Higher SARS-CoV-2 detection of oropharyngeal compared with nasopharyngeal or saliva specimen for molecular testing: a multicentre randomised comparative accuracy study.

BACKGROUND: Testing is critical for detecting SARS-CoV-2 infection, but the best sampling method remains unclear. OBJECTIVES: To determine whether nasopharyngeal swab (NPS), oropharyngeal swab (OPS) or saliva specimen collection has the highest detection rate for SARS-CoV-2 molecular testing. METHODS: We conducted a randomised clinical trial at two COVID-19 outpatient test centres where NPS, OPS and saliva specimens were collected by healthcare workers in different orders for reverse transcriptase PCR testing. The SARS-CoV-2 detection rate was calculated as the number positive by a specific sampling method divided by the number in which any of the three sampling methods was positive. As secondary outcomes, test-related discomfort was measured with an 11-point numeric scale and cost-effectiveness was calculated. RESULTS: Among 23 102 adults completing the trial, 381 (1.65%) were SARS-CoV-2 positive. The SARS-CoV-2 detection rate was higher for OPSs, 78.7% (95% CI 74.3 to 82.7), compared with NPSs, 72.7% (95% CI 67.9 to 77.1) (p=0.049) and compared with saliva sampling, 61.9% (95% CI 56.9 to 66.8) (p<0.001). The discomfort score was highest for NPSs, at 5.76 (SD, 2.52), followed by OPSs, at 3.16 (SD 3.16) and saliva samples, at 1.03 (SD 18.8), p<0.001 between all measurements. Saliva specimens were associated with the lowest cost, and the incremental costs per detected SARS-CoV-2 infection for NPSs and OPSs were US$3258 and US$1832, respectively. CONCLUSIONS: OPSs were associated with higher SARS-CoV-2 detection and lower test-related discomfort than NPSs for SARS-CoV-2 testing. Saliva sampling had the lowest SARS-CoV-2 detection but was the least costly strategy for mass testing. TRIAL REGISTRATION NUMBER: NCT04715607.

Olfactory and Gustatory Outcomes Including Health-Related Quality of Life 3-6 and 12 Months after Severe-to-Critical COVID-19: A SECURe Prospective Cohort Study.

Background: Long-term follow-up studies of COVID-19 olfactory and gustatory disorders (OGDs) are scarce. OGD, parosmia, and dysgeusia affect health-related quality of life (HRQoL) and the ability to detect potential hazards. Methods: In this study, 29 patients reporting OGD 1 month after severe-to-critical COVID-19 were tested at 3-6 months and retested at 12 months in case of hyposmia/anosmia. We used Sniffin Sticks Threshold, Discrimination, and Identification (TDI) test, Sniffin Sticks Identification Test (SIT16), Brief Smell Identification Test (BSIT), taste strips, and HRQoL. The patients were part of the prospective SECURe cohort. Results: Overall, 28% OD (TDI), 12% GD, 24% parosmia, and 24% dysgeusia (questionnaire) at 3-6 months (n = 29) and 28% OD (TDI), 38% parosmia, and 25% dysgeusia (questionnaire) at 12 months (n = 8) were observed. OGD decreased HRQoL: For 13%, it had a negative effect on daily life and, for 17%, it affected nutrition, 17% reported decreased mood, and 87-90% felt unable to navigate everyday life using their sense of smell and taste. A comparison of SIT16 and BSIT to TDI found sensitivity/specificity values of 75%/100% and 88%/86%. Conclusions: This is the first study to examine TDI, SIT16, BSIT, taste strips, and HRQoL up to 1 year after severe-to-critical COVID-19. The patients suffering from prolonged OGD, parosmia, and dysgeusia experienced severely decreasing HRQoL. We recommend including ear-nose-throat specialists in multidisciplinary post-COVID clinics.

Optimal Insertion Depth for Nasal Mid-Turbinate and Nasopharyngeal Swabs.

