Pregnancy during COVID-19: social contact patterns and vaccine coverage of pregnant women from CoMix in 19 European countries

CoMix Europe Working Group: Daniela Paolotti, André Karch, Veronika Jäger, Joaquin Baruch, Tanya Melillo, Henrieta Hudeckova, Magdalena Rosinska, Marta Niedzwiedzka-Stadnik, Krista Fischer, Sigrid Vorobjov, Hanna Sõnajalg, Christian Althaus, Nicola Low, Martina Reichmuth, Kari Auranen, Markku Nurhonen, Goranka Petrović, Zvjezdana Lovric Makaric, Sónia Namorado, Constantino Caetano, Ana João Santos, Gergely Röst, Beatrix Oroszi, Márton Karsai, Mario Fafangel, Petra Klepac, Natalija Kranjec, Cristina Vilaplana, Jordi Casabona.CoMix Europe Working Group: Sónia Namorado, Constantino Caetano, and Ana João Santos (Department of Epidemiology, National Institute of Health Dr Ricardo Jorge, Portugal)Background: Evidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries. Methods: In each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the adjusted mean number of contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap. Findings: We recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18-49. Pregnant women made slightly fewer contacts (3.6, 95%CI = 3.5-3.7) than non-pregnant women (4.0, 95%CI = 3.9-4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15-20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period. COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women. Interpretation: Limited social contact to avoid pathogen exposure during the COVID-19 pandemic has been a challenge to many, especially women going through pregnancy. More recognition of maternal social support desire is needed in the ongoing pandemic. As COVID-19 vaccination continues to remain an important pillar of outbreak response, strategies to promote correct information can provide reassurance and facilitate informed pregnancy vaccine decisions in this vulnerable group.HPRU in Modelling & Health Economics,NIHR200908,European Union’s Horizon 2020 research and innovation programme,EpiPose 101003688,TransMID 682540,TransMID 682540,TransMID 682540,EpiPose 101003688,Wellcome Trust,213589/Z/18/Z,National Institute for Health Research,CV220-088—COMIX,CV220-088—COMIX,CV220-088— COMIX,Global Challenges Research Fund,ES/P010873/1,Medical Research Council,MC_PC_19065,NIHR,PR-OD-1017-20002 HPRU in Modelling & Health Economics (NIHR200908: KLMW); European Union Horizon 2020 research and innovation programme – (EpiPose 101,003,688: AG, WJE). Wellcome Trust (213,589/Z/18/Z: ESP). European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (TransMID 682,540: CF, PN, NH). This research was partly funded by the Global Challenges Research Fund (GCRF) project RECAP managed through RCUK and ESRC (ES/P010873/1: CIJ). NIHR (PR-OD-1017–20,002: WJE) UK MRC (MC_PC_19065—Covid 19: Understanding the dynamics and drivers of the COVID-19 epidemic using real-time outbreak analytics: WJE).info:eu-repo/semantics/publishedVersio

Social contact patterns during the COVID-19 pandemic in 21 European countries - evidence from a two-year study

