Details of SARS-CoV-2 reinfections at a major UK tertiary centre
Authors: Mark I. Garvey, Anna L. Casey, Martyn A.C. Wilkinson, Liz Ratcliffe, Claire McMurray, Joanne Stockton, Elisabeth Holden, Husam Osman, Nick J Loman
Journal: Journal of Infection (2021)

•There remains uncertainty surrounding reinfection with SARS-CoV-2.•The 'second wave' of transmission in the UK offered an opportunity to examine this.•We observed reinfections in our patients, whole genome sequencing implied variants not previously identified in wave 1 were responsible for these recent infections.•Further studies are required to define the true impact of reinfections.•Real time whole genome sequencing will be useful to rapidly identify new variants within the hospital setting to facilitate appropriate management of patients. Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been demonstrated to generate a detectable immune response, the susceptibility of previously infected individuals to reinfection is poorly understood.1Tillett R.L. Sevinsky J.R. Hartley P.D. et al.Genomic evidence for reinfection with SARS-CoV-2: a case study.Lancet. 2020; 21: 52-58Abstract Full Text Full Text PDF Scopus (518) Google Scholar Hanrath et al., (2020) suggested prior SARS-CoV-2 infection in healthcare workers is associated with protection against symptomatic reinfection for up to 6 months.2Hanrath A.T. Payne B.A.I. Duncan C.J.A. Prior SARS-CoV-2 infection is associated with protection against symptomatic reinfection.J Infect. 2020; https://doi.org/10.1016/j.jinf.2020.12.023Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar However, in studies of immunity to other coronaviruses, loss of immunity to infection occurs within 1–3 years.3Callow K.A. Parry H.F. Sergeant M. Tyrrell D.A. The time course of the immune response to experimental coronavirus infection of man.Epidemiol Infect. 1990; 105: 435-446Crossref PubMed Scopus (421) Google Scholar Reports of SARS-CoV-2 reinfection events have been published from Brazil, Hong Kong, the Netherlands and Belgium.1Tillett R.L. Sevinsky J.R. Hartley P.D. et al.Genomic evidence for reinfection with SARS-CoV-2: a case study.Lancet. 2020; 21: 52-58Abstract Full Text Full Text PDF Scopus (518) Google Scholar,4Sabino E.C. Buss L.F. Carvalho M.P.S. et al.Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence.Lancet. 2021; 397: P452-P455Abstract Full Text Full Text PDF PubMed Scopus (536) Google Scholar Here, we discuss SARS-CoV-2 reinfections of patients at University Hospitals Birmingham (UHB) NHS Foundation Trust, using whole genome sequencing to identify responsible variants. UHB is one of the largest Trusts in the UK, covering 4 NHS hospital sites, treating over 2.2 million patients per year and housing one of the largest single critical care units in the world. UHB's patient testing programme detects SARS-CoV-2 RNA from nasopharyngeal swabs/sputum using molecular platforms including Panther, Hologic, M2000, Abbott and GeneXpert, Cepheid. A database of SARS-CoV-2 positive patients was analysed for potential reinfections, defined as patients with a positive result ≥ 90 days after their first. This was based on Public Health England (PHE) guidance for management of exposures in healthcare settings, which states immunocompetent staff and patients testing positive for SARS-CoV-2 by PCR should be exempt from routine retesting within 90 days of initial illness onset/test unless they develop new COVID-19 symptoms.5Public Health England (PHE) Guidance. COVID-19: Management of Staff and Exposed Patients or Residents in Health and Social Care Settings. Available at: https://www.gov.uk/government/publications/covid-19-management-of-exposed-healthcare-workers-and-patients-in-hospital-settings/covid-19-management-of-exposed-healthcare-workers-and-patients-in-hospital-settings#section6 (last accessed 23rd February 2021)Google Scholar Potential reinfection samples underwent whole-genome sequencing at the University of Birmingham. Lineages were assigned with Pangolin.6Rambaut A. Holmes E.D. Hill V. et al.A dynamic nomenclature proposal for SARS-CoV-2 to assist genomic epidemiology.Nat Microbiol. 2020; 5: 1403-1407Crossref PubMed Scopus (1506) Google Scholar UHB has seen more COVID-19 cases than any other UK Trust. Between 01/03/20 and 21/02/21, there were 12,960 COVID-19 cases. Thirty-six of these had a positive result beyond 90 days of their first positive. Three of these patients had at least one negative result in between and had one sample which successfully generated sequence data. Case 1. A 92 year old white British male, with a background of dementia, presented in April 2020 with pyrexia, a dry cough and shortness of breath. Chest X-ray showed bilateral infiltrates suggestive of COVID-19 pneumonia, confirmed with SARS-CoV-2 PCR detection (01/04/2020, Abbott M2000 cycle threshold (Ct) value 15.89). Sequencing of this sample failed. This patient re-presented to UHB on 25/10/20 with lethargy, persistent cough and pyrexia; a diagnosis of aspiration pneumonia was made. His day 7 swab was SARS-CoV-2 positive (02/11/21, Hologic, Panther, Relative Light Unit (RLU) value 1290). Swabs on days 0 and 5 were negative. The sample was sequenced and identified as the variant, B.1.177. A follow up sample could not be obtained as the patient died. Case 