Millions of people are tested for COVID-19 daily during the pandemic, and a lack of evidence to guide optimal nasal swab testing can increase the risk of false-negative test results. This study aimed to determine the optimal insertion depth for nasal mid-turbinate and nasopharyngeal swabs. The measurements were made with a flexible endoscope during the collection of clinical specimens with a nasopharyngeal swab at a public COVID-19 test center in Copenhagen, Denmark. Participants were volunteer adults undergoing a nasopharyngeal SARS-CoV-2 rapid antigen test. All 109 participants (100%) completed the endoscopic measurements; 52 (48%) women; 103 (94%) white; mean age 34.39 (SD, 13.2) years; and mean height 176.7 (SD, 9.29) cm. The mean swab length to the posterior nasopharyngeal wall was 9.40 (SD, 0.64) cm. The mean endoscopic distance to the anterior and posterior end of the inferior turbinate was 1.95 (SD, 0.61) cm and 6.39 (SD, 0.62) cm, respectively. The mean depth to nasal mid-turbinate was calculated as 4.17 (SD, 0.48) cm. The optimal depths of insertion for nasal mid-turbinate swabs are underestimated in current guidelines compared with our findings. This study provides clinical evidence to guide the performance of anatomically correct nasal and nasopharyngeal swab specimen collection for virus testing.

Accuracy of anterior nasal swab rapid antigen tests compared with RT-PCR for massive SARS-CoV-2 screening in low prevalence population.

The aim was to determine the accuracy of anterior nasal swab in rapid antigen (Ag) tests in a low SARS-CoV-2 prevalence and massive screened community. Individuals, aged 18 years or older, who self-booked an appointment for real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test in March 2021 at a public test center in Copenhagen, Denmark were included. An oropharyngeal swab was collected for RT-PCR testing, followed by a swab from the anterior parts of the nose examined by Ag test (SD Biosensor). Accuracy of the Ag test was calculated with RT-PCR as reference. We included 7074 paired conclusive tests (n = 3461, female: 50.7%). The median age was 48 years (IQR: 36-57 years). The prevalence was 0.9%, that is, 66 tests were positive on RT-PCR. Thirty-two had a paired positive Ag test. The sensitivity was 48.5% and the specificity was 100%. This study conducted in a low prevalence setting in a massive screening set-up showed that the Ag test had a sensitivity of 48.5% and a specificity of 100%, that is, no false positive tests. The lower sensitivity is a challenge especially if Ag testing is not repeated frequently allowing this scalable test to be a robust supplement to RT-PCR testing in an ambitious public SARS-CoV-2 screening.

Valid and Reliable Assessment of Upper Respiratory Tract Specimen Collection Skills during the COVID-19 Pandemic.

Proper specimen collection is the most important step to ensure accurate testing for the coronavirus disease 2019 (COVID-19) and other infectious diseases. Assessment of healthcare workers' upper respiratory tract specimen collection skills is needed to ensure samples of high-quality clinical specimens for COVID-19 testing. This study explored the validity evidence for a theoretical MCQ-test and checklists developed for nasopharyngeal (NPS) and oropharyngeal (OPS) specimen collection skills assessment. We found good inter-item reliability (Cronbach's alpha = 0.76) for the items of the MCQ-test and high inter-rater reliability using the checklist for the assessment of OPS and NPS skills on 0.86 and 0.87, respectively. The MCQ scores were significantly different between experts (mean 98%) and novices (mean 66%), p < 0.001, and a pass/fail score of 91% was established. We found a significant discrimination between checklist scores of experts (mean 95% score for OPS and 89% for NPS) and novices (mean 50% score for OPS and 36% for NPS), p < 0.001, and a pass/fail score was established of 76% for OPS and 61% for NPS. Further, the results also demonstrated that a group of non-healthcare educated workers can perform upper respiratory tract specimen collection comparably to experts after a short and focused simulation-based training session. This study, therefore, provides validity evidence for the use of a theoretical and practical test for upper respiratory specimens' collection skills that can be used for competency-based training of the workers in the COVID-19 test centers.

Stress reactions in a tertiary oto-rhino-laryngological department during the first wave of the COVID-19 pandemic in the Danish Capital region.

