CELLULAR AND HUMORAL IMMUNOGENICITY OF THE NEOANTIGEN S1 FROM SARS-COV-2 VACCINES IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES

BackgroundData on cellular and humoral immunogenicity triggered by SARS-CoV-2 vaccines in patients with autoimmune rheumatic diseases (ARDs) are limited. While current vaccine efforts have focused on the induction of neutralizing antibodies against SARS-CoV-2, T-cell immunity may also provide protection against infection. Experimental data suggest that CD8+ T cell responses may have a protective role in the presence of decreasing or sub protective antibody titers [1].ObjectivesThe aim of this project is to describe the serological and T cell responses to the third dose of vaccine (either with BNT162b2 mRNA or ChAdOx1 nCoV-19 replication-deficient adenoviral vector vaccines) in a cohort of patients with ARDs (rheumatoid arthritis and spondyloarthropathies) treated with biologic therapies, to describe the impact of these treatments on vaccine response in this patient population. As a second objective, we will describe the characteristics of patients who did not present an adequate immunogenic response.MethodsCase-control study. We studied in 79 patients with ARDs and in 31 healthy controls, anti-SARS-CoV-2 specific interferon-gamma (IFN-γ) production measured by IGRA between 8-12 weeks after the third dose of anti-SARS-CoV-2 vaccine. In addition, humoral response was measured by anti-S1 IgG antibody production measured by chemiluminescent microparticle immunoassay. Statistical comparison between categorical variables was performed by Fisher's or χ2 test. For quantitative variables by Kruskal-Wallis test or Mann-Whitney test.Results79 patients with ARDs (48 women, 31 men;mean age 58±11.4) 43 (54%), with rheumatoid arthritis and 36 (45.6%) with spondyloarthropathies. 32 (49.5%) of them were on glucocorticoid treatment (mean dose 4.92 mg/day), 25 (31.6%) on methotrexate and 56 (70.9%) on anti-TNF. Post-vaccination results showed positive T-cell immune responses in 68 of 79 (86.1%) ARDs patients with mean IFN- γ anti-SARS-CoV-2 titers of 1,606.85 mUI/ml. 7 (8.9%) of ARDs patients showed negative IFN-γ SARS-CoV-2 levels, while 4 (5%) had borderline titers. 100% of patients with previous COVID 19 disease had positive cellular responses. Within the group of negative or borderline cellular responses, 7 of 10 were men (70%), with no significant differences in terms of diagnosis, comorbidities or immunosuppressive treatments used. In the control group, 100% presented positive cellular responses. Anti-Spike IgG antibodies were detectable in all patients with ARDs as in the control group.ConclusionOur preliminary data show that most patients with ARD were able to generate an adequate specific cellular response after vaccination against SARS-CoV-2, emphasizing the relevance of vaccination in this group. Specific antibody responses secondary to anti-SARS-CoV-2 vaccination were detected in all patients with ARD. Our data could support the relevance of these immune responses to personalize prevention, vaccination decision-making and treatment in this subgroup of patients.References[1]Sieiro Santos C, Calleja Antolin S, Moriano Morales C, Garcia Herrero J, Diez Alvarez E, Ramos Ortega F, et al. Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases. RMD Open. 2022 Jan 5;8(1).Figure 1.Specific anti-SARS-CoV-2-IFN- γ responses measured by IGRA. Dotted lines represent positivity cut-off: ≥200mUI/ml. HC: Healthy controls. AIRDs: Autoimmune rheumatic diseases.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Sense of Belonging and Student Commitment in the Context of Higher Distance Learning with Virtual Mediation

