key: cord-1023728-f5u6lrjz authors: Leber, W.; Lammel, O.; Redlberger-Fritz, M.; Mustafa-Korninger, M. E.; Stiasny, K.; Glehr, R. C.; Hochstrasser, E.-M.; Hoellinger, C.; Siebenhofer, A.; Griffiths, C.; Panovska-Griffiths, J. title: RT-PCR testing to detect a COVID-19 outbreak in Austria: rapid, accurate and early diagnosis in primary care (The REAP study) date: 2020-07-15 journal: nan DOI: 10.1101/2020.07.13.20152439 sha: 8eadd2821ef55ad72054be5c35516439f90936da doc_id: 1023728 cord_uid: f5u6lrjz Background Delay in COVID-19 detection has led to a major pandemic. We report rapid early detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR), comparing it to the serostatus of convalescent infection, at an Austrian National Sentinel Surveillance Practice in an isolated ski-resort serving a population of 22,829 people. Methods Retrospective dataset of all 73 patients presenting with mild to moderate flu-like symptoms to a sentinel practice in the ski-resort of Schladming-Dachstein, Austria, between 24 February and 03 April, 2020. We split the outbreak in two halves, by dividing the period from the first to the last case by two, to characterise the following three cohorts of patients with confirmed infection: people with reactive RT-PCR presenting during the first half (early acute infection) vs. those presenting in the second half (late acute), and people with non-reactive RT-PCR (late convalescent). For each cohort we report the number of cases detected, the accuracy of RT-PCR and the duration of symptoms. We also report multivariate regression of 15 clinical symptoms as covariates, comparing all people with convalescent infection to those with acute infection. Findings All 73 patients had SARS-CoV-2 RT-PCR testing. 22 patients were diagnosed with COVID-19, comprising: 8 patients presenting early acute, and 7 presenting late acute and 7 late convalescent respectively; 44 patients tested SARS-COV-2 negative, and 7 were excluded. RT-PCR sensitivity was high (100%) among acute presenters, but dropped to 50% in the second half of the outbreak; specificity was 100%. The mean duration of symptoms was 2 days (range 1-4) among early acute presenters, and 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent presenters respectively. Convalescent infection was only associated with loss of taste (ORs=6.02;p=0.047). Acute infection was associated with loss of taste (OR=571.72;p=0.029), nausea and vomiting (OR=370.11;p=0.018), breathlessness (OR=134.46;p=0.049), and myalgia (OR=121.82;p=0.032); but not loss of smell, fever or cough. Interpretation RT-PCR rapidly and reliably detects early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. RT-PCR testing in primary care should be prioritised for effective COVID-19 prevention and control. Evidence before this study A comprehensive and effective test-trace-isolate (TTI) strategy is necessary to keep track of current and future COVID-19 infection in the UK and avoid a secondary wave later this year, as society reopens. As part of a wider TTI strategy, it is important to assess the feasibility of COVID-19 testing in primary care. We searched PubMed for implementation of SARS-CoV-2 testing in primary care using the following search terms: ("SARS-CoV-2" OR "COVID-19") AND "testing" AND ("primary care" OR "general practice"). We did not find any studies that met these criteria. To our knowledge, our study provides first evidence that extension of a National Influenza Surveillance Programme to include SARS-CoV-2 RT-PCR testing in primary care leads to viral detection among patients presenting with mild to moderate flu-like illness during a local outbreak of COVID- 19 . We show that the sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR), the technique to detect viral RNA, is high (100%) in the initial phase of the outbreak and among patients who were acutely unwell. Acute infection was associated with multiply symptoms: loss of taste, nausea and vomiting, breathlessness, myalgia and sore throat; but not loss of smell, fever or cough. We also show high correlation between reactive RT-PCR and seropositivity. Our findings suggest that RT-PCR can rapidly and reliably detect early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. Furthermore RT-PCR testing in primary care can effectively detect new COVID-19 clusters in the community and should be included in any strategy for prevention and control of the disease. The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, continues to spread globally with more than 8.5 million cases, and over 450,000 deaths reported as of June 19, 2020 . Undetected infection and delays in implementing an effective test-trace-isolate (TTI) strategy have contributed to the spread of the virus becoming a pandemic. SARS-CoV-2 virus has a wide spectrum of manifestations including no symptoms (asymptomatic infection), mild to moderate to severe flu-like illness, pneumonia and acute respiratory distress syndrome (ARDS), sepsis, multi-organ failure and death. 1 As well as the symptoms associated with flu-like illnesses such as cough, sore throat, fever, fatigue and headaches, altered taste or smell have recently been accepted as markers of COVID-19 infection. [2] [3] [4] In studies to date, the reported time for the infection to become symptomatic (incubation period) varies among different cohorts and settings, with a median incubation period around 5.1 days, 5 infectivity starting 2.3 days before symptom onset, peaking 1-2 days before that, 6, 7 and gradually declining over 7-10 days. 8, 9 SARS-CoV-2 has the potential for 'superspreading' events, resulting in clusters of disease outbreaks among a large number of people. 