Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19: An observational cohort.

Background: There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high dependency unit (HDU). On the other hand, limited resources at times of high demand may lead to rationing. Nevertheless, these variables may be used as static proxies for disease severity, as outcome measures for trials, and to inform planning and logistics. Methods: We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay. Results: Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors. Conclusions: Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly evolving situation. Funding: This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017-18: a retrospective observational study.

BACKGROUND: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the 2017-18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea. METHODS: We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017-18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used. FINDINGS: In 2017-18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0-21% to ceftriaxone and 0-22% to cefixime, and that of resistance was 0-60% to azithromycin and 0-100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015-16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions. INTERPRETATION: In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative. FUNDING: None.

Correction: Underestimation of Leptospirosis Incidence in the French West Indies.

[This corrects the article DOI: 10.1371/journal.pntd.0004668.].

A large prolonged outbreak of hepatitis A associated with consumption of frozen berries, Italy, 2013-14.

PURPOSE: In 2013/2014, Italy experienced one of the largest community-wide prolonged outbreaks of hepatitis A virus (HAV) throughout the country. The article provides a comprehensive description of the outbreak and the investigation carried out by a multidisciplinary National Task Force, in collaboration with regional and local public health authorities. Control strategies of food-borne HAV infection in both the human and food sectors are also described. METHODOLOGY: Enhanced human epidemiological and microbiological surveillance together with microbiological monitoring of HAV in food and trace-back investigation were conducted. RESULTS: A total of 1803 HAV cases were identified from 1 January 2013 to 31 August 2014, in Italy. Sequencing was possible for 368 cases (20.4 %), mostly collected between 1 January 2013 and 28 February 2014, and 246 cases (66.8 %) harboured an HAV outbreak strain. Imported frozen berries contaminated with HAV were identified as the vehicle of the outbreak which also involved many other European countries in 2013 and 2014. Epidemiological evidence obtained through a case-control study was supported by the finding of a 100 % nucleotide similarity of the VP1/2A sequences of HAVs detected in human and food samples. Trace-back investigation revealed an extremely complex supplying network with no possibility for a point source potentially explaining the vast contamination of berries found in Italy. CONCLUSION: The investigation benefited from an excellent collaboration among different sectors who shared proactively the available information. Our findings highlight the importance of considering frozen berries among the highest risk factors for HAV.

Underestimation of Leptospirosis Incidence in the French West Indies.

BACKGROUND: Leptospirosis is a neglected zoonosis affecting mainly tropical and subtropical regions worldwide, particularly South America and the Caribbean. As in many other countries, under-reporting of cases was suspected in the French West Indies because of inadequate access to diagnostic tests for the general population. METHODOLOGY/PRINCIPAL FINDINGS: In order to estimate the real incidence of leptospirosis in Guadeloupe and Martinique, a study was performed in 2011 using the three prevailing available biological tests for diagnosis: Microscopic Agglutination Test (MAT), IgM ELISA and PCR. The study investigated inpatients and outpatients and used active case ascertainment from data provided by a general practitioners' sentinel network. The epidemiology of the disease was also described in terms of severity and demographic characteristics. Leptospirosis incidence was estimated at 69.4 (95%CI 47.6-91.1) and 60.6 (95%CI 36.3-85.0) annual cases per 100,000 inhabitants in Guadeloupe and Martinique, respectively, which was 3 and 4 times higher than previous estimations. CONCLUSION/SIGNIFICANCE: Inclusion of PCR and IgM ELISA tests for diagnosis of leptospirosis resulted in improved sensitivity in comparison with MAT alone. Our results highlighted the substantial health burden of the disease in these two territories and the importance of access to appropriate laboratory tests. Based on our results, PCR and IgM ELISA tests have now been included in the list of tests reimbursed by the national system of social security insurance in France. Our results also underline the relevance of implementing an integrated strategy for the surveillance, prevention and control of leptospirosis in the French West Indies.

Timely detection of bronchiolitis epidemics in Guadeloupe.

