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1.
Scientific Reports ; 12(1):22571, 2022.
Article in English | MEDLINE | ID: covidwho-2186008

ABSTRACT

The SARS-CoV-2 Omicron variant emerged showing higher transmissibility and possibly higher resistance to current COVID-19 vaccines than other variants dominating the global pandemic. In March 2020 we performed a study in clinical samples, where we found that a portion of genomes in the SARS-CoV-2 viral population accumulated deletions immediately before the S1/S2 cleavage site (furin-like cleavage site, PRRAR/S) of the spike gene, generating a frameshift and appearance of a premature stop codon. The main aim of this study was to determine the frequency of defective deletions in prevalent variants from the first to sixth pandemic waves in our setting and discuss whether the differences observed might support epidemiological proposals. The complete SARS-CoV-2 spike gene was deeply studied by next-generation sequencing using the MiSeq platform. More than 90 million reads were obtained from respiratory swab specimens of 78 COVID-19 patients with mild infection caused by the predominant variants circulating in the Barcelona city area during the six pandemic waves: B.1.5, B.1.1, B.1.177, Alpha, Beta, Delta, and Omicron. The frequency of defective genomes found in variants dominating the first and second waves was similar to that seen in Omicron, but differed from the frequencies seen in the Alpha, Beta and Delta variants. The changing pattern of mutations seen in the various SARS-CoV-2 variants driving the pandemic waves over time can affect viral transmission and immune escape. Here we discuss the putative biological effects of defective deletions naturally occurring before the S1/S2 cleavage site during adaption of the virus to human infection.

2.
Multiple Sclerosis Journal ; 28(3 Supplement):653-654, 2022.
Article in English | EMBASE | ID: covidwho-2138851

ABSTRACT

Background: Vaccination during immunosuppression can result in impaired vaccine responses. In highly active patients requiring a rapid treatment initiation, vaccination can delay treatment onset. Natalizumab (NTZ) is a high-efficacy agent with potential low interference in vaccination responses, and could be a bridge therapy to achieve an adequate immunisation before starting another treatment. Objective(s): To assess the safety and immunogenicity of inactivated vaccines administered during NTZ treatment. Method(s): Self-controlled study based on an ongoing prospective cohort that included adult MS patients with complete immunisation schedules for hepatitis B vaccine (HBV), hepatitis A vaccine (HAV) and/or COVID-19 vaccine during NTZ treatment, between September 2016 and February 2022. Seroprotection rates were calculated for each vaccine. Demographic, clinical and radiological characteristics were collected the year before (pre-exposure period) and after vaccination (post-exposure period). Differences in annual relapse rate (ARR), contrast-enhancing lesions (CELs), new T2 lesions (NewT2) and changes in Expanded Disability Status Scale (EDSS) during pre and post exposure period were evaluated. Patients were also categorised according to time on NTZ exposure before vaccination (long-term exposure >1 year and short-exposure <=1 year) and according to JCV status. Result(s): From 248 patients treated with NTZ, 60 were vaccinated during NTZ exposure: 44 (73%) women, mean age 45 years, mean disease duration 17 (SD 8.7) years. Thirty (50%) patients bridged to anti-CD20 after immunisation, because of high titers of JC virus. Between the pre and post-exposure period, we observed a decrease in both the AAR (0.28 vs 0.01;p=0.004) and newT2 (0.8 vs 0.02;p=0.1) and no changes in disability accumulation (EDSS 3.5 vs 3.5 p=0.6). The global seroprotection rate was 93% (91.6% (IC95% 73-99) for HAV (n=24), 92.6% (IC95% 76- 99) for HBV (n=27), 100% (IC95% 84-100) for Covid-19 (n=23)). No differences were seen between short and long term NTZ exposure or between JCV positive or negative patients, in terms of safety and immunogenicity. Conclusion(s): Immunisation with inactivated vaccines during NTZ treatment is safe and effective, both for short and long term NTZ exposure. In highly active PwMS who need immunisation, NTZ could be a valuable strategy to avoid delays in the onset of high-efficacy DMD, even in JC virus positive in which it could be used as a bridge therapy strategy.

