Robust epidemiological investigations in hospital-based COVID-19 outbreaks cannot be overlooked-even in the era of whole-genome sequencing

We read with interest the recent article by O'Connell et al. [[1]O’Connell L. Asad H. Hall G. Jones T. Walters J. Manchipp-Taylor L. et al.Detailed analysis of in-hospital transmission of SARS-CoV-2 using whole genome sequencing.J Hosp Infect. 2023; 131: 23-33Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar] which describes a COVID-19 acute-care outbreak and questions the protection afforded by recommended personal protective equipment (PPE) using a surgical mask, eye protection, gowns and gloves against the transmission of SARS-CoV-2. The authors highlight the following: (1) Extensive spread from a patient they identified as their index case (P0) despite this patient having a relatively short stay (10 h) and a PCR test at a relatively high cycle threshold value (Ct = 32) in the range not normally associated with culturable and transmissible virus [[2]Lin Y.-C. Malott R.J. Ward L. Kiplagat L. Pabbaraju K. Gill K. et al.Detection and quantification of infectious severe acute respiratory coronavirus-2 in diverse clinical and environmental samples.Sci Rep. 2022; 12: 5418Crossref PubMed Scopus (22) Google Scholar,[3]Bruce E.A. Mills M.G. Sampoleo R. Perchetti G.A. Huang M.-L. Despres H.W. et al.Predicting infectivity: comparing four PCR-based assays to detect culturable SARS-CoV-2 in clinical samples.EMBO Mol Med. 2022; 14e15290Crossref PubMed Scopus (16) Google Scholar]; (2) concerns regarding the infection control measures in place at the time suggesting the non-use of N95 respirators may have contributed to the spread; and (3) the value of whole genome sequencing (WGS) in understanding outbreaks. We have concerns about missing and/or less fully described details and the conclusions drawn from this study. We believe there are alternate explanations for this outbreak that are equally, if not more plausible than those proposed by the authors and think these should be given due consideration. Firstly, we are concerned that the case definitions employed cannot completely rule out community acquisition (CA) or hospital-identified COVID-19 cases from visitors or designated support persons. No details are provided into how comprehensive the investigation was regarding COVID-19 case acquisition. While CA cases were excluded, investigating all patients and staff members working on the affected unit for community- or visitor-related acquisition provides a more complete picture. Secondly, the authors suggest an airborne event as the main means of transmission but the supportive data for this hypothesis are inadequate. Contact as the primary means of transmission is equally plausible as not all healthcare workers (HCWs) were tested, the role of visitors or wandering patients were not mentioned and improper PPE use was described at a busy hub to the various care areas. No environmental sampling was completed to allow assessment of the level of potential contamination within the affected areas. No reference to cleaning protocols for rooms, shared medical equipment or enhanced cleaning following discharge of a COVID-19 patient was presented. A lack of direct contact was highlighted as indicative of airborne transmission. However, indirect contact transmission via fomites was not considered which we believe may be plausible in this setting [[4]O’Grady H.M. Harrison R. Snedeker K. Trufen L. Yue P. Ward L. et al.A two-ward acute care hospital outbreak of SARS-CoV-2 delta variant including a point-source outbreak associated with the use of a mobile vital signs cart and sub-optimal doffing of personal protective equipment.J Hosp Infect. 2022; 131: 1-11Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,[5]Onakpoya I.J. Heneghan C.J. Spencer E.A. Brassey J. Plüddemann A. Evans D.H. et al.SARS-CoV-2 and the role of fomite transmission: a systematic review.F1000Research. 2021; 10: 233Crossref PubMed Google Scholar] and no data are presented to exclude this possibility. Patient 0 was bed bound, presumably requiring increased level of care, in close proximity and possibly for prolonged periods of time, which may present an increased risk for staff exposure (direct and indirect) and environmental contamination. Thirdly, the authors point to the fact that no one was infected in the ITU and hypothesize this may be due to increased use of FFP3 respirators more routinely on that unit, yet it is noted that no one was infected on Ward 3, where presumably surgical masks were used. The observations that two HCWs who wore respirators were not infected while one HCW wearing a surgical mask allows no conclusions to be drawn regarding airborne transmission, especially where the ventilation was described as robust, and with the recent publication of a randomized trial which demonstrated no significant differences between medical masks versus N95 respirators in preventing COVID-19 among HCWs, even during the more transmissible Omicron variant era [[6]Loeb M. Bartholomew A. Hashmi M. Tarhuni W. Hassany M. Youngster I. et al.Medical masks versus N95 respirators for preventing COVID-19 among health care workers : a randomized trial.Ann Intern Med. 2022; 175: 1629-1638Crossref PubMed Scopus (15) Google Scholar]. Furthermore, on the point of PPE, adherence to existing recommendations was not evaluated or summarized beyond mention that “routine mask wearing around the desk was identified, retrospectively, as suboptimal”. Inappropriate PPE doffing, which is a recognized risk factor for transmission of highly communicable viruses [[7]Mumma J.M. Durso F.T. Ferguson A.N. Gipson C.L. Casanova L. Erukunuakpor K. et al.Human factors risk analyses of a doffing protocol for ebola-level personal protective equipment: mapping errors to contamination.Clin Infect Dis. 2018; 66: 950-958Crossref PubMed Scopus (57) Google Scholar], was not accurately assessed or audited. A recent study [[4]O’Grady H.M. Harrison R. Snedeker K. Trufen L. Yue P. Ward L. et al.A two-ward acute care hospital outbreak of SARS-CoV-2 delta variant including a point-source outbreak associated with the use of a mobile vital signs cart and sub-optimal doffing of personal protective equipment.J Hosp Infect. 2022; 131: 1-11Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] found a highly significant association with sub-optimal adherence to doffing, hand hygiene and order of doffing in a hospital ward COVID-19 outbreak and the authors provide no data on this crucial component of safe care delivery. Finally, the authors emphasize the utility of WGS in outbreak investigation. However, we would argue that the WGS sequencing data is incomplete with only approximately half of the cases actually typed so having a mixed outbreak due to two independent sources cannot be ruled out. In addition, the actual single nucleotide polymorphism differences between case strains were not described. Epidemiological detail for two of the infected HCWs are described yet the similarities between the genotypes of P0 and the HCWs are not reported. The conclusions proposed by O'Connell et al. [[1]O’Connell L. Asad H. Hall G. Jones T. Walters J. Manchipp-Taylor L. et al.Detailed analysis of in-hospital transmission of SARS-CoV-2 using whole genome sequencing.J Hosp Infect. 2023; 131: 23-33Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar], that the absence of FFP3 or N95 respirator use contributed to spread, or that long-range airborne transmission was the major explanation for the outbreak have inconsistencies based upon the information provided. In hospital-based outbreaks, it is our view that WGS is best used as an adjunct [[8]Berggreen H. Løvestad A.H. Helmersen K. Jørgensen S.B. Aamot H.V. Lessons learned: use of WGS in real-time investigation of suspected intrahospital SARS-CoV-2 outbreaks.J Hosp Infect. 2023; 131: 81-88Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar] to real-time detailed contact tracing (including consideration of all community exposures and all contacts and visitors), and when WGS is applied to all individuals investigated in the outbreak. None of the authors have relevant direct conflicts of interest to declare. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.