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Background: Coronavirus Disease 2019 (COVID-19) is a highly contagious disease that resulted in 4533645 deaths until September first, 2021. Multiple Sclerosis (MS) patients receive immunosuppressive drugs. Thus, there is a concern that these drugs will reduce the patient's immune system resistance against COVID19. Objective(s): This study aimed to evaluate the epidemiology of COVID19 and its impact on MS patients in our university hospital in Tehran City, Iran. Material(s) and Method(s): A cross-sectional study was conducted based on hospital-based registry data from May 2020 to March 2021. Among more than 500 registered MS patients in Imam Khomeini Hospital in Tehran City, Iran, referring within our study period, 84 patients reported SARS-COV2 infection. The diagnosis of MS was confirmed by the McDonald criteria. Moreover, the diagnosis of COVID-19 in MS patients was established by the real-time-PCR technique and chest computed tomography. Result(s): Out of 84 MS patients with SARS-COV2 infection, 55(65.5%) were women, and their mean age was 37.48 years. The most commonly used medications by MS patients were Rituximab 20 (26.3%) and Dimethyl Fumarate 14(18.4%). Totally, 9(10.8%) of the patients needed to be hospitalized due to COVID-19, with a mean hospitalization duration of 5.88 days. A total of 1 (1.2%) death was reported. Conclusion(s): Compared to the healthy population, COVID-19 is not more serious in MS patients. Most MS patients with COVID-19 infection were not hospitalized and continued their medication during the infection.Copyright © 2022 The Authors. This is an open access article under the CC-By-NC license. All Rights Reserved.
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Introduction/Aim: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is critical for COVID-19 outcomes. Our objective was to examine the prophylactic potential of IFN treatment to limit viral transmission Methods: A cluster-randomised clinical trial was undertaken to determine effects of IFNbeta-1a treatment on SARS-CoV-2 household transmission (clinicaltrials.gov: NCT04552379). Index cases were identified from confirmed SARS-CoV-2 cases in Santiago, Chile, with 341 index cases and 831 household contacts enrolled. Households received 125 mug subcutaneous pegylated-IFNbeta-1a on days 1, 6, & 11 (172 households, 607 participants), or standard care (169 households, 565 participants). Primary outcomes included: (1) duration of viral shedding in infected cases (IC-INF), (2) transmission to treatment-eligible household contacts (EHC-ITT) at day 11. Result(s): Of 1172 individuals randomised, 53 individuals withdrew from the study (IFNbeta-1a = 35, SOC = 18). Eighty-two households (IFNbeta-1a = 36, SOC = 46) where the index case was SARS-CoV-2 negative on days 1 & 6, or with no SARS-CoV-2 negative contacts at recruitment, were excluded from exploratory analyses. Treatment with IFNbeta-1a: had no effect on duration of viral shedding in the IC-INF population (primary outcome 1), had no effect on transmission of SARS-CoV-2 at day 11 in the EHC-ITT population (primary outcome 2) but an effect was observed in a sensitivity analysis at day 6 (EHC-ITT: OR = 0.493, 95% CI = 0.256-0.949), reduced duration of hospitalisation in the IC-INF population and incidence of hospitalisation in per-protocol index cases (secondary outcome 3). In exploratory frequentist analysis, a significant effect of IFNbeta-1a treatment on SARS-CoV-2 transmission by day 11 (OR = 0.55, 95% CI = 0.36-0.99), and a Bayesian analysis identified a significant reduction in the odds of transmission (OR = -0.85, 95% credible interval = -1.59--0.16). Conclusion(s): Ring prophylaxis with IFNbeta-1a had no effect on duration of viral shedding but reduces the probability of SARS-CoV-2 transmission to uninfected, post-exposure contacts within a household.
