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Coronavirus disease (COVID-19)
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Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020
Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.
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Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020
We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.
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Age-specific SARS-CoV-2 infection fatality ratio and associated risk factors, Italy, February to April 2020
We analysed 5,484 close contacts of coronavirus disease (COVID-19) cases in Italy, all tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection fatality ratio was 0.43% (95% confidence interval (CI): 0.21–0.79) for individuals younger than 70 years and 10.5% (95% CI: 8.0–13.6) for older individuals. Risk of death after infection was 62% lower (95% CI: 31–80) in clusters identified after 16 March 2020 and 1.8-fold higher for males (95% CI: 1.03–3.16).
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Epidemiology of measles during the COVID-19 pandemic, a description of the surveillance data, 29 EU/EEA countries and the United Kingdom, January to May 2020
The number of measles cases declined in European Union/European Economic Area countries and the United Kingdom in 2020. Reported cases to The European Centre for Disease Prevention and Control decreased from 710 to 54 between January and May. Epidemic intelligence screening observed a similar trend. Under-diagnoses and under-reporting during the coronavirus disease (COVID-19) pandemic should be ruled out before concluding reduced measles circulation is because of social distancing and any community control measures taken to control COVID-19.
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Repeated leftover serosurvey of SARS-CoV-2 IgG antibodies, Greece, March and April 2020
Zacharoula Bogogiannidou , Alexandros Vontas , Katerina Dadouli , Maria A Kyritsi , Soteris Soteriades , Dimitrios J Nikoulis , Varvara Α Mouchtouri , Michalis Koureas , Evangelos I Kazakos , Emmanouil G Spanos , Georgia Gioula , Evangelia E Ntzani , Alexandros A Eleftheriou , Alkiviadis Vatopoulos , Efthimia Petinaki , Vassiliki Papaevangelou , Matthaios Speletas , Sotirios Tsiodras and Christos HadjichristodoulouA serosurvey of IgG antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) was performed during March and April 2020. Among 6,586 leftover sera, 24 (0.36%) were positive, with higher prevalence in females, older individuals and residents of large urban areas. Seroprevalence was estimated at 0.02% and 0.25%, respectively, in March and April, infection fatality rate at 2.66% and 0.54%. Our findings confirm low COVID-19 incidence in Greece and possibly the effectiveness of early measures.
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Duration of SARS-CoV-2 RNA detection in COVID-19 patients in home isolation, Rhineland-Palatinate, Germany, 2020 – an interval-censored survival analysis
Sarah Omar , Christoph Bartz , Sabine Becker , Silke Basenach , Sandra Pfeifer , Corinna Trapp , Hildegard Hamm , Hans Christoph Schlichting , Magdalena Friederichs , Ulrich Koch , Christian Jestrabek , Ernst Hilger , Manfred Vogt , Klaus Jahn , Simiao Chen , Till Bärnighausen , Philipp Zanger and on behalf of the Palatina Public Health Study GroupWe analysed consecutive RT-qPCR results of 537 symptomatic coronavirus disease (COVID-19) patients in home quarantine. Respectively 2, 3, and 4 weeks after symptom onset, 50%, 25% and 10% of patients had detectable RNA from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In patients with mild COVID-19, RNA detection is likely to outlast currently known periods of infectiousness by far and fixed time periods seem more appropriate in determining the length of home isolation than laboratory-based approaches.
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Legionella pneumonia: increased risk after COVID-19 lockdown? Italy, May to June 2020
We report a case of Legionella pneumonia in a dishwasher of a restaurant in Rome, Italy, just after the end of the lockdown that was in place to control the SARS-CoV-2 epidemic. The case highlights the importance of strict monitoring of water and air systems immediately before reopening business or public sector buildings, and the need to consider Legionella infections among the differential diagnosis of respiratory infections after lockdown due to the ongoing COVID-19 pandemic.
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A large COVID-19 outbreak in a high school 10 days after schools’ reopening, Israel, May 2020
On 13 March 2020, Israel’s government declared closure of all schools. Schools fully reopened on 17 May 2020. Ten days later, a major outbreak of coronavirus disease (COVID-19) occurred in a high school. The first case was registered on 26 May, the second on 27 May. They were not epidemiologically linked. Testing of the complete school community revealed 153 students (attack rate: 13.2%) and 25 staff members (attack rate: 16.6%) who were COVID-19 positive.
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All-cause excess mortality observed by age group and regions in the first wave of the COVID-19 pandemic in England
England has experienced one of the highest excess in all-cause mortality in Europe during the current COVID-19 pandemic. As COVID-19 emerged, the excess in all-cause mortality rapidly increased, starting in March 2020. The excess observed during the pandemic was higher than excesses noted in the past 5 years. It concerned all regions and all age groups, except the 0–14 year olds, but was more pronounced in the London region and in those aged ≥ 85 years.
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Convalescent plasma treatment for SARS-CoV-2 infection: analysis of the first 436 donors in England, 22 April to 12 May 2020
Serological reactivity was analysed in plasma from 436 individuals with a history of disease compatible with COVID-19, including 256 who had been laboratory-confirmed with SARS-CoV-2 infection. Over 99% of laboratory-confirmed cases developed a measurable antibody response (254/256) and 88% harboured neutralising antibodies (226/256). Antibody levels declined over 3 months following diagnosis, emphasising the importance of the timing of convalescent plasma collections. Binding antibody measurements can inform selection of convalescent plasma donors with high neutralising antibody levels.
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Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2
BackgroundA novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.
AimThe cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.
MethodsThe SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.
ResultsAn immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.
ConclusionThe cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.