CoMix Europe Working Group: Daniela Paolotti, Michele Tizzani, Ciro Cattuto, Andrea Schmidt, Gerald Gredinger, Sophie Stumpfl, Joaquin Baruch, Tanya Melillo, Henrieta Hudeckova, Jana Zibolenova, Zuzana Chladna, Magdalena Rosinska, Marta Niedzwiedzka-Stadnik, Krista Fischer, Sigrid Vorobjov, Hanna Sõnajalg, Christian Althaus, Nicola Low, Martina Reichmuth, Kari Auranen, Markku Nurhonen, Goranka Petrović, Zvjezdana Lovric Makaric, Sónia Namorado, Constantino Caetano, Ana João Santos, Gergely Röst, Beatrix Oroszi, Márton Karsai, Mario Fafangel, Petra Klepac, Natalija Kranjec, Cristina Vilaplana, Jordi Casabona.Sónia Namorado, Constantino Caetano, and Ana João Santos (Department of Epidemiology, National Institute of Health Dr Ricardo Jorge, Portugal).Background: Most countries have enacted some restrictions to reduce social contacts to slow down disease transmission during the COVID-19 pandemic. For nearly two years, individuals likely also adopted new behaviours to avoid pathogen exposure based on personal circumstances. We aimed to understand the way in which different factors affect social contacts - a critical step to improving future pandemic responses. Methods: The analysis was based on repeated cross-sectional contact survey data collected in a standardized international study from 21 European countries between March 2020 and March 2022. We calculated the mean daily contacts reported using a clustered bootstrap by country and by settings (at home, at work, or in other settings). Where data were available, contact rates during the study period were compared with rates recorded prior to the pandemic. We fitted censored individual-level generalized additive mixed models to examine the effects of various factors on the number of social contacts. Results: The survey recorded 463,336 observations from 96,456 participants. In all countries where comparison data were available, contact rates over the previous two years were substantially lower than those seen prior to the pandemic (approximately from over 10 to < 5), predominantly due to fewer contacts outside the home. Government restrictions imposed immediate effect on contacts, and these effects lingered after the restrictions were lifted. Across countries, the relationships between national policy, individual perceptions, or personal circumstances determining contacts varied. Conclusions: Our study, coordinated at the regional level, provides important insights into the understanding of the factors associated with social contacts to support future infectious disease outbreak responses.The following funding sources are acknowledged as providing funding for the named authors. HPRU in Modelling & Health Economics (NIHR200908: KLMW); European Union Horizon 2020 research and innovation programme (EpiPose 101003688: AG, WJE); European Research Council under the European Union Horizon 2020 research and innovation programme (TransMID 682540: CF, PB, NH) This research was partly funded by the Global Challenges Research Fund (GCRF) project RECAP managed through RCUK and ESRC (ES/P010873/1: CIJ) NIHR (PR_OD_1017_20002: WJE) UK MRC (MC_PC_19065—Covid 19: Under standing the dynamics and drivers of the COVID-19 epidemic using real-time outbreak analytics: WJE). In Belgium, CoMix data collection in Belgium was made possible with fnancial support of Janssen Pharmaceuticals and the national public health institute of Belgium, Sciensano. In Germany, the COVIMOD project is funded by intramural funds of the Institute of Epidemiology and Social Medicine, University of Münster, and of the Institute of Medical Epidemiology, Biometry and Informatics, Martin Luther University Halle-Wittenberg, as well as by funds provided by the Robert Koch Institute, Berlin, the Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V. via the HZEpiAdHoc "The Helmholtz Epidemiologic Response against the COVID-19 Pandemic" project, the Saxonian COVID-19 Research Consortium SaxoCOV (co-fnanced with tax funds on the basis of the budget passed by the Saxon state parliament), the Federal Ministry of Education and Research (BMBF) as part of the Network University Medicine (NUM) via the egePan Unimed project (funding code: 01KX2021) and the Deutsche Forschungsge meinschaft (DFG, German Research Foundation, project number 458526380)info:eu-repo/semantics/publishedVersio

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021

Members of the I-MOVE-COVID-19 and VEBIS hospital study teams (in addition to the named authors): Svjetlana Karabuva, Petra Tomaš Petrić, Marija Marković, Sandra Ljubičić, Bojana Mahmutović, Irena Tabain, Petra Smoljo, Iva Pem Novosel, Tanya Melillo, John Paul Cauchi, Benédicte Lissoir, Xavier Holemans, Marc Hainaut, Nicolas Dauby, Benedicte Delaere, Marc Bourgeois, Evelyn Petit, Marijke Reynders, Door Jouck, Koen Magerman, Marieke Bleyen, Melissa Vermeulen, Sébastien Fierens, François Dufrasne, Siel Daelemans, Ala’a Al Kerwi, Francoise Berthet, Guy Fagherazzi, Myriam Alexandre, Charlene Bennett, Jim Christle, Jeff Connell, Peter Doran, Laura Feeney, Binita Maharjan, Sinead McDermott, Rosa McNamara, Nadra Nurdin, Salif Mamadou Cissé, Anne-Sophie L'Honneur, Xavier Duval, Yolande Costa, Fidouh Nadhira, Florence Galtier, Laura Crantelle, Vincent Foulongne, Phillipe Vanhems, Sélilah Amour, Bruno Lina, Fabrice Lainé, Laetitia Gallais, Gisèle Lagathu, Anna Maisa, Yacine Saidi, Christine Durier, Rebecca Bauer, Ana Paula Rodrigues, Adriana Silva, Raquel Guiomar, Margarida Tavares, Débora Pereira, Maria José Manata, Heidi Gruner, André Almeida, Paula Pinto, Cristina Bárbara, Itziar Casado, Ana Miqueleiz, Ana Navascués, Camino Trobajo-Sanmartín, Miguel Fernández-Huerta, María Eugenia Portillo, Carmen Ezpeleta, Nerea Egüés, Manuel García Cenoz, Eva Ardanaz, Marcela Guevara, Conchi Moreno-Iribas, Hana Orlíková, Carmen Mihaela Dorobat, Carmen Manciuc, Simin Aysel Florescu, Alexandru Marin, Sorin Dinu, Catalina Pascu, Alina Ivanciuc, Iulia Bistriceanu, Mihaela Oprea, Maria Elena Mihai, Silke Buda, Ute Preuss, Marianne Wedde, Auksė Mickienė, Giedrė Gefenaitė, Alain Moren, Anthony NardoneIntroduction: Two large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021. Aim: We aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March–June)- and Delta (June–December)-dominant periods, 2021. Methods: Forty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case–control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset. Results: We included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69–92) overall and 75% (95% CI: 42–90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18–74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57–98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90–179 days before onset. Conclusions: Our results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.Key public health message: - What did you want to address in this study? To understand how well the COVID-19 vaccine was performing in Europe against hospitalisation during SARS-CoV-2 Alpha and Delta variant periods, we present vaccine effectiveness results from a multi-country study of complete and booster dose COVID-19 vaccination among adults (aged 20 years and over). - What have we learnt from this study? Between March and June 2021 (Alpha period), vaccine effectiveness against hospitalisation with laboratory-confirmed SARS-CoV-2 was 43% for partial vaccination and 86% for complete vaccination. For June to December 2021 (Delta period), vaccine effectiveness for complete vaccination was lower (52%) but with addition of an mRNA booster dose, effectiveness reached 91%, and remained > 90% up to 119 days after the booster dose. - What are the implications of your findings for public health? In Europe in 2021, COVID-19 vaccine effectiveness results for the Alpha period indicated an excellent benefit for preventing hospitalisation after complete vaccination. During Delta variant circulation, however, a booster dose was required to achieve this level of effectiveness, and this was maintained for up to 4 months post booster.info:eu-repo/semantics/publishedVersio