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Background: SARS-CoV-2 variants resistant to monoclonal antibodies, and drug-drug interactions and potential mutagenicity of direct acting antivirals, heightens the need for additional therapeutics to prevent progression to severe COVID-19. Exogenous interferon beta is a promising therapeutic option against SARS-CoV-2 given its broad-spectrum antiviral activity and data suggesting impaired endogenous IFN production in individuals with severe disease. Method(s): The safety and efficacy of orally inhaled nebulized interferon-beta1a (SNG001) was evaluated in a Phase II randomized controlled trial on the ACTIV-2/ A5401 platform (NCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized to SNG001 once daily for 14 days or blinded pooled placebo. Primary outcomes included treatment-emergent Grade >=3 adverse event (TEAE) through day 28;time to symptom improvement of 13 targeted COVID-19 symptoms collected by daily study diary through day 28;and SARS-CoV-2 RNA < lower limit of quantification (LLoQ) from nasopharyngeal (NP) swabs at days 3, 7, and 14. All-cause hospitalization or death through day 28 was a key secondary outcome. Result(s): Of 221 participants enrolled at 25 US sites between February and August 2021, 220 (110 SNG001, 110 placebo) initiated study intervention, with a median age of 40 years, 55% female, and 20% SARS-CoV-2 vaccinated. There was no significant difference between SNG001 and placebo in Grade >=3 TEAEs (4% vs 8%, Fisher's exact test p=0.25). Median time to symptom improvement was 13 days for SNG001 and 9 days for placebo (Gehan-Wilcoxon test p=0.17). There was no difference in the proportion of participants with SARS-CoV-2 RNA < LLoQ at day 3, 7 or 14 (SNG001 vs placebo, Day 3: 28% vs. 39%;Day 7: 65% vs. 66%;Day 10: 91% vs. 91%;joint Wald test p=0.41). There were fewer hospitalizations with SNG001 (n=1;1%) compared with placebo (n=7;6%), but this difference was not statistically significant (Fisher's exact test p=0.07;Figure). All hospitalizations were due to COVID-19 and occurred among unvaccinated participants without protocol-defined high-risk factors. Conclusion(s): Inhaled nebulized SNG001 was safe and well tolerated but did not reduce SARS-CoV-2 RNA levels in the nasopharynx nor decrease time to improvement of COVID-19 symptoms in outpatients with mild-to-moderate COVID-19. The non-statistically significant decrease in hospitalizations among SNG001 participants warrants further investigation in a phase 3 clinical trial. Cumulative incidence of hospitalization or death comparing SNG001 vs. placebo.
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Objective(s): The objectives were to provide an overview of the current practices of Near East (NE) healthcare practitioners (HCPs) by probing their prescribing decisions, to report the COVID-19 impacts on neurologists' prescribing habits, and to explore the future relevance of current medication used in MS management among other newcomers Material(s) and Method(s): A cross-sectional study was carried out using an online survey from April 27, 2022, to July 5, 2022. The questionnaire was designed with the input of five neurologists representing five NE countries (Iran, Iraq, Lebanon, Jordan & Palestine). They identified several factors that play a crucial role in the optimal care of MS patients. The link was shared among neurologists using snowball sampling Result(s): The survey included 98 neurologists from the included NE countries, the majority of whom had more than 15 years of experience in the field, and 39% were seeing more than 40 MS patients a month. Effectiveness and safety balance was the most important factor considered when selecting the MS treatment. In the treatment of mild to moderate RRMS in men, Interferon beta 1a SC, Fingolimod, and Glatiramer acetate were the most commonly recommended treatments. Dimethyl fumarate substituted fingolimod in female patients. According to 80.7% of participants, interferon beta 1a SC was the safest treatment for mild to moderate RRMS. Interferon beta 1a SC was preferred over other treatments for patients with mild to moderate MS and planning for pregnancy (56.6%) or breastfeeding (60.2%). Fingolimod was not a choice for these patients. Neurologists seemed to discuss the top three treatments of Natalizumab, Ocrelizumab, and Cladribine with patients with highly active MS. Conclusion(s): Most neurologists in the NE region followed MENACTRIMS recommendations for prescribing treatment. The treatment choice also depended on the availability of DMTs in the region. Regarding the use of upcoming DMTs such as Ofatumumab, Siponimod, Ozanimod, and BTK inhibitors, there is a clear need for real-world data, long-term extension studies, and comparative studies to support their efficacy and safety profiles in treating patients with MSCopyright © 2022
