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Novel coronavirus disease (Covid-19): The first two patients in the UK with person to person transmission

  • Patrick J. Lillie
    Affiliations
    Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
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  • Anda Samson
    Affiliations
    Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
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  • Ang Li
    Affiliations
    Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
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  • Kate Adams
    Affiliations
    Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
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  • Richard Capstick
    Affiliations
    Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
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  • Gavin D. Barlow
    Affiliations
    Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom

    Hull York Medical School, University of York, United Kingdom
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  • Nicholas Easom
    Affiliations
    Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
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  • Eve Hamilton
    Affiliations
    Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
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  • Peter J. Moss
    Affiliations
    Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
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  • Adam Evans
    Affiliations
    Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
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  • Monica Ivan
    Affiliations
    Department of Infection, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
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  • PHE Incident Team
    Affiliations
    PHE Incident Team, Public Health England, National Infection Service, London NW9 5EQ, United Kingdom
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  • Yusri Taha
    Affiliations
    Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
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  • Christopher J.A. Duncan
    Correspondence
    Corresponding author at: Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
    Affiliations
    Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom

    Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, United Kingdom
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  • Matthias L. Schmid
    Correspondence
    Corresponding author.
    Affiliations
    Department of Infection and Tropical Medicine, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
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  • Author Footnotes
    1 Nicholas M Price (Network Lead); Department of Infection, Guy's and St Thomas’ NHS Trust. Michael Jacobs; Department of Infection, Royal Free Hospital NHS Trust. Michael BJ Beadsworth; Tropical and Infectious Disease Unit, Royal Liverpool University Hospital. Matthias L Schmid; Department of Infection & Tropical Medicine, Newcastle upon Tyne Hospitals NHS FT. Anne Tunbridge; Department of Infectious Diseases, Sheffield Teaching Hospitals NHS FT.
    the Airborne HCID Network
    Footnotes
    1 Nicholas M Price (Network Lead); Department of Infection, Guy's and St Thomas’ NHS Trust. Michael Jacobs; Department of Infection, Royal Free Hospital NHS Trust. Michael BJ Beadsworth; Tropical and Infectious Disease Unit, Royal Liverpool University Hospital. Matthias L Schmid; Department of Infection & Tropical Medicine, Newcastle upon Tyne Hospitals NHS FT. Anne Tunbridge; Department of Infectious Diseases, Sheffield Teaching Hospitals NHS FT.
    Affiliations
    Airborne HCID Network, United Kingdom
    Search for articles by this author
  • Author Footnotes
    1 Nicholas M Price (Network Lead); Department of Infection, Guy's and St Thomas’ NHS Trust. Michael Jacobs; Department of Infection, Royal Free Hospital NHS Trust. Michael BJ Beadsworth; Tropical and Infectious Disease Unit, Royal Liverpool University Hospital. Matthias L Schmid; Department of Infection & Tropical Medicine, Newcastle upon Tyne Hospitals NHS FT. Anne Tunbridge; Department of Infectious Diseases, Sheffield Teaching Hospitals NHS FT.
Published:February 28, 2020DOI:https://doi.org/10.1016/j.jinf.2020.02.020
      Tang and colleagues reported in this journal their experience with COVID-19 disease
      • Tang J.W.
      • Tambyah P.A.
      • Hui D.S.C.
      Emergence of a novel coronavirus causing respiratory illness from Wuhan, China.
      , the outbreak of which began in December 2019 in Wuhan, Hubei province, China
      • Q L.i.
      The nCoV Outbreak Joint Field Epidemiology Investigation Team
      An outbreak of NCIP (SARS-CoV-2) infection in China — Wuhan, Hubei province, 2019−2020.
      ,
      • Zhu N.
      • Zhang D.
      • Wang W.
      • et al.
      A novel coronavirus from patients with pneumonia in China, 2019.
      with spread to 33 additional countries
      • Chan J.F.-W.
      • Yuan S.
      • Kok K.-.H.
      • et al.
      A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.
      • Li Q.
      • Guan X.
      • Wu P.
      • et al.
      Early transmission dynamics in wuhan, china, of novel coronavirus–infected pneumonia.
      • Phan L.T.
      • Nguyen T.V.
      • Luong Q.C.
      • et al.
      Importation and human-to-human transmission of a novel coronavirus in Vietnam.
      • Rothe C.
      • Schunk M.
      • Sothmann P.
      • et al.
      Transmission of SARS-CoV-2 infection from an asymptomatic contact in Germany.
      • Holshue M.L.
      • DeBolt C.
      • Lindquist S.
      • et al.
      First case of 2019 novel coronavirus in the United States.
      as of the 21st February 2020. Here we report the clinical features and outcome of the first two cases of disease caused by SARS-CoV-2 infection in the United Kingdom (UK) – the first imported and the second associated with probable person-to-person transmission within the UK. Public health management will be reported separately.
      The index case (A) entered the UK on 23/01/20 from Hubei province in China. Initially asymptomatic, this individual, a 50 year-old female with no past medical history and on no regular medications, developed symptoms of fever and malaise on 26/01/20, accompanied by sore throat and dry cough. She had travelled with her partner and reported no infectious contacts prior to travel. On 28/01/20, a close household contact of the index case, a resident of the UK, developed symptoms of fever (38.5 °C), followed the next day by diffuse myalgia and a dry cough. This patient (case B) is a previously fit and well 23 year-old male. He had returned to the UK from Hubei province on 06/01/20.