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022

Introduction: The I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021. Aim: We aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period). Methods: In both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition. Results: We included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively. Conclusions: Our results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.Key public health message: 1. What did you want to address in this study? In order to understand how well the COVID-19 vaccine is performing in Europe against hospitalisation during the period when the SARS-CoV-2 Omicron variant was circulating, we investigated vaccine effectiveness using data from a multi-country study of complete and booster-dose COVID-19 vaccination among adults aged 20 years and over. 2. What have we learnt from this study? Between December 2021 and July 2022, vaccine effectiveness against hospitalisation with laboratory-confirmed SARS-CoV-2 was 43% for complete vaccination. With addition of an mRNA booster dose, effectiveness was 59% overall. It was higher when onset of illness was close to the date of the last vaccination, at 85% when last booster dose was 14–59 days before onset, at 70% for 60–119 days, and falling below 40% for 120–179 days. 3. What are the implications of your findings for public health? In European hospital settings in 2022, during the Omicron period, COVID-19 mRNA booster vaccine provided an improved benefit for preventing hospitalisation, particularly if disease onset was within 4 months of receiving the booster dose.info:eu-repo/semantics/publishedVersio

Diagnostics and risk factors for bovine respiratory disease

Doctor of PhilosophyDepartment of Diagnostic Medicine/PathobiologyNatalia CernicchiaroDavid G. RenterDiagnostic inaccuracy and unknown risk distributions for bovine respiratory disease (BRD) are some of the most important issues faced by the feedlot industry. Given these issues, the overarching themes of this thesis are on the evaluation of point-of-care diagnostic methods for BRD and on summarizing, synthesizing, and simulating the impact of risk factors and disease interventions on BRD morbidity. The objectives of the research chapters included in this thesis are to: 1) evaluate BRD disease progression using point-of-care diagnostic methods in a challenge study, 2) map the available literature on risk factors for BRD morbidity in beef cattle using a scoping review, 3) evaluate associations between vaccination programs and BRD morbidity in beef feedlot cattle, and 4) define BRD risk distributions based on cattle characteristics and disease interventions. When evaluating point-of-care diagnostic methods, we observed that computer-aided-stethoscope scores, oxygen saturation levels, and ultrasound-measured consolidation varied by study day and disease stage (viral or bacterial). Clinical illness scores and temperature measurements, commonly used as metrics for BRD diagnosis on the field, did vary by study day but may not be discriminative of disease stage. Lymphocyte, neutrophil, and fibrinogen concentrations, and lymphocyte/neutrophil ratio, demonstrated differences following bacterial inoculation and, therefore, could be used to assess disease progression. Metaphylaxis, vaccination, dietary supplements, and preconditioning programs were the most studied risk factors for BRD morbidity in beef cattle. Although unclear why these risk factors were studied more often than those related to animal management practices, sources of funding, and the potential market value of these interventions seem to be plausible explanations. Vaccination programs for BRD prevention implemented before feedlot arrival were associated with reduced BRD morbidity; however, vaccination programs implemented at feedlot arrival were not. These associations indicate that preconditioning programs, which normally include vaccination before cattle arrive at the feedlot, might be better strategies for reducing BRD’s burden to the beef industry. Metaphylaxis was the most effective intervention at feedlot arrival to reduce BRD morbidity, but its efficacy depended on the antimicrobial drug used and cattle characteristics. The lowest median BRD morbidities were estimated for tilmicosin, gamithromycin, tulathromycin, and tildipirosin, but estimations of BRD morbidity with other antimicrobials were similar to those obtained by feedlot arrival vaccinations on weaned animals. Therefore, whereas metaphylaxis can effectively reduce BRD morbidity, non-antimicrobial alternatives could be implemented to reduce the use of less effective antimicrobials. Overall, the results described in this thesis contribute to improving the knowledge on point-of-care diagnostics methods, availability of data on risk factors for BRD, effectiveness of vaccination timing on BRD morbidity, and defining BRD risk distributions based on cattle characteristics and disease interventions