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Objective(s): Type 1 Interferons (IFNs) modulate the antiviral immune response and have been used for the treatment of coronaviruses. This study aimed to determine any possible effects and safety concerns of the two most promising exogenously administrable interferons (IFNbeta1a and IFNbeta1b) on the severity outcomes of COVID-19 in multiple sclerosis (MS) patients hospitalized with COVID-19. Material(s) and Method(s): Using the electronic health records systems;this is a cross-sectional study of two years of hospital admissions in terms of COVID-19 in Iran from March 2019 to August 2021. The severities of COVID-19 outcomes were admitted to ICU, hospitalization days, and in-hospital mortality. MS patients with positive results from PCR were included. The data included demographic information, admission, and discharge dates, initial and final diagnoses, hospital inpatient services, including all drugs, admitted wards, procedures, and hospital mortality. A questionnaire was filled out with information on their MS diagnosis, MS medications at the time of COVID-19 admission, history of other chronic illnesses, history of smoking, height and weight, co-morbidity, and MS course (MS type, EDSS, MS duration) and disease-modifying therapies (DMT) at the time of COVID-19 admission (Rituximab, Fingolimod, IFNs, Glatiramer acetate, Dimethyl fumarate, Teriflunomide, Tysabri, and Azathioprine). Result(s): A total of 993 hospitalized MS patients were included in the study. IFNs were used in 28.8% of patients for the treatment of SARS-CoV-2 infection;26% IFNbeta1a and 3.5% IFNbeta1b. Among studied patients, 5.6% did not receive any DMT before their hospital admission. Almost half of the patients were under Rituximab(50.3%). The data were classified based on consuming DMTs. Except for patients who received Rituximab;there was not any significant association between taking IFNs and reducing the severity of COVID-19 outcomes in each DMT sub-group. In patients who were under Rituximab;taking IFNbeta1a for COVID-19 treatment had a significant association with longer hospitalization than patients not receiving it (median (IQR);8(7) vs. 6(4) days, respectively, p=0.000). In the logistic regression model, after adjusting confounding factors, there was a constant association between receiving IFNbeta1a and the risk of longer hospitalization (adjusted OR=2.46 95%CI: 1.46, 4.13). Conclusion(s): The current data suggest that MS healthcare providers should consider specific risks of exogenously IFNbeta1a for the treatment of COVID-19 based on MS medication therapies.Copyright © 2022
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Rationale: Interferon beta (IFN-beta) is key in host defence against viruses but can be suppressed by virus or host factors locally at the site of infection. Inhalation of SNG001 (IFN-beta-1a nebuliser solution) aims to restore lung IFN-beta levels. Method(s): Adults hospitalised due to COVID-19 requiring low flow oxygen were randomized to receive SNG001 (314) or placebo (309) OD for 14 days, plus standard-of-care. Efficacy was assessed by change in clinical condition using the WHO 9-point Ordinal Scale for Clinical Improvement (OSCI). Primary endpoints: time to discharge (OSCI <=2) and time to recovery (OSCI <=1). Key secondary endpoints: progression to severe disease or death (OSCI >=5), progression to intubation or death (OSCI >=6), and death. Result(s): Most patients were discharged rapidly from hospital and there was no effect of SNG001 on time to discharge or recovery. However, there was an encouraging signal for prevention of progression to severe disease or death (ITT 26% relative risk reduction (RRR);Odds Ratio (95% CI): 0.71 (0.44, 1.15);Per Protocol 36% RRR;OR 0.63 (0.35, 1.13)). Post hoc analyses supported this observation with enhanced effects favouring SNG001 in subgroups at higher risk of progression (>=65 years;>=1 comorbidity;oxygen saturation <=92% and/or respiratory rate >=21 breaths/min on oxygen). Conclusion(s): If the encouraging signal in the relative risk of disease progression or death (~30% reduction) observed in this 300 patient/arm trial were confirmed in a larger trial, SNG001 could become a useful treatment option for hospitalised COVID-19 patients.
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Objective: To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19. Method(s): This study was a single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design on 68 patients with COVID-19. According to the 1:1 ratio between the study groups (ivermectin group and standard treatment group), patients were randomly admitted to each intervention arm. Result(s): The mean age of the participants in the ivermectin group was (48.37+/-13.32) years. Eighteen of them were males (54.5%) and the participants in the control group had a mean age of (46.28+/-14.47) years, with nineteen of them being males (59.4%). As a primary outcome, after 5 days of randomization, there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital (P=0.168). ICU admission (P=0.764), length of stay in ICU (P=0.622), in-hospital mortality (P=0.427), adverse drug reactions, and changes in the mean difference of laboratory data had not any significant difference between the two groups (except for urea change). In addition, the radiologic findings of the two groups of patients were not significantly different. Linear regression analysis showed that for every 10 years increase of age, 0.6 day of hospitalization duration was increased. There was no statistically significant association between other variables and clinical outcomes. Conclusion(s): Among adult hospitalized patients with moderate to severe COVID-19, there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement, and mortality of the participants.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.
