Cohort profile: a multicenter European study of acute respiratory infections: the MERMAIDS-ARI 2.0 cohort study

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Cohort profile: a multicenter European study of acute respiratory infections: the MERMAIDS-ARI 2.0 cohort study | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Cohort profile: a multicenter European study of acute respiratory infections: the MERMAIDS-ARI 2.0 cohort study View ORCID Profile Marieke L.A. de Hoog , View ORCID Profile Cristina Prat-Aymerich , View ORCID Profile Darren P.R. Troeman , James Lee , Greet Ieven , Peter Horby , Frank Leus , View ORCID Profile Marc J. M. Bonten , View ORCID Profile Herman J.A. Goossens , View ORCID Profile Patricia C.J.L. Bruijning-Verhagen doi: https://doi.org/10.1101/2024.01.16.24301377 Marieke L.A. de Hoog 1 Julius Centre for Health Sciences and Primary Care, Department of Epidemiology, University Medical Centre Utrecht , Utrecht, The Netherlands Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marieke L.A. de Hoog For correspondence: M.L.A.deHoog{at}umcutrecht.nl Cristina Prat-Aymerich 1 Julius Centre for Health Sciences and Primary Care, Department of Epidemiology, University Medical Centre Utrecht , Utrecht, The Netherlands Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Cristina Prat-Aymerich Darren P.R. Troeman 1 Julius Centre for Health Sciences and Primary Care, Department of Epidemiology, University Medical Centre Utrecht , Utrecht, The Netherlands Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Darren P.R. Troeman James Lee 2 University of Oxford, Nuffield Department of Medicine , Oxford, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Greet Ieven 3 Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp , Antwerp, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Peter Horby 2 University of Oxford, Nuffield Department of Medicine , Oxford, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Frank Leus 1 Julius Centre for Health Sciences and Primary Care, Department of Epidemiology, University Medical Centre Utrecht , Utrecht, The Netherlands Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marc J. M. Bonten 1 Julius Centre for Health Sciences and Primary Care, Department of Epidemiology, University Medical Centre Utrecht , Utrecht, The Netherlands Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marc J. M. Bonten Herman J.A. Goossens 3 Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp , Antwerp, Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Herman J.A. Goossens Patricia C.J.L. Bruijning-Verhagen 1 Julius Centre for Health Sciences and Primary Care, Department of Epidemiology, University Medical Centre Utrecht , Utrecht, The Netherlands Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Patricia C.J.L. Bruijning-Verhagen Abstract Full Text Info/History Metrics Data/Code Preview PDF ABSTRACT Purpose Multi-centre EuRopean study of MAjor Infectious Disease Syndromes – Acute Respiratory Infections (MERMAIDS-ARI) cohort study is a European prospective cohort study. It was originally launched in 2016 as MERMAIDS-ARI to study acute respiratory infections. When the COVID-19 pandemic hit, the study re-started inclusion under an amended protocol as MERMAIDS-ARI 2.0 focusing on SARS-CoV-2. The objectives of this study were to describe the disease spectrum, clinical features, and outcomes of SARS-CoV-2 infections in hospital care, to determine relevant risk factors and the assess prevalence and within hospital spread compared to other respiratory infections. An important second objective was to establish an extensive biobank supplemented with detailed clinical data to be able to address future virological, immunological, and clinical research questions. Methods Patients with either 1) ARI presenting to hospital care during the SARS-CoV-2 epidemic (including both COVID-19 and non-COVID-19 patients) or 2) confirmed COVID-19 infection, but with atypical presentation (non-ARI) or with nosocomial acquisition were included. Clinical data and biological samples were collected on enrolment day and repeatedly thereafter until discharge. A subset of COVID-19 patients was also followed up to 12 months post-discharge to study clinical recovery and long-term sequelae. Findings to date In total 297 patients from 8 countries and 11 sites were recruited between June 2020 and September 2021. We reached high sample completeness for most sample types (>97% for single samples and >86% for serial samples). 