OBJECTIVE: To develop a criterion for early detection of bronchiolitis epidemics in Guadeloupe so that prevention and control strategies can be implemented in a more timely manner. METHODS: Weekly figures of bronchiolitis cases reported from July 2005-July 2010 by Guadeloupe's sentinel network were used. The criterion for detecting epidemics was created with data from the 2005-2009 bronchiolitis seasons. First, the baseline level for bronchiolitis (BL) was predicted by fitting a periodic regression on the non-epidemic observations; then a test was conducted of nine possible criteria to define epidemics by combining a statistical threshold set at different levels and a number of consecutive weeks with observations above and below them; lastly, the optimal criterion was selected considering its performances using expert advice as the gold standard. The selected criterion was validated with data from 2009-2010 season. RESULTS: The BL accounted for a linear trend and two sinusoidal functions of 52 and 26 weeks (R2 = 45%). According to the epidemic criterion selected, the statistical threshold was set at the upper limit of the one-sided 95% Confidence Interval of the predicted BL; 2 consecutive weeks with cases above it were necessary to set the start of an epidemic, and three again below to set the end. The median delay in launching the alerts was 2 weeks; there was one false alert; and the sensitivity, specificity, and positive predictive value for detecting epidemic weeks were 98%, 96%, 95%, respectively. During the validation period, the criterion launched one false alert and detected the epidemic with 4 weeks of delay. CONCLUSIONS: This criterion supports epidemiologists in timely interpretation of bronchiolitis epidemiological data for decision makers in Guadeloupe. In the future, it should be updated in accordance with trends in bronchiolitis epidemiology, and improved by integrating virological indicators. Its inclusion in an integrated management strategy for bronchiolitis prevention and control, supported by a bronchiolitis public health network, should also be encouraged.

Timely detection of bronchiolitis epidemics in Guadeloupe / Detección oportuna de epidemias de bronquiolitis en Guadalupe

Objective. To develop a criterion for early detection of bronchiolitis epidemics in Guadeloupe so that prevention and control strategies can be implemented in a more timely manner. Methods. Weekly figures of bronchiolitis cases reported from July 2005­July 2010 by Guadeloupe's sentinel network were used. The criterion for detecting epidemics was created with data from the 2005­2009 bronchiolitis seasons. First, the baseline level for bronchiolitis (BL) was predicted by fitting a periodic regression on the non-epidemic observations; then a test was conducted of nine possible criteria to define epidemics by combining a statistical threshold set at different levels and a number of consecutive weeks with observations above and below them; lastly, the optimal criterion was selected considering its performances using expert advice as the gold standard. The selected criterion was validated with data from 2009­2010 season. Results. The BL accounted for a linear trend and two sinusoidal functions of 52 and 26 weeks (R2 = 45%). According to the epidemic criterion selected, the statistical threshold was set at the upper limit of the one-sided 95% Confidence Interval of the predicted BL; 2 consecutive weeks with cases above it were necessary to set the start of an epidemic, and three again below to set the end. The median delay in launching the alerts was 2 weeks; there was one false alert; and the sensitivity, specificity, and positive predictive value for detecting epidemic weeks were 98%, 96%, 95%, respectively. During the validation period, the criterion launched one false alert and detected the epidemic with 4 weeks of delay. Conclusions. This criterion supports epidemiologists in timely interpretation of bronchiolitis epidemiological data for decision makers in Guadeloupe. In the future, it should be updated in accordance with trends in bronchiolitis epidemiology, and improved by integrating virological indicators. Its inclusion in an integrated management strategy for bronchiolitis prevention and control, supported by a bronchiolitis public health network, should also be encouraged.

