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European Heart Journal ; 42(SUPPL 1):1078, 2021.
Article in English | EMBASE | ID: covidwho-1554079


Background: New-onset chest pain occurs in around 20% of patients with long COVID syndrome (LCS). Being the vascular endothelium one of the targets of the SARS-CoV-2 virus, we hypothesized that new onset anginal symptoms in LCS could be due to endothelium dysfunction and other non-obstructive causes of myocardial ischaemia. Methods: We investigated 11 consecutive patients who developed new onset anginal chest pain, suggestive of myocardial ischaemia, after documented SARS-CoV-2 infection. Intracoronary assessment included endothelium-dependent evaluation with acetylcholine testing (Ach), and endothelium-independent assessment with coronary flow reserve (CFR) and microcirculatory resistance (MR). Criteria for positiveness of these tests and medical treatment recommendation were obtained from 2019 ESC guidelines and 2020 EAPCI consensus document on ischaemia with non-obstructive coronary arteries (INOCA). Results: Mean patient age was 56 years (SD ± 15);10 (91%) were female. In the acute COVID-19 phase, 4 patients (36%) had had pulmonary infiltrates and 2 (18%) required hospitalization. Conclusive non-invasive tests were obtained in 7 (64%), showing exercise-related myocardial ischaemia in 6 (86%). Coronary angiography ruled out obstructive epicardial stenoses in all the patients. Ach testing revealed abnormal endothelium-dependent responses in 9 (82%) patients: 5 (56%) had epicardial vessel and 4 (44%) microvascular spasm. Endothelium-independent assessment was abnormal in 6 (54%) cases, with abnormal CFR in 2 (33%), abnormal MR in 2 (33) and both abnormal CFR and MR in 2 (33%) patients. The most frequent endotype was combined endothelium dependent- and independent abnormalities (6/9, 67%). Stratified medical treatment according to endotype led to significant improvement in Seattle Angina Scores for angina frequency (+22 points, p=0.013) and a notable trend towards angina stability (+25 points, p=0.093) at a mean follow-up time of 222 days. Conclusions: Myocardial ischaemia of non-obstructive origin is common in patients with chest pain and LCS. Vasomotor abnormalities related to endothelial dysfunction occurred in 82% of patients, frequently associated to impaired microvascular vasodilation or high microvascular resistance. Stratified medical treatment led to significant improvement in angina stability and frequency.

Multiple Sclerosis Journal ; 27(2 SUPPL):758-759, 2021.
Article in English | EMBASE | ID: covidwho-1496076


Introduction: Information about how SARS-CoV-2 specific humoral and cellular response is modified by disease-modifying therapies (DMTs) is scarce. Objective: To investigate humoral and cellular responses to SARS-CoV-2 and factors for presenting them in a Barcelona cohort of pwMS. Methods: Retrospective cohort study of adult unvaccinated PwMS with confirmed COVID-19 with at least one SARS-CoV-2 antibody (Ab) determination included from February 2020 to May 2021 and followed until May 2021. Demographic, clinical and laboratory data were obtained. Humoral SARS-CoV-2 response was measured with commercial chemiluminescence immunoassays targeting specific Ab against spike (IgG-S) and nucleocapsid proteins (Ig-N), as per clinical practice. SARS-CoV-2 specific T-cell response was studied in 42 selected pwMS according to DMT by a whole blood Interferon-Gamma (IFN-y) Release Immunoassay. Humoral and cellular response was assesed using a logistic regression model corrected for age, sex, comorbidities, MS form, expanded disability status scale, DMT, COVID-19 severity and PCR result. Results: 145 pwMS were enrolled (mean age 46.8 years;64.1% female;18.6% progressive forms, 20.7% untreated, 22.8% on anti-CD20s therapies and 56.6% on other DMTs). Humoral and cellular tests were performed from 0.3 to 13.1 months after COVID-19. 121(83.5%) presented positive Ab (57.6% anti-CD20 therapy, 90.2% other DMTs, 93.3% untreated). Untreated patients presented higher Ig-N titres (34.3[128.8]) compared to those with anti-CD20s (0.08[0.13], p<0.01), and other DMTs (19.55[42.92], p<0.01). Humoral response persisted over 6 months in 12/12 untreated, 9/22 with anti-CD20s and 22/28 with other DMTs (p=0.068). 31/42(73.8%) presented cellular response (81.0% anti- CD20, 62.5% other DMTs, 80.0% untreated), with similar levels of IFN-y levels among DMTs. 5/12(41.7%) anti-CD20-treated PwMS with negative Ab presented cellular response. In the multivariate analysis, humoral response decreased in anti-CD20 therapy (OR 0.08[95% CI,0.01-0.55]) and was associated with male sex (OR 3.59[1.02-12.68]). Cellular response was associated with seropositivity (OR13.0[1.29-130.4]), but can be present even in the absence of Ab. Conclusions: Humoral response is altered by DMTs, specially in anti-CD20-treated PwMS. Cellular response is associated with seropositivity but can be present in anti-CD20-treated PwMS even in the absence of Ab. Both can be detected up to 13.1 months after COVID-19.

