RHEUMATOID ARTHRITIS FLARE FOLLOWING COVID-19 VACCINATION IN MALAYSIAN POPULATION AND ITS ASSOCIATED RISK FACTORS

BackgroundFlare of Rheumatoid Arthritis (RA) following COVID-19 vaccination has been reported with a low occurrence observed in those patients with disease remission. However, no local data is available in our multi-ethnic Malaysian population.ObjectivesTo evaluate the prevalence of RA flare in Malaysian patients following COVID-19 vaccination and its associated risk factors.MethodsThis was a cross-sectional study assessing RA flare based on patient-reported disease flare through self-administered questionnaires and physician-reported flare. Patient self-reported disease flare was defined as ‘a sudden worsening of rheumatology condition or arthritis within 1 month post-vaccination' while physician-reported flare was defined as ‘an increment of disease activity score 28-joint documented within 3 months post-vaccination‘ from either a scheduled or unscheduled clinic visit. A total of 186 RA patients attended the rheumatology clinic in Hospital Putrajaya from May to July 2022 who completed the primary COVID-19 vaccination under the Malaysian National Vaccination Programme were recruited. Demographic data, disease parameters including serology for rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), cessation of disease modifying anti-rheumatic drugs (DMARDs) around vaccination, type of vaccines and adverse events were examined using descriptive and univariate analyses.ResultsMajority (93%) of RA patients enrolled were female with a mean age of 58 years old (standard deviation, SD 12.2) and mean disease duration was 12 years (SD 7.7). More than half were seropositive (66% RF, 63% ACPA) with 47.4% had double seropositivity (RF and ACPA positive). All patients received DMARDs with the majority (71%) were on methotrexate (MTX), 21.5% were on leflunomide, 17.7% on other DMARDs, with a small proportion (14%) of patients were receiving prednisolone. Only 4.8% of patients were on biologics or targeted synthetic disease modifying anti-rheumatic drugs. Half of the patients were in remission prior to vaccination. 62% of patients received Pfizer-BioNTech vaccine as the primary vaccine, followed by Sinovac-CoronaVac (24.6%) and Oxford-AstraZeneca (13.4%) vaccines. A booster dose had been administered to 80% of patients, of which 88.7% was Pfizer-BioNTech vaccine. MTX therapy were discontinued in 39.4% of patients (n=52) post-vaccination for a week duration. The prevalence of RA flare was only 12.9% (n=24) in which 14 were self-reported and 10 were physician-reported flares (4 severe flare, 6 mild-moderate flare). Flare rates were higher during the first and second dose of vaccination with 29.2% respectively, and only 12.5% were reported after booster vaccination. Common vaccine adverse effects were fever (16.8%), myalgia (8.6%) and arthralgia (6.4%). There were no significant differences in the occurrence of flare post-vaccination between age, gender, disease activity prior to vaccination, types of vaccine, usage of MTX and prednisolone, and discontinuation of MTX post-vaccination. Although seropositivity did not exhibit statistically significant flare rate post vaccination, sub-analysis revealed four times higher rate of flare in those who has double positivity compared to seronegative RA patients (12% vs 4%).ConclusionPrevelance of RA flare post-COVID-19 vaccination in Malaysian RA population is low. No significant associated risk factors were identified although double seropositivity appeared to have higher number of flares.References[1]Bixio, R., Bertelle, D., Masia, M., Pistillo, F., Carletto, A. and Rossini, M. (2021), Incidence of Disease Flare After BNT162b2 Coronavirus Disease 2019 Vaccination in Patients With Rheumatoid Arthritis in Remission. ACR Open Rheumatology, 3: 832-833.[2]Li X, Tong X, Yeung WWY, Kuan P, Yum SHH, Chui CSL, Lai FTT, Wan EYF, Wong CKH, Chan EWY, Lau CS, Wong ICK. Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong. Ann Rheum Dis. 2022 Apr;81(4):564-568.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

The association between the elevated serum levels of cardiac Trop I and mortality in patients with and without pre-existing CAD in COVID-19 patients: A retrospective observational study