Objetivo. Formular un criterio para la detección temprana de las epidemias de bronquiolitis en Guadalupe, a fin de aplicar de manera más oportuna mejores estrategias de prevención y control. Métodos. Se usaron las cifras semanales de los casos de bronquiolitis notificados desde julio del 2005 hasta julio del 2010 por la red de vigilancia de Guadalupe. El criterio para detectar las epidemias se estableció con los datos de las temporadas de bronquiolitis del 2005 al 2009. En primer lugar, se predijo el nivel basal de bronquiolitis ajustando una regresión periódica a los casos observados fuera de las epidemias; luego se pusieron a prueba nueve posibles criterios para definir las epidemias combinando un umbral estadístico establecido a diferentes niveles y un número de semanas consecutivas con las observaciones ubicadas por encima y por debajo de ellos; por último, se seleccionó el criterio óptimo conforme a su desempeño, usando el asesoramiento de expertos como criterio de referencia. El criterio seleccionado se validó con los datos de la temporada 2009­2010. Resultados. El nivel basal de bronquiolitis presentaba una tendencia lineal y dos funciones sinusoidales de 52 y 26 semanas (R2 = 45%). Según el criterio de epidemia seleccionado, se fijó el umbral estadístico en el límite superior del intervalo de confianza de 95% unilateral del nivel basal de bronquiolitis previsto; para establecer el comienzo de una epidemia se requerían 2 semanas consecutivas con casos por encima de él, y 3 semanas con casos por debajo para determinar su finalización. La mediana del retraso para lanzar las alertas fue 2 semanas; hubo una alerta falsa; y la sensibilidad, la especificidad y el valor predictivo positivo para detectar las semanas de epidemia fueron 98%, 96% y 95%, respectivamente. Durante el período de validación se emitió, según el criterio, una alerta falsa y se detectó la epidemia con 4 semanas de retraso. Conclusiones. Este criterio ayuda a los epidemiólogos a interpretar de manera oportuna los datos epidemiológicos de bronquiolitis a fin de tomar decisiones en Guadalupe. En el futuro, debe actualizarse según las tendencias en la epidemiología de la bronquiolitis, y mejorarse mediante su integración con indicadores virológicos. También debe promoverse su inclusión en una estrategia integrada de manejo para la prevención y el control de la bronquiolitis, apoyada por una red de salud pública relacionada con la bronquiolitis

Use of antimicrobials in companion animal practice: a retrospective study in a veterinary teaching hospital in Italy.

OBJECTIVES: To describe the use of antimicrobials in a veterinary teaching hospital for companion animals in Italy, with particular regard to the agreement with recommendations of prudent use METHODS: The study was conducted with a retrospective, cross-sectional design. The population under investigation included 18,905 cats and dogs that were referred to the hospital between 2000 and 2007. Two different samples of the clinical paper forms were randomly selected to estimate the prevalence of animals receiving an antimicrobial prescription and to describe the pattern of antimicrobials used in relation to the condition being treated. The proportion of antimicrobials prescribed accomplishing recommendations of prudent use was also estimated, as well as the level of agreement with specific, diagnosis-based guidelines for antimicrobial use. RESULTS: Broad-spectrum antimicrobials, including penicillins with ß-lactamase inhibitors, first-generation cephalosporins and fluoroquinolones, were the most frequently prescribed compounds. Antimicrobials prescribed with the support of microbiological analyses and susceptibility testing were less than 5%. Among the recommendation of prudent use, the availability of information from laboratory testing had the poorest degree of agreement, while the other evaluated items were accomplished in most of the cases. CONCLUSIONS: Our results highlight the need to improve the procedures of antimicrobial prescription in the study setting. This can be achieved by supporting the guidance for antimicrobial use at the local level, with the adoption of specific guidelines, and at the national level with a further implementation of the policies of prudent prescriptions.

Enteroaggregative Escherichia coli associated with a foodborne outbreak of gastroenteritis.

This study investigated two foodborne outbreaks of gastroenteritis that occurred 10 days apart among individuals who had meals at the restaurant of a farm holiday resort. Mild gastrointestinal symptoms were reported and none of the patients needed hospitalization. Mean incubation times were 45 and 33 h, and the overall attack rates were 43.5 and 58.3%, respectively. Stool sample examination was negative for common enteric pathogens in both outbreaks. Specimens from 13 people involved in the second outbreak and 3 restaurant staff were examined for diarrhoeagenic Escherichia coli. An enteroaggregative E. coli (EAEC) strain of serotype O92:H33 was isolated from six participants and one member of staff. In particular, the EAEC strain was isolated from five of the six cases of diarrhoea examined. The strain showed an aggregative pattern of adherence to HEp-2 cells, did not produce a biofilm and possessed the virulence-related genes aat, aggR, aap and set1A, but not the astA gene. A retrospective cohort study indicated a pecorino cheese made with unpasteurized sheep milk as the possible source (P<0.001). Samples of the cheese had E. coli counts higher than 10(6) c.f.u. g(-1), but the outbreak EAEC strain was not isolated. This report confirms that EAEC infections are probably underdiagnosed because of the limited availability of laboratories capable of identifying this group of pathogenic E. coli.