10 Although most infections remain isolated cases, a small number of individuals (10%) may cause up to 80% of secondary transmissions. 11 Undocumented infection may constitute the majority of cases (86%), causing more than half (55%) of all documented infections. 12 Superspreading events have been reported from across the globe, and countries achieving early viral suppression took rapid and decisive action to implement comprehensive case identification and testing, combined with contact tracing and isolation. 13, 14 For epidemic control of COVID-19, the reproduction number R needs to be less than 1, so that each newly infected person passes the infection on to less than one other person, ensuring infections decline. The presence of undetected and persistent infection within the population, even if very small, can increase R and induce a secondary peak of infections. Therefore, rapid identification and containment of infection is a key factor for the prevention of onward transmission and controlling the virus to protect the public. 15 In Austria, the first two COVID-19 cases were reported among travelers from Italy from a hotel in the city of Innsbruck on 25 February, 2020. Multiple superspreading events then occurred among tourists visiting Austrian ski resorts, including the town of Ischgl, that are believed to have led to further outbreaks in the tourists' home countries, including Germany, Denmark and Sweden. 16 Austria was one of the first countries to adopt comprehensive lockdown measures on March 16, 2020, including protection of vulnerable groups, penalty fees for breaching self-isolation, and the National health hotline 1450 to facilitate testing at acute care settings and via mobile units. 17 The first death from COVID-19 associated complications occurred on 12 March, 2020, and as of July 03, 17,959 cases and 705 COVID-19 related deaths have been reported. General practice is considered a key partner in case recording, managing high risk groups and delivery of equitable care. 18-21 The European Centre for Disease Prevent and Control (ECDC) recommended integration of "COVID-19 surveillance with sentinel surveillance of influenza-like illness or acute respiratory infection". 22 However, in some countries like the UK and the USA primary care has been largely excluded from the National TTI strategy. 23 From February 24, 2020, SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing was offered to people presenting with mild to moderate flu-like symptoms to any of the 92 sentinel sites (general practices and paediatric practices) participating in the Austrian National Influenza Surveillance Network. 24 The new service supplemented the existing National health hotline 1450 for people at risk of The overall aim of this work is to explore whether rapid early RT-PCR testing in primary care can accurately diagnose COVID-19 infection. To attest this we report the outcomes of SARS-CoV-2 RT-PCR testing at a sentinel practice in the ski resort of Schladming-Dachstein, Austria. RT-PCR is an established technique to detect viral RNA from nasopharyngeal sampling used to diagnose COVID-19. 26 Our study is the first to suggest RT-PCR testing in primary care as an effective method to rapidly, early and accurately diagnose COVID-19 and an important component of an effective TTI strategy. We report the accuracy (via sensitivity and specificity) of rapidly deployed RT-PCR testing in patients presenting with acute infection by comparing it to anti-SARS-CoV-2 antibody status during convalescence in the same geographically defined study cohort. We also report the earliness of viral RNA detection by comparing the duration and number of symptoms among patients presenting during the first half (early presenters) and the second half (late presenters) of the outbreak, measured by the number of days from the first to the last case detected and dividing that period by two. We also identify the key clinical symptoms of acute and convalescent disease and determine a correlation between these. This study was set in a sentinel general practice participating in the National Influenza Surveillance Network in the ski resort of Schladming-Dachstein, political subdistrict of Groebming (population 22,829), Austria. The study was conducted during a local COVID-19 outbreak between March to April 2020, where 29 cases detected by RT-PCR were documented. All patients presenting with mild to moderate flu-like illness were included. Following the report of the first cases in Austria, people with flu-like symptoms were advised to call the National health advice hotline 1450 instead of directly presenting to the hospital or general practice. Patients were advised to phone the general practitioner or receive hometesting by mobile testing units, and home self-isolate and self-care. We conducted a longitudinal evaluation comprising a pragmatic cohort to examine the impact of SARS-Cov-2 RT-PCR testing on COVID-19 case detection. Between 24 February and 03 April 2020, RT-PCR testing and seropositivity data were collected to compare two groups within this cohort of patients: • Patients testing RT-PCR reactive at presentation with acute disease Between November and March, participating practices routinely collect nasopharyngeal All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . swabs from patients presenting with flu-like symptoms. Specimens are sent to the Center for Virology, Medical University of Vienna, Austria, for virus isolation on tissue cultures and