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SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020
More LessMost cases of coronavirus disease 2019 are mild or asymptomatic. Therefore, many cases remain unrecorded. We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. The IgG seroprevalence was 0.91% (95% confidence interval (CI): 0.58–1.24) overall, ranging from 0.66% (95% CI: 0.13–1.19) in Hesse to 1.22% (95% CI: 0.33–2.10) in Lower-Saxony.
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International external quality assessment for SARS-CoV-2 molecular detection and survey on clinical laboratory preparedness during the COVID-19 pandemic, April/May 2020
Laboratory preparedness with quality-assured diagnostic assays is essential for controlling the current coronavirus disease (COVID-19) outbreak. We conducted an external quality assessment study with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples to support clinical laboratories with a proficiency testing option for molecular assays. To analyse SARS-CoV-2 testing performance, we used an online questionnaire developed for the European Union project RECOVER to assess molecular testing capacities in clinical diagnostic laboratories.
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Excess all-cause mortality during the COVID-19 pandemic in Europe – preliminary pooled estimates from the EuroMOMO network, March to April 2020
Lasse S Vestergaard , Jens Nielsen , Lukas Richter , Daniela Schmid , Natalia Bustos , Toon Braeye , Gleb Denissov , Tatjana Veideman , Oskari Luomala , Teemu Möttönen , Anne Fouillet , Céline Caserio-Schönemann , Matthias an der Heiden , Helmut Uphoff , Theodore Lytras , Kassiani Gkolfinopoulou , Anna Paldy , Lisa Domegan , Joan O'Donnell , Francesca de’ Donato , Fiammetta Noccioli , Patrick Hoffmann , Telma Velez , Kathleen England , Liselotte van Asten , Richard A White , Ragnhild Tønnessen , Susana P da Silva , Ana P Rodrigues , Amparo Larrauri , Concepción Delgado-Sanz , Ahmed Farah , Ilias Galanis , Christoph Junker , Damir Perisa , Mary Sinnathamby , Nick Andrews , Mark O'Doherty , Diogo FP Marquess , Sharon Kennedy , Sonja J Olsen , Richard Pebody , ECDC Public Health Emergency Team for COVID-19 , Tyra G Krause and Kåre MølbakA remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March–April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45–64 (8%) and 15–44 year olds (1%). No excess mortality was observed in 0–14 year olds.
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Introductions and early spread of SARS-CoV-2 in France, 24 January to 23 March 2020
Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.
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SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines
More LessThe advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen’s eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.
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Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020
Maximilian Muenchhoff , Helga Mairhofer , Hans Nitschko , Natascha Grzimek-Koschewa , Dieter Hoffmann , Annemarie Berger , Holger Rabenau , Marek Widera , Nikolaus Ackermann , Regina Konrad , Sabine Zange , Alexander Graf , Stefan Krebs , Helmut Blum , Andreas Sing , Bernhard Liebl , Roman Wölfel , Sandra Ciesek , Christian Drosten , Ulrike Protzer , Stephan Boehm and Oliver T KepplerContainment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.
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Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 April 2020
We evaluated SARS-CoV-2 RNA and neutralising antibodies in blood donors (BD) residing in the Lodi Red Zone, Italy. Of 390 BDs recruited after 20 February 2020 − when the first COVID-19 case in Lombardy was identified, 91 (23%) aged 19–70 years were antibody positive. Viral RNA was detected in an additional 17 (4.3%) BDs, yielding ca 28% (108/390) with evidence of virus exposure. Five stored samples collected as early as 12 February were seropositive.
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Descriptive study of COVID-19 outbreak among passengers and crew on Diamond Princess cruise ship, Yokohama Port, Japan, 20 January to 9 February 2020
More LessAn outbreak of coronavirus disease (COVID-19) occurred on the Diamond Princess cruise ship making an international journey, which led to quarantine of the ship at Yokohama Port, Japan. A suspected COVID-19 case was defined as a passenger or crew member who developed a fever or respiratory symptoms, and a confirmed COVID-19 case had laboratory-confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Between 3 and 9 February 2020, 490 individuals were tested for SARS-CoV-2 and 172 were positive (152 passengers (median age: 70 years; interquartile range (IQR): 64–75; males: 45%) and 20 crew (median age: 40 years; IQR: 35–48.5; males: 80%). Other than the Hong Kong-related index case, symptom onset for the earliest confirmed case was 22 January, 2 days after the cruise ship left port. Attack rates among passengers were similar across the decks, while beverage (3.3%, 2/61) and food service staff (5.7%, 14/245) were most affected. Attack rates tended to increase with age. A comprehensive outbreak response was implemented, including surveillance, provision of essential medical care, food and medicine delivery, isolation, infection prevention and control, sampling and disembarkation.
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Measuring the effectiveness of an automated text messaging active surveillance system for COVID-19 in the south of Ireland, March to April 2020
We report the effectiveness of automated text messaging for active surveillance of asymptomatic close contacts of coronavirus disease (COVID-19) cases in the Cork/Kerry region of Ireland. In the first 7 weeks of the COVID-19 outbreak, 1,336 close contacts received 12,421 automated texts. Overall, 120 contacts (9.0%) reported symptoms which required referral for testing and 35 (2.6%) tested positive for COVID-19. Non-response was high (n = 2,121; 17.1%) and this required substantial clinical and administrative resources for follow-up.
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Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications
We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.
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SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020
Nadia Oreshkova , Robert Jan Molenaar , Sandra Vreman , Frank Harders , Bas B Oude Munnink , Renate W Hakze-van der Honing , Nora Gerhards , Paulien Tolsma , Ruth Bouwstra , Reina S Sikkema , Mirriam GJ Tacken , Myrna MT de Rooij , Eefke Weesendorp , Marc Y Engelsma , Christianne JM Bruschke , Lidwien AM Smit , Marion Koopmans , Wim HM van der Poel and Arjan StegemanRespiratory disease and increased mortality occurred in minks on two farms in the Netherlands, with interstitial pneumonia and SARS-CoV-2 RNA in organ and swab samples. On both farms, at least one worker had coronavirus disease-associated symptoms before the outbreak. Variations in mink-derived viral genomes showed between-mink transmission and no infection link between the farms. Inhalable dust contained viral RNA, indicating possible exposure of workers. One worker is assumed to have attracted the virus from mink.
