Diagnostic accuracy of SARS-CoV-2 rapid antigen self-tests in asymptomatic individuals in the Omicron period: cross sectional study (preprint)

Objectives To assess the performances of three commonly used rapid antigen diagnostic tests (Ag-RDTs) used as self-tests in asymptomatic individuals in the Omicron period. Design Cross-sectional diagnostic test accuracy study. Setting Three public health service COVID-19 test sites in the Netherlands. Participants 3,600 asymptomatic individuals aged ≥16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Interventions Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex (Flowflex), MP Biomedicals (MPBio), or Siemens-Healthineers Clinitest (Clinitest)) to perform unsupervised at home within three hours and blinded to the RT-PCR result. Main Outcome(s) and Measures(s) Diagnostic accuracies (sensitivity, specificity, positive and negative predictive values) of each self-test compared to RT-PCR. Results Overall sensitivities of the three self-tests were 27.5% (95% CI: 21.3-34.3%) for Flowflex, 20.9% (13.9-29.4%) for MPBio, and 25.6% (19.1-33.1%) for Clinitest. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (95% CI: 37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively. No consistent differences were found in sensitivities by COVID-19 vaccination status, having had a prior SARS-CoV-2 infection, gender or age across the three self-tests. Specificities were >99% for all tests in most analyses. Conclusions The sensitivities of three commonly used SARS-CoV-2 Ag-RDTs when used as self-tests in asymptomatic individuals in the Omicron period, were very low. Our findings indicate that Ag-RDT self-testing in asymptomatic individuals may only detect the minority of infections at that point in time and may not be sufficient to prevent the spreading of the virus to other (vulnerable) persons. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield of the self-tests, and individuals should certainly be advised to re-test when symptoms develop. Summary box What is already known on this topic If sufficiently reliable, SARS-CoV-2 self-testing by asymptomatic persons prior to admission in places where groups gather could have a huge public health impact by lowering the reproduction number or keep it below one for longer periods. Current evidence suggests that SARS-CoV-2 rapid antigen diagnostic tests (Ag-RDTs) when used as self-tests by asymptomatic individuals perform suboptimal, but sample sizes of the previous studies were too small to draw robust conclusions, and also empirical data on the accuracy of Ag-RDT self-tests in asymptomatic individuals during the Omicron period are scarce. What this study adds Compared to RT-PCR testing, overall sensitivities of three commercially available SARS-CoV-2 Ag-RDTs when used as self-tests by asymptomatic individuals (primary analysis population of non-confirmatory testers; n= 3600, 87% of full analysis population) in the Omicron period, were very low: 27.5% (95% CI: 21.3-34.3%) for the Acon Flowflex test, 20.9% (13.9-29.4%) for the MP Biomedicals test, and 25.6% (19.1-33.1%) for the Siemens Healthineers Clinitest Ag-RDT, which increased to 48.3% (95% CI: 37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively, when applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL). Our findings indicate that Ag-RDT self-testing in asymptomatic individuals may only detect the minority of infections at that point in time and may not be sufficient to prevent the spreading of the virus to other (vulnerable) persons. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield of the self-tests, and individuals should certainly be advised to re-test when symptoms develop.

Accuracy of COVID-19 self-tests with unsupervised nasal or nasal plus oropharyngeal self-sampling in symptomatic individuals in the Omicron period (preprint)