294 (99.0%) patients were admitted to hospital with SARS-CoV-2. The population primarily consists of patients (median age 61 years) of Caucasian ethnicity, with the majority being male (62.0%) and having ≥1 comorbidities (67.3%). The median hospital stay was 10 days, and most patients (87.5%) received treatment with systemic corticosteroids and respiratory support (81.4%). A total of 64 (21.7%) patients were admitted to the Intensive Care Unit (ICU), and 6.5% died during hospitalization. Long-term follow-up of 94 patients revealed that most individuals resumed their regular activities and work within three months, with improvements observed in mobility and personal care over time. Instances of severe and extreme pain and anxiety were rarely reported (≤1.1%). Conclusion This pan-European study offers a valuable resource for conducting in-depth virological, immunological, and pathophysiological investigations pertaining to SARS-CoV-2. INTRODUCTION The COVID-19 pandemic caused a massive influx of patients in hospitals and intensive care units around the world and led to enormous pressures on healthcare systems. Newly emerging infectious diseases require well-documented patient cohorts rich in biological samples to unravel immunological and pathophysiological disease processes, identify predictive biomarkers and novel targets for therapeutic interventions. In March 2020, the Rapid European COVID-19 Emergency Research response (RECoVER) project involving 10 international partners was selected for funding by the European Union under the Horizon 2020 research framework. RECoVER addressed the most urgent questions related to COVID-19 for patient and public health. One of the RECOVER activities involved the relaunch of the adapted Multi-centre EuRopean study of MAjor Infectious Disease Syndromes – Acute Respiratory Infections (MERMAIDS-ARI). This study originated in 2016 within the Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) led by the University of Oxford. The primary aim of MERMAIDS-ARI was to identify host and pathogen related determinants of disease severity of ARI of patients presenting in primary of hospital care. To accommodate specific disease and pathogen characteristics of COVID-19, an adapted version of the MERMAIDS-ARI protocol was developed (MERMAIDS-ARI 2.0) in Spring 2020 with specific focus on SARS-CoV-2 infected and hospitalized patients. This cohort profile provides a detailed description of the established MERMAIDS-ARI 2.0 cohort and biobank. The cohort and its description can be used to identify suitable patient and sample collections for outstanding clinical, virological and immunological research questions related to COVID-19, for biomarker research and to explore novel targets for therapeutic interventions. COHORT DESCRIPTION The MERMAIDS-ARI 2.0 aimed to investigate the clinical, immunological, and virological characteristics of SARS-CoV-2 in hospital care in European countries. In addition, the study was setup to establish a biobank containing appropriate clinical samples for the study of pathogen replication and excretion within the host, of the host responses to infection and therapy over time (including innate and acquired immune responses), and of host genetic variants associated with disease severity. Site selection The clinical research infrastructure of COMBACTE network ( 1 ) was used for site selection providing access to a large patient population across all age groups and different healthcare environments. An eligibility form was implemented for checking inclusion and exclusion criteria in hospitals that: 1) had a local SARS-COV-2 PCR up and running for clinical care; 2) performed tests on regular basis and 3) kept records of PCRs tests performed including test results and patient identifier. In total 8 European countries (Serbia, Estonia, Greece, Montenegro, Italy, Romania, Spain and the Netherlands) with 11 sites participated in the study ( Figure 1 ). The study was approved by Ethic Committees in each participating country. Download figure Open in new tab Figure 1: Map of participating countries ( www.mapchart.net ). Patient enrollment and eligibility Patient screening and enrollment began in June 2020 and continued until September 2021. Patient eligibility was determined by hospital workers within 48 hours after hospital admission. The patient had to fulfill criteria A or criteria B: Criteria A: Children or adults admitted to hospital with respiratory symptoms as reason for admission and meeting the following criteria: clinical suspicion of a new episode of ARI with a high probability of SARS-CoV-2 infection (e.g. based on epidemiological linkage or diagnostic procedures); clinical suspicion of ARI as the primary reason for hospital