ABSTRACT
BackgroundCOVID-19 is associated with higher morbidity and mortality burdens in immunocompromised individuals, including patients with systemic lupus erythematosus (SLE;1). These patients might benefit from treatment with anti-SARS-CoV-2-specific antiviral agents and monoclonal antibodies, but clinical evidence is to date limited.Objectivesto comparatively assess the course of COVID-19 in patients with SLE treated or untreated with COVID-19-specific agents.MethodsPatients with SLE and COVID-19 treated with antivirals and/or monoclonal antibodies from February 2020 to December 2022 were identified within a three-centre cohort of tertiary referral centres and age-, sex- SLE extension- and SLE duration-matched 1:2 with patients with a history of untreated COVID-19. Data on COVID-19 presentation, course (including time to viral clearance) and sequelae, along with SLE treatment at COVID-19 onset and SLE course after COVID-19 were collected. COVID-19 severity at presentation was quantitated through a 0-4 analogue scale [2]. Data are expressed as median (interquartile range, IQR) unless otherwise specified.ResultsOver three years, 39% of patients with SLE had at least one COVID-19 event. Eighteen subjects (16 women) were treated with antivirals (n=12) or monoclonal antibodies (n=6) and were matched with 36 controls. There was no difference in the frequency of organ involvement between the two groups. Treated patients were receiving significantly higher prednisone daily doses at COVID-19 onset (6.25 (0-10) vs 0 (0-2.5) mg;p=0.005) and had a higher prevalence of previous high-dose steroid treatments (83% vs 47%;p=0.019) compared to controls. SLE disease activity index (3 (0-5) vs 1 (0-4)) and SLE International Collaborating Clinics Damage Index scores (1 (0-3) vs 0 (0-1)) were also numerically higher in treated patients at COVID-19 onset. Patients in the treated group had more severe COVID-19 at presentation but showed no significant differences with control subjects in terms of COVID-19 resolution, prevalence of sequelae and viral clearance (Table 1). There was also no difference in flare occurrence between the two groups (Log-rank=0.02, p=0.889). Two patients reported mild adverse events with monoclonal antibodies (muscle cramps and chest pain, both self-resolving).ConclusionThese data support the safe use of COVID-19 specific treatments in patients with SLE. Patients treated with antivirals and monoclonal antibodies had a favourable COVID-19 course, despite a more severe presentation and a higher risk of deterioration due to SLE and corticosteroid treatment burden, suggesting the potential efficacy of COVID-specific treatments in preventing severe COVID-19 in patients with SLE.References[1]Strangfeld A et al, Ann Rheum Dis, 2021[2]World Health Organization. Clinical management of COVID-19;Interim guidance 27 May 2020.Table 1.COVID-19 presentation and courseTreated (n=18)Untreated (n=36)Number of vaccine doses3 (2-3)3 (2-3)Time from last vaccine administration (days)118 (53-184)134 (30-210)COVID-19 featuresWHO class at presentation1 (1-1)**0 (0-1)Symptoms at presentation: n(%)Dyspnoea3 (17)3 (8)Fever10 (56)22 (61)Upper Respiratory Symptoms16 (89)29 (81)GI symptoms1 (6)2 (6)Pneumonia3 (17)3 (8)COVID-19 courseTime to symptom resolution (days)5 (4-8)7 (3-8)Time to viral clearance (days)10 (7-14)9 (7-14)Any complication: n(%)1 (6)6 (17)Hospitalisations: n(%)1 (6)0 (0)Long COVID: n(%)3 (17)6 (17)Deaths: n(%)0 (0)1 (3)AcknowledgementsWe thank Dr. Giordano Vitali and his staff for assisting and treating patients with SLE and COVID-19 from IRCCS San Raffaele Hospital in the local mild COVID-19 clinic.Disclosure of InterestsGiuseppe Alvise Ramirez Consultant of: Astrazeneca, Maria Gerosa: None declared, Daniel Arroyo-Sánchez: None declared, Chiara Asperti: None declared, Lorenza Maria Argolini: None declared, Gabriele Gallina: None declared, Chiara Bellocchi: None declared, Martina Cornalba: None declared, Isabella Scotti: None declared, Ilaria Suardi: None declared, Lorenzo Beretta: None declared, Luca Moroni Consultant of: strazeneca, Enrica Bozzolo: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB, Lorenzo Dagna Consultant of: Abbvie, Amgen, Astra-Zeneca, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, Swedish Orphan Biovitrium (SOBI), and Takeda, Grant/research support from: Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.
