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1.
Multiple Sclerosis Journal ; 28(3 Supplement):515-516, 2022.
Article in English | EMBASE | ID: covidwho-2138878

ABSTRACT

Introduction: Some multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with blunted humoral vaccination responses, but relevance for SARS-CoV-2 infection is unclear. Objective(s): To determine SARS-CoV-2 exposure rates and formation of antibody memory among participants of the COMparison Between All immunoTherapies for MS (COMBAT-MS;NCT03193866) and the Immunomodulation and MS Epidemiology (IMSE) studies. Aim(s): To determine SARS-CoV2 serological response of people living with MS (pwMS). Method(s): Using a multiplex bead-based assay we determined SARS-CoV-2 spike and nucleocapsid antibody levels in 3,723 pwMS in paired serum samples (n=7,157) donated prior (<January 31st 2020) and during the pandemic (July-October 2020);16.6% had natalizumab, 6.4% fingolimod, 9.7% dimethyl fumarate, 1.9% interferon beta, 50.4% rituximab, 1.4% cladribine, 7.6% other DMTs, and 6.1% were untreated. Median fluorescent intensity (MFI) and bead-count were determined for spike and nucleocapsid antibodies, and samples were regarded as positive only when reactive to both viral antigens. Hazard ratios, from multivariable Cox regression models, were derived to assess association between antibody levels above cut-off for each antigen, comparing exposure to rituximab or fingolimod at time of sampling vs. other reference DMTs. All models were adjusted for age, sex, treatment center, time since reported infection, MS severity, disease duration, and number of previous DMTs. Result(s): Specificity and sensitivity of the assay for SARS-CoV-2 was 100% and 99.7%, respectively. The proportion of positive samples for SARS-CoV-2 differed moderately across DMTs with the highest values among cladribine-treated (7.4%) and the lowest number among rituximab-treated pwMS (3.9%). Similarly, the proportion of positive cases not reported in the Swedish MS registry varied from 100% for cladribine to 33.3% among untreated pwMS. Comparing levels of antibodies titers showed that levels were lower among those treated with rituximab or fingolimod vs interferon treated pwMS. Point estimates indicated a similar trend comparing rituximab or fingolimod vs untreated pwMS. Conclusion(s): Overall rates of SARS-CoV-2 antibody positivity after the first COVID-19 wave differed only moderately across DMTs, while antibody levels were lower with rituximab or fingolimod compared to interferon-treated pwMS. This indicates quantitative rather than qualitative differences in the humoral response to infection.

2.
Gastroenterology ; 162(7):S-159, 2022.
Article in English | EMBASE | ID: covidwho-1967249

ABSTRACT

Objectives Colorectal cancer (CRC)-related services decreased substantially as a result of the COVID-19 pandemic. Large numbers of procedures were suspended and many have not yet been completed. Resulting delays in cancer screening and diagnosis may negatively impact CRC outcomes. In this study, we predict this impact, and compare different recovery scenarios in the United States. Methods The MISCAN-Colon model was used to simulate the US population in 2020, and evaluate different impact and recovery scenarios. Scenarios were defined in terms of the duration and severity of the disruption (% of eligible adults affected), the length of delays, and the duration of the recovery. In the base-case analysis, we considered a 12-month disruption period, starting in March 2020. During this period, part of preventive and diagnostic procedures were cancelled and delayed. The severity of disruption by month was based on published literature (Embase and Ovid Medline, through December 21, 2020). The assumed delays in services followed a discrete-time distribution, which was a function of the severity of disruption. During recovery, colonoscopy capacity was increased to catch up missed procedures, over a period of 6, 12, or 24 months. In sensitivity analyses, we varied the disruption period (6-18 months) and severity of disruption (lower/higher). Primary outcomes were excess CRC cases and deaths, required excess colonoscopy capacity during recovery, and additional number-needed-to-scope during recovery to prevent one death. Results The COVID-19 pandemic reduced preventive colonoscopies by an estimated 30% in 2020, and overall colonoscopies by 25%. For a 24-month recovery period, the model predicted 8,010 (0.21%) excess CRC cases during 2020-2040, 7,370 (0.69%) excess CRC deaths (Figure 1), and required 103,900 (8.3%) excess colonoscopies per recovery month (Table 1). Shorter recovery periods decreased long-term excess CRC cases to 5,540 and 2,740, for 12 and 6 months, respectively and excess deaths to 5,150 and 4,820. However, this reduction in excess cases came at a cost of 254,600 and 579,600 excess colonoscopies per month. The prevention of the excess CRC deaths through the shorter recovery periods of 6 or 12 months required an additional 1,150 and 840 colonoscopies per excess death prevented compared to the 24-month recovery. In sensitivity analysis, the predicted overall impact varied between 1,930-12,630 deaths, and 83,600-887,700 colonoscopies (Table 1). Conclusions Delayed cancer-related services due the pandemic will likely cause thousands of CRC cases and deaths in the next 20 years. The impact could be limited if the backlog were cleared within 6 or 12 months vs. 24 months. However, additional endoscopy capacity needs should be balanced against competing medical interests. Keywords: COVID-19, Colorectal cancer, screening, diagnosis (Figure Presented) (Table Presented)