admission, and had onset of the following symptoms within the time window of last 14 days: Sudden onset of self-reported fever OR temperature of ≥38°C at presentation AND At least one respiratory symptom (cough, sore throat, runny or congested nose, dyspnea) AND At least one systemic symptom (headache, muscle ache, sweats or chills or tiredness). Criteria B: Children or adults without respiratory symptoms as reason for admission who had a laboratory confirmed SARS-CoV-2 infection at the time of eligibility check. This allowed for additional identification of (i). severe SARS-CoV-2 cases presented to care but without fever, and (ii). nosocomial cases of SARS-CoV-2. Microbiological diagnosis was confirmed by molecular testing. If additional tests such as antigen detection were validated and available at the time of inclusion, it was confirmed by a reference method. Patients who could not or did not provide informed consent, attended primary care but the physician decided to send patient to the hospital for assessment and possible hospital admission or were transferred from another hospital were excluded. Data collection and sampling At enrollment, patient demographics were collected including sex, ethnicity, educational status, and employment. Detailed clinical information included contact and travel history, medical comorbidities, vaccination status, BMI along with signs and symptoms, vital signs, and laboratory values on admission. Clinical data were subsequently collected at each study visit including signs and symptoms, vital signs, laboratory values, complications, medication, and supportive care received.Serial biological sampling included respiratory, blood and stool specimens at multiple time points. See Table 1 for an overview of the study visit scheme, data collection and biological sampling of MERMAIDS-ARI 2.0. View this table: View inline View popup Download powerpoint Table 1: Measurements and biological sampling scheme MERMAIDS-ARI 2.0. For all patients, combined nose and throat swab or sample-nasopharyngeal swab were collected at enrollment, day 7, day 28 and at discharge. Stool samples were collected on day 2, 7, 28 and discharge. Blood samples included serum, EDTA and Tempus RNA tubes at enrollment, day 2, day 7, day 28 and at discharge for serology, hematology, blood chemistry as well as host transcriptome studies. Sites could opt-in for collection of additional blood cell-preparation tubes to study adaptive (cellular) immune responses (Tier 2). Patients were followed until discharge and on day 28 for mortality. In addition, in a subset of sites COVID-19 patients were invited to participate in a post-discharge follow-up with visits at 3-, 6- and 12-months including questionnaires, blood sampling and pulmonary function tests ( 2 , 3 ) to assess long-term outcomes. All information was collected in an online eCRF by using the Research Online research data platform. The MERMAIDS-ARI 2.0 data collection was aligned with the ISARIC-CCP data model to improve interoperability and joined data analyses across multiple cohorts.( 4 ) The CRF forms used in MERMAIDS-ARI 2.0 are attached in the supplement. Laboratory testing All samples were shipped to the central laboratory at University of Antwerp for storage or further processing. SARS-CoV-2 analyses was performed on all sequential NP swabs. Baseline NP swabs were further analyzed by PCR using a respiratory panel that included the following viruses: influenza A, B, A-H1 and A-H3, human coronaviruses NL63, 229E, OC43 and HKU1, Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 1 and 2, parainfluenza viruses 1, 2, 3 and 4, human metapneumovirus, rhinovirus, respiratory syncytial virus A and B, adenovirus, enterovirus, enterovirus D68, parechovirus, and bocavirus. And included the following bacteria: Bordetella pertussis, Chlamydophila pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, Staphylocococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae. Details of the methods have been described elsewhere.