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Coronavirus disease (COVID-19)
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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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