Both technological advances and the context of the pandemic have positioned virtual mediation as a strong alternative for the transit and projection of higher education institutions and their adaptability to new demands, contexts, and changes.The implementation of remote virtual mediation as a consequence of the Covid-19 pandemic has impacted the sense of belonging and student commitment in higher education with face-to-face modality. However, the question arises as to how the behavior of these variables is consolidated in higher education institutions in which remote virtual mediation has always been their methodological hallmark. Seeking to establish the profile of the students of the National Open and Distance University (UNAD) in these contexts and to analyze the interaction of the variables of student commitment and sense of belonging, in this order of ideas and in a random manner, the investigators took a sample of 312 students from the aforementioned university. In this way, the study was developed from a positivist paradigm, with a descriptive-inferential level of depth, with a prospective, cross-sectional and non-experimental record. In addition, the authors used 2 instruments for data collection.The first one was focused on the measurement of the degree and the orientation of the student commitment, while the second one identified determinant factors in the sense of belonging. Finally, the investigators concluded that there is a tangible difference between the profile of the distance education student and that of face-to-face education. Likewise, it is recommended to delve into research focused on the processes of a sense of belonging and student commitment, even more so in distance Higher Education, which has not been sufficiently explored.

[Serenity and objectivity in the face of severe childhood hepatitis: the diagnostic challenge]

The appearance of acute hepatitis of unknown aetiology in children has set off alarms in the World Health Organization and in member countries;identifying it and studying it lay out a diagnostic challenge for first-contact medical personnel and especially for pediatricians of Mexico, as well as for the coordination of care in health services. The international outlook and an analysis of the clinical manifestations are described, as well as key points for the identification and an observation of the samples that are requested for their study in Mexico.

Phase II trial of palbociclib in advanced sarcoma overexpressing CDK4 gene excluding dedifferentiated liposarcoma (DD LPS): A study from the Spanish Group for Research on Sarcoma (GEIS)

Background: CDK4/6 inhibitors showed a favorable progression-free survival (PFS) in DD LPS, a sarcoma bearing 12q 13-15 amplicon that implies CDK4 amplification. The median PFS was 4 and 7 months (m) for palbociclib and abemaciclib, respectively. Preclinical experiments in 10 sarcoma cell lines and 6 PDX models, including only one DD LPS, showed higher efficacy of anti-CDK4 in cases with high expression of CDK4 and low expression of p16. This rationale supported the design of a phase II trial exploring palbociclib in a wide range of sarcomas, excluding DD LPS. Methods: Progressing pretreated advanced soft tissue sarcoma, excluding DD LPS, or osteosarcoma adult patients (pts), whose tumors overexpressed CDK4 and underexpressed CDKN2A mRNA in a baseline mandatory biopsy, were enrolled. CDK4 and CDKN2A expression were assessed by qRT-PCR, using an external control as reference (Universal human reference RNA;Agilent Technologies). The primary endpoint was 6-m PFS rate. Minimax Simon's two-stage with type 1 and 2 errors of 10%, and null and alternative hypothesis of H0 15%, H1 40%, 6-month PFS rates were specified. The study will warrant further investigation if 6 or more pts had a PFS > 6 m from 21 evaluable pts. Palbociclib was administered orally at 125 mg/ day 21 out of 28 days. Pre-screening intended to increase the probability of positive profile in the baseline biopsy. Results: A total of 214 pts with 236 CDK4/ CDKN2A determinations were assessed for enrolment;141 for prescreening, in archive tumor sample, and 95 for screening, in a baseline biopsy. There were 38/141 (27%) and 28/95 (29%) pts with favorable mRNA profile from pre and screening, respectively. Twenty-two pts were enrolled with a median of previous systemic lines of 3 (1- 5). There were 9 different sarcoma subtypes, including 2 osteosarcomas. With a median FU of 10 m (0.4-23.3), the median PFS was 4.2 m (95% CI 0.9-7.4), while the 6- and 12-m PFS rates were 30% (95% CI 9-51) and 18% (95% CI 12-48) respectively. From 19 evaluable pts (1 early death by COVID, 1 withdrew consent and for 1 it was too early to be assessed) 11 had stable disease (58%) and 8 progressed (42%) as the best response. Patients with CDK4 expression above the median value had significantly longer mPFS in the univariate analysis: 5.9 m (95% CI 1.4-10.4) vs 1.9 m (95% CI 0.6- 3.2), p = 0.046;and longer OS: 15.5 m (95% CI 6.8-24.3) vs 10.6 m (95% CI 0-23.2), p = 0.047, respectively. The probability to find a positive profile in the screening was 29%, but this proportion increased up to 41% if in pre-screening had been positive. Conclusions: Palbociclib showed to be effective in a wide variety of sarcoma subtypes, other than DD LPS, selected by CDK4/CDKN2A biomarkers.

