Dear Editor,
We note with interest these previous studies into household and hospital influenza outbreaks.
1
, 2
Such community and hospital-based respiratory virus transmission and outbreak investigations often suffer from the potential confounding arising from possible exposures to undiagnosed index cases outside of the outbreak cohort, leading to an overestimate of virus transmissibility, and potentially unnecessary costly and restrictive infection control interventions.To avoid such confounding, we performed a small pilot study in a closed population of adult research scientists (n = 43 out of a possible 48). All participants signed informed consent forms, following ethical approval from Plymouth University Ethics Committee.
These scientists were confined to a British Antarctic Survey base for 1 month (March 2017), during which no personnel entered nor left the base. Therefore any detectable human respiratory viruses could only have been brought into the base by personnel at the beginning of this ‘closed period’.
Participants were given anonymous codes to maintain confidentiality. Each agreed to give nasal swabs (collected in virus transport medium, Virocult, Medical Wire and Equipment Ltd, Corsham, Wiltshire, England) upon entry (Day 0, 14/3/17), then at days 4 (18/3/17), 10 (24/3/17) and 17 (31/3/17) post-entry. All viral swabs were stored at −80° C until they could be shipped back to the UK and tested at the Leicester Royal Infirmary. This was performed using a respiratory multiplex PCR assay (16-well, AusDiagnostics UK Ltd., Chesham, UK) that could detect any of: influenza A, B, respiratory syncytial virus (RSV), parainfluenza (PIV) types 1-4, human metapneumo (hMPV)-, entero-/rhino-, corona- (229E, OC43, NL63, HKU1) and adeno- viruses.
No specific instructions about infection control were given to the participants. They were left to act as they would normally behave throughout the period of the study. Any participants who developed any of 9, self-assessed, influenza-like symptoms (fever, cough, stuffy nose and/or sinuses, headache, sore throat, myalgia, fatigue, shortness of breath, nausea or vomiting) would complete a tick-box questionnaire (on a scale of 1-‘very mild’ to 5-‘very severe’) to describe the relative severity of their symptoms.
This same questionnaire also requested the contact intensity (i.e. number, nature and frequency) of their daily contacts with other participants as a self-assessed, linear graded score (from 1-‘sharing just one meal together’ to 5-‘spending the majority of the day and evening with the other person’), depending on the frequency of contact whilst working, eating meals and socialising together. The daily location of all personnel in any of the four station zones at 0830, 1100, 1400, 1630 and 2000 h was also recorded routinely for safety and security, using a ‘tagboard’ system.
Out of the 43 participants who consented, 3 later declined to have any viral swabs taken, and of the resulting 160 (i.e. 40 × 4 swabbing time-points) possible swabs, 153 were successfully collected and stored for testing. Testing revealed 2 positive results: on Day 4, Participant 21 - coronavirus NL63 positive; on Day 7, Participant 74 - coronavirus OC43 positive.
Five symptomatic participants completed questionnaires: on Day 0, by Participants 40 and 47; on Day 2, by Participant 21 (linking to the Day 4 coronavirus NL63 positive result); on Day 7, by Participant 74 (linking to the Day 10 coronavirus OC43 POS); on Day 17, by Participant 107. The self-reported symptoms consisted of mainly fatigue and sore throat, with/without some degree of ‘stuffy nose and/or sinuses’.
The incubation period of human coronaviruses is around 2-5 days,
3
which can be used to link symptomatic cases together, epidemiologically,4
with viral shedding being reported for up to 6 days post-symptom onset.5
So the symptoms and positive NL63 and OC43 results for Participants 21 and 74, respectively, could have been acquired from Participants 40 and 47, who may have been the original index cases (sources) for these viruses. Although no respiratory virus was detected in their samples, Participants 40, 47 and 107 all reported similar symptoms to those of 21 and 74 during the study period, which were typical common cold symptoms.- Davis B.M.
- Foxman B.
- Monto A.S.
- Baric R.S.
- Martin E.T.
- Uzicanin A.
- et al.
Human coronaviruses and other respiratory infections in young adults on a university campus: prevalence, symptoms, and shedding.
Influenza Other Respir Viruses. 2018 Apr 16; ([Epub ahead of print])https://doi.org/10.1111/irv.12563
Note that the participants’ self-reported contact intensities were not entirely robust, e.g. both Participants 40 and 47 list Participant 21 as a contact, so could both have been index cases for him/her. However, 21 did not list either 40 or 47 as a contact (such contacts should be reciprocal). This may have just been a simple oversight, but it makes the contact link less reliable. Similarly, Participant 74 could have served as the index case for Participant 107, but neither lists the other as a contact. Regardless of the contact intensities reported in the questionnaires, there were no secondary cases of either NL63 or OC43 coronaviruses detected in any of the other study participants’ weekly swabs. One possible explanation for this may have been an insufficient sensitivity of the assay to detect low levels of these respiratory viruses.