( 5 ) Peripheral Blood Mononuclear Cells (PBMCs) were isolated from the blood collected at day 2, 7, 28 and discharge in Cell Preparation Tubes (CPT) (Becton Dickinson Diagnostics, Franklin Lakes, NJ, USA) by density gradient centrifugation. Afterwards, they were washed twice with RPMI (Biowest, Nuaillé, France) supplemented with 10% fetal bovine serum (FBS; Biowest, Nuaillé, France) and finally counted using trypan blue in an inverted microscope. For cryopreservation, cells were suspended in 10% DMSO FBS (Sigma-Aldrich, Saint Louis, MO, USA), transferred into cryovials, and then stored at ™80 °C in a cold Nalgene Mr. Frosty Cryo 1 °C Freezing Container (ThermoFisher, Waltham, MA, USA). Cells were then transferred to liquid nitrogen within a week. Left-over baseline sample NP, PBMC’s, as well as all other samples were biobanked at -80 * Celsius. COHORT CHARACTERISTICS A total of 297 patients were enrolled in MERMAIDS-ARI 2.0 between June 2020 and September 2021. Of the 297 patients, 294 (99.0%) were admitted to hospital with SARS-CoV-2 and for 237 patients this was confirmed in the baseline NP swab upon study inclusion. Figure 2 provides an overview of monthly patient enrolment over time. At least one biological sample was obtained from 290 patients (97.6%). Per sample type, completeness varied between 56.9% for at least one stool sample to 97.6% for at least one blood sample and NP swab. Completeness was highest for baseline samples (> 95.6%, except for stool). Serial samples were available for 35.4% (stool) to 92.6% (blood) of sample types ( Table 2 ). View this table: View inline View popup Download powerpoint Table 2: Sample completeness (hospital) sites of MERMAIDS-ARI 2.0. Download figure Open in new tab Figure 2: Monthly inclusions in the MERMAIDS-ARI 2.0 study patients. Patient characteristics and medical history Table 3 shows baseline characteristics of the 297 patients. More males than females were included (62.0% males and 38.0% females). The majority was of white/Caucasian ethnicity (95.6%). The median age of the hospitalized patients was 61 year and one child (5-year-old) was included in the study. View this table: View inline View popup Table 3: Patient demographics and medical history by SARS-CoV-2 result and hospital versus GP. Most patients had ≥1 comorbidity (67.3%). The most reported comorbidities across all patients were obesity (38.5%), chronic cardiovascular disease (34.1%) and chronic pulmonary disease (28.7%). Hospitalization, treatment, and survival The median hospital stay was 10 days (range 2-71 days; Table 4 ). Most patients (87.5%) were treated with systemic corticosteroids and received respiratory support (81.4%). In total 64 (21.7%) patients were admitted to the ICU and 28 (9.5%) received mechanical ventilation. Any kind of complication occurred in 57.5% of patients (57.5%) and 19 patients (6.5%) died during hospital admission. View this table: View inline View popup Download powerpoint Table 4: Treatment during hospital stay. View this table: View inline View popup Download powerpoint Table 5: Complications and survival. Long term outcomes at 3-, 6- and 12-months In total 94 COVID-19 patients participated in the post-discharge substudy with follow-up visits at 3 (n=94), 6 (N=77) and 12 months (n=78) after discharge. Table 6 shows the characteristics and the physical and mental recovery of these patients. View this table: View inline View popup Table 6: Characteristics and recovery of patients in extended follow-up. Three months after discharge, most patients had resumed their usual activities (85.6%; the unemployed) or returned to work (94.3%; the employed). Of the employed patients, 11.3% had to make significant changes to their work duties or occupation because of their COVID-19 illness episode. Most of the patients reported no or only slight problems with mobility (no problem: 59.6% and slight problem: 21.3%), personal care (no problem: 88.3% and slight problem: 9.6%), and usual activities (no problem: 69.9% and slight problem: 19.4%). Pain or discomfort and anxiety or depression were not reported very often (16.2% of the patients reported moderate to extreme pain and discomfort and 9.6% reported moderate to extreme anxiety and depression). All parameters improved over time at 6- and 12 months. Median health rating was 80 (range 20-100) on a scale from 0-100 three months after discharge and improved to 85 at 6- and 12 months after discharge. DISCUSSION This longitudinal, hospital-based cohort study enrolled 297 patients from eight different European countries in the COVID-19 pandemic covering infections with the Wild-type, Alpha, and Delta variant. Strengths of our cohort study include the prospective design with detailed and standardized clinical follow-up and the serial sampling resulting in an extensive biobank and the Pan-European coverage. Jointly, this collection enables in-depths mechanistic studies on host-pathogen interactions, pathways for disease progression and virus evolution and has already contributed to some key insights on these topics.