key: cord-345603-mirsz6m8
authors: Wehrhahn, Michael C.; Robson, Jennifer; Brown, Suzanne; Bursle, Evan; Byrne, Shane; New, David; Chong, Smathi; Newcombe, James P.; Siversten, Terri; Hadlow, Narelle
title: Self-collection: an appropriate alternative during the SARS-CoV-2 pandemic
date: 2020-05-04
journal: J Clin Virol
DOI: 10.1016/j.jcv.2020.104417
sha: 
doc_id: 345603
cord_uid: mirsz6m8

OBJECTIVES: To evaluate the reliability of self-collection for SARS-CoV-2 and other respiratory viruses because swab collections for SARS-CoV-2 put health workers at risk of infection and require use of personal protective equipment (PPE). METHODS: In a prospective study, patients from two states in Australia attending dedicated COVID-19 collection clinics were offered the option to first self-collect (SC) throat and nasal swabs (SCNT) prior to health worker collect (HC) using throat and nasal swabs (Site 1) or throat and nasopharyngeal swabs (Site 2). Samples were analysed for SARS-CoV-2 as well as common respiratory viruses. Concordance of results between methods was assessed using Cohen's kappa (κ) and Cycle threshold (Ct) values were recorded for all positive results as a surrogate measure for viral load. RESULTS: Of 236 patients sampled by HC and SC, 25 had SARS-CoV-2 (24 by HC and 25 by SC) and 63 had other respiratory viruses (56 by HC and 58 y SC). SC was highly concordant with HC (κ = 0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (κ = 0.959 vs 0.933). Mean SARS-CoV-2 E-gene and N-gene, rhinovirus and parainfluenza Ct values did not differ between HC and SCNT. CONCLUSIONS: Self-collection of throat and nasal swabs offers a reliable alternative to health worker collection for the diagnosis of SARS-CoV-2 and other respiratory viruses and provides patients with easier access to testing, reduces exposure of the community and health workers to those being tested and reduces requirement for PPE.

On the 11 th March 2020, the World Health Organisation (WHO) announced COVID-19 as a pandemic. 1 The WHO Director-General issued a call for urgent action and encouraged all countries to 'innovate and learn' in their response to this crisis.

Self-collected swabs in the community for SARS-CoV-2, the agent of COVID-19, and for other respiratory viruses offers potential significant benefit in the current pandemic by J o u r n a l P r e -p r o o f reducing requirement for PPE, limiting exposure of patients and staff to infection, increased convenience and access for patients and timeliness of a sample receipt. 2, 3 Patients report selfcollected nasal swabs are easy to perform 2,4,5 and highly acceptable. 2, 4 A meta-analysis of 9 studies comparing self-collect (SC) and health care worker collect (HC) for influenza testing reported a pooled sensitivity of 87% and specificity of 99% for SC compared to HC. 6 Irving et al studied paired samples from 240 adults and found sensitivity using nasal or nasopharyngeal (NP) collection for influenza did not vary significantly when using a highly sensitive molecular test. 7 A study in 230 children reported equivalent sensitivity for all respiratory viruses except respiratory syncytial virus (RSV) when comparing nasal swab and NP aspirate. 8 Larios et al demonstrated that using flocked swabs and sensitive molecular methods, equivalent sensitivity and specificity was obtained for matched self-collected midturbinate nasal swabs and NP swabs in 38 individuals for a range of respiratory viruses including human coronaviruses. 9 Recent reports on SARS-CoV-2 in respiratory specimens indicate early high viral loads in symptomatic and asymptomatic patients in a variety of clinical specimens including nasal and throat swabs, sputum and saliva samples. [10] [11] [12] [13] [14] Wang et al reported that in 205 patients with COVID-19 the highest positive rates were found from bronchoalveolar lavage fluid, sputum and nasal swabs respectively. 15 Wolfel 14 and colleagues reported that in hospitalized cases of COVID-19 there was no discernible difference between NP and throat swabs with high viral load present in both specimens early in the illness and suggested that simple throat swabs may provide sufficient sensitivity when patients are first tested with mild symptoms of COVID-19.

The aim of this study was to compare prospectively the performance of HC with separate SC nasal (SCN) and throat swabs (SCT) and the combination of the two (SCNT) for respiratory viruses including SARS-CoV-2.