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Background: The SARS-CoV-2 invades the cells by attachment of virus spike proteins (S1, S2) to cell membrane and engages angiotensin-converting enzyme 2 (ACE2), which is highly expressed in the epithelium of cerebral vasculature. Here, we describe a patient with encephalitis following SARS-CoV-2 infection. Case presentation: A 77-year-old male patient presented with mild cough and coryza lasting for eight days without a prior history of underlying disease or neurologic disorder. Oxygen saturation (SatO2) was decreased and behavioral changes, confusion, and headaches were started within three days prior to admission. Bilateral ground glass opacifications and consolidations were noted on chest CT scan. Lymphopenia, highly elevated D-Dimer and ferritin were noted in laboratory results. Brain CT and MRI showed no changes regarding encephalitis. Cerebrospinal fluid was collected as the symptoms persisted. The results of SARS-CoV-2 RNA RT-PCR from CSF and nasopharyngeal samples were positive. The combination therapy with remdesivir, interferon beta-1alpha and methylprednisolone was started. Due to deterioration of the patient's status and SatO2, he was admitted to the ICU and intubated. Tocilizumab, dexamethasone, and mannitol were started. The patient was extubated on the 16th day of ICU admission. The patient's level of consciousness and SatO2 were improved. He was discharged from the hospital a week later. Conclusion(s): RT-PCR of CSF sample along with brain imaging can help with diagnosis when encephalitis due to SARS-CoV-2 is suspected. However, no changes regarding encephalitis may be seen on brain CT or MRI. Combination therapy with antivirals, interferon beta, corticosteroids, and tocilizumab can help patients recover in these conditions.Copyright © 2022 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.
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Background: Dimethyl fumarate (DMF) is an approved treatment for multiple sclerosis (MS). Due to its efficacy and safety profile, DMF is the most prescribed oral medication for relapsing remitting (RR) MS. Given the long-term course of treatment with DMF in MS, continuous surveillance of opportunistic infections is fundamental. Case presentation: We report the occurrence of facial herpes zoster (HZ) associated with MS disease reactivation in a person with RRMS after 6 years of DMF therapy. Case report: A 44-year-old woman with RRMS developed right temple pain and blisters over the right cheek, suggestive of facial HZ. A normal lymphocyte count with however relatively lower proportions of CD8+ T cells and higher percentages of natural killer cells were detected in blood. The patient failed oral treatment and required hospitalization for intravenous acyclovir. She eventually developed symptoms of an MS exacerbation featured by lower extremities weakness and urinary retention. Conclusion(s): Our case highlights the importance of counseling patients on the possibility of HZ reactivation even in the setting of a normal lymphocyte count, the risk of MS exacerbation possibly associated with HZ occurrence and the importance of timely vaccination.Copyright © 2022
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The 32nd European Respiratory Society (ERS) International Congress was held again in person at the FIRA Barcelona Gran Via Conference Center in Spain, as well as online. On-site attendance was limited to 10,000 delegates, with the spaces selling out before the conference began. The program included live streamed presentations, thematic poster discussion sessions, oral presentations, mini-symposia, industry exhibitors and skills workshops to discuss major respiratory fields that included thoracic oncology, respiratory infections, interstitial lung diseases, respiratory critical care, sleep and breathing disorders and pulmonary vascular diseases. This report will cover some of the most interesting presentations related to respiratory disease treatment. Copyright © 2022 Clarivate.
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Background: Recent Covid-19 outbreak around the world turned into an international public health concern. Generally, people who receives immunosuppressive treatments or have an underlying disease are more likely to be infected. Multiple sclerosis (MS) patients also may have higher risk of infection due to the taking immunosuppressive or immunomodulatory drugs. Our objectives were to identify the epidemiological characteristics of Covid-19 in patients with MS for improve quality of care and achievement to better diagnosis and treatment in MS patients in Iran. Material(s) and Method(s): The present data were obtained from a hospital-based registry in Imam Khomeini hospital, Tehran, Iran. Totally, 88 MS patients who was infected by Covid-19 were registered from May, 2020 to March 2021. Demographic and clinical data was collected (2). Result(s): 55 (65.5%) of participants were female by the mean age (SD) of 37.48 ± 10.05 years. Covid-19 diagnosis of 4 (4.5%) of patients was based on positive PCR test. The most MS treatment was receiving by patients was Rituximab (20 (22.7%)) following by Dimethyl Fumarate (14 (15.9%)), Fingolimod (10 (11.4%)), Glatiramer acetate (8 (9.1%)), Interferon β-1a (IM) (5 (5.7%)), Interferon β-1a (SQ) (5 (5.7%)), Interferon β-1b (3 (3.4%)), Triflunomide (2 (2.3%)) and Natalizumab (1 (1.1%)). The mean (SD) interval from the last Rituximab injection to Covid-19 infection was 3.80 ± 3.40 months. 37 (42.0%) MS patients continued to take their drugs after Covid-19 infection, while 10 (11.4%) of them stopped taking MS medicine and 7 (8.0%) of them was taking no treatment for controlling MS. 2 (2.3%) of participants was diagnosed by MS after Covid-19 infection. 9 (9.7%) subjects hospitalized due to Covid-19 infection. The mean (SD) duration of hospitalization was 5 ± 7.81 days. One (1.1%) death cases was reported. Conclusion(s): Our findings revealed valuable data of Covid-19 characteristics in patients with MS which could be useful for improving health services for MS patients during the Covid-19 pandemic (3-4).