BACKGROUND: Health care workers (HCW) at otorhinolaryngological departments have an increased risk of contracting COVID-19, due to aerosol-inducing diagnostic and surgical procedures in the airways. The ongoing exposure to physical and psychological stressors could impact the mental health of HCW. AIM/OBJECTIVE: To investigate the impact on mental health in an otorhinolaryngological department during the COVID-19 pandemic. MATERIALS/METHOD: Cross-sectional questionnaire study, assessing symptoms of depression (PHQ-9) and anxiety (GAD-10). Physicians, nurses, and secretaries were included at a tertiary department of otorhinolaryngology in the Capital Region of Denmark during the COVID-19 lockdown in spring 2020. RESULTS: Positive screenings for stress reactions were found in 22% for depressive symptoms and 15.5% anxiety. 27% feared becoming infected, 47% feared infecting their families in relation to work. 27% felt others were distancing from them, and 38% isolated themselves from others because of their work. Women had an odds ratio of 9.18 (CI 1.49-179) for depressive stress reactions. CONCLUSION: HCW were primarily concerned with transmitting COVID-19 to their relatives. Secondarily, there was a concern about becoming infected despite feeling adequately protected by personal protective equipment. Women were at higher risk of more severe depressive symptoms when corrected for professions.

Danish citizens' preferences for at-home oropharyngeal/nasal SARS-CoV-2 specimen collection.

INTRODUCTION: Diagnostic confirmation of SARS-CoV-2 by self-collection of specimens is a reliable method compared with healthcare worker collected samples. Citizens' preferences for collection methods are unknown, but at-home collection could have several advantages. METHODS: This study investigated the preference for guided at-home self-collection versus at-hospital specimen collection by healthcare workers. RESULTS: Among the 3709 participants, at-home swab collection was the preferred setting for 2362 (63.7%) compared with 1347 (36.3%) reporting a preference for an at-hospital swabbing procedure. CONCLUSION: A high preference for guided at-home self-collection of oropharyngeal/nasal SARS-CoV-2 specimens exists and could be a future norm beyond COVID-19.

COVID-19 infection rate among tertiary referral center otorhinolaryngology healthcare workers.

IMPORTANCE: Otorhinolaryngology is considered one of the medical specialties with a high risk for exposure to corona disease 2019 (COVID-19). Uncontrolled transmission in a hospital department poses a risk to both healthcare workers (HCWs) and patients. OBJECTIVE: To monitor SARS-CoV-2 incidence, transmission, and antibody development among HCWs to identify high risk procedures, pathways, and work areas within the department. METHODS: Prospective cohort study of HCWs using repetitive oro- and nasopharygeal swab samples, antibody tests, and self-reported symptoms questionnaires at a tertiary referral center in Copenhagen, Denmark. RESULTS: 347/361 (96%) HCWs participated. Seven (1.9%) were positive on swab tests and none had symptoms. Fifteen (4.2%) developed antibodies. Only one case of potential transmission between HCWs was identified. Infection rates were low and no procedures or areas within the department were identified as exposing HCWs to a higher risk. CONCLUSIONS AND RELEVANCE: Adherence to the surveillance program was high. The low incidence among HCW during the first wave of the COVID-19 pandemic may reflect local transmission and infection control precautions, as well as a low infectious burden in the Danish society.

The impact and prevalence of SARS-CoV-2 in patients with head and neck cancer and acute upper airway infection in a tertiary otorhinolaryngology referral center in Denmark.

PURPOSE: To determine the prevalence of SARS-CoV-2 at a Danish tertiary referral otorhinolaryngology clinic during the first wave of the COVID-19 pandemic among patients with suspected acute upper airway infection (UAI) and patients operated for head and neck cancer (HNC), respectively. To monitor changes in the number of patient encounters for acute UAI and the number of referrals for the workup of HNC. TRIAL REGISTRATION: NCT-04356560 (Clinicaltrials.gov). METHODS: Prospective enrolled case series of all patients with suspected acute UAI (n = 88) and of patients undergoing surgery for HNC (n = 96), respectively, from March 23rd to May 5th, 2020, at a public tertiary referral otorhinolaryngology clinic in Denmark. SARS-CoV-2 was diagnosed with nasopharyngeal and oropharyngeal swabbing. Patients with suspected acute UAI had symptoms and definitive diagnoses registered in a database. Trends in the number of referrals and patient encounters were retrieved from an electronic patient journal system and analyzed retrospectively. RESULTS: Eighty-eight patients with acute UAI were enrolled including 55 men and 34 women, median age of 31 years (range: 10 months to 82 years). One patient (1.1%) tested positive. Among 96 patients operated for HNC, zero tested positive. The number of referrals for HNC workup, and patient encounters for peritonsillar abscesses, decreased markedly in the first 3 weeks. CONCLUSION: The prevalence of SARS-CoV-2 during the first 6 weeks of the first wave was minimal among patients with acute UAI and zero among patients operated for HNC. The decrease in referrals for the workup of HNC may increase time to treatment initiation and patient morbidity.