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Genetic structure of SARS-CoV-2 reflects clonal superspreading and multiple independent introduction events, North-Rhine Westphalia, Germany, February and March 2020
We whole-genome sequenced 55 SARS-CoV-2 isolates from Germany to investigate SARS-CoV-2 outbreaks in 2020 in the Heinsberg district and Düsseldorf. While the genetic structure of the Heinsberg outbreak indicates a clonal origin, reflecting superspreading dynamics from mid-February during the carnival season, distinct viral strains were circulating in Düsseldorf in March, reflecting the city’s international links. Limited detection of Heinsberg strains in the Düsseldorf area despite geographical proximity may reflect efficient containment and contact-tracing efforts.
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High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020
ECDC Public Health Emergency Team , Kostas Danis , Laure Fonteneau , Scarlett Georges , Côme Daniau , Sibylle Bernard-Stoecklin , Lisa Domegan , Joan O’Donnell , Siri Helene Hauge , Sara Dequeker , Eline Vandael , Johan Van der Heyden , Françoise Renard , Natalia Bustos Sierra , Enrico Ricchizzi , Birgitta Schweickert , Nicole Schmidt , Muna Abu Sin , Tim Eckmanns , José-Artur Paiva and Elke SchneiderResidents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30–60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.
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Infection prevention guidelines and considerations for paediatric risk groups when reopening primary schools during COVID-19 pandemic, Norway, April 2020
In response to the coronavirus disease (COVID-19) pandemic, most countries implemented school closures. In Norway, schools closed on 13 March 2020. The evidence of effect on disease transmission was limited, while negative consequences were evident. Before reopening, risk-assessment for paediatric risk groups was performed, concluding that most children can attend school with few conditions requiring preventative homeschooling. We here present infection prevention and control guidelines for primary schools and recommendations for paediatric risk groups.
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SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020
End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.
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No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020
More LessAs many countries begin to lift some of the restrictions to contain COVID-19 spread, lack of evidence of transmission in the school setting remains. We examined Irish notifications of SARS-CoV2 in the school setting before school closures on 12 March 2020 and identified no paediatric transmission. This adds to current evidence that children do not appear to be drivers of transmission, and we argue that reopening schools should be considered safe accompanied by certain measures.
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Rapid response infrastructure for pandemic preparedness in a tertiary care hospital: lessons learned from the COVID-19 outbreak in Cologne, Germany, February to March 2020
Max Augustin , Philipp Schommers , Isabelle Suárez , Philipp Koehler , Henning Gruell , Florian Klein , Christian Maurer , Petra Langerbeins , Vanessa Priesner , Kirsten Schmidt-Hellerau , Jakob J Malin , Melanie Stecher , Norma Jung , Gerhard Wiesmüller , Arne Meissner , Janine Zweigner , Georg Langebartels , Felix Kolibay , Victor Suárez , Volker Burst , Philippe Valentin , Dirk Schedler , Oliver A Cornely , Michael Hallek , Gerd Fätkenheuer , Jan Rybniker and Clara LehmannThe coronavirus disease (COVID-19) pandemic has caused tremendous pressure on hospital infrastructures such as emergency rooms (ER) and outpatient departments. To avoid malfunctioning of critical services because of large numbers of potentially infected patients seeking consultation, we established a COVID-19 rapid response infrastructure (CRRI), which instantly restored ER functionality. The CRRI was also used for testing of hospital personnel, provided epidemiological data and was a highly effective response to increasing numbers of suspected COVID-19 cases.
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Early impact of the coronavirus disease (COVID-19) pandemic and physical distancing measures on routine childhood vaccinations in England, January to April 2020
Using electronic health records, we assessed the early impact of coronavirus disease (COVID-19) on routine childhood vaccination in England by 26 April 2020. Measles-mumps-rubella vaccination counts fell from February 2020, and in the 3 weeks after introduction of physical distancing measures were 19.8% lower (95% confidence interval: −20.7 to −18.9) than the same period in 2019, before improving in mid-April. A gradual decline in hexavalent vaccination counts throughout 2020 was not accentuated by physical distancing.
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Mortality impacts of the coronavirus disease (COVID-19) outbreak by sex and age: rapid mortality surveillance system, Italy, 1 February to 18 April 2020
Data from the rapid mortality surveillance system in 19 major Italian cities were used to carry out a timely assessment of the health impact of the COVID-19 epidemic. By 18 April, a + 45% excess in mortality was observed, with a higher impact in the north of the country (+ 76%). The excess was greatest among men, with an increasing trend by age. Surveillance data can be used to evaluate the lockdown and re-opening phases.
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Rapid reviews for rapid decision-making during the coronavirus disease (COVID-19) pandemic, Norway, 2020
More LessIn response to urgent needs for updated evidence for decision-making on various aspects related to coronavirus disease (COVID-19), the Norwegian Institute of Public Health established a rapid review team. Using simplified processes and shortcuts, this team produces summary reviews on request within 1–3 days that inform advice provided by the institute. All reviews are published with explicit messages about the risk of overlooking key evidence or making misguided judgements by using such rapid processes.
