2020.07.20.212837:
    [Google Scholar]
  78. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020; 27:992–1000 [View Article]
    [Google Scholar]
  79. Malaguarnera M, Di Fazio I, Romeo MA, Restuccia S, Laurino A et al. Elevation of interleukin 6 levels in patients with chronic hepatitis due to hepatitis C virus. J Gastroenterol 1997; 32:211–215 [View Article]
    [Google Scholar]
  80. Nawaz R, Zahid S, Idrees M, Rafique S, Shahid M et al. HCV-induced regulatory alterations of IL-1β, IL-6, TNF-α, and IFN-ϒ operative, leading liver en-route to non-alcoholic steatohepatitis. Inflammation research : official journal of the European Histamine Research Society [et al].; 2017; 66477–486
  81. Oja AE, Saris A, Ghandour CA, Kragten NAM, Hogema BM et al. Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19.. Eur J Immunol. 2020On-line ahead of print
    [Google Scholar]
  82. Kellam P, Barclay W. The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection. J Gen Virol. 2020
    [Google Scholar]
  83. Bubenikova J, Vrabelova J, Stejskalova K, Futas J, Plasil M et al. Candidate gene markers associated with fecal shedding of the feline enteric coronavirus (FECV). Pathogens 2020; 9:958 [View Article]
    [Google Scholar]
  84. Isaacson B, Mandelboim O. Natural killer cells control metastasis via structural editing of primary tumors in mice. Cancer Immunol Immunother 2019; 68:1721–1724 [View Article]
    [Google Scholar]
  85. Hamdan TA, Lang PA, Lang KS. The diverse functions of the ubiquitous Fcγ receptors and their unique constituent, FcRγ subunit. Pathogens 2020; 9:140 [View Article]
    [Google Scholar]
  86. Duhan V, Hamdan TA, Xu HC, Shinde P, Bhat H et al. Nk cell–intrinsic FcεRIγ limits CD8+ T-cell expansion and thereby turns an acute into a chronic viral infection. PLoS Pathog 2019; 15:e1007797 [View Article]
    [Google Scholar]
  87. Zhou B, Thao TTN, Hoffmann D, Taddeo A, Ebert N et al. SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility. bioRxiv. 2020
    [Google Scholar]
  88. Wu K, Peng G, Wilken M, Geraghty RJ, Li F. Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. J Biol Chem 2012; 287:8904–8911 [View Article]
    [Google Scholar]
  89. Cotten M, Watson SJ, Zumla AI, Makhdoom HQ, Palser AL et al. Spread, circulation, and evolution of the middle East respiratory syndrome coronavirus. mBio 2014; 5: [View Article]
    [Google Scholar]
  90. Danzetta ML, Amato L, Cito F, Di Giuseppe A, Morelli D et al. SARS-CoV-2 RNA persistence in Naso-Pharyngeal swabs. Microorganisms 2020; 8:1124 [View Article]
    [Google Scholar]
  91. Han J, Shi L-xia, Xie Y, Zhang Y-jin, Huang S-ping et al. Analysis of factors affecting the prognosis of COVID-19 patients and viral shedding duration. Epidemiol Infect 2020; 148:e125 [View Article]
    [Google Scholar]
  92. Qi L, Yang Y, Jiang D, Tu C, Wan L et al. Factors associated with the duration of viral shedding in adults with COVID-19 outside of Wuhan, China: a retrospective cohort study. Int J Infect Dis 2020; 96:531–537 [View Article]
    [Google Scholar]
  93. Fu Y, Han P, Zhu R, Bai T, Yi J et al. Risk factors for viral RNA shedding in COVID-19 patients. Eur Respir J 2020; 56:2001190 [View Article]
    [Google Scholar]
  94. Lu Y, Li Y, Deng W, Liu M, He Y et al. Symptomatic infection is associated with prolonged duration of viral shedding in mild coronavirus disease 2019: a retrospective study of 110 children in Wuhan. Pediatr Infect Dis J 2020; 39:e95–e9
    [Google Scholar]
  95. Chen X, Zhu B, Hong W, Zeng J, He X et al. Associations of clinical characteristics and treatment regimens with the duration of viral RNA shedding in patients with COVID-19. Int J Infect Dis 2020; 98:252–260 [View Article]
    [Google Scholar]
  96. Omar S, Bartz C, Becker S, Basenach S, Pfeifer S et al. Duration of SARS-CoV-2 RNA detection in COVID-19 patients in home isolation, Rhineland-Palatinate, Germany, 2020 - an interval-censored survival analysis. Euro Surveill 2020; 25:
    [Google Scholar]
  97. Zhou F, Yu T, Du R, Fan G, Liu Y et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020
    [Google Scholar]
/content/journal/jgv/10.1099/jgv.0.001545
Loading
/content/journal/jgv/10.1099/jgv.0.001545
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error