Face masks for the prevention of COVID-19 - Rationale and design of the randomised controlled trial DANMASK-19.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), progresses globally, and means to reduce the transmission are needed. In the community, the use of face masks is increasing world-wide, but documentation for the efficacy of this remedy is lacking. This trial investigates whether the use of face masks in the community will reduce wearers' risk of SARS-CoV-2 infection. METHODS: This study will be a two-arm, unblinded, randomised controlled trial. We will include adults (>18 years of age) without prior confirmed COVID-19 or symptoms suggestive of COVID-19, who spend more than three hours per day outside the home with exposure to other people. A total of 6,000 participants are randomly assigned 1:1 to use face masks or not for a 30-day period during the pandemic. Participants will perform self-testing; quick test for SARS-CoV-2 antibodies (immunoglobulin M (IgM) and immunoglobulin G (IgG)) (the Livzon lateral flow test) and oropharyngeal/nasal swabs for viral detection using polymerase chain reaction (PCR). The primary endpoint following the 30-day study period is the difference in the number of SARS-CoV-2-infected individuals between the two study groups as assessed by a positive nasopharyngeal swap, a positive antibody test or a hospital-based diagnosis of SARS-CoV-2 infection. CONCLUSIONS: We will study whether a face mask protects the wearer of the mask against SARS-CoV-2 infection. The findings are expected to apply to the present pandemic and to future viral outbreaks and to provide evidence for authority recommendations across the world. FUNDING: This study was funded by Salling Fondene. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04337541.

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541). SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use. MEASUREMENTS: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses. RESULTS: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection. LIMITATION: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others. CONCLUSION: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection. PRIMARY FUNDING SOURCE: The Salling Foundations.

Self-Collected versus Healthcare Worker-Collected Swabs in the Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2.

The aim of this study was to compare the sensitivity of self-collected versus healthcare worker (HCW)-collected swabs for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. Symptomatic individuals referred for SARS-CoV-2 testing were invited to provide mobile-phone video-instructed self-collected oropharyngeal and nasal samples followed by a HCW-collected oropharyngeal sample. All samples were sent for analysis to the same microbiology laboratory, and the number of SARS-CoV-2-positive participants in the two tests was compared. A total of 109 participants were included, and 19 participants had SARS-CoV-2-positive results. The diagnostic sensitivity of the self-collected and HCW-collected swabs was 84.2% and 89.5%, respectively, with an acceptable agreement, Cohens kappa 0.82, p < 0.001. Further, results from a questionnaire answered by the participants found that loss of smell as a self-reported symptom was a strong predictor for a SARS-CoV-2-positive test. In conclusion, we found that self-collected oropharyngeal and nasal swabs for SARS-CoV-2 testing can be reliable compared to HCW-collected oropharyngeal samples.

Face masks for the prevention of COVID-19 - Rationale and design of the randomised controlled trial DANMASK-19

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), progresses globally, and means to reduce the transmission are needed. In the community, the use of face masks is increasing world-wide, but documentation for the efficacy of this remedy is lacking. This trial investigates whether the use of face masks in the community will reduce wearers' risk of SARS-CoV-2 infection. METHODS: This study will be a two-arm, unblinded, randomised controlled trial. We will include adults (>18 years of age) without prior confirmed COVID-19 or symptoms suggestive of COVID-19, who spend more than three hours per day outside the home with exposure to other people. A total of 6,000 participants are randomly assigned 1:1 to use face masks or not for a 30-day period during the pandemic. Participants will perform self-testing;quick test for SARS-CoV-2 antibodies (immunoglobulin M (IgM) and immunoglobulin G (IgG)) (the Livzon lateral flow test) and oropharyngeal/nasal swabs for viral detection using polymerase chain reaction (PCR). The primary endpoint following the 30-day study period is the difference in the number of SARS-CoV-2-infected individuals between the two study groups as assessed by a positive nasopharyngeal swap, a positive antibody test or a hospital-based diagnosis of SARS-CoV-2 infection. CONCLUSIONS: We will study whether a face mask protects the wearer of the mask against SARS-CoV-2 infection. The findings are expected to apply to the present pandemic and to future viral outbreaks and to provide evidence for authority recommendations across the world. FUNDING: This study was funded by Salling Fondene. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04337541.