Facteurs prédictifs d'une poussée de psoriasis après une infection par le SARS-CoV-2 chez l'enfant

Introduction: La pandémie à SARS-CoV-2 a été source de nombreuses questions quant à l'impact de l'infection sur les dermatoses inflammatoires chroniques, et de l'impact des traitements de ces dermatoses sur la sévérité de l'infection. Le registre international Chi-PsoCov (enfants psoriasique souffrant de psoriasis et ayant développé une infection à SARS-CoV-2) a permis de montrer que les biothérapies n'augmentaient pas le risque de formes sévères de COVID-19 chez les enfants atteints de psoriasis. Par ailleurs, il était montré que le COVID-19 était responsable du développement de psoriasis de novo ou de l'aggravation d'un psoriasis connu chez certains enfants.Dans cette partie du travail nous nous sommes concentrés sur les enfants ayant développé une poussée de psoriasis après l'infection : aspects phénotypiques des poussées, et recherche de facteurs de risque liés à la maladie, au psoriasis, ou aux traitements, associés à l'aggravation du psoriasis après l'infection. Matériel et méthodes: Les données ont été collectées de février 2021 à mai 2022 en provenance de 14 pays. Les enfants étaient inclus s'ils avaient moins de 18 ans, un antécédent de psoriasis ou psoriasis apparu dans le moins suivant l'infection COVID-19, et avaient été infectés par le SARS-CoV-2 avec ou sans symptômes. Les enfants ayant développé un psoriasis de novo étaient exclus de cette étude. Résultats: Sur les 152 inclusions du registre Chi-PsoCov, dix enfants ont développé un psoriasis dans le mois suivant l'infection et n'ont pas été retenus dans ce travail. L'analyse a porté sur 135 enfants ayant développé 142 COVID-19. Le psoriasis était stable dans 120 cas (84,5 %) et s'aggravait dans le mois suivant l'infection dans 22 cas (15,5 %).Dans 20 cas, lors de la poussée, le phénotype était inchangé, et dans 2 cas, il y avait un changement de phénotype : psoriasis en plaques en psoriasis en gouttes (n = 1) ou inversé (n = 1).Ni les caractéristiques démographiques, ni les aspects du psoriasis (notamment psoriasis actif vs en rémission), ni la sévérité de l'infection à SARS-CoV-2 n'étaient associés à des poussées de psoriasis. Seule l'utilisation de traitements systémiques du psoriasis, conventionnels ou biothérapies, lors de l'infection semblait protectrice de la survenue de poussées (50,0 % dans le groupe stable vs 27,3 % dans le groupe poussées, p = 0,049). Discussion: L'infection à SARS-CoV-2 est responsable dans environ 15 % des cas de poussées de psoriasis. Dans la grande majorité des cas, le phénotype précédent l'infection est conservé. Ces poussées ne sont pas associées à la sévérité du psoriasis, de l'infection ou autres paramètre cliniques. Seuls les traitements systémiques semblent réduire ce risque, probablement en « contrôlant » la poussée. Il est possible qu'une susceptibilité d'ordre génétique, non explorée ici, explique aussi cette susceptibilité à l'infection.

COVID-19 et psoriasis de l'enfant : facteurs associés à une évolution défavorable de la COVID-19 et impact de l'infection sur le psoriasis. Registre Chi-PsoCov