Background: COVID-19 has appeared as a pandemic and public health issue at a universal level. First documented as a respiratory disease, COVID-19 has been found to interrelate with and disturb the cardiovascular system causing myocardial injury and also cardiac dysfunction. Initial documentation of cardiac pathology can play a substantial role in dropping the death rate. This study emphasizes on the relationship between the serum levels of cardiac Trop I and prognosis in patients with and without pre-existing CAD in COVID-19 patients. Aims and Objectives: The first objective was to explore the association among the serum levels of cardiac Trop I and bad prognosis in patients with antiquity of CAD and without CAD. The secondary objective was to explore and understand whether increased Trop I is an appreciated prognostic indicator for COVID-19 patient antagonistic prognosis. Material(s) and Method(s): This was conducted as a retrospective observational study in which a whole of 45 patients admitted in COVID Hospital of Malabar Medical College and Research Center category C were studied. The medical record of the patients whose COVID-19 confirmation done by combined conclusions of reverse transcription PCR, symptoms, and chest X-ray was studies by the team. Result(s): Mean age of the study participants was 59.3 +/- 13.7. Every study participants had elevated Trop I levels with a median Trop I in study subjects being 397.9. There was a statistically significant elevation in Trop I levels in patients with CAD linked with non-CAD patients with a median IQR of 641.6 and P = 0.003 and there was a significant increase in Trop I levels in patients who expired related to patients who got discharged with a median IQR of 587.3 and P = 0.003. Conclusion(s): From this study, we accomplish that rise in cardiac troponin-I level is connected with elevated mortality in patients with COVID-19. Hence, it can be used as significant biomarker of disease evolution, hospitalization, and worse prognosis in COVID-19 patients.Copyright © 2023, Mr Bhawani Singh. All rights reserved.

Findings from the ECHO Cohorts Regarding the Effects of the COVID-19 Pandemic

Background: Studies suggest perinatal infection with SARSCoV- 2 can induce adverse birth outcomes, but studies published to date have substantial limitations. Most have identified cases based upon their presentation for clinical care, and very few have examined pandemic-related stress which may also impact adverse birth outcomes. Objective(s): To evaluate the relationships between SARSCoV- 2 infection in pregnancy and pandemic-related stress with birth outcomes. Study Design: We conducted an observational study of 211 mother-newborn dyads in three urban cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) Program. Serology for SARS-CoV-2 was assessed in a convenience sample of prenatal maternal, cord serum or dried blood spots from births occurring between January 2020-September 2021. Specimens were assessed for IgG, IgM, and IgA antibodies to nucleocapsid, S1 spike, S2 spike, and receptor-binding domain. A Pandemic-related Traumatic Stress (PTS) scale was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Acute Stress Disorder criteria. Result(s): 36% were positive for at least one antibody type, chiefly IgG. Self-report of infection was not significantly correlated with combined serology. There were no differences in gestational age (GA), birth weight, preterm birth (PTB), or low birth weight (LBW) among seropositive mothers. However, IgM seropositive mothers had children with lower BW (434g, 95% CI: 116- 752), BW Z score-for-GA (0.73 SD, 95% CI 0.10-1.36) and were more likely to deliver preterm (OR 8.75, 95% CI 1.22-62.4). Associations with LBW sustained in sensitivity analyses limited to pre-vaccine samples, and PTS symptoms were not associated with birth outcomes. The addition of PTS did not substantially change associations with BW, although associations with PTB attenuated to near-significance. Conclusion(s): We identified decreased birth weight and increased prematurity in mothers IgM seropositive to SARS-CoV-2, independent of PTS. Though there are limits to interpretation, the data support efforts to prevent SARS-CoV-2 infections in pregnancy.

Serological Evidence and Self-Reported Outcomes in Patients with Adrenal Insufficiency During The First Waves of COVID-19 in the North- East Italy

Background: East during COVID-19 is a potentially serious and fatal new infection that first broke out in Italys North Eastduring Spring 2020. Among subjects considered more clinically vulnerable, patients with adrenal insufficiency (AI) have a known increased risk of infections, that could lead to poor prognosis and death due to adrenal crisis. Even the psychological and sociooccupational impact of COVID-19 could affect the health of AI patients, requiring a dynamic and continuous adaptation of the daily glucocorticoid (GC) therapy. Aim(s): To investigate if AI patients have a higher risk for COVID-19 infection than the general population, all residents in the red zone Veneto, in North-East Italy. Moreover, based on a purpose-built ADDI-COVID questionnaire, the study aimed to evaluate the subjective perception of an increased risk for COVID-19 infection and pandemic-related psycho-social impact, working life and self-adjustments of GC therapy. Method(s): Open-label, cross-sectional monocentric study on 84 (65 primary and 19 secondary) AI patients, all resident in Veneto, followed-up at the Endocrinology Unit, University-Hospital of Padua, for at least 3 years, in good and stable clinical conditions. At the end of the first COVID-19 wave (by August 2020), all patients underwent serological investigation of anti-SARS-CoV2 IgG and ADDI-COVID questionnaire. All AI patients enrolled were contacted during March-April 2021 to evaluate eventual COVID-19 infection occurrence after the second and third waves, completing a follow-up period of about 12 months. Result(s): All AI patients resulted negative to the serological test for anti-SARS-CoV2 IgG at the end of the first wave of COVID-19. After the second and third pandemic waves, COVID-19 infection occurred in 8 (10%) patients, and none needed intensive care or hospitalization. Half patients felt an increased risk of COVID-19 infection, significantly associated with an increased stress (p = 0,009) and the consequent increase of GC stress-dose (p = 0,002). Only one patient reported adrenal crisis stress correlated. The great majority of the 61 (73%) worker patients changed their working habits during the lockdown, which was inversely related with COVID-19-related stress (p = 0,0015). A significant association was found between workers and endocri- nologist contact (p= 0,046) since 18 among 20 AI patients who contacted the endocrinologist were workers. Discussion and Conclusion(s): Patients with AI residence in Veneto did not show a higher incidence of COVID19-infection compared with general population residents in Veneto after the first pandemic waves. However, the perception of increased COVID- 19 infection risk significantly impacted the psychological well-being, working habits and GC daily doses of AI patients. Especially during this pandemic period, therapeutic patient education was crucial to prevent and treat situations or conditions that could lead to an adrenal crisis. The endocrinologic consultation could help to strengthen the awareness of AI patients, especially if they were workers.