BackgroundPerformances of rapid antigen diagnostic tests (Ag-RDTs) with nasal self-sampling, and oropharyngeal plus nasal (OP-N) self-sampling, in the Omicron period are unknown. MethodsProspective diagnostic accuracy study among 6,497 symptomatic individuals aged >16 years presenting for SARS-CoV-2 testing at three test-sites. Participants were sampled for RT-PCR (reference test) and received one Ag-RDT to perform unsupervised with either nasal self-sampling (during the emergence of Omicron, and after Omicron share was >90%, phase-1) or with OP-N self-sampling (in a subsequent phase-2; Omicron share >99%). The evaluated tests were Acon Flowflex (Flowflex; phase-1 only), MP Biomedicals (MPBio), and Siemens-Healthineers Clinitest (Clinitest). FindingsDuring phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for Flowflex, 69.9% (65.1-74.4%) for MPBio, and 70.2% (65.6-74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points, respectively, when transitioning from 29% to >95% Omicron. During phase-2, 53% of MPBio, and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. Comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively). InterpretatioSensitivities of three Ag-RDTs with nasal self-sampling decreased during Omicron emergence but was only statistically significant for Clinitest. Sensitivities were substantially influenced by the proportion of confirmatory testers. Addition of oropharyngeal to nasal self-sampling improved sensitivities of MPBio and Clinitest. FundingDutch Ministry of Health, Welfare, and Sport. Research into contextO_ST_ABSEvidence before this studyC_ST_ABSSARS-CoV-2 rapid antigen diagnostic tests (Ag-RDTs) require no or minimal equipment, provide a result within 15-30 minutes, and can be used in a range of settings including for self-testing at home. Self-testing may potentially lower the threshold to testing and allows individuals to obtain a test result quickly and at their own convenience, which could support the early detection of infectious cases and reduce community transmission. Real world evidence on the performance of unsupervised nasal and oropharyngeal plus nasal (OP-N) self-sampling in the Omicron variant period is needed to accurately inform end-users and policymakers. Therefore, we conducted a large prospective diagnostic accuracy study of three commercially available Ag-RDTs with self-sampling (the Acon Flowflex test, the MP Biomedicals test, and the Siemens-Healthineers Clinitest) during and after the emergence of Omicron using RT-PCR as the reference standard. Our aims were to evaluate whether the accuracies of Ag-RDTs with nasal self-sampling changed over time with the emergence of Omicron; and to determine whether addition of oropharyngeal to nasal self-sampling with the same swab yielded higher diagnostic accuracies. What this study addsThe large comprehensive study was conducted in almost 6,500 participants with symptoms when presenting for routine SARS-CoV-2 testing at three public health service COVID-19 test-sites in the Netherlands. During the study, conducted between 21 December 2021 and 10 February 2022, the percentage of the Omicron variant in samples from the national SARS-CoV-2 pathogen surveillance increased from 29% in the first week to 99% in the last week of the study. The period during which the Omicron variant was dominant was divided into a nasal sampling phase (phase-1; Omicron present in >90% of surveillance samples) and an OP-N sampling phase (phase-2; Omicron share was >99%). In phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants visited the test-site because of a positive self-test (confirmatory testers). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for the Flowflex, 69.9% (65.1-74.4%) for the MPBio, and 70.2% (65.6-74.5%) for the Clinitest Ag-RDT. Sensitivities were 94%, 84%, and 86%, respectively, for confirmatory testers, and 52%, 52%, and 50%, respectively, for those who had other reasons for getting tested. Sensitivities were 87.0% (79.7-92.4%), 83.1% (72.9-90.7%), and 80.0% (51.9-95.7%), respectively, in the first week, and decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points in the final week of the study. In Phase-2, 53% of MPBio and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. When comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%). Implications of all the available evidenceThe sensitivities of three commercially available Ag-RDTs performed with nasal self-sampling decreased during the emergence of Omicron, but this trend was only statistically significant for Clinitest. Addition of oropharyngeal to nasal self-sampling improved the sensitivity of the MPBio and Clinitest, most notably in individuals who visited the test-site for other reasons than to confirm a positive self-test. Based on these findings, the manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal sampling, and other manufacturers may consider evaluating this as well.