( 6 , 7 ) Furthermore, data collection was harmonized to international initiatives improving interoperability and joint analyses of multiple cohorts. Requests for individual level patient data and biobank access can be sent to first author (MLAH) who will seek agreement from the core research team. Planned further analyses include virus-virus and virus-bacterial interactions and transcriptomic analyses for biomarker discovery. The study also has some limitations. First, we did not succeed in enrolling pediatric subjects into the study. Main reason for this was the very low admission rate for COVID-19 among children, which later led to a protocol adaptation shifting focus entirely to adult patients. Second, we were unable to obtain serial samples from all enrolled subjects, which will impact the sample size available for some research questions. Third, most patients were enrolled in the first half of the pandemic. About half of patients had received at least one dose of COVID-19 vaccination and a limited number received (repeated) booster doses. Also, the proportion of patients with known prior SARS-CoV-2 infection is low. This may impact the ability to generalize (immunological) findings to the current era of SARS-CoV2 endemicity. Similarly, our cohort represents infections with wild-type and early variants of SARS-CoV-2. Conclusions We describe a prospective pan-European hospital based COVID-19 patient cohort and extensive biobank established during the COVID19 pandemic, which can provide a rich source for further virological, immunological, and pathophysiological studies related to SARS-CoV2. Data Availability All data produced in the present study are available upon reasonable request to the authors FUNDING This work is supported by RECOVER (Rapid European COVID-19 Emergency research Response), which has received funding from the EU Horizon 2020 Research and Innovation program [grant agreement number 101003589]. DISCLOSURE STATEMENT The authors alone are responsible for the content and writing of the paper. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Ethical statement Regulatory approvals were sought in each country. The following Ethics Boards were consulted: Medical Ethics Committee of the: University Medical Centre Utrecht-the Netherlands, Clinical Center of Serbia-Serbia, Clinical Centre of Kragujevac-Serbia, Tartu University Clinic-Estonia, Attikon University General Hospital-Greece, Brescia Hospital-Italy, Clinic Center of Podgorcia-Montenegro, National Institute for Infectious Diseases ‘Prof. Dr. Matei Bals’-Romania, University Hospital Brothers Trias I Pujol-Spain, HU Virgen Macarena-Spain and the Regional Hospital de M Laga-Spain. Dates of approval letters and/or numbers available on request. ACKNOWLEDGEMENTS We want to express our gratitude to the 11 hospital research teams, their doctors/nurses and practice personnel for implementing the study. References 1. ↵ Available from : https://www.combacte.com/ [dd.5-12-2023]. 2. ↵ Graham BL , Steenbruggen I , Miller MR , Barjaktarevic IZ , Cooper BG , Hall GL , et al. Standardization of Spirometry 2019 Update . An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med . 2019 ; 200 ( 8 ): e70 – e88 . OpenUrl 3. ↵ Hall GL , Filipow N , Ruppel G , Okitika T , Thompson B , Kirkby J , et al. Official ERS technical standard: Global Lung Function Initiative reference values for static lung volumes in individuals of European ancestry . Eur Respir J . 2021 ; 57 ( 3 ). 4. ↵ Group ICC , Garcia-Gallo E , Merson L , Kennon K , Kelly S , Citarella BW , et al. ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19 . Sci Data . 2022 ; 9 ( 1 ): 454 . OpenUrl 5. ↵ van der Velden AW , Shanyinde M , Bongard E , Bohmer F , Chlabicz S , Colliers A , et al. Clinical diagnosis of SARS-CoV-2 infection: An observational study of respiratory tract infection in primary care in the early phase of the pandemic . Eur J Gen Prac . 2023 ; 29 ( 1 ). 6. ↵ Huygens S , Oude Munnink B , Gharbharan A , Koopmans M , Rijnders B. Sotrovimab Resistance and Viral Persistence After Treatment of Immunocompromised Patients Infected With the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant . Clin Infect Dis . 2023 ; 76 ( 3 ): e507 – e9 . OpenUrl 7. ↵ van Kampen JJA , van de Vijver D , Fraaij PLA , Haagmans BL , Lamers MM , Okba N , et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19) . Nat Commun . 2021 ; 12 ( 1 ): 267 . OpenUrl CrossRef PubMed 8. Charlson ME , Pompei P , Ales KL , MacKenzie CR . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation . J Chronic Dis . 1987 ; 40 ( 5 ): 373 – 83 . OpenUrl CrossRef PubMed Web of Science View the discussion thread. Back to top Previous Next Posted January 17, 2024. 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