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Estimating number of cases and spread of coronavirus disease (COVID-19) using critical care admissions, United Kingdom, February to March 2020
An exponential growth model was fitted to critical care admissions from two surveillance databases to determine likely coronavirus disease (COVID-19) case numbers, critical care admissions and epidemic growth in the United Kingdom before the national lockdown. We estimate, on 23 March, a median of 114,000 (95% credible interval (CrI): 78,000–173,000) new cases and 258 (95% CrI: 220–319) new critical care reports, with 527,000 (95% CrI: 362,000–797,000) cumulative cases since 16 February.
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Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples
Antibody-screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be validated. We evaluated SARS-CoV-2 IgG and IgA ELISAs in conjunction with the EUROLabworkstation (Euroimmun, Lübeck, Germany). Overall specificities were 91.9% and 73.0% for IgG and IgA ELISAs, respectively. Of 39 coronavirus disease patients, 13 were IgG and IgA positive and 11 IgA alone at sampling. IgGs and IgAs were respectively detected at a median of 12 and 11 days after symptom onset.
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Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020
Silvia Garazzino , Carlotta Montagnani , Daniele Donà , Antonella Meini , Enrico Felici , Gianluca Vergine , Stefania Bernardi , Roberta Giacchero , Andrea Lo Vecchio , Paola Marchisio , Giangiacomo Nicolini , Luca Pierantoni , Ivana Rabbone , Giuseppe Banderali , Marco Denina , Elisabetta Venturini , Andrzej Krzysztofiak , Raffaele Badolato , Sonia Bianchini , Luisa Galli , Alberto Villani , Guido Castelli-Gattinara and the Italian SITIP-SIP Pediatric Infection Study GroupData on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.
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Projected early spread of COVID-19 in Africa through 1 June 2020
For 45 African countries/territories already reporting COVID-19 cases before 23 March 2020, we estimate the dates of reporting 1,000 and 10,000 cases. Assuming early epidemic trends without interventions, all 45 were likely to exceed 1,000 confirmed cases by the end of April 2020, with most exceeding 10,000 a few weeks later.
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Early experience of an infectious and tropical diseases unit during the coronavirus disease (COVID-19) pandemic, Florence, Italy, February to March 2020
Filippo Lagi , Matteo Piccica , Lucia Graziani , Iacopo Vellere , Annarita Botta , Marta Tilli , Letizia Ottino , Beatrice Borchi , Marco Pozzi , Filippo Bartalesi , Jessica Mencarini , Michele Spinicci , Lorenzo Zammarchi , Filippo Pieralli , Giovanni Zagli , Carlo Nozzoli , Stefano Romagnoli , Alessandro Bartoloni and the COCORA working groupWe analysed the first 84 coronavirus disease (COVID-19) patients hospitalised in an infectious and tropical disease unit in Florence, Italy, over 30 days after the start of the COVID-19 outbreak in Italy. A 12% reduction in the rate of intensive care unit transfer was observed after the implementation of intensity care measures in the regular ward such as increasing the nurse/patient ratio, presence of critical care physicians and using high flow nasal cannulae oxygenation.
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Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020
BackgroundEstimating key infectious disease parameters from the coronavirus disease (COVID-19) outbreak is essential for modelling studies and guiding intervention strategies.
AimWe estimate the generation interval, serial interval, proportion of pre-symptomatic transmission and effective reproduction number of COVID-19. We illustrate that reproduction numbers calculated based on serial interval estimates can be biased.
MethodsWe used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates, we obtained the serial interval, proportions of pre-symptomatic transmission and reproduction numbers.
ResultsThe mean generation interval was 5.20 days (95% credible interval (CrI): 3.78–6.78) for Singapore and 3.95 days (95% CrI: 3.01–4.91) for Tianjin. The proportion of pre-symptomatic transmission was 48% (95% CrI: 32–67) for Singapore and 62% (95% CrI: 50–76) for Tianjin. Reproduction number estimates based on the generation interval distribution were slightly higher than those based on the serial interval distribution. Sensitivity analyses showed that estimating these quantities from outbreak data requires detailed contact tracing information.
ConclusionHigh estimates of the proportion of pre-symptomatic transmission imply that case finding and contact tracing need to be supplemented by physical distancing measures in order to control the COVID-19 outbreak. Notably, quarantine and other containment measures were already in place at the time of data collection, which may inflate the proportion of infections from pre-symptomatic individuals.
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Temporal rise in the proportion of younger adults and older adolescents among coronavirus disease (COVID-19) cases following the introduction of physical distancing measures, Germany, March to April 2020
More LessUsing data on coronavirus disease (COVID-19) cases in Germany from the Robert Koch Institute, we found a relative increase with time in the prevalence in 15–34 year-olds (particularly 20–24-year-olds) compared with 35–49- and 10–14-year-olds (we excluded older and younger ages because of different healthcare seeking behaviour). This suggests an elevated role for that age group in propagating the epidemic following the introduction of physical distancing measures.
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Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020
Marta Colaneri , Paolo Sacchi , Valentina Zuccaro , Simona Biscarini , Michele Sachs , Silvia Roda , Teresa Chiara Pieri , Pietro Valsecchi , Antonio Piralla , Elena Seminari , Angela Di Matteo , Stefano Novati , Laura Maiocchi , Layla Pagnucco , Marcello Tirani , Fausto Baldanti , Francesco Mojoli , Stefano Perlini , Raffaele Bruno and the COVID19 IRCCS San Matteo Pavia Task ForceWe describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21–28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.
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Epidemiological characteristics of the first 53 laboratory-confirmed cases of COVID-19 epidemic in Hong Kong, 13 February 2020
More LessBackgroundCOVID-19, caused by SARS-CoV-2, first appeared in China and subsequently developed into an ongoing epidemic. Understanding epidemiological factors characterising the transmission dynamics of this disease is of fundamental importance.
