SARS-CoV-2; Diabetes mellitus; Invasive fungal infections SARS-CoV-2; Diabetes mellitus; Infecciones fúngicas invasivas SARS-CoV-2; Diabetis mellitus; Infeccions fúngiques invasives A mucormycosis surge was reported during the COVID-19 pandemic in India. A literature search until 14 July 2022, with the aim of updating COVID-19-associated mucormycosis (CAM), identified 663 studies and 88 met inclusion criteria (8727 patients). India reported 8388 patients, Egypt 208 and Europe 40. Rhino-orbito-cerebral mucormycosis (ROCM) was identified among 8082 (98.3%) patients, followed by 98 (1.2%) with pulmonary. In India, 82.6% of patients had diabetes mellitus, with 82% receiving corticosteroids. In Europe, 75% presented pulmonary CAM, 32.5% had diabetes and 40% were immunocompromised. CAM was identified at a median of 17.4 days (IQR 7.5 days) post COVID-19 diagnosis, and PCR was performed in five studies. Rhino-orbital invasion is clinically obvious, while cerebral involvement presents with cavernous sinus thrombosis, meningitis and cerebrovascular disease. Symptoms of pulmonary CAM usually overlap with severe COVID-19 pneumonia. High-dose liposomal Amphotericin B (and early surgical debridement in ROCM) are the mainstay of therapy. The median mortality rate was estimated to be 21.4% (IQR 31.9%), increased by the presence of pulmonary (80% (IQR 50%) or cerebral involvement (50% (IQR 63.9%). In summary, different CAM clinical phenotypes need to be distinguished, influenced by geographical presentation. Opportunities exist for diagnosis and therapy optimization, based on earlier high-dose antifungal therapy, early source control, strict glycemic control and restriction of steroids to COVID-19 patients with oxygen requirements.
COVID-19 vaccine; Adverse drug reaction; Myocarditis Vacuna contra el COVID-19; Reacció adversa a fàrmacs; Miocarditis Vacuna contra el COVID-19; Reacción adversa a medicamentos; Miocarditis Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39–49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed. The project received support from the European Medicines Agency (EMA/2018/23/PE).
descriptionPublicationkeyboard_double_arrow_right Other literature type , Article 2022 Netherlands, Turkey, Italy, Denmark, Italy, Turkey, France, Croatia, Belgium, Netherlands, Hungary MDPI AG
Authors: Chiara Cattaneo; Jon Salmanton-García; Francesco Marchesi; Shaimaa El-Ashwah; +72 Authors
Chiara Cattaneo; Jon Salmanton-García; Francesco Marchesi; Shaimaa El-Ashwah; Federico Itri; Barbora Weinbergerová; Maria Gomes Da Silva; Michelina Dargenio; Julio Dávila-Valls; Sonia Martín-Pérez; Francesca Farina; Jaap Van Doesum; Toni Valković; Caroline Besson; Christian Bjørn Poulsen; Alberto López-García; Pavel Žák; Martin Schönlein; Klára Piukovics; Ozren Jaksic; Alba Cabirta; Natasha Ali; Uluhan Sili; Nicola Fracchiolla; Giulia Dragonetti; Tatjana Adžić-Vukičević; Monia Marchetti; Marina Machado; Andreas Glenthøj; Olimpia Finizio; Fatih Demirkan; Ola Blennow; Maria Chiara Tisi; Ali S. Omrani; Milan Navrátil; Zdeněk Ráčil; Jan Novák; Gabriele Magliano; Moraima Jiménez; Carolina Garcia-Vidal; Nurettin Erben; Maria Ilaria Del Principe; Caterina Buquicchio; Rui Bergantim; Josip Batinić; Murtadha Al-Khabori; Luisa Verga; Tomáš Szotkowski; Michail Samarkos; Irati Ormazabal-Vélez; Stef Meers; Johan Maertens; László Imre Pinczés; Martin Hoenigl; Ľuboš Drgoňa; Annarosa Cuccaro; Yavuz M. Bilgin; Avinash Aujayeb; Laman Rahimli; Stefanie Gräfe; Mariarita Sciumè; Miloš Mladenović; Gökçe Melis Çolak; Maria Vittoria Sacchi; Anna Nordlander; Caroline Berg Venemyr; Michaela Hanáková; Nicole García-Poutón; Ziad Emarah; Giovanni Paolo Maria Zambrotta; Raquel Nunes Rodrigues; Raul Cordoba; Gustavo-Adolfo Méndez; Monika M. Biernat; Oliver A. Cornely; Livio Pagano;
Simple Summary Patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 are an even greater challenge for hematologists. To better clarify their outcome, we describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Overall, 343 (76.2%) patients received treatment for HM, and an overall response rate was observed in 140 (40.8%) patients after the first line of treatment. Thirty-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004). Statistical analysis showed that, together with age, severe/critical COVID-19, >= 2 comorbidities, lack of HM treatment was an independent risk factors for mortality. These observations suggest the importance of HM treatment in these patients; therefore, it should be delivered as soon as possible for patients requiring immediate therapy. Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p = 2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.