Introduction: La pandémie à SARS-CoV-2 a soulevé de nombreuses questions sur la prise en charge des maladies chroniques et leurs traitements. Les données concernant l'utilisation des biothérapies chez les adultes atteints de psoriasis sont rassurantes, mais manquent chez l'enfant. Par ailleurs, l'infection à SARS-CoV-2 pourrait influencer l'évolution du psoriasis chez l'enfant. L'objectif de cette étude était d'évaluer l'impact de l'infection à SARS-CoV-2 sur le psoriasis, et la sévérité de l'infection selon le traitement systémique reçu. Matériel et méthodes: Les données ont été collectées de février 2021 à février 2022 en provenance de 14 pays. Les enfants étaient inclus s'ils avaient moins de 18 ans, un antécédent de psoriasis ou apparu dans le moins suivant l'infection COVID-19, et avaient été infectés par le SARS-CoV-2 avec ou sans symptômes. Résultats: Au total, 117 enfants ont été inclus (filles : 49,6 %, âge moyen : 12,4 ans) avec 120 infections) SARS-CoV-2. La principale forme de psoriasis était le psoriasis en plaques (69,4 %) ;le psoriasis était actif avant l'infection dans 70,1 % des cas. La majorité des enfants ne prenaient pas de traitement systémique au moment de l'infection (54,2 %), 33 enfants (28,3 %) étaient sous biothérapie (principalement anti-TNF alpha et ustékinumab), et 24 (20,0 %) sous traitement systémique conventionnel (principalement méthotrexate). L'infection était confirmée chez 106 enfants (88,3 %) et 3 ont eu la maladie 2 fois (1 enfant asymptomatique sous ustékinumab et 2 enfants symptomatiques sans traitement systémique). L'infection était symptomatique chez 75 enfants (62,5 %) avec une durée moyenne des symptômes de 6,5 jours, significativement plus longue chez les enfants sous traitement systémique conventionnel (p = 0,002) ou sans traitement systémique (p = 0,006) par rapport aux enfants traités par biothérapies. Six enfants ont nécessité une hospitalisation, dont un enfant en réanimation ;ils étaient plus fréquemment sous traitements systémiques conventionnels par rapport aux autres enfants (p = 0,01), et principalement sous méthotrexate (p = 0,03). Aucun enfant sous biothérapie n'a été hospitalisé, et aucun décès n'a été rapporté.Après l'infection, le psoriasis s'est aggravé dans 17 cas (15,2 %), sans modification du phénotype sauf pour un enfant avec un psoriasis initialement en plaques qui a eu suite à l'infection une poussée de psoriasis en gouttes. Neuf enfants (8,0 %) ont développé un psoriasis de novo dans le mois qui a suivi l'infection, plus souvent un psoriasis en gouttes (p = 0,01) par rapport aux enfants ayant un antécédent connu de psoriasis. Ces enfants avaient un antécédent familial de psoriasis dans 75,0 % des cas. Discussion: L'utilisation des biothérapies semble rassurante sans augmentation du risque de forme sévère de COVID-19 chez les enfants atteints de psoriasis. L'infection à SARS-CoV-2 était responsable du développement de psoriasis de novo ou de l'aggravation d'un psoriasis connu chez certains enfants.

Remote Programming for Deep Brain Stimulation (DBS) therapy management in Parkinson's disease and Essential Tremor

Objective: To assess the utility of the recently FDA approved Virtual Clinic platform that enables clinicians to remotely make programming changes in DBS patients. Background: DBS in Parkinson's disease and Essential tremor requires multiple in-person programming sessions for therapy optimization and management. Until recently, this was only possible through inperson clinic sessions which place time, travel and fiscal burdens on patients and caregivers limiting their access to care. This has an even greater bearing on patients that are dependent on caregivers, need to take time off from work or are concerned about exposure during COVID-19. The recent FDA approved NeuroSphere™ Virtual Clinic enables clinicians for the first time to remotely make programming changes over the internet to help DBS patients. Methods: 34 patients provided signed written consent to Abbott or verbal consent to the Clinician to be enrolled. The enrolled Abbott Infinity™ IPGs were securely mapped to authorized Clinicians. Software on programming devices was upgraded without requiring any hardware or firmware changes. Patients initiated remote sessions and Clinicians securely connected to the IPGs using unique logins and multi-factor authentication. Stimulation changes were synchronized with integrated video and a failsafe mechanism ensured continuity of therapy in case of network failure. Results: Of the 34 patients programmed remotely, 74% benefited from stimulation changes, 26% from side effects resolution, 9% from battery status check, 6% were out of the country when they needed intervention, 29% completed routine follow-up. The use of this platform has allowed seamless virtual patient visits reducing the patient burdens related to access to care as well as increasing throughput in our clinic. We have also billed for these sessions for reimbursement in the US using the Telemedicine modifier code (95). The average time to establish a session has been less than 1 minute with no perceptible difference in system checks and stimulation changes. Remote programming is both clinically viable and valuable to patients, caregivers and clinicians. Conclusion: Remote programming is both clinically viable and valuable to patients, caregivers and clinicians.