AimsThis study aimed to describe key epidemiological parameters of COVID-19 in Hong Kong.
MethodsWe extracted data of confirmed COVID-19 cases and their close contacts from the publicly available information released by the Hong Kong Centre for Health Protection. We used doubly interval censored likelihood to estimate containment delay and serial interval, by fitting gamma, lognormal and Weibull distributions to respective empirical values using Bayesian framework with right truncation. A generalised linear regression model was employed to identify factors associated with containment delay. Secondary attack rate was also estimated.
ResultsThe empirical containment delay was 6.39 days; whereas after adjusting for right truncation with the best-fit Weibull distribution, it was 10.4 days (95% CrI: 7.15 to 19.81). Containment delay increased significantly over time. Local source of infection and number of doctor consultations before isolation were associated with longer containment delay. The empirical serial interval was 4.58–6.06 days; whereas the best-fit lognormal distribution to 26 certain-and-probable infector–infectee paired data gave an estimate of 4.77 days (95% CrI: 3.47 to 6.90) with right-truncation. The secondary attack rate among close contacts was 11.7%.
ConclusionWith a considerable containment delay and short serial interval, contact-tracing effectiveness may not be optimised to halt the transmission with rapid generations replacement. Our study highlights the transmission risk of social interaction and pivotal role of physical distancing in suppressing the epidemic.
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Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020
Ranawaka APM Perera , Chris KP Mok , Owen TY Tsang , Huibin Lv , Ronald LW Ko , Nicholas C Wu , Meng Yuan , Wai Shing Leung , Jacky MC Chan , Thomas SH Chik , Chris YC Choi , Kathy Leung , Kin Ho Chan , Karl CK Chan , Ka-Chi Li , Joseph T Wu , Ian A Wilson , Arnold S Monto , Leo LM Poon and Malik PeirisBackgroundThe ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making.
AimOur objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies.
MethodsWe developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT90) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls.
ResultsIgG and IgM RBD ELISA, MN and PRNT90 were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT90 tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test.
ConclusionUsing IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT90, is a valid approach for large-scale sero-epidemiology studies.
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Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020
Healthcare workers (n = 803) with mild symptoms were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 90 positive) and asked to complete a symptom questionnaire. Anosmia, muscle ache, ocular pain, general malaise, headache, extreme tiredness and fever were associated with positivity. A predictive model based on these symptoms showed moderate discriminative value (sensitivity: 91.2%; specificity: 55.6%). While our models would not justify presumptive SARS-CoV-2 diagnosis without molecular confirmation, it can contribute to targeted screening strategies.
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Coronavirus disease (COVID-19): a scoping review
Meng Lv , Xufei Luo , Janne Estill , Yunlan Liu , Mengjuan Ren , Jianjian Wang , Qi Wang , Siya Zhao , Xiaohui Wang , Shu Yang , Xixi Feng , Weiguo Li , Enmei Liu , Xianzhuo Zhang , Ling Wang , Qi Zhou , Wenbo Meng , Xiaolong Qi , Yangqin Xun , Xuan Yu , Yaolong Chen and on behalf of the COVID-19 evidence and recommendations working groupBackgroundIn December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then.
AimThis study aims to understand the research gaps related to COVID-19 and propose recommendations for future research.
MethodsWe undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies.
ResultsWe included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R0). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January.
ConclusionThe number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.
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Potential lethal outbreak of coronavirus disease (COVID-19) among the elderly in retirement homes and long-term facilities, France, March 2020
More LessMotivated by the potential devastating effect of a COVID-19 outbreak in retirement homes and long-term facilities for dependent elderly, we present the impact of worst-case scenarios in French institutions using a specific age structure and case–age fatality ratios. The death toll could equal the yearly death toll caused by seasonal influenza in those older than 65 years or could largely exceed that, depending on the final attack rate and proportion of infected institutions.
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An alternative workflow for molecular detection of SARS-CoV-2 – escape from the NA extraction kit-shortage, Copenhagen, Denmark, March 2020
More LessThe World Health Organization has declared COVID-19 caused by the newly discovered SARS-CoV-2 a pandemic. Due to growing demand for reagents and/or kits to extract SARS-CoV-2 RNA for subsequent RT-qPCR diagnostics, there is a worldwide risk of shortages. With a detection sensitivity of 97.4% (95% CI: 86.2–99.9%), we describe a simple, fast, alternative workflow for molecular detection of SARS-CoV-2, where samples are simply heat-processed for 5 min at 98 °C before a commonly-used RT-qPCR procedure.
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Excess cases of influenza-like illnesses synchronous with coronavirus disease (COVID-19) epidemic, France, March 2020
Several French regions where coronavirus disease (COVID-19) has been reported currently show a renewed increase in ILI cases in the general practice-based Sentinelles network. We computed the number of excess cases by region from 24 February to 8 March 2020 and found a correlation with the number of reported COVID-19 cases so far. The data suggest larger circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the French population than apparent from confirmed cases.
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Roll-out of SARS-CoV-2 testing for healthcare workers at a large NHS Foundation Trust in the United Kingdom, March 2020
Healthcare workers (HCW) are potentially at increased risk of infection with coronavirus disease (COVID-19) and may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to vulnerable patients. We present results from staff testing at Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom. Between 16 and 29 March 2020, 1,533 symptomatic HCW were tested, of whom 282 (18%) were positive for SARS-CoV-2. Testing HCW is a crucial strategy to optimise staffing levels during this outbreak.