3.
American Journal of Transplantation ; 22(Supplement 3):768, 2022.
Article in English | EMBASE | ID: covidwho-2063440

ABSTRACT

Purpose: Short-term adaptive immune memory has been reported among immunocompetent (IC) and convalescent Solid Organ Transplant (SOT) individuals following SARS-CoV-2 infection as well as after active vaccination. However, quality and longevity of anti-viral immune memory comparisons between natural and active immunization has not been thoroughly assessed among SOT. Method(s): SARS-CoV-2-specific adaptive immune memory was assessed at different compartments (serological, memory B cells [mBC] and cytokine [Th1: IFN-gamma, IL-2, IFN-gamma/IL-2 and Th2: IL-21 and IL-5] producing T cells) by ELISA and FluoroSpotbased assays, respectively, in 41 convalescent patients with severe COVID-19 (22 SOT and 19 IC) and 39 vaccinated patients (19 SOT and 20 IC) with a mRNA-based vaccine) at different time-points post immunization (T1=21days after infection/1st dose;T2=3months after infection/2nd dose;T3=6months after infection/2nd dose). Additionally, a group of convalescent mild (19 SOT and 19 IC) and asymptomatic patients (9 SOT and 10 IC) were also evaluated at T3. Result(s): Overall, statistically significant higher immune responses in all immune compartments were observed in convalescent patients than among those after vaccination. After vaccination, low seropositivity rates (5,88%) were observed among SOT after 1st dose, whereas seroconversion was fully achieved in IC patients and SOT with severe COVID-19 (p<0.001). Similarly, while the presence of mBc after vaccination progressively increased over time, it was less pronounced and significantly delayed among SOT than convalescent patients in all time points (p<0.001 T1, T2 and T3). SARS-CoV-2-specific Th1 and Th2 frequencies were significantly higher among vaccinated IC patients than SOT, being these responses significantly lower than those observed in convalescent among SOTT and IC patients (p<0.001 T1, T2 and T3). At 6 months after vaccination, IgG titers, mBc frequencies and Th1/ Th2 T-cell responses after two-dose vaccination in SOT mimicked those observed in convalescent SOT with an asymptomatic/mild clinical COVID-19 infection. Conclusion(s): The type of immunization against SARS-CoV-2, either natural or active after vaccination, clearly differentiates the quality and length of adaptive immune memory, with a clear weaker immune response observed among SOT.

5.
Journal of Crohn's and Colitis ; 16:i525, 2022.
Article in English | EMBASE | ID: covidwho-1722346

ABSTRACT

Background: Treatment with anti-TNF agents and thiopurines has been associated with an impaired immune response to some vaccines. SARSCoV- 2 vaccination is very effective in healthy individuals, but studies in inflammatory bowel disease (IBD) populations are scarce, especially regarding T cell response. We aimed to evaluate the T cell and antibody response in a cohort of IBD patients on anti-TNF and thiopurine treatment who received two doses of the SARS-CoV2 mRNA vaccine. Methods: An observational, prospective study was carried out at our IBD clinic. We included Crohn's disease (CD) and Ulcerative colitis (UC) patients receiving anti-TNF as monotherapy or anti-TNF + thiopurine (combo) or thiopurines only for at least six months at inclusion. Blood samples were drawn for interferon-gamma release assay (IGRA) and antibody determination six (+/- 2) weeks after the second vaccine dose. The specific T cell response to SARS-CoV-2 was determined by IGRA using Qiagen® QuantiFERON® SARS-CoV-2 RUO tubes with a patented Spike protein combination. Interferon-gamma was measured by CLIA using the LIAISON® QuantiFERON-®TB Gold Plus assay. As there is no validated cut-off point, we used those obtained in a cohort of 20 healthy health professionals published by our group (doi. org/10.1016/j.medcli.2021.09.013). Antibodies to the Spike (S) SARSCoV- 2 protein were analyzed by CLIA. Adverse events (AEs) and clinical activity were recorded. Results: We recruited 148 IBD patients, 57 treated with anti-TNF monotherapy, 53 with combo, and 38 with thiopurine only. Seventy percent had CD, and 60% were male. Using the cut-off value of the cohort mentioned above, the T-cell response was positive in 92% of anti-TNF monotherapy, 83% in combo, and 87% of the thiopurine group (p=ns). The anti-S antibodies were positive in 100% of our cohort. There were no changes in disease activity rates after the second vaccination, nor were severe AEs detected. Conclusion: SARS-CoV-2 mRNA vaccination was very effective in IBD patients receiving anti-TNF (combo or monotherapy) or thiopurine treatment as measured by both T cell and antibody response. IGRA-specific tests may constitute a valuable tool in assessing cellular immunity in immunocompromised patients.

6.
Multiple Sclerosis Journal ; 27(2 SUPPL):758-759, 2021.
Article in English | EMBASE | ID: covidwho-1496076

ABSTRACT

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.

7.
Multiple Sclerosis Journal ; 27(2 SUPPL):769-770, 2021.
Article in English | EMBASE | ID: covidwho-1496075

ABSTRACT

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.

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