Background Tracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective. Aim We demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters. Methods Genomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021. Results Cluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf. Conclusion IGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.
Abstract Objectives We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs). Methods This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis. Results Among 10,900 respondents [42 (30–55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4–0.8, and OR = 0.3, 95% CI 0.2–0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2–5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3–5.3 in BI]. In a multivariate regression analysis, age 30–60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5–1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1–2.7). Conclusions Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.
descriptionPublicationkeyboard_double_arrow_right Other literature type , Article 2022 Italy, United Kingdom, Italy, Belgium, Turkey Springer Science and Business Media LLC UKRI | 'Mechanisms of impaired n..., SNSF | Epidemiology and determin...
UKRI| 'Mechanisms of impaired neutrophil phagosome maturation and its impact on invasive bacterial infections ,
SNSF| Epidemiology and determinants of catheter-related and hospital-acquired bloodstream infections: from a large university hospital to a global picture
Abstract Background The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019. Funder: Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund Funder: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Funder: European society of Intensive Care Medicine
descriptionPublicationkeyboard_double_arrow_right Article , Other literature type 2022 Netherlands, Italy, Croatia, Belgium, Croatia, Croatia, Hungary, Turkey, Denmark, Belgium, Spain Frontiers Media SA
Authors: Maria Stefania Infante; Jon Salmanton-García; Ana Fernández-Cruz; Francesco Marchesi; +61 Authors
Maria Stefania Infante; Jon Salmanton-García; Ana Fernández-Cruz; Francesco Marchesi; Ozren Jaksic; Barbora Weinbergerová; Caroline Besson; Rafael F. Duarte; Federico Itri; Toni Valković; Tomáš Szotkovski; Alessandro Busca; Anna Guidetti; Andreas Glenthøj; Graham P. Collins; Valentina Bonuomo; Uluhan Sili; Guldane Cengiz Seval; Marina Machado; Raul Cordoba; Ola Blennow; Ghaith Abu-Zeinah; Sylvain Lamure; Austin Kulasekararaj; Iker Falces-Romero; Chiara Cattaneo; Jaap Van Doesum; Klára Piukovics; Ali S. Omrani; Gabriele Magliano; Marie-Pierre Ledoux; Cristina de Ramon; Alba Cabirta; Luisa Verga; Alberto López-García; Maria Gomes Da Silva; Zlate Stojanoski; Stef Meers; Tobias Lahmer; Sonia Martín-Pérez; Julio Dávila-Vals; Jens Van Praet; Michail Samarkos; Yavuz M. Bilgin; Linda Katharina Karlsson; Josip Batinić; Anna Nordlander; Martin Schönlein; Martin Hoenigl; Zdeněk Ráčil; Miloš Mladenović; Michaela Hanakova; Giovanni Paolo Maria Zambrotta; Nick De Jonge; Tatjana Adžić-Vukičević; Raquel Nunes-Rodrigues; Lucia Prezioso; Milan Navrátil; Monia Marchetti; Annarosa Cuccaro; Maria Calbacho; Antonio Giordano; Oliver A. Cornely; José-Ángel Hernández-Rivas; Livio Pagano;
Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs. EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223). Peer reviewed
descriptionPublicationkeyboard_double_arrow_right Article , Other literature type 2022 Netherlands, Italy, United Kingdom, France, Netherlands, Italy, France, France, Italy, Italy Springer Science and Business Media LLC WT | Understanding cross-react..., EC | RECoVER, UKRI | ISARIC - Coronavirus Clin... +3 projects
WT| Understanding cross-reactive immunity to Japanese encephalitis virus ,
Invasive mechanical ventilation; COVID-19; Critical care Ventilación mecánica invasiva; COVID-19; Cuidado crítico Ventilació mecànica invasiva; COVID-19; Atenció crítica Background Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. 