SARS-COV-2 INFECTION after VACCINATION in PATIENTS with RHEUMATIC DISEASES from ARGENTINA

Background: Patients with rheumatic diseases (RD) have been excluded from SARS-CoV-2 vaccine trials. Though data appear to show safety and efficacy, mostly evidence remains in mRNA vaccines. However in our country, adenovirus and inactivated vaccines, as well as heterologous schemes are frequently used. Objectives: To describe clinical characteristics and outcomes of SARS-CoV-2 infection after vaccination in patients with RD from de the SAR-CoVAC registry and to compare them with patients who got infected before vaccination. Additionally, factors associated with COVID-19 unfavorable outcome were assessed. Methods: Adult patients with RD who have been vaccinated for SARS-CoV-2 were consecutively included between June 1st and December 21st, 2021. Con-frmed SARS-CoV-2 infection (RT-PCR o serology) was reported by the treated physician. Infection after an incomplete scheme was defned when the event was diagnosed at least 14 days after frst dose;and after a complete scheme when it occurred > 14 days after second dose. Homologous scheme is defned by two same doses of vaccine and heterologous by two different doses. Patients with previous SARS-CoV-2 infection were excluded. To compare SARS-CoV-2 infection characteristics in not vaccinated patients, subjects from the SAR-COVID registry, which includes patients with RD and SARS-CoV-2 infection, were matched 2:1 by gender, age and RD. WHO-Ordinal Scale ≥5 was used to defne unfavorable infection outcome. Descriptive statics, Chi2 test, Fischer test, T test and ANOVA were used. Results: A total of 1350 patients from the SAR COVAC registry were included, 67 (5%) presented SARS-CoV-2 infection after vaccination. The later were mostly (72%) females with a mean age of 57 (SD 15) years old. The most frequent RD were rheumatoid arthritis (41%), psoriatic arthritis (12%) and systemic lupus erythematosus (10%). At vaccination, most of them (75%) had low disease activity or remission, 19% were taking steroids, 39% methotrex-ate, 27% bDMARDs and 6% JAK inhibitors. A total of 11 (16%) patients had SARS-CoV-2 infection <14 days after the frst vaccine dose, 39 (58%) after an incomplete scheme and 17 (25 %) following a complete one. In the incomplete scheme group, 59% received Gam-COVID-Vac, 31% ChAdOx1 nCov-19 and 10% BBIBP-CorV;and in patients with complete scheme 47%, 24% and 29%, respectively. No event was reported after a complete heterologous scheme. No signifcant differences regarding sociodemoghraphic characteristics, RD, disease treatment, type of vaccine and regimen was found between in those with infection and those without it. After vaccination only 8 (12%) of the patients who got infected had an unfavorable course, 88% of them following an incomplete scheme (5 received Gam-COVID-Vac, 1 ChAdOx1 nCov-19 and 1 BBIBP-CorV) and one subject after a complete homologous Gam-COVID-Vac scheme. Having an unfavorable outcome of SARS-CoV-2 infection was associated to: male gender [63% vs 24%, p=0.036], older age [mean 70 years (SD 7) vs 55 years (SD 15), p=0.005], being Caucasian [100% vs 54%, p=0.018], higher education [mean 17 years (SD 4) vs 12 years (SD 4), p=0.010], the presence of comorbid-ities [100% vs 39%, p=0.001, having pulmonary disease [37% vs 5%, p=0.019], dyslipidemia [63% vs 17%, p=0.011] and arterial hypertension [63% vs 24%, p=0.036], RD, treatments, disease activity and types of vaccines received were comparable between groups. When comparing patients with and without vaccination prior SARS-CoV-2 infection, those who received at least one dose of vaccine had less frequently severe COVID-19 (12% vs 24%, p=0.067) and presented lower mortality due to COVID-19 (3% vs 6%, p=0.498). However these differences did not reach statistical signifcance. Conclusion: In the SAR-CoVAC registry 5% of the patients had SARS-CoV-2 infection after vaccination, most of them mild and 25% after a complete scheme. Any vaccine was associated with severe COVID-19. When comparing with non-vaccinated patients, those with at least one dose, had less frequently severe disease and died due COVID-19.