The limit of detection (LOD) for the AusDiagnostics assay varies significantly with each virus (as given in the kit insert, all in copies/ml): influenza A (1900-2375), B (525), RSV (50-2125), PIV types 1-4 (50-2500), hMPV (100-625), entero-/rhino- (75-1025), corona- (229E, OC43, NL63, HKU1) (1350-4175) and adeno- (1075) viruses. However, in the acute infection stage respiratory viruses are generally present in relatively high copy numbers, with median values of mostly 4-8 log10 (i.e. 10,000-100,000,000 copies/ml) for adeno-, corona-, hMPV, influenza, PIV and RSV, as reported in one comprehensive paediatric study.
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Although children generally shed higher viral loads than adults, it is likely that the coronavirus loads in acutely infected adults would still be mostly detectable on this assay, which is approved (i.e. CE-marked) for routine diagnostic testing. Yet, it is still possible for viruses that are infecting individuals at the lowest loads within these ranges, to fail to be detected by this assay.Given the results that are currently available from this study, one of the key questions is: from where did the NL63 and OC43 coronaviruses arise? In addition, the lack of any secondary NL63 or OC43 coronaviruses cases (symptomatic or asymptomatic) arising from the known positive sources (Participants 21 and 74), suggests that the transmissibility of these common cold viruses may be limited. This seems unexpected, given the potential stress on the body immune system whilst living and working in such an extreme environment. However, such relatively poor transmission of respiratory viruses has been previously described in Antarctic base personnel for rhinovirus and adenovirus,
7
, 8
for reasons that are still unclear.Another potential confounding factor is the unknown status of the 5 individuals who were also present at the base (mostly base personnel) but who declined to participate in the study. It is possible that one or more of these non-participants could have been the original sources (i.e. index cases) of the NL63 and OC43 coronaviruses at the start of the study.
Whilst there are some limitations to this study, there are plans to repeat this on a larger scale, over a longer ‘closed’ period, with the use of real-time, point-of-care testing (POCT) to detect such respiratory viruses. Although previous respiratory virus outbreaks have been described in remote research bases,
7
, 8
these were unable to utilise the greater sensitivity and spectrum of respiratory viral targets provided by modern, molecular, diagnostic tools.9
, 10
Thus, some positive cases in these earlier studies may have been missed, leading to an underestimate of the transmissibility of these respiratory viruses in these populations.Respiratory infections in research personnel can impact significantly on their productivity, an important consideration when their time at such remote research bases is limited. This and future studies will enable medical teams to enhance the healthcare of research base personnel to optimise their precious research time spent there.
Conflicts of interest
None of the authors have any conflicts of interests to declare. We thank the following for their support of this study: UK Clinical Virology Network (CVN), for general funding support; Medical Wire & Equipment Ltd., for donating some of the sampling swabs; Ausdiagnostics UK Ltd., for donating the respiratory multiplex PCR tests. None of these companies were involved in the writing of this article.
Acknowledgments
We thank the following for their support of this study: UK Clinical Virology Network (CVN), for general funding support; Medical Wire & Equipment Ltd., for donating some of the sampling swabs; Ausdiagnostics UK Ltd., for donating the respiratory multiplex PCR tests.
References
- Case-ascertained study of household transmission of seasonal influenza - South Africa, 2013.J Infect. 2015; 71: 578-586
- Haemagglutinin and neuraminidase sequencing delineate nosocomial influenza outbreaks with accuracy equivalent to whole genome sequencing.J Infect. 2017; 74: 377-384
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- Human coronaviruses and other respiratory infections in young adults on a university campus: prevalence, symptoms, and shedding.Influenza Other Respir Viruses. 2018 Apr 16; ([Epub ahead of print])https://doi.org/10.1111/irv.12563
- Is higher viral load in the upper respiratory tract associated with severe pneumonia? Findings from the PERCH study.Clin Infect Dis. 2017; 64: S337-S346
- Rhinovirus infections in an isolated antarctic station. Transmission of the viruses and susceptibility of the population.Am J Epidemiol. 1989; 129: 319-340
- Adenovirus 21 infection in an isolated antarctic station: transmission of the virus and susceptibility of the population.Am J Epidemiol. 1991; 133: 599-607
- Impact of early detection of respiratory viruses by multiplex PCR assay on clinical outcomes in adult patients.J Clin Microbiol. 2016; 54: 2096-2103
- Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis.Clin Microbiol Infect. 2018; 24: 1055-1063
Article info
Publication history
Published online: March 13, 2019
Accepted:
March 12,
2019
Received in revised form:
March 6,
2019
Received:
February 25,
2019
Identification
Copyright
© 2019 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
