ABSTRACT
Hematologic malignancy is a risk factor for severe coronavirus disease 2019 (COVID-19) in adults;however, data specific to children with leukemia are limited. High-quality infectious adverse event data from the ongoing Children's Oncology Group (COG) standard-risk B acute lymphoblastic leukemia/lymphoma (ALL/LLy) trial, AALL1731, were analyzed to provide a disease-specific estimate of SARS-CoV-2 infection outcomes in pediatric ALL. Of 253 patients with reported infections, the majority (77.1%) were asymptomatic or mildly symptomatic (CTCAE grade 1/2) and there was a single COVID-19-related death. These data suggest SARS-CoV-2 infection does not confer substantial morbidity among young patients with B-lymphoblastic leukemia/lymphoma (B-ALL/LLy).Copyright © 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.
ABSTRACT
Objective: Assess the SARS-CoV2 Spike antibody response in multiple sclerosis (MS) patients on high efficacy immunotherapies. Background: There is limited knowledge about SARS-CoV2 mRNA vaccine response in MS patients on immunotherapy. Design/Methods: Patients with MS, aged 18-65, on fingolimod, siponimod, ofatumumab, or ocrelizumab for at least 3 months prior to first mRNA SARS-CoV2 vaccine (Pfizer or Moderna) were offered enrollment. A cohort of healthy controls who received the mRNA vaccines were also enrolled. Blood samples for the SARS-CoV2 Spike antibody (Anti-SARS-CoV2 S, RocheElecsys) were collected 2-3 months after the second mRNA vaccine. The proportion who seroconverted (antibody>0.4 U/ml), and SARS-CoV2 Spike antibody levels were assessed. Results: A total of 39 MS patients (6 fingolimod, 33 ocrelizumab) and 31 controls were included in this interim analysis. 33%(13/39) of MS patients seroconverted, compared to 100%(31/31) in the control group, with an estimated risk difference of -0.67,(95% confidence interval: -0.81, -0.52;Fisher's exact test, p=9.0∗10-10 ). There was no difference in seroconversion rates between MS patients who received the Pfizer (34%, 10/29) versus the Moderna vaccine (30%, 3/10) (95% confidence interval -0.38, 0.29;Fisher's exact test=1). Seroconversion was found in 100% (31/31) of controls, 66.7% (4/6) of fingolimod-treated patients, and 27.3% (9/33) of ocrelizumab-treated patients (three group comparison, Fisher's exact test p-value =2.7∗10 -10). The median Spike antibody level was <0.4 U/ml in MS patients, and 1,663 U/ml in controls (Wilcoxon rank sum test, p-value= 1.0∗10-12 ). The median Spike antibody level in the ocrelizumab group was <0.4 U/ml, 3.45 U/ml in the fingolimod group, and 1,663 U/ml in the control group (Kruskal Wallis test, p-value=5.9∗10-12 ). Total IgG correlated with Spike antibody levels in the ocrelizumab-treated group only (Spearman correlation, p=0.025). Conclusions: MS patients on ocrelizumab and fingolimod have significantly lower rates of seroconversion, and lower median Spike antibody levels in response to the mRNA SARS-CoV2 vaccines compared to controls.