IMPAIRED CYTOTOXIC IMMUNE RESPONSE and EBV REACTIVATION in PATIENTS with LONG COVID19

Background: About 10% of individuals with mild infection with SARS-CoV-2 suffer from Long COVID-19, defined as signs and symptoms developed during or following COVID-19 that continue for more than twelve weeks and cannot be explained by an alternative diagnosis. In this study, we analyzed the ADCC response and the reactivation of CMV and EBV in Long COVID-19 syndrome, in comparison with patients who completely recovered from mild COVID-19 Methods: 30 patients with Long COVID-19 (Long COVID-19) and 20 individuals who suffered mild COVID-19 and were completely recovered (Recovered) were recruited for this study. Specific anti-SARS-CoV-2 IgG titers were analyzed by direct ELISA and their neutralizing capability was measured by using pseudovirus neutralization assay. Phenotype of CD4+ and CD8+ T cells, NK, NKT, and B cells in peripheral blood was analyzed by flow cytometry. ADCC activity was analyzed using rituximab-coated Raji cells as target. EBV and CMV reactivation in plasma was analyzed by qPCR. Results: 1) 86.6% and 55.50% participants were female in Long COVID-19 and Recovered cohorts, respectively. Median age at COVID-19 diagnosis was 42y(IQR 37-46) and 45y (IQR 28-57), respectively. 2) Similar levels of CD4+ T cells were observed in both groups. However, Tregs were increased 2.8-fold in Long COVID-19 participants (p=0.0007). 3) CD8+ T cells, CD8+TCRγδ and CD8+TCRγδ were increased 1.3-(p=0.0005), 2.0-(p=0.049), and 2.5-fold (p=0.005) in Long COVID-19 individuals. 4) Expression of CD56 in NK cells and CD3-CD56+CD16+ cells were increased 1.7-(p=0.0005) and 1.7-fold (p=0.032) in Long COVID-19, respectively. 5) Specific anti-SARS-CoV-2 IgG titers were increased 2.3-fold in Long COVID-19 individuals (p=0.02) and their neutralizing capacity was increased 4.2-fold (p=0.034) in this cohort. However, ADCC activity was decreased 1.4-fold (p=0.0044). 6) Resting memory B cells were increased 2.3-fold during Long COVID-19, whereas plasmablasts were reduced 3.1-fold. 7) EBV was reactivated in 33.3% of Long COVID-19 individuals (p<0.0001), whereas CMV was not reactivated in any individual. Conclusion: Despite high levels of neutralizing antibodies and cytotoxic immune populations, an impaired antibody-dependent cytotoxic activity was observed in PBMCs from individuals with Long COVID-19. This defective cytotoxic immune response may impede viral clearance, which may also contribute to EBV reactivation observed in these individuals, thereby influencing on the persistent COVID-19 symptoms.

Impact of the COVID-19 pandemic on antimicrobial consumption and antimicrobial resistance

5PSQ-154 Table 1Antimicrobial COVID/pre-COVID (DDD/100D) Increase DDD/100D (%) Amoxicillin 60.23/2.19 +2650.98 Azithromycin 107.73/5.69 +1791.68 Cefotaxime 0.99/0.18 +461.22 Ceftriaxone 139.24/28.97 +380.67 Vancomycin 24.25/8.33 +199.40 Aztreonam 2.61/0.92 +185.49 Meropenem 43.29/24.39 +77.48 Cefuroxime 14.6/9.23 +60.77 Linezolid 27.57/17.19 +60.40 Cefixime 2.72/1.82 +49.32 Piperacillin/tazobactam 49.81/33.75 +47.58 Amoxicillin/clavulanate 95.23/79.96 +19.09 The most important changes in bacterial sensitivity are detailed in table 2. 5PSQ-154 Table 2Microorganism No. isolated January-December 2019 No. isolated January-June 2021 Antimicrobial Sensitivity January-December 2019 (%) Sensitivity January-June 2021 (%) Pearson’s Chi-square significance Escherichia coli 4085 1648 No change Klebsiella spp 1095 425 Gentamicin 93 86 p=0.000 Cefuroxime 78 73 p=0.036 Cefotaxime 81 76 p=0.028 Nitrofurantoin 87 81 p=0.010 Aztreonam 74 70 p=0.226 Ceftazidime 81 77 p=0.076 cefepime 82 78 p=0.069 Pseudomonas aeruginosa 507 195 Gentamicin 83 78 p=0.114 Staphylococcus aureus 878 400 No change Enterococcus faecalis 572 266 No change Enterococcus faecium 146 87 Nitrofurantoin 92 83 p=0.120 Ampicillin 12 6 p=0.305 Conclusion and relevanceImportant increase in hospital antimicrobial consumption was observed, especially for the beta-lactams and carbapenems.Minimal changes in antimicrobial susceptibility was observed, detected only in Klebsiella spp, Pseudomonas aeruginosa and Enterococcus faecium.Antimicrobial stewardship strategies can help to keep the consumption of antimicrobials within acceptable levels.References and/or acknowledgementsConflict of interestNo conflict of interest

Worse outcomes of out-of-hospital cardiac arrest in covid-19 versus non-covid-19: A systematic review and meta analysis dyutima