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Background: Several factors rendered patients with multiple sclerosis (pwMS) likely to be affected by the rapidly evolving events of the COVID-19 pandemic. Globally, pwMS were confronted with limited access to their healthcare team, potential treatment interruption, and concerns about the risk of infection while treated with immunomodulatory disease-modifying therapies (DMTs), particularly high-efficacy DMTs. The current study explored treatment-related concerns and their impact on medication adherence during the COVID-19 pandemic in pwMS treated with subcutaneous interferon beta-1a (sc IFN β-1a) in the Near East region. Material(s) and Method(s): A total of 3,348 pwMS treated with sc IFN β-1a across five countries of the Near East region (Iran, Iraq, Jordan, Lebanon, and Palestine) participated in a telephone survey. The survey was conducted by nurses, on behalf of the Merck Patient Support Program in the Near East region, from May 1–30, 2021. A standardized questionnaire allowed participants to report their concerns related to COVID-19 and their MS treatment, along with medication adherence over the previous 3 months. Concern with current MS treatment was rated on a scale of 1–10, with levels 1–3 reflecting a low level of concern, levels 4–7 reflecting a moderate level of concern, and levels 8–10 reflecting a high level of concern. Adherence to sc IFN β-1a was defined as administration of the prescribed three weekly injections. Result(s): Amongst the countries surveyed, a total of 3,074 participants (92%) reported being concerned about sc IFN β-1a increasing their risk of COVID-19 infection. However, a majority of participants from Iraq (94%), Palestine (88%), Jordan (84%), and Iran (84%) reported a low level of concern.More participants from Lebanon reported high (51%) and moderate (38%) levels of concern about their MS treatment and the risk of COVID-19 infection. Full adherence to sc IFN β-1a over the previous 3 months was reported by 3,293 (98%) participants. Key factors influencing medication adherence included the lack of access to sc IFN β-1a, physician supervision, and adverse events. Conclusion(s): This study explored the impact of treatment-related concerns on medication adherence in pwMS treated with sc IFN β-1a during the COVID-19 pandemic in the Near East. Despite a large proportion of study participants being concerned about a potential increase in the risk of COVID-19 infection while on their current treatment, participants were only mildly concerned and the majority remained adherent to the prescribed medication. Furthermore, the fear of COVID-19 infection by participants was not a key factor associated with non-adherence. Instead, limited access to medication and decisions of supervising physicians negatively impacted medication adherence. More than a year after the World Health Organization declared the COVID-19 outbreak a pandemic, safety concerns related to DMTs still exist. Interferons can be prescribed as usual in COVID-19 times, and this should be communicated effectively to clinicians and patients.