Children with psoriasis infected by SARS-CoV-2

Objectives: To evaluate the impact of SARS-CoV-2 on psoriasis in children during and after SARS CoV- 2 infection. Method: We performed a retrospective study on children hospitalised with COVID-19 infection and diagnosed previously with severe psoriasis. Results: Case 1: A 16-year old boy, diagnosed with plaque psoriasis at the age of 10, was hospitalised 10 days for COVID-19 (confirmed by PCR) with fever, cough, headache. Before admission to the hospital for COVID-19 infection psoriasis was treated with phototherapy. During hospitalisation psoriasis remained the same and no Long-COVID was noted. Case 2: A 17-year-old boy diagnosed with plaque psoriasis at the age of 13 was hospitalised 12 days for COVID-19 (confirmed by PCR) with fever, cough, headache. Before admission to the hospital for COVID-19 infection psoriasis was treated with MTX. During hospitalisation psoriasis remained the same and no Long-COVID was noted. Case 3: A 16-year-old girl, diagnosed with plaque psoriasis at the age of 12, was hospitalised 12 days for COVID-19 (confirmed by PCR) with fever, cough, headache. Before admission to the hospital for COVID-19 infection psoriasis was treated with MTX. During hospitalisation psoriasis remained the same and no Long-COVID was noted. Discussion: No impact of SARS Cov2 infection was noted on evolution of children diagnosed and treated previously for severe psoriasis.

MYOCARDIAL INVOLVEMENT IN ANTI-PHOSPHOLIPID SYNDROME: A CASE OF AYOUNG BREASTFEEDING WOMAN

Introduction: In Antiphospholipid Syndrome (APS) myocardial tissue can be involved through immune-mediated or thrombotic mechanisms, giving chest pain and increase of myocardial cytolysis markers. This may occur without any signs of myocardial injury at the moment of echocardiography, coronarography and cardiac magnetic resonance (CMR). The aim is to increase the awareness about this life-threating condition.Case summary. We present the case of 26-year-old woman few days after childbirth, affected by APS in anticoagulant therapy with previous deep vein thrombosis and without any other cardiovascular risk factors. She was symptomatic for intermittent chest-epigastric pain, fever and skin livedo reticularis. Lab Tests: TnI 750 ng/L, C-reactive protein 9.6 mg/dL, D-dimer 1693 μg/L;anemia;Antithyroid Antibodies and ANA 1:160 (SSB/LA). Blood cultures and COVID test were negative.Results. Echocardiography showed normal left/right ventricular function, but minimal pericardial effusion was present. Pulmonary Angio-CT revealed small thromboembolic event, ground-glass lungs compatible with hemorrhagic alveolitis.After a few days, the patient presented increased epigastric pain, headache, vomiting up to presenting a comatose state. Thrombotic or hemorrhagic events with cerebral CT and MR were excluded. Total-body CT was negative, except for peri-splenic and recto-uterine pouches.For the increase of TnI up to 4741 ng/L, the patient underwent coronary angiography which demonstrated non-obstructive coronary arteries. The assembled Neuro-Cardio-Rheumatology team suspected a rapidly developing Catastrophic APS which was developing quickly with multi-organ and life-threatening involvement.The patient underwent 4 cycles of plasmapheresis, intravenous human IgG and corticosteroids, with rapid clinical improvement. CMR subsequently demonstrated a small transmural late enhancement area on lateral left ventricle wall.The patient was discharged from the hospital on Day 6 post- therapies.Conclusions. APS may involve more organs, including myocardial tissue with different mechanisms of damage and high mortality rate. The presented case poses a multidisciplinary challenge, because thrombotic multiorgan microangiopathy may be not always diagnosed. Imaging methods such as CMR could be optimized with adenosine stress-CMR. Clinical attention is required among women with APS, to reach early diagnosis of myocardial thrombotic microangiopathy and to establish the best effective treatment.

