Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

Lung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (kappa = 0.74), with only a fair IRR for the presence of individual B-lines (kappa = 0.36) and for confluent B-lines occupying < 50% (kappa = 0.26) and a moderate IRR in consolidations and B-lines > 50% (kappa = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.

Associations of DMT therapies with COVID-19 severity in multiple sclerosis (preprint)

Background: People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods: Data from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression. Results: 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

Associations of DMT Therapies with COVID-19 Severity in Multiple Sclerosis: An International Cohort Study (preprint)

Background: People with multiple sclerosis (MS) may be a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs).Objectives: To examine characteristics of COVID-19 severity in an international sample of people with MS.Methods: Clinician and patient-reported data from 82 countries were aggregated into two datasets of 1,625 and 7,365 patients, respectively. Characteristics of hospitalisation, admission to Intensive Care Unit (ICU), requiring artificial ventilation, and death were assessed in patients with suspected/confirmed COVID-19 using log-binomial regression.Findings: Only clinician-reported data were used for all analyses. Of 1,625 patients, 481 (29·6%) with suspected and 811 (49·9%) with confirmed COVID-19 were included. Older age, progressive MS, and higher disability were positively associated with worse COVID-19 outcomes. Anti-CD20 DMTs (ocrelizumab/rituximab) were positively associated with hospitalisation (aPR=1·31, 95%CI=0·88-1·95; aPR=1·63, 95%CI=1·08-2·46), ICU admission (aPR=3·38, 95%CI=1·01-11·32; aPR=3·85, 95%CI=1·13-13·11), and ventilation (aPR=2·78, 95%CI=0·61-12·65; aPR=6·73, 95%CI=1·57-28·84) vs dimethyl fumarate, as well as pooled anti-CD20 DMTs vs all other DMTs (hospitalisation aPR=1·59, 95%CI=1·24-2·03; ICU aPR=2·63, 95%CI=1·48-4·68; ventilation aPR=3·18, 95%CI=1·54-6·58) and vs natalizumab (hospitalisation aPR=1·79, 95%CI=1·07-3·01; ICU aPR=2·03, 95%CI=0·66-6·24; ventilation aPR=2·34, 95%CI=0·57-9·63). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.Interpretation: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of anti-CD20 DMTs with increased risk of hospitalisation, ICU admission, and need for artificial ventilation, suggesting their use may be a risk factor for more severe COVID-19.Funding: Operational costs were funded by the Multiple Sclerosis International Federation (MSIF) and the Multiple Sclerosis Data Alliance (MSDA), acting under the European Charcot Foundation. MSDA and MSIF receive income from a range of corporate sponsors. This research received funding from the Flemish Government under the Onderzoeksprogramma Artificiële Intelligentie Vlaanderen programme. The central platform was provided by QMENTA and computational resources were provided by Amazon.Declaration of Interests: TK has served on scientific advisory boards for Roche, Sanofi-Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi-Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL and Merck and received research support from Biogen. NR & CW have no personal pecuniary interests to disclose, other than being an employee of MSIF, which receives income from a range of corporate sponsors, recently including: Biogen, BristolMyersSquibb (formerly Celgene), Genzyme, Med-Day, Merck, Mylan, Novartis, Roche. JH has received honoraria for serving on advisory boards for Biogen, Celgene, Sanofi-Genzyme, Merck KGaA, Novartis and Sandoz and speaker’s fees from Biogen, Novartis, Merck KGaA, Teva and Sanofi-Genzyme, has served as principal investigator for projects, or received unrestricted research support from Biogen, Celgene, Merck KGaA, Novartis, Roche and Sanofi-Genzyme, and his MS research was funded by the Swedish Research Council and the Swedish Brain foundation. GE has received consulting/speaking fees and research support from Bayer, Novartis, Teva, Sanofi Genzyme, Merck Serono, Biogen Idec, and Roche. TS has served on scientific advisory boards for Biogen. RMcB & HS, work for the Accelerated Cure Project for MS (ACP), which has received grants, collaboration funding, payments for use of assets, or in-kind contributions from the following companies: EMD Serono, Sanofi/Genzyme, Biogen, Genentech, AbbVie, Octave, GlycoMinds, Pfizer, MedDay, AstraZeneca, Teva, Mallinckrodt, MSDx, Regeneron Genetics Center, BC Platforms, and Celgene. ACP has also received funding from the Patient-Centered Outcomes Research Institute (PCORI) and the National MS Society (NMSS). RMcB. has received consulting payments from EMD Serono, which have been donated to ACP. AB has