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Indications for healthcare surge capacity in European countries facing an exponential increase in coronavirus disease (COVID-19) cases, March 2020
More LessEuropean healthcare systems face extreme pressure from coronavirus disease (COVID-19). We relate country-specific accumulated COVID-19 deaths (intensity approach) and active COVID-19 cases (magnitude approach) to measures of healthcare system capacity: hospital beds, healthcare workers and healthcare expenditure. Modelled by the intensity approach with a composite measure for healthcare capacity, the countries experiencing the highest pressure on 25 March 2020 - relative to Italy on 11 March - were Italy, Spain, the Netherlands and France (www.covid-hcpressure.org).
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Only strict quarantine measures can curb the coronavirus disease (COVID-19) outbreak in Italy, 2020
More LessSeveral Italian towns are under lockdown to contain the COVID-19 outbreak. The level of transmission reduction required for physical distancing interventions to mitigate the epidemic is a crucial question. We show that very high adherence to community quarantine (total stay-home policy) and a small household size is necessary for curbing the outbreak in a locked-down town. The larger the household size and amount of time in the public, the longer the lockdown period needed.
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The impact of unplanned school closure on children’s social contact: rapid evidence review
BackgroundEmergency school closures are often used as public health interventions during infectious disease outbreaks to minimise the spread of infection. However, if children continue mixing with others outside the home during closures, the effect of these measures may be limited.
AimThis review aimed to summarise existing literature on children’s activities and contacts made outside the home during unplanned school closures.
MethodsIn February 2020, we searched four databases, MEDLINE, PsycInfo, Embase and Web of Science, from inception to 5 February 2020 for papers published in English or Italian in peer-reviewed journals reporting on primary research exploring children’s social activities during unplanned school closures. Main findings were extracted.
ResultsA total of 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures, but contact remained common. All studies reported children leaving the home or being cared for by non-household members. There was some evidence that older child age (two studies) and parental disagreement (two studies) with closure were predictive of children leaving the home, and mixed evidence regarding the relationship between infection status and such. Parental agreement with closure was generally high, but some disagreed because of perceived low risk of infection and issues regarding childcare and financial impact.
ConclusionEvidence suggests that many children continue to leave home and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.
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Understanding coronavirus disease (COVID-19) risk perceptions among the public to enhance risk communication efforts: a practical approach for outbreaks, Finland, February 2020
More LessUnderstanding risk perceptions of the public is critical for risk communication. In February 2020, the Finnish Institute for Health and Welfare started collecting weekly qualitative data on coronavirus disease (COVID-19) risk perception that informs risk communication efforts. The process is based on thematic analysis of emails and social media messages from the public and identifies factors linked to appraisal of risk magnitude, which are developed into risk communication recommendations together with health and communication experts.
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Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe
Paola Stefanelli , Giovanni Faggioni , Alessandra Lo Presti , Stefano Fiore , Antonella Marchi , Eleonora Benedetti , Concetta Fabiani , Anna Anselmo , Andrea Ciammaruconi , Antonella Fortunato , Riccardo De Santis , Silvia Fillo , Maria Rosaria Capobianchi , Maria Rita Gismondo , Alessandra Ciervo , Giovanni Rezza , Maria Rita Castrucci , Florigio Lista and on behalf of ISS COVID-19 study groupWhole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient’s sequence clustered with sequences from Germany while the tourist’s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients’ sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.
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Coronavirus disease (COVID-19) Community Testing Team in Scotland: A 14-day review, 6 to 20 February 2020
In response to the outbreak of COVID-19, we set up a team to carry out sampling in the community. This enabled individuals to remain in self-isolation in their own homes and to prevent healthcare settings and services from being overwhelmed by admissions for sampling of suspected cases. There is evidence that this is a cost effective, safe and necessary service to complement COVID-19 testing in hospitals.
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Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020
Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89–6.7) and 1.3% (95% CI: 0.38–3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3–2.7) and 0.6% (95% CI: 0.2–1.3), respectively.
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Potential short-term outcome of an uncontrolled COVID-19 epidemic in Lombardy, Italy, February to March 2020
Sustained coronavirus disease (COVID-19) transmission is ongoing in Italy, with 7,375 reported cases and 366 deaths by 8 March 2020. We provide a model-based evaluation of patient records from Lombardy, predicting the impact of an uncontrolled epidemic on the healthcare system. It has the potential to cause more than 250,039 (95% credible interval (CrI): 147,717–459,890) cases within 3 weeks, including 37,194 (95% CrI: 22,250–67,632) patients requiring intensive care. Aggressive containment strategies are required.
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Rapid assessment of regional SARS-CoV-2 community transmission through a convenience sample of healthcare workers, the Netherlands, March 2020
Chantal B Reusken , Anton Buiting , Chantal Bleeker-Rovers , Bram Diederen , Mariëtte Hooiveld , Ingrid Friesema , Marion Koopmans , Titia Kortbeek , Suzanne PM Lutgens , Adam Meijer , Jean-Luc Murk , Ilse Overdevest , Thera Trienekens , Aura Timen , Wouter Van den Bijllaardt , Jaap Van Dissel , Arianne Van Gageldonk-Lafeber , Dewi Van der Vegt , Peter C Wever , Wim Van der Hoek and Jan KluytmansTo rapidly assess possible community transmission in Noord-Brabant, the Netherlands, healthcare workers (HCW) with mild respiratory complaints and without epidemiological link (contact with confirmed case or visited areas with active circulation) were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within 2 days, 1,097 HCW in nine hospitals were tested; 45 (4.1%) were positive. Of six hospitals with positive HCW, two accounted for 38 positive HCW. The results informed local and national risk management.