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Rationale: New effective treatments are urgently needed for patients hospitalized with COVID-19, due to lower respiratory tract illness caused by the SARS-CoV-2 virus. SARS-CoV-2 suppresses production of interferon-beta (IFN-β), a naturally occurring protein and key driver of innate antiviral immunity, to evade host immune responses. Patients with severe disease have reduced ability to generate a primary interferon response in the lungs because of genetic, comorbid and/or autoantibody host responses. In vitro, IFN-β has potent antiviral activity against SARS-CoV-2, including known variants of concern. SNG001 is an IFN-β-1a nebulizer solution administered directly into the lungs to boost IFN-β levels at the site of infection. In trials of patients with chronic respiratory diseases and viral infections, SNG001 was well tolerated and improved lung function, providing the rationale to treat patients with COVID-19, at risk of progressing to severe disease. In a phase 2 trial, non-ventilated hospitalized patients with COVID-19 receiving SNG001 were more than twice as likely to recover to “no limitation of activities” and experienced significantly reduced breathlessness over the treatment period versus those receiving placebo. These encouraging results with inhaled IFN-β supported progression of SNG001 into a phase 3 trial in patients hospitalized due to COVID-19 (SPRINTER). Methods: Adults (≥18 years) hospitalized with COVID-19, requiring supplemental oxygen via nasal prongs or mask were randomized to receive SNG001 or placebo (1:1) by inhalation once daily for 14 days, in addition to standard-of-care treatment. Efficacy was assessed in the intention-to-treat population by change in clinical condition using the WHO 9-point Ordinal Scale for Clinical Improvement (OSCI;Table). Primary endpoints: time to hospital discharge (OSCI ≤2) and time to recovery to “no limitation of activities” (OSCI ≤1). Key secondary endpoints: progression to severe disease or death (OSCI ≥5), progression to intubation or death (OSCI ≥6), and death. Cox proportional hazards modeling was used to evaluate primary endpoints. Key secondary endpoints were analyzed using logistic regression. Results: Between January and November 2021, 623 patients were randomized to treatment. Preliminary, blinded data show that median duration of symptoms was 9 days;22% (135/623) of patients were partially/fully vaccinated;median duration of hospital stay was 7 days;84% (525/623) of patients were discharged by Day 35;13% (80/623) progressed to severe disease or died within 35 days;and 5% (31/623) died within 35 days. Conclusions: Recruitment into the SPRINTER trial was completed in November 2021. Unblinded efficacy and safety results (expected Q1 2022) will be presented. (Table Presented).
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Objective: To gain an understanding of COVID-19 practices and experiences among patients with multiple sclerosis (MS) enrolled in MS LifeLines, a disease-modifying therapy patientsupport program. Background: Research into the impact of COVID-19 on people with MS is ongoing. Design/Methods: Enrollees from MS LifeLines were invited to participate in an internet-based survey. Participants were included if they self-reported physician-diagnosed relapsing MS, initiated cladribine tablets or were currently being treated with interferon beta-1a (scIFNβ1a), and aged ≥18 years. Information collected included demographics, clinical characteristics, MS treatment/disease history, and COVID-19 understanding, preventive measures, exposure, and vaccination experiences. Findings were analyzed descriptively. Results: Among 1095 patients completing the survey from May 12-July 2, 2021 (616 cladribine tablets, 479 scIFNβ1a), mean (SD) age was 50 (11.9), 77.9% female, 76.9% non-Hispanic White/9.4% non-Hispanic Black/6.7% Hispanic;and mean (SD) Charlson Comorbidity Index 0.41 (0.89). Half (51.6%) had changed from in-person visits to telephone/video, 44.7% discussed COVID-19 concerns with their physician, and 26.4% discussed MS medication concerns. Patients described their understanding of the risk of developing complications with COVID-19 as 'very well'(48.5%) or 'fairly well'(26.6%). COVID-19 preventive measures were widely practiced (% responding 'always': mask wearing, 79.7%;monitoring symptoms, 68.0%;hand washing, 66.9%;6-foot social distancing, 56.5%;staying home, 51.5%;cleaning/disinfecting surfaces, 35.5%). For the total cohort, 7.8% received a positive COVID-19 test, 54.8% had a COVID-19 test, 16.3% had COVID-19 symptoms, and 30.9% had close contact with someone with COVID-19. Most (74.6%) were vaccinated, 8.3% were planning to get vaccinated, 12.1% were not planning to get vaccinated, and 5.0% were unsure. Similarly, 76.3% discussed COVID19 vaccination with their physician, 8.2% were planning to discuss vaccination with their physician, 11.1% were not planning to discuss vaccination with their physician, and 4.4% were unsure. Conclusions: The findings provide insight into COVID-19 understanding, preventive measures, exposure, and vaccination experiences of patients with MS.