ABSTRACT
Introduction: SARs-CoV-19 infection (COVID-19) is associated with various neurologic symptoms. A full range of neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 illness is not well understood. Objectives: To investigate neurologic outcomes in patients with MSRD post COVID-19. Methods: This was a retrospective medical records review study of adult patients with MSRD who had confirmed COVID-19 infection at the Brigham MS Center, between March 9, 2020 and April 1, 2021. We reviewed demographics, MS history, COVID-19 outcomes, neurologic symptoms, and MRI data. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudo-relapse, new brain MRI activity, worsening of preexisting MS symptoms, or development of other long-term neurologic symptoms. Results: 111 patients, 85 (77%) females, with a mean [SD] age of 49 [12.2] years, and a mean [SD] EDSS of 3.4 [2.7] were identified. 72 (65%) had relapsing remitting MS, 21 (19%) had secondary and 8 (7%) had primary progressive MS, 2 (2%) had clinically isolated syndrome, and 8 (7%) had related disorders. 17 (15%) patients were asymptomatic, 63 (57%) had mild COVID-19 defined as symptoms not requiring hospitalization, 22 (20%) had moderate COVID-19 requiring hospitalization, 3 (3%) had severe COVID-19 requiring ICU admission, 2 (2%) died due to COVID-19 and 4 (4%) had unknown COVID-19 outcomes. 85 (77%) completely recovered from COVID-19. 41 patients (37%) had neurologic worsening post COVID-19. Of those with neurologic worsening, 19 (46%) had pseudo-relapses, 2 (4.8%) had relapses, and 27 (66%) patients reported worsening of preexisting MS symptoms, or other new longterm neurologic symptoms at the last follow up visit. 55 patients had brain MRI scans post COVID-19 with a mean [SD] between MRI and infection of 144.6 [107.8] days. 5 patients had new lesions on T2 or T1Gd+ scans. Neurologic worsening was associated with moderate or severe COVID-19 (p=0.0006), treatment for COVID-19 (p=0.0061), and incomplete COVID-19 recovery (p=0.0267) but not with age, sex, MS type, ethnicity, disease duration, EDSS, vitamin D use, or type or presence of disease modifying therapy. Conclusions: COVID-19 severity and lack of complete systemic recovery was associated with new or worsening neurologic symptoms in 37% of MSRD patients.
ABSTRACT
Background: The American College of Cardiology suggested physicians should only measure troponin and brain natriuretic peptide (BNP) if myocardial infarction or heart failure were suspected in people with COVID-19. We aimed to evaluate the use of biomarkers on admission to hospital and the impact on mortality and morbidity. Methods: Consecutive patients presenting with COVID-19(reverse transcription PCR positive) between Feb27-May20 2020 were included in this retrospective, observational, single-center study. Clinical information was collected on admission and during hospitalization by physicians and later analysed by specialist cardiology registrars. 1675 patients were PCR +ve with 1036 having a high sensitivity troponin T(hsTropT) on admission. 371(35.8%) patients were hs TropT negative(<15ng/L) and 664(64.1%) had evidence of myocardial injury on admission(hsTropT ≥15ng/L). Subsequently demographic details were compared, as well as primary outcomes of death, ICU admission and COVID severity. Secondary outcomes were ARDS, myocardial infarction (MI);comparison with other biomarkers: NT-proBNP, d-dimer, CRP,LDH and ferritin. Results: Demographic data revealed no significant increase in proportions of Black, Asian or ethnic minorities in the myocardial injury group, however, patients were older(74.9±13.5 v 54.7±13.7yrs;p <0.001) and had significantly more co-morbidities such as diabetes(37 v 13%), hypertension(34 v 29%), ischemic heart disease(16 v 2%), other cardiac conditions(59 v 5%), malignancy(11 v 1%), COPD(9 v 4%), CKD stage ≤3 (40 v 3%) (p <0.01). Mortality was significantly higher in the myocardial injury group, 302(45.5%) v 29(7.8%) p <0.001, as were secondary outcomes of critical COVID (47 v 19%;p<0.001), ARDS (20 v 4%;p<0.001), Type 1 MI (1.6 v 0.01%;p<0.01) and Type 2 MI (44 v 26%;p<0.001). Interestingly, ICU admission (19 v 23%;p=0.09), pulmonary embolism (11 v 6%;p=0.22), stroke (1.1 v 0.5%;p=0.05) did not reach significance. Analysis of bio-markers on admission (Fig 1.) demonstrated hs Trop T (AUC 0.75 CI 0.69-0.81) and NT-pro BNP (AUC 0.75 CI 0.69-0.81) had more sensitvity 83%;85% and specificty 52%;58%, respectively at predicting death than d-dimer, CRP, LDH and ferritin. Conclusion: Early detection of elevated hsTropT and NT-proBNP predicts mortality and morbidity in patient with COVID-19. Routine measurement of cardiac biomarkers should be considered in patients with COVID-19 at the time of hospital admission in order to optimise risk stratification and guide monitoring. (Figure Presented).