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Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020
Emanuele Nicastri , Alessandra D’Abramo , Giovanni Faggioni , Riccardo De Santis , Andrea Mariano , Luciana Lepore , Filippo Molinari , Giancarlo Petralito , Silvia Fillo , Diego Munzi , Angela Corpolongo , Licia Bordi , Fabrizio Carletti , Concetta Castiletti , Francesca Colavita , Eleonora Lalle , Nazario Bevilacqua , Maria Letizia Giancola , Laura Scorzolini , Simone Lanini , Claudia Palazzolo , Angelo De Domenico , Maria Anna Spinelli , Paola Scognamiglio , Paolo Piredda , Raffaele Iacomino , Andrea Mone , Vincenzo Puro , Nicola Petrosillo , Antonio Battistini , Francesco Vairo , Florigio Lista , Giuseppe Ippolito and on behalf of INMI and the Italian Army COVID-19 study groupsData concerning the transmission of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) in paucisymptomatic patients are lacking. We report an Italian paucisymptomatic case of coronavirus disease 2019 with multiple biological samples positive for SARS-CoV-2. This case was detected using the World Health Organization protocol on cases and contact investigation. Current discharge criteria and the impact of extra-pulmonary SARS-CoV-2 samples are discussed.
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Influenza-associated pneumonia as reference to assess seriousness of coronavirus disease (COVID-19)
More LessInformation on severity of coronavirus disease (COVID-19) (transmissibility, disease seriousness, impact) is crucial for preparation of healthcare sectors. We present a simple approach to assess disease seriousness, creating a reference cohort of pneumonia patients from sentinel hospitals. First comparisons exposed a higher rate of COVID-19 patients requiring ventilation. There were more case fatalities among COVID-19 patients without comorbidities than in the reference cohort. Hospitals should prepare for high utilisation of ventilation and intensive care resources.
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Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union/European Economic Area and the United Kingdom, 1 January to 15 March 2020
The cumulative incidence of coronavirus disease (COVID-19) cases is showing similar trends in European Union/European Economic Area countries and the United Kingdom confirming that, while at a different stage depending on the country, the COVID-19 pandemic is progressing rapidly in all countries. Based on the experience from Italy, countries, hospitals and intensive care units should increase their preparedness for a surge of patients with COVID-19 who will require healthcare, and in particular intensive care.
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Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020
Anu Haveri , Teemu Smura , Suvi Kuivanen , Pamela Österlund , Jussi Hepojoki , Niina Ikonen , Marjaana Pitkäpaasi , Soile Blomqvist , Esa Rönkkö , Anu Kantele , Tomas Strandin , Hannimari Kallio-Kokko , Laura Mannonen , Maija Lappalainen , Markku Broas , Miao Jiang , Lotta Siira , Mika Salminen , Taneli Puumalainen , Jussi Sane , Merit Melin , Olli Vapalahti and Carita Savolainen-KopraThe first case of coronavirus disease (COVID-19) in Finland was confirmed on 29 January 2020. No secondary cases were detected. We describe the clinical picture and laboratory findings 3–23 days since the first symptoms. The SARS-CoV-2/Finland/1/2020 virus strain was isolated, the genome showing a single nucleotide substitution to the reference strain from Wuhan. Neutralising antibody response appeared within 9 days along with specific IgM and IgG response, targeting particularly nucleocapsid and spike proteins.
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Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020
More LessOn 5 February 2020, in Yokohama, Japan, a cruise ship hosting 3,711 people underwent a 2-week quarantine after a former passenger was found with COVID-19 post-disembarking. As at 20 February, 634 persons on board tested positive for the causative virus. We conducted statistical modelling to derive the delay-adjusted asymptomatic proportion of infections, along with the infections’ timeline. The estimated asymptomatic proportion was 17.9% (95% credible interval (CrI): 15.5–20.2%). Most infections occurred before the quarantine start.
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Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020
Yuanyuan Xing , Pingzheng Mo , Yu Xiao , Oiu Zhao , Yongxi Zhang and Fan WangSince December 2019, 62 medical staff of Zhongnan Hospital in Wuhan, China have been hospitalised with coronavirus disease 2019. During the post-discharge surveillance after clinical recovery, swabs were positive in two asymptomatic cases (3.23%). Case 1 had presented typical clinical and radiological manifestations on admission, while manifestation in Case 2 was very mild. In conclusion, a small proportion of recovered patients may test positive after discharge, and post-discharge surveillance and isolation need to be strengthened.
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Retrospective analysis of the possibility of predicting the COVID-19 outbreak from Internet searches and social media data, China, 2020
Cuilian Li , Li Jia Chen , Xueyu Chen , Mingzhi Zhang , Chi Pui Pang and Haoyu ChenThe peak of Internet searches and social media data about the coronavirus disease 2019 (COVID-19) outbreak occurred 10–14 days earlier than the peak of daily incidences in China. Internet searches and social media data had high correlation with daily incidences, with the maximum r > 0.89 in all correlations. The lag correlations also showed a maximum correlation at 8–12 days for laboratory-confirmed cases and 6–8 days for suspected cases.
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Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system
More LessFacing the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), high-volume respiratory testing is demanded in laboratories worldwide. We evaluated the performance of a molecular assay for the detection of SARS-CoV-2 on a high-throughput platform, the cobas 6800, using the ‘open channel’ for integration of a laboratory-developed assay. We observed good analytical performance in clinical specimens. The fully automated workflow enables high-throughput testing with minimal hands-on time, while offering fast and reliable results.