3.
Clinical Neurophysiology ; 137:e18-e19, 2022.
Article in English | ScienceDirect | ID: covidwho-1783249

ABSTRACT

Background: Patients with neuromuscular diseases (NMD) are classified as risk groups for a potentially severe course of a SARS-CoV-2 infection. An online registry (www.covid19-nme.com) was developed to gather information about the severity of COVID19, a potential progression of NMD through the SARS-CoV-2 infection and the possible influence of medication on the course of the infection. Methods: Since February 2021, patients of all ages (children, adolescents and adults) with NMD and an infection with SARS-CoV-2 have been included in this register. In addition to demographic data, pre-existing diseases and therapies, information about the NMD, the course of the SARS-CoV-2 infection as well as the clinical findings before and after the infection are recorded. Results: So far 94 patients (37% female, age: median 60 years (1-94 years)) from Germany and Austria have been recorded. The diagnoses represent the entire spectrum of NMD: different forms of polyneuropathies (PN) including CIDP and hereditary PN, ICUAW, myasthenic syndromes, motor neuron diseases (SMA and ALS) as well as various muscle diseases such as dystrophinopathies and myotonic syndromes. The collected mRS (measure for description of neurological impairment) depicts a significant worsening after the SARS-CoV2 infection (p = 0.02;Wilcoxon), whereby the patients with ICUAW were excluded from the analysis. The duration of symptoms showed a positive correlation with age (r = 0.343;p = 0.005) and weight (r = 0.291;p = 0.030), but not with the type of NMD. In total, 13 patients deceased due to the SARS-CoV2 infection. The probability of a fatal outcome of COVID19 correlates with increasing age (r = 0.313;p = 0.004) but not the type of NMD. The ventilation situation did not change in NMD patients due to the infection with SARS-CoV2. Summary: The first results of the evaluation of the covid-19.nme registry indicate that the clinical symptoms of NMD progress due to an infection with SARS-CoV2. The underlying cause for this remains unclear. Autoimmunological processes and a possible neurotropy can be considered as pathophysiological mechanisms.

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Multiple Sclerosis Journal ; 27(2 SUPPL):58-59, 2021.
Article in English | EMBASE | ID: covidwho-1495940

ABSTRACT

Introduction and Objectives: Patient with multiple sclerosis (MS) have a higher risk of infection compared to the general population. Viral infections are also indicated as potential environmental risk factors for the disease. On top of this, the patients are treated with disease-modifying therapies (DMTs) meant to suppress the autoimmune immune response, but which are so unspecific that general immune responses are also affected. Given that we live with constant exposure to infectious agencies, an increased risk for infections is expected. Aims and Methods: In a comparative study within the COMBAT-MS project, linkage between the Swedish MS register and national health care and census registries enabled a comparison between MS patients on different treatments and the general population on hospitalized serious infection, antibiotics and herpes anti-viral medication. Results and Conclusions: The rate of infections where higher in MS with all DMTs compared to the general population, but still higher for the second generation compared to the first generation DMTs. No fatal cases were reported due to infections, which might be due to the mitigation strategies already established. Similar strategies were employed during the SARS-CoV-2 pandemic to avoid fatal outcomes. Thus, special considerations have to be taken to protect patients on DMTs against infections, a fact that became clearly apparent during the pandemic.