Antibody levels of COVID-19 vaccine: A comparison between healthy subjects and psychiatric patients on antidepressants

This study compares the serological antibody level post-COVID-19 vaccine among healthy subjects and psychiatric patients on antidepressant therapy. It also examines the difference in antidepressants' side effects experienced by psychiatric patients following the completion of two vaccine doses. A comparative posttest quasi-experimental study was conducted among healthy subjects and psychiatric patients on antidepressant medication in a teaching hospital in Malaysia. Elecsys Anti-SARS-CoV-2 assay was used to detect the antibody titre between weeks 4 and 12 post vaccination. The antidepressant side-effect checklist (ASEC) was used to monitor the occurrence of antidepressant-related side effects pre-and post-vaccination. 24 psychiatric patients and 26 healthy subjects were included. There was no significant difference in the antibody level between the patients (median = 1509 u/ml) and the healthy subjects (median = 995 u/ml). There was no significant worsening in the antidepressant-related side effects. The antibody level post-COVID-19 vaccine did not differ significantly between patients on antidepressant therapy and healthy subjects. Additionally, there was no change in the antidepressant side effects experienced by the patients following the completion of the vaccine.Copyright © 2022, Research Trends (P) LTD.. All rights reserved.

Establishment of an infrastructure for rapid pandemic response at the Frederick National Laboratory

The sudden onset of the 2019 SARS-CoV-2 pandemic required agile development of standards and efficient validation of assays to assess prevalence of infection as well as immune responses to infection and vaccination. Leveraging their experience in HPV serology and standards, the Vaccine, Immunity and Cancer Directorate (VICD) at the Frederick National Laboratory for Cancer Research (FNCLR) pivoted to address this unmet need in SARS-Co-V2 serology clinical testing and research. This standardization effort required the collection and processing of large volumes of blood from SARS-Co-V2 infected and uninfected individuals into serum and peripheral blood mononuclear cells (PBMCs). Collaborations with specimen collection sites across the United States were established. Following qualification for anti-SARS-CoV-2 IgG and IgM levels in independent laboratories, VICD assembled reference evaluation panels, which were used to assist the FDA's performance evaluation of commercial assays submitted for EUA approval. To date, 185 different shipments of the standard or validation panel have been sent to both domestic and international labs. These materials are also available to the SARS-CoV-2 serology community for assay calibration and performance evaluation which greatly facilitates assay data harmonization. In addition, the NCI Serological Sciences Network (SeroNet) was born from this initiative and expertise, resulting in the establishment of Capacity Building Centers (CBCs) for sample collection from different healthy, cancer and immunocompromised cohorts at Mount Sinai, Arizona State University, the University of Minnesota, and Northwell Feinstein. The NCI and FNLCR simultaneously collaborated to develop a network of investigators focused on advancing research on the immune response to SARS-CoV-2 infection and vaccination among diverse and vulnerable populations, including cancer patients. Their research has resulted in over 326 peer-reviewed publications. The CBC's have enrolled patients in longitudinal studies, resulting in a centralized collection of annotated, well characterized serum, PBMCs and clinical data. Numerous cancer cohorts, but predominantly Multiple Myeloma, are included. Furthermore, technology development was supported at the CBC's. Based upon this success, the VICD in collaboration with NCI is pursuing an even more innovative effort in pandemic preparedness to establish a Center for Serology and Data Emergency Preparedness (CESDEP);a global network able to activate and pivot to address pandemic-level threats, while continuing to expand the development of immunological assays that can inform clinical decisions for cancer and other immunocompromised patients.