This study was conducted across two laboratory sites (Site 1 and Site 2) and had ethics approval with all participants providing informed consent. For a period of one week in March 2020, patients presenting for SARS-CoV-2 testing at dedicated COVID-19 collection rooms were offered participation in the study. Demographic data was recorded including the address postcode to assess the Index of Education and Occupation (IEO) which assesses education level based on a scale of 1 to 5 with 5 being the highest level of education. 16 

A positive result on either HC or SC was defined as the benchmark result All Positives (AP).

Concordance between HC and SC swabs and AP was calculated using Cohen's Kappa (κ), which measures agreement between the categorical assignments given by two methods. The statistic takes values typically between zero and one. A κ >0·80 indicates very good agreement, while κ=1 indicates perfect concordance. Cycle threshold (Ct) values were recorded for all positive test results as a surrogate measure for viral load. Mean Ct was compared between HC and SCNT (combined category using the lowest Ct of either SCN or SCT), using linear mixed effects models, with a random effect for patient identification. HC and SC SARS-CoV-2 positivity rates were compared with Pearson's χ 2 test.

From power calculations assuming a significance level of 5% and a null hypothesis of low concordance between the HC and SC methods (H 0 : κ=0·3), there was at least 80% power to detect a concordance of 0·6 or more with a sample size of 66. Significance level α was set at 0·05, however for concordance and regression analyses, a Bonferroni multiple testing correction was applied such that minimum α'=0·05/8=0·0063. Statistical analyses were completed in the R statistical computing environment, 19 including the package irr. Table 1) . A positive result on either HC or SCNT was included in the group AP. Table 2 When all detections by HC and SCNT were compared with AP, the sensitivity of SCNT and HC to detect SARS-CoV-2 was 1·0 (95%CI: 0·86-1) and 0.96 (95%CI: 0·8-1) respectively; for other respiratory viruses it was 0·94 (95%CI: 0·87-0·98) and 0.91 (95%CI: 0·83-0·96) respectively.

J o u r n a l P r e -p r o o f Table 3 summarises concordance between AP and each collection method. Both SCNT and HC showed very high concordance with AP at each site and overall, with SCNT slightly higher (κ=1, 0·934, 0·959 at Site1, Site2, Combined Sites) than HC (κ=0·929, 0·934, 0·933).

Additionally, SCNT was highly concordant with HC (κ=0·929, 0·863, 0·890 at Site 1, Site 2, Combined Sites). When Ct values for COVID-19 cases were compared by collection method (Figure 1) , mean E-gene Ct did not differ between HC and SCNT or SCN (p=0·236, 0·083, against α'=0·0083) but was significantly higher in SCT compared with HC (β=7·31, p<0·001). Mean N-gene Ct did not differ between HC and SCNT (p=0·041; α'=0·0083) but was higher in SCN and SCT (β=4·00, p=0·006; β=7·63, p<0·001). In rhinovirus cases ( Figure 2 ), mean Ct was not significantly higher in SCNT compared with HC (p=0·036; α'=0·.017) but was higher in SCN and SCT (β=2·50, p=0·002; β=6·68, p<0·001). In parainfluenza cases, mean Ct differed between HC and SCN (β=4·67, p=0·014) but not the other methods (SCNT v HC, p=0·231; SCT v HC, p=0·119; α'=0·017).

At Site 1 an analysis of acceptability was performed using a questionnaire and was completed by 42/70 (60%) participants with 31/42 (74%) preferring self-collection over trained collectors, with all considering it acceptable. Analysis of the IEO found that the Median (LQ, UQ) IEO was 3 (2, 4) with participants identified across all educational levels but the majority (30/42, 71%) were in the 3 lowest education levels and a smaller proportion (12/42, 29%) in the highest 2 levels.

Following this study, Site 1 has since processed a small percentage of SC swabs (7% of all collections). There was no significant difference in the SARS-CoV-2 detections between HC with 242/13851 (1·8%) and SC with 20/1035 (1·9%) (p=0·753 from χ 2 test).

In our group of 236 ambulatory, literate, mostly adult patients, the performance of selfcollected nasal and throat swabs was at least equivalent to that of health care worker collected swabs for the detection of SARS-CoV-2 and other respiratory viruses.

This study included two different sites using two different methods of HC (combined N + T and combined NP + T) and also employed two different molecular strategies for detection of SARS-CoV-2. As such these findings are more widely applicable.