7.
Open Forum Infectious Diseases ; 7(SUPPL 1):S338, 2020.
Article in English | EMBASE | ID: covidwho-1185905

ABSTRACT

Background: Children and young adults were initially reported as largely spared from severe complications of SARS-CoV-2 infection, but the impact to this population has been significant. Methods: This observational retrospective cohort study includes 420 symptomatic children and young adults with lab confirmed SARS-CoV-2 infection treated between March 15 and June 16, 2020 at Children's National Hospital in Washington DC. We identified and compared cohorts of non-hospitalized (N=324) and hospitalized (N=96) patients, including non-critically ill (N=64) and critically ill hospitalized (N=32) patients. Clinical and demographic data were extracted from medical records Results: Of 420 SARS-CoV-2-infected symptomatic patients, 23% required hospitalization, of which 67% were non-critically ill and 33% were critically ill. All age groups were represented in the symptomatic cohort, with a median age of 8.6 years. Patients > 15 years of age represented 44% of critical care admissions. Males and females were equally represented in all cohorts. Underlying medical conditions were present in 36%, but more common in hospitalized (59 %) and critically ill (66 %) patients. The most frequent underlying diagnosis overall was asthma (16 %), but also included neurologic (6 %), diabetes (3 %), obesity (3 %), cardiac (3 %), hematologic (3 %) and oncologic (1 %) conditions. The majority (66 %) of SARSCoV- 2 infected patients presented with respiratory symptoms with or without fever. Other symptoms were also present, including diarrhea/vomiting (21 %), myalgia (11 %), chest pain (8 %) and loss of sense of smell or taste (7%). Hospitalized patients required varying levels of respiratory support, including mechanical ventilation, BiPAP, RAM cannula and HFNC. Additional presentations included diabetic hyperglycemia, sickle cell vaso-occlusive crisis, vascular complications, and multisystem inflammation. Treatment included remdesivir, convalescent plasma, tocilizumab and other therapies. Conclusion: Although children/young adults have been less affected than elderly adults, the impact of SARS-CoV2 on this population has been significant in Washington DC and informs other regions anticipating their surge.

8.
Open Forum Infectious Diseases ; 7(SUPPL 1):S338, 2020.
Article in English | EMBASE | ID: covidwho-1185903

ABSTRACT

Background: Background: Multi-system Inflammatory Syndrome of Children (MIS-C) has recently emerged internationally as a serious inflammatory complication of SARS-CoV-2 infection with significant morbidity for the pediatric population. Methods: This observational retrospective cohort study includes 33 children meeting CDC criteria for MIS-C treated between March 15 and June 17, 2020 at Children's National Hospital in Washington DC. Clinical and demographic data were extracted from medical records and are summarized. Results: Of 33 hospitalized MIS-C patients, 42% were critically ill, and 58% were non-critically ill. The median age was 8.9 years (0.7-18.7 years). More males (58 %) than females (43 %) were represented in the MIS-C cohort. The majority (75%) of children had no underlying medical condition. Criteria for incomplete or complete Kawasaki Disease (KD) were present in 39% of patients, while an additional 9% had some features of KD. However the remaining 52% of MIS-C patients presented with other sub-phenotypes including prominent severe abdominal pain and/or nonspecific multiorgan dysfunction. 30% presented with shock requiring volume and/or inotropic support. SARS-CoV-2 antibodies were present in 61% of patients. Virus was detectable by PCR in 36% of patients. At the time of initial evaluation, 39% (13/33) of children had identified cardiac abnormalities including myocardial dysfunction (5/33;15%), coronary ectasia (4/33;12%), coronary aneurysm (3/33;9%), or pericardial effusion 5/33;15%) either alone or in combination. Cytokine profiling identified elevation of several cytokines in this cohort, including IL-6. Treatment has included intravenous immunoglobulin, aspirin, anakinra and other immunomodulatory therapies, with overall rapid response to therapy. No deaths have occurred. Conclusion: The emergence of MIS-C late in the surge of SARS-CoV-2 circulation in the Washington DC metropolitan region has added to the already significant burden of hospitalized and critically ill children in our region. A significant percentage of these children present with cardiac dysfunction and abnormalities, whether or not with KD features at presentation. Detailed characterization of immune responses and long term outcome of these patients is a priority.

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