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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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