PCR detection. This surveillance programme allows for near real-time recording of seasonal influenza virus activity in the country. On February 24, 2020, one day before the first two cases were reported, the National Influenza Screening Network was enhanced to include SARS-CoV-2 RT-PCR testing. Patients with mild to moderate flu-like symptoms calling the study sentinel practice were offered same day appointments for SARS-CoV-2 RT-PCR testing. RT-PCR results were available within 24 hours, and those patients with a reactive outcome were immediately notified by a clinician and advised to self-isolate for a minimum of two weeks following National policy at that time. Repeat follow-up RT-PCR was arranged by the local public health authority (District Captaincy of Liezen, Austria), and people testing non-reactive on repeat RT-PCR were released from self-isolation. After 3-6 weeks, venous blood was obtained to confirm SARS-CoV-2 infection using ELISA IgG and neutralizing antibody assay. We defined the period of the outbreak as the number of days from the first patient to the last patient testing RT-PCR reactive at the practice. We characterise the outbreak using the following testing and clinical outcomes: A) As first outcome we report the diagnostic accuracy (using sensitivity and specificity) of SARS-CoV-2 RT-PCR testing among patients with mild to moderate flu-like symptoms at presentation by comparing it with anti-SARS-CoV-2 antibody during convalescence. We also report any alternative diagnoses for patients testing COVID-19 negative; and hospital admission and death B) As second outcome we report the earliness of RT-PCR testing by comparing the duration and number of symptoms during the first half of the outbreak (early presenters) and during the second half of the outbreak (late presenters) C) As third outcome, we identify the key clinical symptoms associated with RT-PCR reactivity (acute infection) and convalescent seropositivity (confirmed infection) and determine any potential correlation between these stages of disease. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . https://doi.org/10.1101/2020.07.13.20152439 doi: medRxiv preprint We obtained anonymous patient data held within the practice computer system. The practice lead clinician (OL) generated a clinical master case report form before extracting pseudonymised patient records into an Excel spreadsheet. EMH and CH verified the accuracy of the data extraction for all patients. Data were stored on a secure server at the Institute of (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. We present a descriptive statistics of patient demographics including age, gender and ethnicity; and the following three outcomes: (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. Baseline characteristics for both subgroups were similar for sex, age, and ethnic origin. In the absence of a gold standard, we used a consensus statement on serostatus, irrespective of RT-PCR outcomes, to establish whether an infection had occurred. We considered an infection as confirmed in any patient who tested IgG ELISA positive on all five screening platforms (concordant results) or in any patient with mismatch between ELISA test results All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. The mean duration of symptoms was 2 days (range 1-4) among early acute presenters, 4.4 days (range 1-7) among late acute presenters, and 8 days (range 2-12) among people with late convalescent infection; and 3.9 days (range 1-14) among non-Covid-19 controls ( Figure 2C ). The mean number of symptoms was 6.75 (range 4-9) among early acute presenters, 6.86 (3-12) among late acute presenters and 6.3 (1-11) among people with convalescent infection; and 5.23 (range 2-11) among non-Covid-19 controls ( Figure 2C ). Multivariate regression on all 66 patients, including 22 (31.9%) with confirmed infection, suggested that loss of taste, but not loss of smell, was the key covariate significantly associated with positive serostatus (ORs=6.03; p=0.047). (Table 1 ) Breathlessness (OR=6.9, p=0.054) and cough (OR=0.12, p=0.053) were also possible covariates of confirmed infection. All 15 patients with acute disease reported fatigue and therefore, this covariate was removed from the analysis; and observations from two patients with non-reactive RT-PCR, who did not report fatigue, were also removed ( Table 1) . The multivariate logistic regression on the remaining 66 patients showed that the following covariates were associated with acute disease: loss of taste (OR=571.72; p=0.029), nausea and vomiting (OR=370.11; p=0.018), breathlessness (OR=134.46; p=0.049), myalgia (OR=121.82; p=0.032) and sore throat (OR=0.002, p=0.039); and but not loss of smell (OR=0.37, p=0.607), fever (OR=1.44, p=0.825) or cough (OR=0.01, p=0.069). Testing RT-PCR reactive was correlated with testing seropositive for COVID-19 infection (r=0.77 (95%CI=(0.65,0.89)). Among early and acute presenters, the correlation between the two tests was perfect (green and amber in Figure 2 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . https://doi.org/10.1101/2020.07.13.20152439 doi: medRxiv preprint Figure 2B : Cumulative weekly numbers of confirmed COVID-19 cases during the outbreak. Timing of patient presentation during the outbreak (N=22) split into people presenting with early acute disease during the first half (12 days) of the outbreak (green colour, N=8), and those presenting with late acute (amber, N=7) and late convalescent disease (red, N=7) in the second half of the outbreak. RT-PCR was 100% sensitive among all early acute and late acute presenters. RT-PCR did not detect any of the late convalescent presenters. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . https://doi.org/10.1101/2020.07.13.20152439 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . https://doi.org/10.1101/2020.07.13.20152439 doi: medRxiv preprint Our results demonstrate that SARS-CoV-2 RT-PCR testing, when added to a National influenza surveillance programme in primary care, can rapidly, early and accurately diagnose COVID-19 infection. In a cohort of 73 patients tested in the course of the outbreak, 22 patients were diagnosed with COVID-19, comprising: 8 patients presenting early acute, and 7 presenting late acute and 7 late convalescent respectively; 44 patients tested SARS-COV-2 negative, and 7 were excluded. Overall, RT-PCR was 100% specific; and sensitivity among all acute presenters was 100%, but dropped to 50% in the second half of the outbreak. Testing RT-PCR reactive showed perfect correlation with seropositivity during the first half of the outbreak and among early acute and late acute presenters. RT-PCR did, however, not detect any late convalescent presenters that were identified by antibody testing in the second half of the outbreak. Strikingly, the mean duration of symptoms of early presenters (2 days) was less than half of late acute presenters (4.4 days) and a quarter of late convalescent presenters (8 days). These findings highlight the need to undertake RT-PCR testing rapidly and early as soon as symptoms occur. The mean number of symptoms was higher among people with COVID-19 compared to controls. While loss of taste, nausea and vomiting, breathlessness, myalgia and sore throat were strongly associated with acute infection; loss of smell, fever and cough were not. Surprisingly, loss of taste, but not any other clinical symptom, was significantly associated with convalescent infection. Our study highlights the importance of early RT-PCR testing in primary care among patients presenting with multiple flu-like symptoms. Our results agree with the findings of the King's College group that loss of taste is an overall marker of COVID-19 infection. 31 However, our study suggests that the presence of multiple symptoms among patients presenting shortly after symptom onset might indicate acute COVID-19. Furthermore, unlike the Kings' College study, where the suggestion is made that people use a mobile phone application to selfdiagnose and self-isolate, we suggest that people with acute COVID-19 can be accurately diagnosed by RT-PCR in primary care. Given the high accuracy of RT-PCR during acute SARS-CoV-2 infection, a paradigm shift in the management of flu-like illness in primary car may be needed: active testing of patients presenting within the first 1-2 days of showing multiple symptoms should be encouraged rather than self-isolation of symptomatic people. This is aligned to the suggestions in a recent Lancet Editorial. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. Our work is an important step towards primary care testing for COVID-19 infection. Firstly, our study is the first one to show that early RT-PCR testing in primary care can accurately detect COVID-19 infection. Secondly, the Austrian experience demonstrates that primary care can be a reliable partner for the control and prevention of COVID-19. Notably, countries with major epidemics, including the UK and the USA, have excluded primary care as an important testing site. Primary care in the UK has highly sophisticated linked searchable coded systems, meaning that prioritising testing in this setting rapidly creates exceptional real-time epidemiological data critical to identify risk groups and is capable of evaluating impacts of interventions such as social distancing and lockdown. Thirdly, evidence from countries like South Korea, 33 where large-scale TTI strategies have been able to control the spread of COVID-19, and existing modelling studies in the UK 34 highlight the need for comprehensive and effective TTI strategies to prevent onwards transmission of COVID-19 and suppress the virus preventing a secondary epidemic peak. Our study adds to this evidence and suggests that additional testing should be done in primary care and encouraged as early as symptoms appear. To our knowledge, our study is the first to highlight the need for largescale and early primary care RT-PCR testing as part of an effective TTI strategy. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . https://doi.org/10.1101/2020.07.13.20152439 doi: medRxiv preprint Our study has many strengths. Firstly, we included data from a well-established sentinel practice, participating in the National Influenza Screening Programme, covering a political subdistrict in Austria. Secondly, national SARS-CoV-2 screening was adopted early, starting the day before the first two cases were reported in Austria; and 16 of 29 cases documented in the Schladming-Dachstein region, including the first and the last case, were detected at the sentinel practice. The National health hotline 1450 and local general practitioners systematically referred people with mild to moderate symptoms to the sentinel practice, and patient self-referral was encouraged in the local media and on the practice home page. RT-PCR testing was rapidly deployed by offering same day GP appointments, and result reporting and case notification within 24 hours. To protect patients and staff, an internal safety protocol was developed to include physical separation of patients presenting with flulike symptoms from those people receiving