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Objective: To report on the post-approval safety profile of subcutaneous interferon beta-1a (sc IFNβ-1a) in patients with relapsing multiple sclerosis (RMS), including COVID-19 and other respiratory viral infections. Background: sc IFNβ-1a is a well-established disease-modifying therapy for RMS, with an estimated cumulative exposure of 1,831,698 patient-years (to 30 April 2021). Design/Methods: Serious and non-serious adverse events (AEs)/adverse drug reactions (ADRs) from post-approval spontaneous individual case safety reports are presented cumulative to May 2021. AE rates are shown as total number of patients. Current COVID-19 findings are summarized. Results: A total of 527,833 ADRs have been reported;6.6% of events were serious. Analysis of the most common respiratory viral infection ADRs reported spontaneously (influenza [2374 cases, constituting 0.45% of all ADRs], viral infection [319], H1N1 influenza [15], viral bronchitis [6], and viral upper respiratory tract infection [5]) did not reveal any abnormal trend outside the known safety profile of sc IFNβ-1a;cases were typically non-serious. There was no suggestion of an increased risk of more severe respiratory viral infection or other ADRs in RMS patients who experienced such infection while being treated with sc IFNβ-1a. As of 17 August 2021, the Merck KGaA safety database included 1256 suspected or confirmed cases of COVID-19 in sc IFNβ-1a treated RMS patients;the majority were non-serious events. Among confirmed cases (n=1029), 110 patients were hospitalized with 5 requiring mechanical ventilation. There were 24 fatalities (18 fatal COVID-19 events and 6 other fatalities unconfirmed for COVID-19 involvement). At time of reporting, around half of COVID-19 confirmed AEs were recovered or resolving. Conclusions: Cumulative to 17 August 2021, there was no increased risk of COVID-19 in sc IFNβ-1a treated RMS patients and the majority of cases were non-serious, consistent with previously reported registries. No new safety concern was identified from post-approval cases in scope of this review.
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SARS-CoV-2 is a coronavirus that infects epithelial cells in the naso- and oropharynx before infecting epithelial cells of the lower airways and alveoli and in severe COVID-19 spreading systemically and inducing a systemic inflammatory response. SARS-CoV-2 is spread mainly by virus particles in droplets and aerosols. This suggests that inhaled therapies may be useful in the treatment of early COVID-19 disease before severe respiratory systemic features develop and potentially in reducing transmission of the virus in the community. To be effective any inhaled therapy must be rapidly acting to prevent viral replication in respiratory epithelial cells to prevent the disease spreading down the respiratory tract and into the systemic circulation. It also needs to be safe and available for early prescription in order to prevent severe disease and hospitalisation. The development of inhaled therapies for COVID-19 may involved repurposing of existing inhaled therapies or developing inhaled formulations of new drugs with antiviral effects. Patients with asthma and COPD were reported to be less likely to be hospitalised with SARS-CoV-2 infection despite the concern that this coronavirus would have severe consequences for these patients as coronaviruses are known to trigger severe exacerbations. One possibility was that this may be due to the widespread treatment with inhaled corticosteroids (ICS), which are known to suppress ACE2 and TMPRSS2 on epithelial cells that are key entry receptors for the virus and also reduce virus replication in vitro. A community based open label parallel group phase 2 study of the ICS budesonide (800 lg bid until recovery) in people with early symptoms (within 7 days of onset) of COVID-19 and confirmed by PCR testing (STOIC) showed that only 1/69 people in the ICS group developed severe disease compared with 10/70 in the usual care group.1 Clinical recovery was also shorter in the ICS group. This finding was confirmed in an open label study of inhaled budesonide in individuals over the age of 65 years at risk from severe COVID-19 (PRINCIPLE), which showed a reduction in time to recovery and a trend towards reduced hospitalisation and death.2 Several other trials, including double-blind studies, of ICS in early COVID-19 are currently underway with different corticosteroids, including ciclesonide, which appears to be the most effective against SARS-CoV-2 in vitro.3 However, a recent double-blind study of nasal and inhaled ciclesonide failed to show any benefit in early COVID-19, although the population was mainly young adults who have a low risk of disease progression.4 The mechanism of action of ICS in COVID- 19 has not yet been established, but may involve reduced viral entry due to suppression of ACE2 and TMPRSS2 in airway epithelial cells, reduced viral proliferation or reduced inflammatory mediators secreted by airway epithelial cells that may promote viral spreading. Interferon b1 is currently approve for treating multiple sclerosis. Nebulised IFN-b1a (SNG001) gave a greater degree of clinical improvement in hospitalised COVID-19 patients and a reduction on symptoms (mainly dyspnoea) compared to with placebo and was well tolerated.5 However, studies in early disease are underway but have not yet been reported, although there are logistical problems in the need for a nebuliser to deliver the drug. Inhaled PUL-42 is a combination of a TLR2/6 and a TLR9 inhibitors which is effective in a single inhaled dose against SARS-CoV and MERS-CoV infection in mice and reduces the lung viral load.6 This drug is now in clinical trials for COVID-19. Other inhaled drugs, including antivirals such as remdesivir and niclosamide, are also in development.