Performance of Various Lateral Flow SARS-CoV-2 Antigen Self Testing Methods in Healthcare Workers: a Multicenter Study. (preprint)

Introduction: Rapid antigen detection tests (RDT) are suitable for large-scale testing for SARS-CoV-2 among the population and recent studies have shown that self-testing with RDT in the general population is feasible and yields acceptable sensitivities with high specificity. We aimed to determine the accuracy of two different RDT, with two different sample collection methods for one of the RDT among healthcare workers (HCW). Secondary objectives were to determine the accuracy of RDT using a viral load cut-off as proxy of infectiousness and to identify predictors for a false negative RDT. Methods: Centers that participated were secondary care hospitals, academic teaching hospitals, and long-term care facilities. All HCW that met inclusion criteria were asked to perform a RDT self-test next to a regular SARS-CoV-2 nucleic acid amplification test (NAAT). Three study groups were created. Study group 1; Veritor System, Becton Dickinson, Franklin Lakes, USA (BD-RDT) with combined oropharyngeal - mid-turbinate nasal sampling, group 2; BD-RDT with mid-turbinate nasal sampling only and group 3; SD Biosensor SARS-CoV-2 Rapid Antigen Test, Roche, Basel, Switzerland (Roche-RDT) with combined oropharyngeal - mid-turbinate nasal sampling. RDT accuracy was calculated using NAAT as reference standard. For samples processed in the cobas(R) 6800/8800 platform (Roche Diagnostics, Basel, Switzerland), established cycle threshold values (Ct-values) could be converted into viral loads. A viral load cut-off of [≥]5.2 log10 SARS-CoV-2 E gene copies/ml was used as proxy of infectiousness. Logistic regression analysis was performed to identify predictors for a false negative RDT. Results: In total, 7,196 HCW were included. Calculated sensitivities were 61.5% (95%CI 56.6%-66.3%), 50.3% (95%CI 42.8%-57.7%) and 74.2% (95%CI 66.4%-80.9%) for study groups 1, 2 and 3, respectively. After application of a viral load cut-off as a proxy for infectiousness for samples processed in the cobas(R) 6800/8800 platform sensitivities increased to 82.2% (95%CI 76.6-86.9%), 61.9% (95%CI 48.8%-73.9%) and 90.2% (95%CI 76.9%-97.3%) for group 1, group 2 and group 3, respectively. Multivariable regression analysis showed that use of Roche-RDT (p <0.01), combined oropharyngeal - mid-turbinate nasal sampling (p <0.05) and the presence of COVID-19 like symptoms at the time of testing (p <0.01) significantly reduced the likeliness of a false-negative RDT result. Conclusion: SARS-CoV-2 RDT has proven able to identify infectious individuals, especially when upper respiratory specimen is collected through combined oropharyngeal - mid-turbinate sampling. Reliability of self-testing with RDT among HCW seems to depend on the type of RDT, the sampling method and the presence of COVID-19 like symptoms at the time of testing.

Accuracy and usability of saliva and nasal rapid antigen self-testing for detection of SARS-CoV-2 infection in the general population: a head-to-head comparison (preprint)