ABSTRACT
Background: Vulnerable subjects, including systemic lupus erythematosus (SLE) patients have been prioritised to receive anti-SARS-CoV-2 vaccine. Questions have been raised about the effect of vaccines on immunity and their potential role as trigger for fare. Few data about the safety of these vaccines in SLE are available Objectives: To investigate the safety of different anti-SARS-CoV-2 vaccines in SLE Methods: Data on SLE patients who have received anti-SARS-CoV-2 vaccine (from 12/2020 to 10/2021) were collected. Patients referred to 7 SLE tertiary centres (Lupus Clinic, ASST Pini-CTO, Milan;Nephrology Unit of Ospedale Giovanni Bosco, Turin;IRCCS Humanitas Research Hospital;Renal and Rheumatology Units, San Gerardo Hospital, Monza;ASST Spedali Civili Brescia;Lupus Clinic IRCCS Ospedale S. Raffaele, Milan, Italy;IRCCS Policlinico, Milan) Results: 452 SLE patients who had received anti-SARS-CoV-2 vaccines were included (91% BNT162b2 mRNA, 8% mRNA-1273, 1% ChAdOx1-S). 12 (3%) were off therapy, 71% were on low-medium dose prednisone, 83% on anti-ma-larials, 50% were treated with an immunosuppressant. 9 patients transiently discontinued therapy. 119 (26%) reported adverse symptoms after the frst/second shot (12% and 21%) The most frequent were fever, local reaction, fatigue and arthralgias. Nineteen (4%) patients fared up after immunisation with a 7 days median time to relapse. Baseline demographics, SLE characteristics and therapy stratifed by adverse events and disease fare are reported in Table 1. Anti-dsDNA positivity, moderate/high DAS before vaccine and use of Belimumab were sig-nifcantly more frequent in the group of patients fared. These patients displayed a signifcantly higher rate of adverse events after vaccination. Flares consisted mainly musculoskeletal and constitutional manifestations (32%), involvement of renal (21%), cardio-respiratory (16%), hematological (16%) or mucocutaneous domains (10%) was less frequent Conclusion: our reassuring data confrm that anti-SARS-CoV-2 vaccine is safe in SLE patients and should be recommended in this clinical setting, as potential benefts widely outweigh the risk of adverse events. Treatment adjustment might be considered with the aim of minimizing the risk of side effects and/or fare, while ensuring a satisfying protection against infection.
ABSTRACT
Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.
ABSTRACT
In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.
ABSTRACT
Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ;IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mug/m;IQR, 5.0-23.8 mug/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P = 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. Trial registration: ClinicalTrials.gov identifier: NCT04318366.
ABSTRACT
At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute - a large tertiary hospital and research centre in Milan, Italy - was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.
ABSTRACT
Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 10(3) per mm(3);IQR, 0.58-1.00 x 10(3) per mm(3)), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mu g/m;IQR, 5.0-23.8 mu g/m) were present. Median tidal volume was 6.7 mUkg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH(2)O (IQR, 10-14 cmH(2)O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median followup of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P= 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (Pao(2) ) to fraction of inspired oxygen (Fio(2)) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors.
ABSTRACT
We suggest the use of MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) as a new name for severe pulmonary coronavirus disease 2019 (COVID-19). We hypothesise that, in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death. Future steps in the understanding of the disease and in the identification of treatments may benefit from this definition and hypothesised sequence of events.