      Case B promptly sought advice via the National Health Service (NHS) self-referral service NHS 111, and he and case A were assessed as being possibly at risk of Covid-19, and were admitted to the regional infectious diseases unit at Castle Hill Hospital, Hull University Teaching Hospitals for isolation, assessment and diagnostic sampling. They were managed in separate negative pressure cubicles with anterooms. Nursing and medical staff donned personal protective equipment (PPE) as recommended by Public Health England (PHE). The clinical observations of each of the patients, together with their initial blood tests, are shown in Table 1. Diagnostic PCR testing of nasopharyngeal swabs using the BioFire FilmArray Respiratory Panel 2 plus (bioMérieux, Marcy l'Etoile, France) detected rhinovirus/enterovirus RNA in patient B and was negative in patient A. SARS-CoV-2 RNA was detected by parallel PCR testing of nasopharyngeal swabs from cases A and B at the Public Health England (PHE) Respiratory Virus Unit, Colindale, London, and reported on 30/01/20. The NHS England Airborne High Consequence Infectious Disease (HCID) network was activated and the decision was made to transfer the patients by Hazardous Area Response Team ambulance to the HCID High-Level Isolation Unit (HLIU) at The Newcastle-upon Tyne NHS Foundation Trust in the early hours of 31/01/20.
      Table 1Baseline clinical parameters on admission (bloods on case A done on admission to HLIU).
      ParameterCase ACase B
      Heart rate/min11691
      Respiratory rate/min1817
      Oxygen saturation (room air)97%97%
      Blood pressure (mmHg)120/80115/74
      Temperature (°C)37.637.0
      Total white cell count (× 109/l)3.410.5
      Neutrophil count (× 109/l)2.48.67
      Lymphocyte count (× 109/l)0.61.1
      C-Reactive Protein (mg/L)1540
      Upon arrival in the HLIU (d0) both patients remained clinically stable. Symptomatology consisted of dry cough in case A and in case B comprised fever, myalgia, malaise and sinus congestion (Fig. 1). Clinical examination findings were unremarkable. Initial investigations revealed only mild lymphopenia and elevation of CRP, with mild neutrophilia in case B. Periodic fever of 38–38.5°C was observed in case B until d3 of admission. Repeat blood tests in this individual on d3 demonstrated mild acute kidney injury (AKI, serum creatinine 144 µmol/L). The AKI was thought most likely due to dehydration, and resolved within 24 h with administration of intravenous infusion of crystalloid at 125 ml/h. CXR was normal. Empirical oral antibiotic therapy (co-amoxyclav 500/125 mg p.o. t.d.s.) was administered on d3, to cover the possibility of secondary bacterial infection, but was subsequently discontinued. Symptoms resolved in case A by d3 and in case B by d4 of admission. PCR testing of SARS-CoV-2 from nose and throat swabs taken daily was negative from d2 onwards in case A and from d5 in case B (throat swabs from this individual were negative throughout). There was no clinical indication for the use of experimental antiviral therapies. Patients were deisolated according to current PHE guidance, based on complete resolution of symptoms and two sequential negative respiratory PCR tests at least 24 h apart. Rooms were decontaminated with 0.1% hypochlorite followed by UV light treatment. The contact of these individuals remained asymptomatic throughout the 14 days incubation period but was isolated as a precaution and to be close to family
      Fig 1
      Fig. 1Timeline of symptoms and SARS-CoV-2 PCR positivity on nasopharyngeal swabs.
      These first cases of SARS-CoV-2 are informative for clinicians caring for suspected and confirmed cases in the UK and elsewhere. Reassuringly, illness in both individuals was relatively mild and short-lived, with no evidence of parenchymal lung disease (reflected by normal oxygenation and the absence of radiological infiltrates) or of the late-stage deterioration that has been reported in case series
      • Huang C.
      • Wang Y.
      • Li X.
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      , possibly due to the absence of comorbidities. Experimental antiviral therapeutic options for severe disease were not considered necessary given the mild clinical nature of the illness. Clinical illness correlated with the presence of viral RNA in upper airway samples (Fig. 1), with no evidence of prolonged asymptomatic shedding, although discordance between nose and throat samples in case B highlights the need to sample both areas. It was reasonably assumed that the source of infection in case B was close contact with symptomatic case A, given that the time from travel to China to onset of symptoms in case B was 22 days, although this cannot be proven. Based on this assumption, the period from exposure to disease onset appeared short, at approximately 48 h, consistent with recent reports of the incubation period of SARS-CoV-26. Co-occurrence of respiratory viral infection, as we observed in case B with rhinovirus, has been described in the context of SARS-CoV-2 (https://www.medrxiv.org/content/10.1101/2020.02.12.20022327v1) as it has with many other respiratory viruses spread by similar routes, and may have contributed to the increased symptomatology in case B. Interestingly the partner of case A, who was a close household contact, remained asymptomatic throughout and had negative tests for SARS-CoV-2 shedding. It will be of interest to investigate the serological responses in this individual to ascertain evidence of subclinical infection.
      Isolation, minimisation of contacts and use of appropriate PPE is a cornerstone of management of high consequence respiratory viral infection. In the cases reported here, PHE recommendations for PPE were followed

      Novel coronavirus (SARS-CoV-2) infection prevention and control guidance. Public Health England. www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/wuhan-novel-coronavirus-wn-cov-infection-prevention-and-control-guidanceAccessed 3rd February 2020.

      and there were no breeches in PPE or nosocomial transmission. This should provide reassurance to healthcare workers managing patients with suspected Covid-19 in the UK that current PPE is both feasible and effective.

      Declaration of Competing Interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Acknowledgements

      We are grateful to the patients for providing their written informed consent to publish this report. Our thanks go to nursing, laboratory and medical colleagues in Hull University Teaching Hospitals NHS Trust and The Newcastle Upon Tyne Hospitals NHS Foundation Trust who contributed directly and indirectly to patient care, and to many colleagues in Public Health England and across the HCID network who contributed their time and expertise to the management of these cases. CJAD is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust ( 211153/Z/18/Z ).

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