PERSISTENT POST-DISCHARGE SYMPTOMS after COVID-19 in RHEUMATIC and MUSCULOSKELETAL DISEASES

Background: The COVID-19 pandemic continues worldwide and has had a strong impact on public health. As the pandemic evolves, efforts have been inten-sifed to identify persistent symptoms associated with the infection once resolved have intensifed. Objectives: We aimed to describe persistent symptoms and sequelae in patients with rheumatic and musculoskeletal diseases (RMD) after admission due to Covid-19. We also compared the role of autoimmune rheumatic diseases (ARD) with that of non-autoimmune rheumatic and musculoskeletal diseases (NARD) in persistent symptoms and sequelae. Methods: We performed an observational study of patients with RMD who attended a rheumatology outpatient clinic in Madrid and required admission to hospital due to Covid-19 (1st March-30th May 2020) and survived. The study began at discharge and ran until 1st October 2020. The main outcomes were persistence of symptoms and sequelae related to Covid19. The independent variable was the RMD group (ARD and NARD). The covariates were sociode-mographic data, clinical fndings, and treatment. We ran a multivariate logistic regression model to assess the risk of the main outcomes by RMD group. Results: We included 105 patients, of whom 51.5% had ARD and 68.57% reported at least 1 persistent symptom. The most frequent were dyspnea, fatigue, and chest pain. Sequelae were recorded in 31 patients. These included lung damage in 10.4% of patients, lymphopenia in 10%, central retinal vein occlusion (1 patient), and optic neuritis (1 patient). Two patients died. Eleven patients required readmission owing to Covid-19 problems (16.7% ARD vs 3.9% NARD;p=0.053). No statistically signifcant differences were found between RMD groups in the fnal models. Conclusion: Many RMD patients have persistent symptoms, as in other populations. Lung damage is the most frequent sequela. Compared to NARD patients, ARD patients do not seem to differ in terms of persistent symptoms or sequelae, although ARD patients might generate more readmissions due to Covid-19.

Mortality rate related to COVID-19 in rheumatic and musculoskeletal diseases (RMDS)