At Site 1 where SCNT was compared with HC using the same swab and collection methods, When data from each site was combined, concordance between SCNT or HC with the All Positive rate was very high, slightly favouring SCNT. The similar SARS-CoV-2 percentpositivity rate in ongoing comparison data between those having only HC or SC provides further reassurance that SCNT is equivalent to HC.

The advantages of self-collection are even more important at a time of global health crisis.

Self-collection greatly reduces the number of patients requiring trained health workers and the necessary PPE to protect them. Access to testing is increased, as swab kits can be J o u r n a l P r e -p r o o f provided quickly by clinicians or available at dedicated COVID-19 collection centres aiding timeliness of testing 3 which is critical in the current pandemic. 2,3 Safety for both patients and staff using a SC model is also increased as exposure to others is limited.

Further, data from patients at site 1 suggests that SC is accessible and achievable over a range of education levels with all finding SC acceptable and the majority having a preference for this method over HC as has previously been reported. 2, 4, 5 This may relate to the ability of patients to control the comfort level of throat and nasal collection better than a trained collector can.

Recent studies suggest there is a high viral load in patients with early COVID-19 across the upper and lower respiratory tracts, including nasal and throat sites [10] [11] [12] 14 as well as in saliva, 13 even in asymptomatic, mild or prodromal states. Wolfel et al noted no discernible difference between nasopharyngeal and oropharyngeal viral loads in hospitalized cases of COVID-19. 14 Given these high viral loads throughout the respiratory tract it may be that requiring NP sampling is not as significant for SARS-CoV-2 as for some other respiratory viruses. It may also be that PCR methods for viral detection are improving the sensitivity of a range of sample and collection methods as shown for a range of respiratory viruses but also Group A Streptococcal detection. 9, 10 We hypothesize that the high viral load of SARS-CoV-2 and sensitive molecular techniques may explain the equivalent sensitivity of SC to HC samples in COVID-19 patients.

Our data support the decision by the Communicable Disease Network of Australia (CDNA) 21 to recommend sampling of both nasal and throat sites for the diagnosis of respiratory viruses including for SARS-CoV-2, due to the concern of a possible missed diagnosis if only one site is sampled. This was the case for two COVID-19 positive patients on SC who were only diagnosed by SCN and another only by SCT. If only one swab site was obtainable, our data Further data on self-collection would be helpful to confirm these findings.

The world is facing unprecedented demands on health care services during the COVID-19 pandemic. Innovative ways to address this crisis are required and we believe that this study provides early evidence that self-collection of throat and nasal swabs for SARS-CoV-2 offers an acceptable and reliable alternative to health care worker collected samples. This is achieved whilst preserving critically needed PPE supplies, optimizing the time to testing and reducing exposure of health care workers to potentially infected patients.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 

WHO Director-General's opening remarks at the media briefing on COVID-19 -11

The acceptability and validity of self-collected nasal swabs for detection of influenza virus infection among older adults in Thailand

Self-Collected Nasal Swabs for Respiratory Virus Surveillance

Equivalence of self-and staff-collected nasal swabs for the detection of viral respiratory pathogens

Effectiveness of patient-collected swabs for influenza testing

Self-collected compared with professionalcollected swabbing in the diagnosis of influenza in symptomatic individuals: A meta-analysis and assessment of validity

Comparison of nasal and nasopharyngeal swabs for influenza detection in adults

Nasal swab versus nasopharyngeal aspirate for isolation of respiratory viruses

Self-collected mid-turbinate swabs for the detection of respiratory viruses in adults with acute respiratory illnesses

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

Viral load of SARS-CoV-2 in clinical samples

Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in

Consistent detection of 2019 novel coronavirus in saliva

Virological assessment of hospitalized patients with COVID-2019

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

Census of Population and Housing: Socio-Economic Indexes for Areas (SEIFA) Australia

2019-Novel Coronavirus (2019-nCoV) Real-time rRT-PCR Panel Primers and Probes

Equal performance of self-collected and health care worker-collected pharyngeal swabs for group a streptococcus testing by PCR

Public Health Laboratory Network (PHLN) guidance on laboratory testing for SARS-CoV-2 (the virus that causes COVID-19)

We thank the patients who participated in this study, the Training and Patient Services departments, the Collection and Clinical Area Managers, Clinical Supervisors, Collection staff, and Molecular Laboratory staff without whom this study would not have been possible.