routine care, use of full personal protective equipment, and regular self-testing of staff. Rapid adoption of new commercial antibody platforms (Lab Mustafa, Salzburg) and in-house neutralising antibody testing assay (Medical University of Vienna) enabled accurate interpretation of RT-PCR results. There are some limitations of our study. Firstly, we used a relatively small patient cohort from a single sentinel practice, potentially limiting conclusions on causality and generalisability of our finding to other areas and secondly, we excluded seven patients for whom COVID-19 serostatus were not available. Lack of association with high fever and cough in our COVID-19 cohort, may be due to the National health hotline 1450 directing patients with more severe disease to attend emergency service. Therefore, people with these symptoms might have preferred to attend acute services rather than general practice. Although we collected data prospectively, recall bias cannot be excluded. This could be suggested by the lack of association of symptoms of acute infection (nausea and vomiting, breathless and myalgia) among all people confirmed with infection (when including those with negative RT-PCR), compared to those people presenting early (reactive RT-PCR). Specific recall bias of taste is less likely, as it featured in both groups and data collection was completed prior to publication of the first systematic review of altered taste and smell in the media. 3 To our knowledge, this is the first study to show that primary care can contribute to early case detection and termination of a SARS-CoV-2 outbreak in the community. Our study has All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 15, 2020. . https://doi.org/10.1101/2020.07.13.20152439 doi: medRxiv preprint important implications for patients, public health, and health systems; nationally and internationally for outbreak epidemiology and control. Strict adherence to safety protocols allows continuation of routine care, potentially reducing the chance of excess non-COVIDrelated and mortality among the practice population. As countries enter the viral suppression phase, early detection will be crucial in the prevention and control of the disease. Early testing at onset of disease, followed by timely contact tracing and case isolation of secondary cases should prevent onward transmission and reduce the reproduction number R below 1. Austria has increased the number of its sentinels sites from 91 to 231 due to COVID-19, indicating that primary care has become an essential partner in a comprehensive surveillance strategy for disease prevention and control. Key priorities for future research include clinicalmanagement-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-issuspected The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis Clinical Presentation of COVID-19: A Systematic Review Focusing on Upper Airway Symptoms Anosmia as a presenting symptom of SARS-CoV-2 infection in healthcare workers -A systematic review of the literature, case series, and recommendations for clinical assessment and management The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility -King County Predicting infectious SARS-CoV-2 from diagnostic samples Virological assessment of hospitalized patients with COVID-2019 COVID-19 Superspreader Events in 28 Countries: Critical Patterns and Lessons Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China Viral dynamics in mild and severe cases of COVID-19 Rapid Risk Assessment: Coronavirus disease 2019 (COVID-19) in the EU/EEA and the UK-ninth update Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study Identifying and Interrupting Superspreading Events-Implications for Control of Severe Acute Respiratory Syndrome Coronavirus 2 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted Coronavirus disease 2019 (COVID-19) in the EU/EEA and the UK -ninth update Family medicine in times of 'COVID-19': A generalists' voice Suspected COVID-19 in primary care: how GP records contribute to understanding differences in prevalence by ethnicity COVID-19: a danger and an opportunity for the future of general practice European Centres for Disease Control (ECDC) Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study Interpreting a covid-19 test result Diagnostic detection of 2019-nCoV by real-time RT-PCR SARS-CoV-2 Seroconversion in Humans: A Detailed Protocol for a Serological Assay, Antigen Production, and Test Setup Use of Convalescent Plasma Therapy in Two Patients with Acute Respiratory Distress Syndrome in Korea Developing standards for reporting implementation studies of complex interventions (StaRI): a systematic review and e-Delphi Real-time tracking of self-reported symptoms to predict potential COVID-19 Temporal dynamics in viral shedding and transmissibility of COVID-19 Transmission potential and severity of COVID-19 in South Korea Determining the optimal strategy for reopening schools, workplaces and society in the UK: modelling patterns of reopening, the impact of test and trace strategies and risk of occurrence of a secondary COVID-19 pandemic wave We thank Evelyn Marktl for daily updates on the Christian Drosten's COVID-19 podcast (https://www.ndr.de/nachrichten/info/podcast4684.html). We are grateful to the team of Praxis Dr Lammel for their contributions, and in particular to the nurse Sabine Roiderer for providing direct patient care and help with administration. We thank the patients of Schladming-Dachstein for participating in the study. All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted July 15, 2020.