Hybrid immunity and protection against infection during the Omicron wave in Malta

AbstractBackground: By December 2021, administration of the third dose of COVID-19 vaccinations coincided with the spread of the Omicron variant in Europe. Questions had been raised on protection against infection conferred by previous vaccination and/or infection.Method: Our study population included 252,433 participants from the COVID-19 vaccination registry in Malta. Data were then matched with the national testing database. We collected vaccination status, vaccine brand, vaccination date, infection history, and age. Using logistic regression, we examined different combinations of vaccine dose, prior infection status and time, and the odds of infection during the period when the Omicron variant was the dominant variant in Malta.Results: Participants infected with Sars-Cov-2 prior to the Omicron wave had a significantly lower odds of being infected with the Omicron variant. Additionally, the more recent the infection and the more recent the vaccination, the lower the odds of infection. Receiving a third dose within 20 weeks of the start of the Omicron wave in Malta offered similar odds of infection as receiving a second dose within the same period.Conclusion: Time since vaccination was a strong determinant against infection, as was previous infection status and the number of doses taken. This finding reinforces the importance of future booster dose provision especially to vulnerable populations

Symptom‐based case definitions for COVID‐19: Time and geographical variations for detection at hospital admission among 260,000 patients

Introduction: Case definitions are used to guide clinical practice, surveillance and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the Centers for Disease Control (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO) and UK Health Security Agency (UKHSA) case definitions by age, region and time. Case fatality ratios (CFRs) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test result were excluded. Results: A total of 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC) and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients who met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions, risking delayed medical care. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread

Liver injury in hospitalized patients with COVID-19: An International observational cohort study.

BackgroundUsing a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes.MethodsWe included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI).ResultsOf 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]).ConclusionsLiver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes

Digitalizing and Upgrading Severe Acute Respiratory Infections Surveillance in Malta: System Development

BackgroundIn late 2020, the European Centre for Disease Prevention and Control and Epiconcept started implementing a surveillance system for severe acute respiratory infections (SARI) across Europe. ObjectiveWe sought to describe the process of digitizing and upgrading SARI surveillance in Malta, an island country with a centralized health system, during the COVID-19 pandemic from February to November 2021. We described the characteristics of people included in the surveillance system and compared different SARI case definitions, including their advantages and disadvantages. This study also discusses the process, output, and future for SARI and other public health surveillance opportunities. MethodsMalta has one main public hospital where, on admission, patient data are entered into electronic records as free text. Symptoms and comorbidities are manually extracted from these records, whereas other data are collected from registers. Collected data are formatted to produce weekly and monthly reports to inform public health actions. From October 2020 to February 2021, we established an analogue incidence-based system for SARI surveillance. From February 2021 onward, we mapped key stakeholders and digitized most surveillance processes. ResultsBy November 30, 2021, 903 SARI cases were reported, with 380 (42.1%) positive for SARS-CoV-2. Of all SARI hospitalizations, 69 (7.6%) were admitted to the intensive care unit, 769 (85.2%) were discharged, 27 (3%) are still being treated, and 107 (11.8%) died. Among the 107 patients who died, 96 (89.7%) had more than one underlying condition, the most common of which were hypertension (n=57, 53.3%) and chronic heart disease (n=49, 45.8%). ConclusionsThe implementation of enhanced SARI surveillance in Malta was completed by the end of May 2021, allowing the monitoring of SARI incidence and patient characteristics. A future shift to register-based surveillance should improve SARI detection through automated processes

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use