The lung ultrasound in the prognosis of COVID-19 patients

Introduction: Bedside lung ultrasound (LUS) is a useful and noninvasive tool for rapid evaluation of many chest conditions. Following the onset of the COVID-19 pandemic, the use of LUS has become common practice for evaluating lung involvement and for monitoring changes in COVID-19 patients.The prognostic role of LUS in COVID-19 patients has not yet been established. Methods: We retrospectively analysed records from 448 patients (mean age 66,08) with confirmed COVID-19 by nasopharyngeal swab, admitted to our ward of COVID Medicine Unit at Ospedale del Mare in the town of Napoli between March 2020 and May 2021. We performed LUS on all patients with COVID-19 using a 14-zone method (Soldati score from 0 to 42 points) at the admission in COVID Medicine Unit within 3 days from the onset of symptoms.We evaluated the difference in LUS score between the death and survival groups. Results: The mean LUS scores were 30,93±5.01 and 21,53±7.85 in the death group compared with the survival group (weighted mean difference (WMD)=9.51,95% CI=8.20-10.82, P value <0.0001). Conclusions: The LUS score in our COVID- 19 population was associated with mortality. LUS score is important for the risk stratification in COVID-19 patients.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

CUTANEOUS MANIFESTATIONS AMONG COVID-19 AFFECTED HEALTHCARE WORKERS

Introduction: Cutaneous manifestations have been associated with the COVID-19 infection with two different patterns: Inflammatory/exanthematous eruptions and vasculopathic/vasculitic patterns. Materials and method: We considered 126 healthcare workers who tested positive for Sars-CoV2 in the period between March 2020 and January 2021. Those subjects were asked to fulfill a telephonic questionnaire regarding the presence and characteristics of skin symptoms that happened during the period of positivity. Conclusion: The present article aims to demonstrate a causal connection between the appearance of cutaneous and vasculitic manifestations and the positivity of the nasopharynx swab and the title of the antibodies generated after the infection. © 2022 A. CARBONE Editore. All rights reserved.

Implementation of Good Clinical Practice in Early COVID-19 Pandemic

Introduction: The novel Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has spread across the globe generating a pandemic. Every affected country has tried its best to mitigate the virus's effects. Aim: This study was designed to implement the good clinical practice in the Institute of Cardiovascular Diseases Timisoara (ICDT) for Coronavirus Disease-2019 (COVID-19) infection by a retrospective search for patients with a possible COVID-19 infection before widespread testing was available in our country. Materials and Methods: The retrospective study was conducted on selected group of 19 patients admitted to the ICDT, who displayed radiological signs of possible SARS-CoV-2 infection, between September 2019 and May 2020 in collaboration with the Radiology Department. Patients have been followed-up regarding their clinical status and asked to participate in Immunoglobulin G (IgG) antibody testing at a local laboratory. The patients were divided based on the period they were admitted to the hospital into four groups: September-December 2019, January-February 2020, March-April 2020 and May 2020. The patients tested for coronavirus came from all four timeframes. Results: Only 13 patients (male: female ratio was 10:3 ;mean age was 71.69 years) from the initial group were available and willing to answer a short interview and only five agreed to be tested for SARS-CoV-2 IgG antibodies. Most of the patients admitted to the hospital were suffering from acute myocardial infarction (30.7%), as well as heart failure (30.7%), followed by coronary heart disease (15.38%). A 30.7% of the patients had atrial fibrillation, 23% were also diagnosed with pneumonia during their hospital admission, 23% were also being treated for arterial hypertension, 7.69% had diabetes mellitus and Chronic Obstructive Pulmonary Diseases (COPD). Out of the five patients tested for IgG antibodies, two tested positive, with a titre above 1.4. Conclusion: The patients who have gone through the SARS-CoV-2 infection without being previously diagnosed were identified and followed-up on their health status. By conceiving and performing this study, the authors have strived to establish a new set of rules to advance and improve good clinical practice in unprecedented times.

