ABSTRACT
Introduction and aims: Multiple Sclerosis (MS) Centers experienced a significant disruption of their clinical activities during the first waves of COVID-19 pandemic. As part of a national multicenter survey (COVId Ms Patients SATisfaction survey - COVIMPSAT), we collected i) the opinion on quality of care (QoC) received by people with MS (pwMS) from MS Centers (MSC), and ii) data on therapeutic adherence and discontinuation, during the lockdown period (March-May 2020) in Italy. Method(s): In April-May 2021, 16 Italian MSC compiled and sent a digital (35-item) survey to their patients. Statistical analyses were performed with SPSS, version 25. Result(s): 1670 pwMS (67.3% women) completed the survey. Most of them (89.9%) were on disease-modifying therapies (DMTs). The most used DMTs were dimethyl fumarate (18.6%), ocrelizumab (14.4%) and natalizumab (13.9%). During the lockdown period, 88% did not modify their DMT regimen, while 11% reported a change in DMT intake, with a reduction in 7.8% and a drug discontinuation in only 4.2% cases. Almost 9 out of 10 pwMS (89.1%) were able to get in contact with their MSC without difficulties. Thirty-six percent of pwMS contacted their MSC for getting information about COVID-19, while 30% were directly contacted from the MSC personnel to provide information on MS and COVID-19 and preventive behaviours. More than half of the patients (63.5%) performed their check-up visits at the MSC with the same schedule as the pre-pandemic period, while 36.5% of pwMS voluntary skipped follow-up visits mainly because of fear of getting COVID-19 infection (46%) and the sensation of feeling well without an absolute/urgent need of a check-up visit (16.8%). Interestingly, although only 1.3% of pwMS underwent a teleneurology follow-up visit, 80% of patients suggested to invest more in telemedicine programs in order to expand contact channels with MSC. The overall opinion of pwMS on MSC during the pandemic period in Italy was more than positive, with 32% of pwMS declaring a significant increase in trust in their MSC. Conclusion(s): Italian pwMS judged globally well the activity, accessibility and information received by their MSC during the first wave of COVID-19 pandemic. Only 1 out of 10 pwMS underwent a change in their DMT regimen, showing a high drug adherence. Our data also demonstrate that implementing telemedicine programs would further improve the QoC of patients, particularly those with higher disability or living far from the MSC.
ABSTRACT
Introduction: Patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) and Fingolimod (FNG) have shown a blunted humoral response to the first two doses of the BNT162b2 mRNA Covid-19 vaccine. The assessment of the safety and the humoral response to a third booster dose of the same vaccine is therefore relevant within this population. Aim(s): To investigate the safety and the humoral response to a third booster dose of the BNT162b2 mRNA Covid-19 vaccine in pwMS on OCR/FNG, comparing it with age- and sex-matched healthy controls (HCs). Method(s): Serum samples were collected from HCs and pwMS treated with OCR or FNG at the following scheduled time points: before the first of two vaccine doses (T0);8 (T1), 16 (T2), 24 (T3) weeks after the first dose;within 8 weeks before (T0b) and after (T1b) the booster dose. IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) were quantified and expressed as binding antibody units (BAU)/mL. Result(s): 40 HCs and 47 pwMS (28 on OCR and 19 on FNG) were included in the study. All (100%) HCs mounted a positive (>33.8 BAU/mL) humoral response at T1 and preserved it until (T2-T3- T0b) and after (T1b) the third booster dose. At T0b only 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. Anti-TSP IgG titers in HCs were significantly higher than those of pwMS on OCR and on FNG at all time points, while no differences were found at all time points between pwMS on OCR and those on FNG. HCs showed a significant higher (relative) increase of Anti-TSP IgG levels at T1b with respect to OCR (p<.001) and FNG (p=.032) groups. The increase of Anti-TSP IgG levels in the pwMS on FNG was significantly higher than those in the OCR group (p<.001). No socio-demographic, clinical, or laboratory variables were able to predict the increase of anti-TSP IgG levels between T0b and T1b. Neither clinical relapses nor severe adverse events were reported in pwMS after each of the three doses of vaccine during the follow- up period. Conclusion(s): The administration of a third booster dose of BNT162b2 mRNA Covid-19 vaccine to OCR- and FNG-treated pwMS is able to revive the humoral response, independently of any demographic, clinical or laboratory variable, and confirms a good safety and tolerability profile, not only in terms of adverse events but also in terms of MS relapses.
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Introduction, objectives and aims: COVID-19 pandemic caused a significant disruption of clinical activities at Multiple Sclerosis (MS) Centers. As part of a national multicenter survey (COVId Ms Patients SATisfaction survey - COVIMPSAT) aimed at collecting patients' opinion regarding the quality of care and information received from MS Centers (MSC) during the pandemic, we report data about COVID-19 infections and vaccination cycle and how they were managed by the MSC. Material(s) and Method(s): In April-May 2021, 16 Italian MSC developed and sent a digital (35-item) survey by email to their patients. Statistical analyses were performed with SPSS, version 25. Result(s): 1670 people with MS (pwMS;67.3% women) completed the survey. 169 (10.1%) reported a diagnosis of COVID-19 infection: 63% were symptomatic, while 37% were not. As regards treatment for COVID-19, only 3% of the patients were hospitalized. The impact of COVID-19 infection on MS-related neurological symptoms was as follow: 69.3% of pwMS stated that the severity of their MS-related symptoms remained stable, 21.5% reported a worsening of pre-existing symptoms, 7.4% affirmed that new neurological symptoms emerged, while only 1.8% reported an improvement of MS-related symptomatology. At the time of the survey, 60.6% of pwMS were inoculated at least one dose of COVID-19 vaccine. Vaccination appointments were scheduled by: MSC staff alone (44.9%), MSC staff together with the general practitioner (17.5%), the general practitioner alone (16.1%), other Institutions (12.1%), and by the patients themselves (9.3%). At the moment of the survey 39.4% of pwMS were not vaccinated yet. The three major reasons for not being vaccinated yet were: being already on a vaccination list (40.8%), willing to be vaccinated but without an appointment (17.6%), still undecided or not willing to be vaccinated (19.3%). Conclusion(s): The results of this multicentre survey revealed a low hospitalization rate of pwMS, in line with previous studies (Moghadasi et al, 2021). In the majority of the sample, COVID-19 symptomatology did not have a significant impact on MS-related neurological symptoms. MSC promoted and facilitated vaccination procedures and scheduling, alone or in combination with the general practitioner, in more than half of pwMS.
