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Neurology(R) neuroimmunology & neuroinflammation ; 9(6), 2022.
Article in English | MEDLINE | ID: covidwho-2009667


BACKGROUND AND OBJECTIVES: In a phase 1 amyotrophic lateral sclerosis (ALS) study, autologous infusions of expanded regulatory T-lymphocytes (Tregs) combined with subcutaneous interleukin (IL)-2 were safe and well tolerated. Treg suppressive function increased and disease progression stabilized during the study. The present study was conducted to confirm the reliability of these results. METHODS: Participants with ALS underwent leukapheresis, and their Tregs were isolated and expanded in a current Good Manufacturing Practice facility. Seven participants were randomly assigned in a 1:1 ratio to receive Treg infusions (1 × 106 cells/kg) IV every 4 weeks and IL-2 (2 × 105 IU/m2) injections 3 times/wk or matching placebo in a 24-week randomized controlled trial (RCT). Six participants proceeded into a 24-week dose-escalation open-label extension (OLE). Two additional participants entered directly into the OLE. The OLE included dose escalation of Treg infusions to 2 × 106 cells/kg and 3 × 106 cells/kg at 4-week intervals. RESULTS: The Treg/IL-2 treatments were safe and well tolerated, and Treg suppressive function was higher in the active group of the RCT. A meaningful evaluation of progression rates in the RCT between the placebo and active groups was not possible due to the limited number of enrolled participants aggravated by the COVID-19 pandemic. In the 24-week OLE, the Treg/IL-2 treatments were also safe and well tolerated in 8 participants who completed the escalating doses. Treg suppressive function and numbers were increased compared with baseline. Six of 8 participants changed by an average of -2.7 points per the ALS Functional Rating Scale-Revised, whereas the other 2 changed by an average of -10.5 points. Elevated levels of 2 markers of peripheral inflammation (IL-17C and IL-17F) and 2 markers of oxidative stress (oxidized low-density lipoprotein receptor 1 and oxidized LDL) were present in the 2 rapidly progressing participants but not in the slower progressing group. DISCUSSION: Treg/IL-2 treatments were safe and well tolerated in the RCT and OLE with higher Treg suppressive function. During the OLE, 6 of 8 participants showed slow to no progression. The 2 of 8 rapid progressors had elevated markers of oxidative stress and inflammation, which may help delineate responsiveness to therapy. Whether Treg/IL-2 treatments can slow disease progression requires a larger clinical study ( number, NCT04055623). CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that Treg infusions and IL-2 injections are safe and effective for patients with ALS.

PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333631


SARS-CoV-2 is responsible for an ongoing pandemic that affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 months after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen specific memory that could contribute to rapid recall responses. In addition, recovered individuals show enduring immune alterations in relative numbers of CD4 + and CD8 + T cells, expression of activation/exhaustion markers, and cell division. SUMMARY: We show that SARS-CoV-2 infection elicits broadly reactive and highly functional memory T cell responses that persist 6 months after infection. In addition, recovered individuals show enduring immune alterations in CD4 + and CD8 + T cells compartments.

Neurology ; 96(15 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1407878


Objective: To evaluate the frequency of asymptomatic olfactory dysfunction (OD) in nonintubated patients with moderate and severe coronavirus disease 2019 (COVID-19). Background: Many patients with COVID-19 reported OD. However, most studies relied on selfreported data. A few studies have recently used olfactory psychophysical assessment tools, but it is difficult to implement such strategies in a real-life setting. Asymptomatic OD (aOD) has been anecdotally reported during the early stages of COVID-19. Nevertheless, there is currently no study focusing on the prevalence of OD clinically identified through a typical neurologic examination in those patients with COVID-19 who denied this symptom during history taking. Design/Methods: Adult inpatients at the Hospital Juárez de México (Mexico City) were recruited if they were nonintubated and SARS-CoV-2 was detected by real-time RT-PCR in any biological specimen. Olfactory function was assessed using a widely known technique in general neurologic practice. Standard definitions were also taken from the same authoritative source. COVID-19 severity was classified according to Gandhi et al (2020). Results: 23 patients (10 women) were included. The mean age was 45.7±13.6 years. Only five patients reported OD during history taking. Of those who denied this symptom (n = 18), any OD was identified in 8 patients through neurologic examination (44.4%). Two of these patients with aOD reported taste impairment during focused history taking. No differences according to gender were found in OD identified through neurologic examination. OD prevalence increased from 21.7% using history taking alone to 56.5% with the addition of a standard neurologic examination (difference: 34.7%;P = 0.007). Conclusions: In daily practice, simply asking for OD may not be enough to detect this impairment in nonintubated patients with moderate and severe COVID-19. If these findings can be replicated in further studies, consideration should be given to modify our current screening strategies for OD during the COVID-19 pandemic.

J Pediatr ; 233: 283-284, 2021 06.
Article in English | MEDLINE | ID: covidwho-1284246