Multiple Sclerosis Journal ; 27(2 SUPPL):769-770, 2021.
Article in English | EMBASE | ID: covidwho-1496075


Background: Information about humoral and cellular responses to SARS-CoV-2 vaccination in patients with Multiple Sclerosis (PwMS) and other autoimmune diseases (AID) is scarce. Objective: To determine humoral and cellular responses after SARS-CoV-2 vaccination in PwMS and anti-CD20-treated patients with other AID. Methods: Ongoing prospective study performed in two Catalan MS centres from February 2021. Unvaccinated adult pwMS and other anti-CD20-treated AID were recruited. Demographic, clinical and laboratory data were obtained. Whole blood samples were obtained before and 30-90 days after vaccination. The humoral response to SARS-CoV-2 was qualitatively and quantitatively measured before and after vaccination with commercial chemiluminescence immunoassays targeting SARS-CoV-2 antibodies against spike (TrimericS, IgG anti-S) and nucleocasid proteins (Elecsys, Ig anti-N). In 150 selected patients according to diseasemodifying therapy (DMT), the SARS-CoV-2 specific T-cell response was assessed after vaccination by a whole blood Interferon-Gamma Release immuno Assay (IGRA) that uses two Qiagen proprietary mixes of SARS-CoV-2 S protein (Ag.1 and Ag.2) selected to activate both CD4 and CD8 T cells. Results: 457 patients have been enrolled in the study (anti-CD20 therapy n=164, S1P DMTs n=37, natalizumab n=32, cladribine n=29, alemtuzumab n=31, other DMTs n=129, no DMT n=35). Participants characteristics are: mean age 48.1 years (SD 12.0), 69% female, 422 pwMS (29.4% progressive forms) and 35 with other AID, disease duration 13.9 years (IQR 14.1), median EDSS 3.0 (IQR 3.0). 450 have been fully vaccinated (94.2% mRNA vaccine). Pre-vaccination samples were collected 0.33 days (SD 0.5) before the first vaccine dose of which 12 (3.35%) had positive anti S/N immunoglobulin (Ig). As of June 30th, 42 post-vaccination samples have been obtained (1.3 months [SD 0.42] after the 2nd vaccination dose). Positive IgG rates were 44.8% (n=13/29) for CD20s, 100% (8/8) for other DMTs and 100% (4/4) for no DMT. No anti-N Ig were detected. Media titres of anti-S IgG were lower in anti-CD20-treated patients (7.8 [IQR 50.1]) compared to untreated patients (800 [0], p<0.01) or other DMTs (755 [228], p<0.01). Conclusions: Initial results of the study suggest blunted anti-S/N Ig response under anti-CD20 therapy. Knowledge of the cellular response in these patients will be crucial. Data from the cellular study and the completed humoral study will be presented at the meeting.