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Introduction: Since the worldwide launch of the SARS-CoV-2 vaccine campaign, there have been many uncertainties regarding the immune response to vaccination in patients with multiple sclerosis (pwMS), particularly those on high efficacy disease-modifying therapies (DMTs). Aim: To evaluate humoral response to NT162b2-mRNACovid- 19 vaccine in pwMS on high efficacy DMTs compared to healthy controls (HCs). Methods: We collected serum samples before the first dose and 7 days after the second dose of the NT162b2-mRNA-Covid-19 vaccine from 54 HCs and 93 pwMS on high efficacy DMTs (Ocrelizumab/OCR, Fingolimod/FNG, Natalizumab/NTZ). Exclusion criteria: history of Covid-19, baseline positive SARSCoV- 2 IgG antibodies, steroids administration within the month prior to the first dose of vaccine. Sera were tested using the LIAISONRSARS-CoV-2 TrimericSIgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The IgG-titers were expressed in Binding Antibody Units (BAU) with 33.8 BAU/mL as cut-off. Results: Sera of 51 HCs and 80pwMS (31 OCR, 25 FNG, 24 NTZ) were analyzed, while 3 HCs and 13 pwMS (4OCR, 5FNG, 4NTZ) were kept out due to exclusion criteria. Age, sex, and disease duration were similar across groups. Seven days after the second dose of the vaccine, SARS-CoV-2 IgG antibodies were detected in all HCs and pwMS on NTZ, in 17(54.8%) pwMS on OCR and 10(40%) pwMS on FNG. pwMS on OCR (median 59.8 BAU/mL;P25-75 4.81-598) and FNG (median 21.5;P25-75 7.49-116) showed a significant blunted response (p<0.0001, both) when compared with HCs (median 1860;P25-75 1180-4865) and NTZ patients (p<0.0001, both). pwMS on NTZ mounted a humoral response (median 3015;P25-75 1495-4905) similar to HCs (p=0.52). Interestingly, we observed a positive association between humoral response and time elapsed since the last OCR infusion (rho 0.46,p=0.001) and an inverse correlation between humoral response and treatment duration in pwMS on FTY (rho -0.57,p=0.004). No correlation was found with CD20 levels in the OCR group. Discussion: We found a clear blunted humoral response to NT162b2-mRNA-Covid-19 vaccine in pwMS treated with OCR and FNG, with a significant relationship with treatment duration in FNG-treated pwMS and time elapsed since the last infusion in the OCR-treated pwMS. Contrariwise, we found an efficient humoral response in NTZ-treated pwMS. Further data are needed to inform which strategy could optimize the response to vaccines in pwMS on OCR and FTY.
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Background and aims: Since the worldwide launch of the SARS-CoV-2 vaccine campaign, several concerns apply on the response to vaccines in people with multiple sclerosis (pwMS) particularly those on high efficacy disease modifying therapies (DMTs). We report preliminary data on humoral response to Covid-19 vaccine assessed on four pwMS treated with ocrelizumab (OCR) and compared to that measured in a sample of healthy subjects (HS) enrolled in a surveillance programme at our Clinic. Methods: We collected serum samples -at 0,14,21 days after the first dose and 7 days after the second dose of NT162b2-mRNA-Covid-19 vaccine of: i) 55 health-care workers, and ii) four relapsing MS patients on OCR, that were vaccinated with the same Covid-19 vaccine. All subjects did not have a history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.), for the detection of IgG antibodies to SARS-CoV-2 spike protein. The IgG-titers were expressed in Binding Antibody Units (BAU). Results: Seven days after the second dose of NT162b2-mRNA-Covid-19 vaccine, all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I.95%1512.7–2672), while all the four pwMS showed a very low response (range 4,9–175 BAU/mL). Conclusions: As expected and in agreement with previous data, we found a blunted humoral response to NT162b2-mRNA-vaccine in pwMS treated with OCR. Further data are urgently needed in order to confirm and expand these preliminary, yet significant results and to inform if there is any strategy to optimize the response to vaccines such as the count of circulating CD20 cells, time-elapsed since the last anti-CD20 drug administration.
ABSTRACT
In this work, we apply a novel and accurate Physics-Informed Neural Network Theory of Functional Connections (PINN-TFC) based framework, called Extreme Theory of Functional Connections (X-TFC), for data-physics-driven parameters’ discovery of problems modeled via Ordinary Differential Equations (ODEs). The proposed method merges the standard PINNs with a functional interpolation technique named Theory of Functional Connections (TFC). In particular, this work focuses on the capability of X-TFC in solving inverse problems to estimate the parameters govern-ing the epidemiological compartmental models via a deterministic approach. The epidemiological compartmental models treated in this work are Susceptible-Infectious-Recovered (SIR), Susceptible-Exposed-Infectious-Recovered (SEIR), and Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS). The results show the low computational times, the high accuracy, and effectiveness of the X-TFC method in performing data-driven parameters’ discovery systems modeled via parametric ODEs using unperturbed and perturbed data. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.