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]; CIHR Coronavirus Rapid Research Funding Opportunity OV2170359; Grants from Rapid European COVID-19 Emergency Response research (RECOVER) [H2020 Project 101003589] and European Clinical Research Alliance on Infectious Diseases (ECRAID) ; The Imperial NIHR Biomedical Research Centre; The Cambridge NIHR Biomedical Research Centre; and Endorsed by the Irish Critical Care-Clinical Trials Group, co-ordinated in Ireland by the Irish Critical Care-Clinical Trials Network at University College Dublin and funded by the Health Research Board of Ireland [CTN-2014-12]. This work uses Data/Materials provided by patients and collected by the NHS as part of their care and support #DataSavesLives. The Data/materials used for this research were obtained from ISARIC4C. The COVID-19 Clinical Information Network (CO-CIN) data was collated by ISARIC4C Investigators. Data and Material provision were supported by grants from: the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; Grant MC_PC_19059), and the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE), (Award 200907), Wellcome Trust [Turtle, Lance-fellowship 205228/Z/16/Z], NIHR HPRU in Respiratory Infections at Imperial College London with PHE (Award 200927), Liverpool Experimental Cancer Medicine Centre (Grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (Award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. This work was possible due to the dedication and hard work of the Norwegian SARS-CoV-2 study team and supported by grants from Research Council of Norway Grant No. 312780 and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner; The dedication and hard work of the Groote Schuur Hospital Covid ICU Team, and supported by the Groote Schuur nursing and University of Cape Town registrar bodies coordinated by the Division of Critical Care at the University of Cape Town; and supported by the COVID clinical management team, AIIMS, Rishikesh, India.
Background: Worldwide, different strategies have been chosen to face the COVID-19-patient surge, often affecting access to health care for other patients. This observational study aimed to investigate whether the standard of burn care changed globally during the pan-demic, and whether country acute accent s income, geographical location, COVID-19-transmission pat-tern, and levels of specialization of the burn units affected reallocation of resources and access to burn care.Methods: The Burn Care Survey is a questionnaire developed to collect information on the capacity to provide burn care by burn units around the world, before and during the pandemic. The survey was distributed between September and October 2020. McNemar`s test analyzed differences between services provided before and during the pandemic, chi 2 or Fishers exact test differences between groups. Multivariable logistic regression analyzed the independent effect of different factors on keeping the burn units open during the pandemic.Results: The survey was completed by 234 burn units in 43 countries. During the pandemic, presence of burn surgeons did not change (p = 0.06), while that of anesthetists and dedi-cated nursing staff was reduced (< 0.01), and so did the capacity to manage patients in all age groups (p = 0.04). Use of telemedicine was implemented (p < 0.01), collaboration be-tween burn centers was not. Burn units in LMICs and LICs were more likely to be closed, after adjustment for other factors.Conclusions: During the pandemic, most burn units were open, although availability of standard resources diminished worldwide. The use of telemedicine increased, suggesting the implementation of new strategies to manage burns. Low income was independently associated with reduced access to burn care.(c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Authors: Steve Simpson-Yap; Ashkan Pirmani; Tomas Kalincik; Edward De Brouwer; +41 Authors
Steve Simpson-Yap; Ashkan Pirmani; Tomas Kalincik; Edward De Brouwer; Lotte Geys; Tina Parciak; Anne Helme; Nick Rijke; Jan A. Hillert; Yves Moreau; Gilles Edan; Sifat Sharmin; Tim Spelman; Robert McBurney; Hollie Schmidt; Arnfin B. Bergmann; Stefan Braune; Alexander Stahmann; Rod M. Middleton; Amber Salter; Bruce Bebo; Anneke Van der Walt; Helmut Butzkueven; Serkan Ozakbas; Cavit Boz; Rana Karabudak; Raed Alroughani; Juan I. Rojas; Ingrid A. van der Mei; Guilherme Sciascia do Olival; Melinda Magyari; Ricardo N. Alonso; Richard S. Nicholas; Anibal S. Chertcoff; Ana Zabalza de Torres; Georgina Arrambide; Nupur Nag; Annabel Descamps; Lars Costers; Ruth Dobson; Aleisha Miller; Paulo Rodrigues; Vesna Prčkovska; Giancarlo Comi; Liesbet M. Peeters;
Background and Objectives Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed.Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab.Results Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1–7] and 7% [95% CI 4–11]), ICU/artificial ventilation (2% [95% CI 0–4] and 4% [95% CI 2–6]), and death (1% [95% CI 0–2] and 2% [95% CI 1–4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2–8), 3% (95% CI 1–5), and 1% (95% CI 0–3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19.Discussion Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19. BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.