ABSTRACT
Introduction: Recent reports have indicated that a considerable portion of patients experiences a cardiac injury, ranging from 7.2% to 22.2%, which is linked to higher mortality. Nevertheless, previous studies have exclusively focused on the cardiac injury defined as a raised cardiac marker without a definitive diagnosis. To our knowledge, the present retrospective cohort study is the first study to comprehensively address cardiovascular (CV) complications and related outcomes in COVID-19 patients. Purpose: To address CV complications and their relationship to clinical outcomes in hospitalized patients with COVID-19. Methods: A total of 196 adult hospitalized patients admitted to our hospital with a confirmed diagnosis of COVID-19 and a consultation requested from the cardiology department were enrolled in this retrospective single-center cohort study from September 10, 2020, to December 10, 2020, with a median age of 65 years (IQR, 52-77). Cardiac examinations included cardiac biomarkers, electrocardiography, and echocardiography. Data regarding complications during hospitalization were extracted, and patients were categorized into two groups concerning the presence or absence of CV complications. All transthoracic echocardiographic (TTE) assessments were performed by a single cardiologist, who was provided with personal protective gear according to national guidelines. Follow-up continued for 3 months after hospital discharge. Results: CV complication was observed in 54 (27.6%) patients, with arrhythmia being the most prevalent (14.8%) followed by myocarditis, acute coronary syndromes, ST-elevation myocardial infarction, cerebrovascular accident, and deep vein thrombosis in 15 (7.7%), 12 (6.1%), 10 (5.1%), 8 (4.1%), and 4 (2%) patients, respectively. The proportion of patients with elevated hs-TpI, NT-proBPN, left ventricular diastolic dysfunction, and heart failure with preserved ejection fraction was greater in the CV complication group. Severe forms of COVID-19 comprised nearly two-thirds (64.3%) of our study population and constituted a significantly higher share of the CV complication group members (75.9% vs 59.9%;P = 0.036). Intensive care unit admission (64.8% vs 44.4%;P = 0.011) and stay (5.5 days vs 0 day;P = 0.032) were notably higher in patients with CV complications. Among 196 patients, 50 died during hospitalization and 10 died after discharge, yielding allcause mortality of 30.8%. However, there were no between-group differences concerning mortality. Heart failure, cancer/autoimmune disease, severity, interferon beta-1a, and arrhythmia were the independent predictors of all-cause mortality during and after hospitalization. Conclusion: CV complications occurred widely among COVID-19 patients. Moreover, arrhythmia, as the most common complication, was associated with increased mortality.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has imposed a significant burden worldwide, manifesting as a severe disease and causing mortality even in children. Severe COVID-19 disease is characterized by cytokine storm with progression to secondary hemophagocytic lymphohistiocytosis (sHLH). We describe an 18-month-old boy in Iran, previously healthy, diagnosed with COVID-19-induced sHLH. Three weeks after close contact with COVID-19 confirmed cases, he was admitted with high fever, lethargy, mild respiratory distress, skin rash, and conjunctivitis with swollen eyelids and lips. Laboratory data revealed elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and liver enzymes, and mild thrombocytopenia. His clinical condition rapidly deteriorated, with septic shock, hepatosplenomegaly, and respiratory failure. Laboratory tests showed cytopenia, coagulopathy, hy-perferritinemia, and hypertriglyceridemia, which met the criteria for sHLH diagnosis. Chest computed tomography (CT) revealed bilateral infiltrations that suggested acute respiratory distress syndrome (ARDS) of COVID-19 that was confirmed by a positive real-time polymerase chain reaction (RT-PCR) test. Therefore, the child was treated with intravenous immunoglobulin (IVIG), glucocorti-coid, hydroxychloroquine, lopinavir/ritonavir, and interferonβ-1a. This therapeutic strategy enabled complete recovery from fever, regaining consciousness, weaning from respiratory support, and resolving shock. Serial chest radiographs showed diminishing infiltrations. Sequential physical examinations revealed an overall significant reduction in spleen and liver span. Laboratory data showed rapid improvement from cytopenia and coagulopathy, normalization of liver enzyme levels, and reduction in hyperinflam-mation markers. Although ARDS is the most common cause of death from COVID-19, other complications such as sHLH may be lethal;thus, early diagnosis and appropriate treatment are necessary for saving patients’ lives.