BackgroundSARS-CoV-2 self-tests may lower the threshold of testing and produce a result quickly. This could support the early detection of infectious cases and reduce further community transmission. However, the diagnostic accuracy of (unsupervised) self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We therefore conducted a large-scale head-to-head comparison of the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT, each compared to a molecular reference test, in the general population in the Netherlands. MethodsIn this cross-sectional study we consecutively included individuals aged 16 years and older presenting for SARS-CoV-2 testing at three Dutch public health service test sites irrespective of their indication for testing, vaccination status, and symptomatology. Participants were sampled for molecular testing at the test site and received two self-tests (the Hangzhou AllTest saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform at home within a few hours without knowledge of their molecular test result. Information on presence and type of symptoms, user experiences, and results of both self-tests were collected via an online questionnaire. For each self-test, sensitivity, specificity, positive and negative predictive values were determined with molecular testing as reference standard. FindingsThe SARS-CoV-2 molecular reference test positivity rate was 6.5% in the 2,819 participants. Overall sensitivities with 95% confidence intervals were 46.7% (85/182; 39.3%-54.2%) for the saliva Ag-RDT, and 68.9% (124/180; 61.6%-75.6%) for the nasal Ag-RDT. With a viral load cut-off ([≥]5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, sensitivities increased to 54.9% (78/142; 46.4%-63.3%) for the saliva Ag-RDT and 83.9% (120/143; 76.9%-89.5%) for the nasal Ag-RDT. For the nasal Ag-RDT, sensitivities were 78.5% [71.1%-84.8%] and 22.6% [9.6%-41.1%] in those with and without symptoms at the time of sampling, which increased to 90.4% (113/125; 83.8%-94.9%) and 38.9% (7/18; 17.3%-64.3%) after applying the viral load cut-off. In those with and without prior confirmed SARS-CoV-2, sensitivities were 36.8% [19/372; 16.3%-61.6%] and 72.7% [161/2437; 65.1%-79.4%] for the nasal Ag-RDT, which increased to 100% (7/7; 59.0%-100%) and 83.1% (113/126; 75.7%-89.0%) after applying the viral load cut-off. The diagnostic accuracy of the nasal Ag-RDT did not differ by COVID-19 vaccination status, sex, and age. Specificities were >99%, positive predictive values >70% and negative predictive values >95%, for the saliva Ag-RDT, and >99%, >90%, and >95% for the nasal Ag-RDT, respectively, in most analyses. Interpreting the results was considered (very) easy for both self-tests. InterpretationThe Hangzhou AllTest self-performed saliva Ag-RDT is not reliable for SARS-CoV-2 infection detection overall nor in the studied subgroups. The SD Biosensor self-performed nasal Ag-RDT had high sensitivity in individuals with symptoms and in those without a prior SARS-CoV-2 infection. The overall accuracy in individuals with symptoms was comparable to that found in previous studies with professional sampling for this Ag-RDT. The extremely low sensitivity of the nasal Ag-RDT in asymptomatic individuals and in individuals who had had a prior SARS-CoV-2 infection is an important finding and warrants further investigation. FundingDutch Ministry of Health, Welfare, and Sport.

Diagnostic accuracy of three prevailing rapid antigen tests for detection of SARS-CoV-2 infection in the general population: cross sectional study (preprint)

Objective To assess the diagnostic accuracy of three rapid antigen tests (Ag-RDTs) for detecting SARS-CoV-2 infection in the general population. Design Cross-sectional study with follow-up using pseudonymised record linkage. Setting Three Dutch public health service COVID-19 test sites. Participants Consecutively included individuals aged 16 years and older presenting for SARS-CoV-2 testing. Main outcome measures Sensitivity, specificity, positive and negative predictive values of BD-Veritortm System (Becton Dickinson), PanBio (Abbott), and SD-Biosensor (Roche Diagnostics), applying routinely used sampling methods (combined oropharyngeal and nasal [OP-N] or nasopharyngeal [NP] swab), with molecular testing as reference standard. For SDBiosensor, the diagnostic accuracy with OP-N sampling was also assessed. A viral load cutoff ([≥]5.2 log10 SARS-CoV-2 E-gene copies/mL) served as a proxy of infectiousness. Results SARS-CoV-2 prevalence and overall sensitivities with 95% confidence intervals were 188/1441 (13.0%) and 129/188 (68.6% [61.5%-75.2%]) for BD-Veritor, 173/2056 (8.4%) and 119/173 (68.8% [61.3%-75.6%]) for PanBio, and 215/1769 (12.2%) and 160/215 (74.4% [68.0%-80.1%]) for SD-Biosensor with routine sampling, and 164/1689 (9.7%) and 123/164 (75.0% [67.7%-81.4%]) for SD-Biosensor with OP-N sampling. In those symptomatic or asymptomatic at sampling, sensitivities were 72.2%-83.4% and 54.0%-55.9%, respectively. With a viral load cut-off, sensitivities were 125/146 (85.6% [78.9%-90.9%]) for BD-Veritor, 108/121 (89.3% [82.3%-94.2%]) for PanBio, 160/182 (87.9% [82.3%-92.3%]) for SD-Biosensor with routine sampling, and 118/141 (83.7% [76.5%-89.4%]) with OP-N sampling. Specificities were >99%, and positive and negative predictive values >95%, for all tests in most analyses. 61.3% of false negative Ag-RDT participants returned for testing within 14 days (median of 3 days, interquartile range 3) of whom 90.3% tested positive. Conclusions The overall sensitivities of the three Ag-RDTs were 68.6%-75.0%, increasing to at least 85.6% after the viral load cut-off was applied. For SD-Biosensor, the diagnostic accuracy with OP-N and NP sampling was comparable. Over 55% of false negative Ag-RDT participants tested positive during follow-up.

Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests. (preprint)

IntroductionSelf-testing for COVID-19 infection with lateral flow assay SARS-CoV-2 rapid antigen detection tests (RDT), provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2. The objective of this study is to evaluate the performance of self-testing using RDT without assistance. MethodsParticipants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD RDT) or Roche SARS-CoV-2 antigen detection test (Roche RDT). Oro-nasopharyngeal swabs were collected from the participants for qRT-PCR testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture was dropping below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined. ResultsA total of 3,215 participants were included (BD RDT n=1604; Roche RDT n=1611). Sensitivity and specificity of self-testing compared to the qRT-PCR results with Ct-value below the Ct-value cut-off was 78.0% (95% CI:72.5-82.8) and 99.4% (95%CI: 99.0-99.6) respectively. Determinants independently associated with a false-negative self-testing results were: higher age, low viral load and finding self-testing difficult. DiscussionSelf-testing using currently available RDTs has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness. The performance of two tests were comparable. This application has the potential for frequent and extensive testing which may be an aid to lift restrictions to society while controlling the spread of SARS-CoV-2.

PERFORMANCE EVALUATION OF A SARS-COV-2 RAPID ANTIGENTEST: TEST PERFORMANCE IN THE COMMUNITY IN THE NETHERLANDS (preprint)

Objectives: This study was primarily conducted to evaluate clinical sensitivity and specificity of the SARS-CoV-2 rapid antigen test BD Veritor System for Rapid Detection of SARS-CoV-2 (VRD) compared to real time reverse transcriptase polymerase chain reaction (qRT-PCR). Furthermore, the VRD sensitivity for different Ct-value groups (Ct <20; Ct 20-25, Ct 25-30 and Ct > 30) and different intervals since symptom onset (< 7 days; > 7 days) were examined. Design: Prospective performance evaluation study. Setting: Municipal Health Service (GGD) COVID-19 test centres in West-Brabant, the Netherlands Participants: In order to evaluate clinical specificity, 352 symptomatic adults (> 18 years) who presented at a participating GGD test centre for a COVID- 19 test between September 28 and October 7 2020 were included. In order to evaluate clinical sensitivity, 123 symptomatic adults (> 18 years) who were tested positive with qRT-PCR in a participating GGD test centre between September 26 and October 6 were included. Results: An overall clinical specificity of 100% (95%CI : 98.9%-100%) and sensitivity of 80.7% (95% CI: 73,2%-86,9%) was found for the VRD compared to qRT-PCR. Sensitivity was the highest for low Ct-value categories and for specimen obtained within the first days after disease onset. For specimen obtained within 7 days after onset of symptoms, the overall sensitivity was 91.0% (95%: CI 82,4%-96,3%) and 98,6% (95%: CI 92,3%-100%) for samples with qRT-PCR Ct-value beneath 30. Conclusion: The VRD is a promising diagnostic test for COVID-19 community screening for symptomatic individuals within 7 days after symptom onset in function of disease control. The clinical sensitivity was highest when viral load was high, which correlated with the duration of symptoms. Further research on practical applicability and the optimal position of the test within the current testing landscape is needed.