Background: Spain has been one of the countries most impacted by the COVID-19 pandemic. Among Spanish patients, 56,799 deaths have been reported. Although we have been in this situation of pandemic for a year, studies that show risk mortality rates in patients with rheumatic diseases continue to be scarce. Objectives: In patients with rheumatic and musculoskeletal diseases (RMDs) and infected with Covid -19, a) we want to assess the mortality rate (MR) related to COVID-19;and b) to analyze the role of RMDs in mortality risk. Methods: An observational longitudinal study was conducted during the epidemic peak in Madrid (1stMar to 20thMay2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital with a diagnosis of RMDs and SARS -CoV 2 infection were included (according to a medical diagnosis or confirmed with a positive SARS-CoV-2 PCR diagnostic test). All patients were included since the time of COVID-19 diagnosis. Main outcome: death related to COVID-19 infection. Independent variable: type of RMDs including: autoimmune (systemic autoimmune conditions (SAC) and inflammatory joint disease (IJD)) and non-autoimmune (mechanical diseases and inflammatory diseases (microcrystalline arthritis and tendonitis)). Covariates: sociodemographic, comorbidities, chronic use of corticoids prior to COVID-19 infection. Survival techniques were used to estimate the MR related to COVID-19, given per 1,000 persons-month with a 95% confidence interval [CI]. The time of observation comprised the elapsed time between the date of COVID-19 diagnosis of infection until the date of patient's death, or end of study. Cox multiple regression analysis was run to examine the effect of autoimmune RMDs compared to non-autoimmune RMDs on mortality risk adjusted by sex, age and comorbidities. Results were expressed by Hazard Ratio (HR) and [CI]. Results: 406 patients were included with RMD and Covid -19 infection with a total follow-up 642.5 patients-month. 69.21% were women with a mean age at diagnosis of 60 ± 15.26 years. The evolution time from the diagnosis of rheumatic disease was 8 ± 8.38 years. 26% had comorbidity at baseline. 25% were chronically on corticoids prior to the infection. Of the 406 patients, 244 (60.09%) had non-autoimmune RMD (157 mechanic, 87 inflammatory) and 162 (39.9%) (106 (65.43%) IJD, 56 (34.56%) systemic condition) had autoimmune RMD. Of the 406 patients, 45 (11%) died during the follow-up, being 12± 14 days the mean time from infection to death (P50: 6[2-12] and a maximum of 60 days). MR was estimated in 70.03 [52.28-93.79] per 1,000 persons-month. MR was higher for men (MR 105[68-163]) than for women (MR 55 [37.2-81.6]) and in older people (MR <60: 4.4, [0.6-31.7];MR 60-75 years: 38.7[17.3-86.2];MR ≥75Years: 486 [354-1668]). The HR of mortality in autoimmune RMDs compared to non-autoimmune RMDs did not achieved statistical significance (HR: 1.39 [0.77-2.5], p=0.27). After adjusting for confounders, we did not find higher risk of mortality among the different types of RMDs (HR autoimmune vs non-autoinmunes: HR: 1.12 [0.6-2.02], p=0.7;HR IJD vs SAC;1.5 [0.6-3.6], p=0.34;HR non-autoimmune vs SAC: 1.1 [0.5-2.5], P=0.7). Age (HR: 1.12;[1.10-1.15], p<0.001), and the presence of comorbidities (HR: 2.05;[1.08-3.89], p=0.027) increased the Mortality risk. Conclusion: In patients with RMD and COVID-19 infection, we found a mortality rate of 7 per 100 persons-month. This study shows that the mortality risk related to COVID-19 is similar between autoimmune and non-autoimmune diseases after adjusting by confounders. We also found that age and comorbidities are risk factors for mortality related to COVID-19 infection.

Role of systemic autoinmune conditions in hospital admissions related to COVID-19