Process Intensification for the Purification of Peptidomimetics: The Case of Icatibant through Multicolumn Countercurrent Solvent Gradient Purification (MCSGP)

Biopharmaceuticals are subjected to very strict purity requirements to be marketed. At the same time, peptides and other biomolecules are industrially synthesized through techniques (e.g., solid-phase synthesis) often leading to the formation of many impurities with molecular characteristics very similar to the target product. Therefore, the purification of these mixtures via preparative chromatography can be very challenging. This typically involves ternary or central-cut separations, characterized by chromatograms where the central peak, corresponding to the target product, exhibits significant overlapping on both sides with impurities slightly more or less adsorbable. In single-column (batch) preparative chromatography, this leads to a typical yield-purity tradeoff, meaning that high purity can be obtained at the cost of low yield and vice versa, with obvious consequences on the overall production costs. This study demonstrates how this limitation can be alleviated using the continuous countercurrent operating mode, conducted on a multicolumn system, as a tool for process intensification. In particular, the Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) process has been applied to the purification of an industrial crude mixture of icatibant, which is a peptidomimetic antagonist of bradykinin B2-receptor that has been recently also considered for the treatment of patients affected by COVID-19 disease. It is shown that MCSGP allows conjugating process simplicity (using only two columns) with a significant improvement in process performance, compared to the corresponding batch process. This includes all process performance parameters: yield, productivity, and buffer consumption for a given purity specification of icatibant.

Prevalence of comorbidities in hospitalized populationwith COVID-19: Our experience

Background and Aim: Our objective was to evaluate the prevalenceof comorbidities in our hospitalized population with COVID-19.Materials and Methods: Forty-two patients (64.29% males,25.71% females;mean age of 70.75 ±13.73 yrs), admitted toour Hospital between March and June 2020, had been identifiedas having laboratory-confirmed 2019-SARS-CoV infection. Results: On admission 83.33% of patients presented with dyspnea, 80.95% with cough and 78.75% with fever. Diarrhea was uncommon (19.05%). Patients were classified according to their BMI(kg/m2) as lean (18.5-25) or affected by grade 1 obesity (25-29.9), grade II obesity (30-34.9) and grade III obesity (= 35). Obesity was present in 50% of cases;grade I 35.71%, gradeII and grade III 11.90% and 2.38%, respectively. Hypertension waspresent in 92.86% of patients, COPD in 54.76%, chronic kidneydisease in 45.24%, ischemic heart disease in 35.71%, diabetesin 33,33%, dementia in 30,95% and atrial fibrillation in 7.14%.On admission to the hospital lymphocytopenia was a frequent laboratory finding (97.62%). The coagulation profile revealed an elevation of fibrinogen (66.67%) and D-dimer (85.71%) levelsdespite a normal PT and APTT. The elevation of the pro BNP levelswas observed in 61.90% and troponin levels were at the sametime elevated in 13.16% of COVID-19 patients. Twelve patients(28.5%) died. Coronary artery disease was found in 70% of them. Conclusions: Comorbidities are common in patients with COVID-19. Although COVID 19 has been initially associated to a respiratory disease, it may involve the cardiovascular system with adramatic impact.

Skin manifestations of COVID-19 in children: Part 1.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestation of COVID-19, chilblain-like lesions. In Part 2, we review other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome, while in Part 3, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children, for both COVID-19 and any other pre-existing conditions.