Evaluation of the first experience with COVID-19: An observational study on the screening policy among employees and patients of a Dutch teaching hospital (preprint)

BackgroundIn the beginning of March 2020, the Amphia hospital in Breda was one of the first hospitals in the Netherlands that received patients with COVID-19. Within ten days after the first COVID-19 positive patient, the number of (suspected) COVID-19 cases among patients and employees increased rapidly and thus the number of requests for SARS-CoV-2 PCR tests. From mid-March, we changed to a non-test-based strategy for employees whereby a work ban was implemented, based on the presence or absence of respiratory symptoms without the use of a diagnostic test. The objective of our study was to evaluate the safety of the non-test-based strategy. MethodsThe study period was March 1 to May 22, 2020. For all patients in whom the SARS-CoV-2 PCR test was positive > 2 days after admission, the medical record was reviewed by infection control staff for (respiratory) symptoms, laboratory results and lung CT/X-ray images to assess possible hospital-onset COVID-19. For employees, the number of sick reports per week were extracted from the department of Human Resources. Reason for reporting sick was not registered. ResultsTen of the 374 patients (2.7%) developed symptoms suspected for COVID-19 ≥3 days after admission and were tested positive for SARS-CoV-2, of which nosocomial transmission is the most likely cause in three patients. In the period in which the employees were still actively tested for SARS-CoV-2, there was a temporary increase in the number of sick reports (week 10-11). After this two-week period, the number of sick reports decreased rapidly. The total number of sick reports in the first 20 weeks of 2020 is comparable or lower than the total number of sick reports in the same period in previous years.ConclusionWith this non-test-based strategy for employees combined with a restriction of visitors to the patients and strict isolation of COVID-19 (suspected) patients, there was no excessive absenteeism of work due to illness and there were only few patients with indications of COVID-19 acquisition in the hospital.

COVID-19 in healthcare workers in three hospitals in the South of the Netherlands, March 2020 (preprint)

Background: Ten days after the first reported case of SARS-CoV-2 infection in the Netherlands, 3.9% of healthcare workers (HCWs) in nine hospitals located in the South of the Netherlands tested positive for SARS-CoV-2 RNA. The extent of nosocomial transmission that contributed to the HCW infections was unknown. Methods: We combined epidemiological data, collected by means of structured interviews of HCWs, with whole genome sequencing (WGS) of SARS-CoV-2 in clinical samples from HCWs and patients in three of nine hospitals that participated in the HCW screening, to perform an in-depth analysis of sources and modes of transmission of SARS -CoV-2 in HCWs and patients. Results: A total of 1,796 out of 12,022 HCWs (15%) of the three participating hospitals were screened, based on clinical symptoms, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete genome sequences of 50 HCWs and 18 patients. Most sequences grouped in 3 clusters, with 2 clusters displaying local circulation within the region. The observed patterns are most consistent with multiple introductions into the hospitals through community acquired infections, and local amplification in the community. Conclusions: Although direct transmission in the hospitals cannot be ruled out, the data does not support widespread nosocomial transmission as source of infection in patients or healthcare workers.

SARS-CoV-2 infection in 86 healthcare workers in two Dutch hospitals in March 2020 (preprint)

Background On February 27, 2020, the first patient with COVID-19 was reported in the Netherlands. During the following weeks, nine healthcare workers (HCWs) were diagnosed with COVID-19 in two Dutch teaching hospitals, eight of whom had no history of travel to China or Northern-Italy. A low-threshold screening regimen was implemented to determine the prevalence and clinical presentation of COVID-19 among HCWs in these two hospitals. Methods HCWs who suffered from fever or respiratory symptoms were voluntarily tested for SARS-CoV-2 by real-time reverse-transcriptase PCR on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Findings Thirteen-hundred fifty-three (14%) of 9,705 HCWs employed were tested, 86 (6%) of whom were infected with SARS-CoV-2. Most HCWs suffered from relatively mild disease and only 46 (53%) reported fever. Seventy-nine (92%) HCWs met a case definition of fever and/or coughing and/or shortness of breath. None of the HCWs identified through the screening reported a travel history to China or Northern Italy, and 3 (3%) reported to have been exposed to an inpatient known with COVID-19 prior to the onset of symptoms. Interpretation Within two weeks after the first Dutch case was detected, a substantial proportion of HCWs with fever or respiratory symptoms were infected with SARS-CoV-2, probably caused by acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, asks for less stringent use of the currently recommended case-definition for suspected COVID-19.