Background: The COVID-19 pandemic continues worldwide and has had a strong impact on public health, quality of life and economy of the general population. To date, the number of infections and deaths are still increasing. From the beginning of the pandemic, efforts were intensified to identify risk factors for development of the severe form of COVID-19. In this sense underlying medical comorbidities have been shown to have a worse prognosis in these patients. Objectives: In patients with rheumatic and musculoskeletal diseases (RMDs) and infected with Covid -19, we aim to investigate the role of systemic autoimmune conditions compared to other type of RMDs in severity of COVID-19 in terms of hospital admissions. Methods: An observational longitudinal study was conducted during the epidemic peak in Madrid (1stMar to 20thMay2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital with a diagnosis of RMDs and COVID-19 infection were included (according to a medical diagnosis or confirmed with a positive SARS-CoV-2 PCR diagnostic test). All patients were included since the time of COVID-19 diagnosis. Main variable: hospital admission related to Covid -19 infection. Independent variable: type of RMD including: autoimmune (systemic autoimmune conditions and inflammatory joint disease (IJD)) and nonautoimmune (mechanical diseases, and inflammatory diseases (microcrystalline arthritis and tendonitis)). Covariates: sociodemographic, clinical and therapy used. Statistical analysis: description of the sociodemographic, clinical and treatment characteristics of the patients. A multivariate logistic regression adjusted by age, sex and comorbidities was used to evaluate the risk of the different types of RMDs in hospital admissions related to Covid-19. The results were expressed as OR with its corresponding confidence interval (95% CI). Results: 406 patients were included with RMDs and Covid-19 infection. 69.21% were women with a mean age at diagnosis of 60 ± 15.26 years. The evolution time from the diagnosis of RMD was 8 ± 8.38 years. 26% had comorbidity at baseline. 25% were chronically on corticoids prior to the infection. Of the 406 patients, 244 (60.09%) had non-autoimmune RMD (157 mechanic, 87 inflammatory) and 162 (39.9%) (106 (65.43%) IJD, 56 (34.56%) systemic autoimmune condition) had autoimmune RMD. 36% of all patients were admitted (31% from not autoimmune RMDs and 43% from autoimmune RMD (p = 0,013). The risk of hospital admission in autoimmune RMD compared to non-autoimmune RMD was higher (OR: 1.68;[1.11-2.54], p=0.013), being the risk of systemic autoimmune condition compared to both IJD and non-autoimmune RMD higher (OR IJD: 0.41 [0.21-0.51], p=0.01;OR non-autoimmune: 0.33;[0.18-0.61];p=0.000). After adjusting by confounders, autoimmune RMD had higher risk of hospital admissions compared to the rest (OR: 1.75;[1.04-2.95];p=0.03), and specifically systemic autoimmune condition had higher risk compared to IJD (OR of IJD 0.33;[0.14-.076];p=0.009) and compared to non-autoimmune (OR non autoimmune 0.28;[0.13-0.59], p=0.001). Advanced age (OR: 1.10;[1.07-1.12], p<0.001), male (OR 0.58;[0.33-1.02], p=0.06), and more number of comorbidities (OR 1.39;[1.02-1.90] p=0.03) also increased the risk of hospitalization related to COVID-19. Conclusion: One third of the RMD patients infected with COVID-19 required hospital admission. This study shows that patients with autoimmune and specifically with systemic autoimmune conditions have a higher risk of hospitalization related to COVID-19. We also show that advanced age, male sex and a higher number of comorbidities can contribute to worsen the prognosis of the COVID-19 disease.

Patient-reported outcomes in cancer patients admitted during the COVID 19 pandemic in a tertiary Spanish hospital

Background: Patient reported outcomes measures (PROMs) represent a tool to objectively assess the health of cancer patients. PROMs may complement oncological evaluations by adding patients' perspectives on their care priorities. Aim: to address more accurately the management of tumor related symptoms or drug related toxicities to bring he therapies more accurately to bring patients the best quality of life diarrhea, dyspnea, vomiting and nausea. These symptoms were graded according to their severity using the Common Toxicity Criteria v5.0. Results: 49 patients admitted to Medical Oncology Hospitalization were included from July of 2020 to January 2021, 80% in advanced disease. Median age 63yo, 32% above 70 yo. Baseline data showed that 27% patients (19% stage IV) had fever at admission, decreasing at 48h to 4%. Patients who had vomiting at admission were 33% (28% stage IV) median grade 2 becoming 20% and grade 1 at 48h. Nausea was present in 49% patients (35% stage IV) at the time of admission with a median grade 1.5, and it decreased to 16% at 48h with a median grade 2. Diarrhea was reported in 12% patients (6% stage IV) median grade 2 at baseline and it was reduced to 10% median grade 1 at 48h. The median severity of diarrhea at admission was 2 and only 1 at 48h. At admission, 33% (all stage IV) of patients presented dyspnea with a median grade 3, while at 48h it was present in 26% of patients and reduced to median grade 2. Conclusions: By systematically measuring symptoms, patients achieved better control of diarrhea, dyspnea, vomiting and nausea after admission. It should be noted that nausea was the variable that decreased the most at 48h, followed by fever, vomiting, dyspnea and diarrhea. All patients with stage IV disease had dyspnea and most of them had nausea and vomiting. These results reflect that these symptoms are more usual in patients with advanced disease compared to those with localized disease. PROMS also help us educate patients by teaching them how to manage treatments, thus improving therapeutic adherence.