2. An 84 year old white British male with a background of dementia and Paget's disease was admitted in May 2020 with lethargy and confusion, attributed to a catheter associated urinary tract infection. He tested positive for SARS-CoV-2 on day 13 of admission (23/05/20, Abbott M2000, Ct value 26.79), reporting mild symptoms of headache and fatigue. Swabs taken on days 0, 5 and 7 were negative. The positive sample failed to sequence. The patient was readmitted in December 2020 due to a fall, and was negative for SARS-CoV-2 during this admission. In January 2021, the patient re-presented to UHB after another fall and was found to be positive for SARS-CoV-2 (02/01/2021, Hologic, Panther, RLU 1211). A follow up sample confirmed the infection. There were no COVID-19 symptoms. This sample was sequenced and identified as variant B.1.177. Case 3. A 59 year old British Asian male with end stage renal failure presented in May 2020 during routine dialysis with a cough and fluctuating temperature. The patient tested positive for SARS-CoV-2 on 05/06/2020 (Abbott M2000, Ct value 22.03), however, the sample failed sequencing. Multiple dialysis attendances followed, where the patient tested negative, until a positive result was obtained at a routine dialysis session in January 2021 (28/01/2021, Hologic, Panther, RLU 1348). No COVID-19 symptoms were reported. This sample was sequenced and identified as variant of concern (VOC) B.1.1.7. A follow up sample confirmed the positive result. Here, we present details of patients who appear to have SARS-CoV-2 reinfections based on sequencing results. Although we have been unable to sequence samples from the previous infections, we have successfully sequenced samples from their latest admissions. The variants identified, B.1.177 and B.1.1.7 were not present in the UK in April and May.7Hodcroft E.B. Zuber M. Nadeau S. et al.Emergence and Spread of a SARS-CoV-2 Variant Through Europe in the Summer of 2020.2020https://doi.org/10.1101/2020.10.25.20219063Crossref Google Scholar,8COVID-19 Genomics UK Consortium (COG UK), Pangolin lineage B.1.1.7 available at https://cov-lineages.org/global_report_B.1.1.7.html (last accessed 24th February 2021)Google Scholar B.1.177 is thought to have first originated in Spain in early summer 2020.7Hodcroft E.B. Zuber M. Nadeau S. et al.Emergence and Spread of a SARS-CoV-2 Variant Through Europe in the Summer of 2020.2020https://doi.org/10.1101/2020.10.25.20219063Crossref Google Scholar The first sequences in England associated with this lineage were identified on 18th July, when quarantine-free travel between the UK and Spain was allowed (10–26th July 2020).7Hodcroft E.B. Zuber M. Nadeau S. et al.Emergence and Spread of a SARS-CoV-2 Variant Through Europe in the Summer of 2020.2020https://doi.org/10.1101/2020.10.25.20219063Crossref Google Scholar B.1.1.7, the so called Kent variant, was first identified in the UK on 20th September 2020.8COVID-19 Genomics UK Consortium (COG UK), Pangolin lineage B.1.1.7 available at https://cov-lineages.org/global_report_B.1.1.7.html (last accessed 24th February 2021)Google Scholar Using these data, we deduce that our patients have been re-infected with new COVID-19 variants, as neither was circulating in the UK when the patients first tested positive. Only the three cases mentioned had laboratory results suggesting reinfection. The other 33 patients either had samples missing from prior infections or the second sample did not sequence. Sequencing often fails when the Ct value is too high or the RLU is too low.9Public Health England (PHE) Understanding Cycle Threshold (ct) in SARS-CoV-2 RT-PCR. A Guide for Health Protection Teams. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/926410/Understanding_Cycle_Threshold__Ct__in_SARS-CoV-2_RT-PCR_.pdf (last accessed 23rd February 2021).Google Scholar,10Smith E. Zzhen W. Manji R. Schron D. Duong S. Berrya G.J. Analytical and clinical comparison of three nucleic acid amplification tests for SARS-CoV-2 detection.J Clin Micro. 2020; 58 (-20): e01134Crossref PubMed Scopus (49) Google Scholar Further work is warranted to explore this. Another important point is that all these reinfections were in patients who do not meet the PHE criteria for severe immunosuppression which is known to increase the risk of infection.5Public Health England (PHE) Guidance. COVID-19: Management of Staff and Exposed Patients or Residents in Health and Social Care Settings. Available at: https://www.gov.uk/government/publications/covid-19-management-of-exposed-healthcare-workers-and-patients-in-hospital-settings/covid-19-management-of-exposed-healthcare-workers-and-patients-in-hospital-settings#section6 (last accessed 23rd February 2021)Google Scholar Although our data suggest reinfections occur, it is important to note we have been unable to sequence two paired samples from the same patient. Another point to note is we have not re-confirmed these sequence results. Exiting the second UK COVID-19 wave, we must recognise the possibility of reinfection and the implications for managing previous positive patients within hospitals. Real time whole genome sequencing will prove useful to rapidly identify new variants and reinfections, facilitating appropriate patient management. Not applicable. Not applicable. Not applicable. None.