received consulting fees from and is an advisory board/speaker/other activities for NeuroTransData, and has worked on project management/clinical studies for and received travel expenses from Novartis and Servier. AS has no personal pecuniary interests to disclose, other than being the lead of the German MSRegistry, which receives funding from a range of public and corporate sponsors, recently including The German Innovation Fund (G-BA), The German MS Trust, Biogen, German MS Society, Celgene (BMS), Merck and Novartis. RM has received no personal funding from any sources, but works for the UK MS Register which is funded by the UK MS Society and has received funding for specific projects from Novartis, Sanofi-Genzyme and Merck KGaA. RJF has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics, and has served on advisory committees for Actelion, Biogen, Immunic, and Novartis, and received clinical trial contract and research grant funding from Biogen and Novartis. AvdW has received honoraria and unrestricted research funding from Novartis, Biogen, Roche, Merck and Sanofi. JIR has received honoraria from Novartis as a scientific advisor, and has received travel grants and attended courses and conferences on behalf of Merck-Serono Argentina, Novartis Argentina. GSdO has received honoraria for lecturing and support for congress participation from Biogen, Merck, Novartis, Sanofi/Genzyme, EMS and Roche. MM has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie, has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. RA has received honoraria from Novartis as a scientific advisor, travel grants and attended courses and conferences on behalf of Merck-Serono Argentina, Biogen Argentina, Genzyme Argentina, Roche Argentina and Novartis Argentina. RN has received honoraria from Novartis, Roche and Biogen for advisory boards. AZ has received travel expenses for scientific meetings from Biogen, Novartis, and Genzyme, speaking honoraria from Eisai, and a study grant from Novartis. GA has received compensation for consulting services or participation in advisory boards from Sanofi, Merck and Roche; research support from Novartis; travel expenses for scientific meetings from Novartis, Roche, Stendhal, and ECTRIMS; speaking honoraria from Sanofi and Merck; and is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee. GC has received consulting and speaking fees from Novartis, Teva Pharmaceutical Industries Ltd, Teva Italia Srl, Sanofi Genzyme, Genzyme Corporation, Genzyme Europe, Merck KGgA, Merck Serono SpA, Celgene Group, Biogen Idec, Biogen Italia Srl, F. Hoffman-La Roche, Roche SpA, Almirall SpA, Forward Pharma, Medday and Excemed. LMP has no personal pecuniary interests to disclose, other than being the chair of The MS Data Alliance (MSDA), which receives income from a range of corporate sponsors, recently including Biogen, BristolMyersSquibb (formerly Celgene), Canopy Growth Corporation, Genzyme, Icometrix, Merck, Mylan, Novartis, QMENTA, Quanterix, Roche. SSY, EDB, YM, LG, TP, CG, NL, AP, AA, LEF, AG, SB, AS, IvDM, NN, RI, AED, DG, MFM, JB, AF, and AC have no conflicts of interests to disclose.Ethics Approval Statement: This study was approved by the ethical committee of Hasselt University [CME2020/025]. Individual data sources obtained additional ethics approval as required.

Decision-making on management of ms and nmosd patients during the COVID-19 pandemic: A latin american survey.

BACKGROUND: The emergence of COVID-19 and its vertiginous spreading speed represents a unique challenge to neurologists managing multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The need for data on the impact of the virus on these patients grows rapidly. There is an urgent necessity of sharing information to enable evidence-based decision making on the clinical management. There are no data on what physicians are doing on clinical practice in Latin American countries. AIM: to investigate current management opinion of Latin American MS and/or NMOSD expert neurologists based on their experience and recommendations. METHODS: we developed a voluntary web-based survey based on hypothetical situations that these patients may encounter, while taking into account the potential risk of developing severe COVID-19 infection. RESULTS: 60% of the experts had the possibility of monitoring their patients by telemedicine. Most neurologists postpone magnetic resonance. Laboratory blood tests delay is associated with the type of treatment. Platform therapies, dimethyl-fumarate and natalizumab are considered safe options to initiate in naive patients. CONCLUSION: decision-making about MS and NMOSD patients has become even more complex in order to adapt to the COVID-19 pandemic. Risks and benefits should be taken into consideration throughout the patient follow-up.