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First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020
Gianfranco Spiteri , James Fielding , Michaela Diercke , Christine Campese , Vincent Enouf , Alexandre Gaymard , Antonino Bella , Paola Sognamiglio , Maria José Sierra Moros , Antonio Nicolau Riutort , Yulia V. Demina , Romain Mahieu , Markku Broas , Malin Bengnér , Silke Buda , Julia Schilling , Laurent Filleul , Agnès Lepoutre , Christine Saura , Alexandra Mailles , Daniel Levy-Bruhl , Bruno Coignard , Sibylle Bernard-Stoecklin , Sylvie Behillil , Sylvie van der Werf , Martine Valette , Bruno Lina , Flavia Riccardo , Emanuele Nicastri , Inmaculada Casas , Amparo Larrauri , Magdalena Salom Castell , Francisco Pozo , Rinat A. Maksyutov , Charlotte Martin , Marc Van Ranst , Nathalie Bossuyt , Lotta Siira , Jussi Sane , Karin Tegmark-Wisell , Maria Palmérus , Eeva K. Broberg , Julien Beauté , Pernille Jorgensen , Nick Bundle , Dmitriy Pereyaslov , Cornelia Adlhoch , Jukka Pukkila , Richard Pebody , Sonja Olsen and Bruno Christian CiancioIn the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters’ index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.
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Potential scenarios for the progression of a COVID-19 epidemic in the European Union and the European Economic Area, March 2020
Two months after the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the possibility of established and widespread community transmission in the European Union and European Economic Area (EU/EEA) is becoming more likely. We provide scenarios for use in preparedness for a possible widespread epidemic. The EU/EEA is moving towards the ‘limited sustained transmission’ phase. We propose actions to prepare for potential mitigation phases and coordinate efforts to protect the health of citizens.
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Rapid establishment of laboratory diagnostics for the novel coronavirus SARS-CoV-2 in Bavaria, Germany, February 2020
The need for timely establishment of diagnostic assays arose when Germany was confronted with the first travel-associated outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Europe. We describe our laboratory experiences during a large contact tracing investigation, comparing previously published real-time RT-PCR assays in different PCR systems and a commercial kit. We found that assay performance using the same primers and probes with different PCR systems varied and the commercial kit performed well.
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Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020
A novel coronavirus (SARS-CoV-2) has been identified as the causative pathogen of an ongoing outbreak of respiratory disease, now named COVID-19. Most cases and sustained transmission occurred in China, but travel-associated cases have been reported in other countries, including Europe and Italy. Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases.
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Early transmission patterns of coronavirus disease 2019 (COVID-19) in travellers from Wuhan to Thailand, January 2020
Pilailuk Okada , Rome Buathong , Siripaporn Phuygun , Thanutsapa Thanadachakul , Sittiporn Parnmen , Warawan Wongboot , Sunthareeya Waicharoen , Supaporn Wacharapluesadee , Sumonmal Uttayamakul , Apichart Vachiraphan , Malinee Chittaganpitch , Nanthawan Mekha , Noppavan Janejai , Sopon Iamsirithaworn , Raphael TC Lee and Sebastian Maurer-StrohWe report two cases of coronavirus disease 2019 (COVID-19) in travellers from Wuhan, China to Thailand. Both were independent introductions on separate flights, discovered with thermoscanners and confirmed with RT-PCR and genome sequencing. Both cases do not seem directly linked to the Huanan Seafood Market in Hubei but the viral genomes are identical to four other sequences from Wuhan, suggesting early spread within the city already in the first week of January.
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First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020
Sibylle Bernard Stoecklin , Patrick Rolland , Yassoungo Silue , Alexandra Mailles , Christine Campese , Anne Simondon , Matthieu Mechain , Laure Meurice , Mathieu Nguyen , Clément Bassi , Estelle Yamani , Sylvie Behillil , Sophie Ismael , Duc Nguyen , Denis Malvy , François Xavier Lescure , Scarlett Georges , Clément Lazarus , Anouk Tabaï , Morgane Stempfelet , Vincent Enouf , Bruno Coignard , Daniel Levy-Bruhl and Investigation teamA novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.
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Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries, January 2020
Timely detection of novel coronavirus (2019-nCoV) infection cases is crucial to interrupt the spread of this virus. We assessed the required expertise and capacity for molecular detection of 2019-nCoV in specialised laboratories in 30 European Union/European Economic Area (EU/EEA) countries. Thirty-eight laboratories in 24 EU/EEA countries had diagnostic tests available by 29 January 2020. A coverage of all EU/EEA countries was expected by mid-February. Availability of primers/probes, positive controls and personnel were main implementation barriers.
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Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV)
More LessWe evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.
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Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020
More LessA novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.
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Novel coronavirus (2019-nCoV) early-stage importation risk to Europe, January 2020
As at 27 January 2020, 42 novel coronavirus (2019-nCoV) cases were confirmed outside China. We estimate the risk of case importation to Europe from affected areas in China via air travel. We consider travel restrictions in place, three reported cases in France, one in Germany. Estimated risk in Europe remains high. The United Kingdom, Germany and France are at highest risk. Importation from Beijing and Shanghai would lead to higher and widespread risk for Europe.
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Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020
More LessSince December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R0 of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.
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Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR
Victor M Corman , Olfert Landt , Marco Kaiser , Richard Molenkamp , Adam Meijer , Daniel KW Chu , Tobias Bleicker , Sebastian Brünink , Julia Schneider , Marie Luisa Schmidt , Daphne GJC Mulders , Bart L Haagmans , Bas van der Veer , Sharon van den Brink , Lisa Wijsman , Gabriel Goderski , Jean-Louis Romette , Joanna Ellis , Maria Zambon , Malik Peiris , Herman Goossens , Chantal Reusken , Marion PG Koopmans and Christian DrostenBackgroundThe ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur.
AimWe aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available.
MethodsHere we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology.
ResultsThe workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project.
ConclusionThe present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020
A novel coronavirus (2019-nCoV) causing severe acute respiratory disease emerged recently in Wuhan, China. Information on reported cases strongly indicates human-to-human spread, and the most recent information is increasingly indicative of sustained human-to-human transmission. While the overall severity profile among cases may change as more mild cases are identified, we estimate a risk of fatality among hospitalised cases at 14% (95% confidence interval: 3.9–32%).
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