Introduction: A surge in incidence of out-of-hospital cardiac arrest (OHCA) has been reported during COVID-19 outbreak in certain countries. However, limited data exists on a comparison of outcomes among COVID-19 positive OHCA patients vs. non-COVID-19 OHCA patients. Therefore, we aimed to perform a meta-analysis comparing characteristics and outcome of COVID-19 OHCA vs COVID-19 negative OHCA patients. Methods: We reviewed PubMed/Medline, SCOPUS, and EMBASE until April 2021 using relevant keywords COVID-19, SARS-CoV-2, “out of hospital cardiac arrest” or OHCA to identify studies that included outcomes data on OHCA with COVID-19 positive and negative status. Random-effects models were obtained to perform a meta-analysis. I statistics was used for heterogeneity. Results: Of 5789 OHCA patients included from 6 studies, patients who were COVID-19 positive comprised of 61.46% males while COVID-19 negative patients included 63.37% of males (p=0.2). COVID-19 OHCA patients were younger (Mean±SD, 68.94±17.93 vs 70.23±17.93, p=0.03) compared to COVID-19 negative patients. Incidence of OHCA at home/private address was higher (OR=1.92, 95%CI:1.52-2.43), while shockable rhythm (OR=0.34, 95%-CI:0.24-0.46) and use of AED (OR=0.77, 95%CI 0.61-0.97) were less frequently noted in COVID-19 patients (p<0.0001). As shown in Fig. 1, return of spontaneous circulation did not differ significantly (OR=1.01, 95%CI:0.85-1.20, p<0.92);however, survival to admission (OR=0.64, 95%CI:0.48-0.86, p<0.01), and survival to discharge (OR=0.28, 95%CI:0.13-0.59, p<0.01) were significantly lower in COVID-19 OHCA admissions compared to non-COVID-19 OHCA admissions. Conclusions: This meta-analysis demonstrated that the SARS-CoV-2 infection in OHCA patients was associated with poorer outcomes as compared to COVID-19 negative OHCA admissions. Future studies are warranted to assess long-term residual effects of COVID-19 on OHCA risk and outcomes.

Anxiety and cancerophobia in patients with small gastrointestinal subepithelial lesions and tumours: Baseline results of a prospective study (quali-banding-set)

Introduction: Small subepithelial gastrointestinal lesions (SEL), often defined as submucosal tumours, or subepithelial tumours (SET) confirmed once characterized by endoscopic ultrasound (EUS), could generate anxiety and fear of cancer. Aims & Methods: The main aim was to assess the anxiety burden and cancerophobia in patients with a small-sized SEL diagnosis or SET in periodic EUS surveillance. Secondary aims: to evaluate possible factors or patients characteristics influencing on anxiety or fear of cancer degree. Methods: Observational prospective study. Consecutive inclusion of all patients with a small-sized SEL diagnosis (requiring an EUS performance), or patients with a previously catalogued SET under echoendoscopy surveillance. Evaluation of the anxiety-distress degree and fear of cancer using two specific designed and validated instruments-questionnaires: Hospital Anxiety and Depression Scale (HADS), anxiety and depression subscales [0-7 points normal;8-10 borderline;11-21 pathologic], and global-distress scale [0-10 points normal;11-17 borderline;18-42 pathologic];and Cancer Worry Scale (CWS) [6-10 points low;11-15 moderate;16-20 high;21- 24 very high]. ClinicalTrials.gov register: NCT04316000. Due to SARS-CoV2 (Covid-19) pandemia and its implications for outcomes bias, the study was prematurely suspended. Results: Two participating centres, 40 patients (inclusion period: September 2019-February 2020). Mean HADS-anxiety: 7.2 (+/- 4.3) [= borderline anxiety];HADS-distress: 11.4 (+/- 7.7) [= borderline distress];CWS: 11.0 (+/- 4.1) [= moderate concern]. Belief on probability of having GI cancer now: 20.7% (+/- 23.6);belief on probability of getting GI cancer in 10 years: 28.6% (+/- 24.3). Impact on quality of life: Yes 40% (16/40). Female sex (n- 26) vs. male (n-14) subanalysis: HADS-anxiety 8.0 vs. 5.9;HADS-distress 12.7 vs. 9.0;CWS 11.5 vs. 9.9. Family history of cancer YES (n-29) vs. NO (n- 11) subanalysis: HADS-anxiety 8.1 vs. 5.0;HADS-distress 12.7 vs. 8.0;CWS 11.7 vs. 9.1. Conclusion: Patients with SEL diagnosis or SET under EUS surveillance present a moderate anxiety-distress degree and a moderate concern about having cancer, partially affecting their quality of life. Family history of cancer and female gender are factors that can increase anxiety and cancerophobia degree. Modifying the submucosal tumour term use for subepithelial lesion in conventional endoscopy reports, and suggesting the SETs removal in case of significant anxiety-cancerophobia, could be measures to be adopted, providing a transversal approach to patients' health.