Surveillance for SARS-CoV-2 in Norway Rats (Rattus norvegicus) from Southern Ontario

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from wildlife has raised concerns about spillover from humans to animals, the establishment of novel wildlife reservoirs, and the potential for future outbreaks caused by variants of wildlife origin. Norway rats (Rattus norvegicus) are abundant in urban areas and live in close proximity to humans, providing the opportunity for spillover of SARS-CoV-2. Evidence of SARS-CoV-2 infection and exposure has been reported in Norway rats. We investigated SARS-CoV-2 infection and exposure in Norway rats from Southern Ontario, Canada. From October 2019 to June 2021, 224 rats were submitted by collaborating pest control companies. The majority of samples were collected in Windsor (79.9%;n = 179), Hamilton (13.8%;n = 31), and the Greater Toronto Area (5.8%;n = 13). Overall, 50.0% (n = 112) were female and most rats were sexually mature (55.8%;n = 125). Notably, 202 samples were collected prior to the emergence of variants of concern (VOC) and 22 were collected while the Alpha variant (B.1.1.7) was the predominant circulating VOC in humans. Nasal turbinate (n = 164) and small intestinal (n = 213) tissue samples were analyzed for SARS-CoV-2 RNA by RT-PCR. Thoracic cavity fluid samples (n = 213) were tested for neutralizing antibodies using a surrogate virus neutralization test (sVNT) (GenScript cPass);confirmatory plaque reduction neutralization test (PRNT) was conducted on presumptive positive samples. We did not detect SARS-CoV-2 RNA in any samples tested. Two out of eleven samples positive on sVNT had neutralizing antibodies confirmed positive by PRNT (1 : 40 and 1 : 320 PRNT70);both were collected prior to the emergence of VOC. It is imperative that efforts to control and monitor SARS-CoV-2 include surveillance of rats and other relevant wildlife species as novel variants continue to emerge.

Trust in sources of information on COVID-19 at the beginning of the pandemic first wave and incident persistent symptoms: A prospective population-based cohort study

Background: Many patients affected by COVID-19 suffer from persistent symptoms after infection. Compared to biomedical mechanisms, psychosocial mechanisms have been less investigated. This study examined the association between trust in sources of information on COVID-19 and the burden of incident persistent symptoms. Method(s): A prospective study using data from the SAPRIS and SAPRIS-Serologie surveys nested in the French CONSTANCES cohort. Trust in medical doctors, government, scientists, journalists, and social media was measured between April 2020 and May 2020. The number of incident persistent symptoms lasting for at least two months was recorded. Psychological burden was measured with the somatic symptom disorder B criteria scale. Associations between trust in information sources and outcomes were examined with zero-inflated negative binomial regression and general linear models, adjusting for gender, age, education, income, self-rated health, SARS-CoV-2 serology tests, and self-reported COVID-19 Results: Among 20,985 participants, those with higher trust in government/journalists at baseline had fewer incident persistent symptoms at follow-up (estimate (SE): -0.21 (0.03), p < 0.001). Among 3372 participants (16.07%) who reported at least one symptom, those with higher trust in government/journalists and medical doctors/scientists had lower SSD-12 scores (-0.39 (0.17), p = 0.0219 and - 0.85 (0.24), p < 0.001, respectively), whereas higher trust in social media sources predicted higher SSD-12 scores in those with lower trust in government/journalists (0.90 (0.34), p = 0.008). These associations did not depend upon surrogate markers of past infection with SARS-CoV-2 Conclusion(s): Trust in information sources on COVID-19 should be tested as a target in the prevention of incident persistent symptoms.Copyright © 2023

PRE-EXPOSURE PROPHYLAXIS OF COVID-19 WITH TIXAGEVIMAB AND CILGAVIMAB IN RHEUMATOLOGIC PATIENTS TREATED WITH RITUXIMAB: DATA FROM A SINGLE-CENTRE COHORT

BackgroundRheumatologic patients treated with Rituximab (RTX) are at higher risk of severe COVID-19 and death. The B-cell depletive treatment significantly affects B cell functions involved in anti-SARS-CoV-2 response, leading to relevant impacts on the clinical and serological course of infection, long-term immunity, and vaccine responses. In light of these observations, pre-exposure prophylaxis (PrEP) of COVID-19 with Tixagevimab and Cilgavimab (TGM/CGM) was recently approved in Italy for all patients treated with RTX in the previous year, independently of their serological status against SARS-CoV-2.ObjectivesWe aimed to evaluate the efficacy and safety of TGM/CGM in a single-centre cohort of rheumatologic patients treated with RTX.MethodsFrom October 2022, all patients who had been treated with RTX in the previous 12 months and who underwent clinical assessment at our rheumatologic tertiary centre were screened for eligibility to PrEP of COVID-19 with TGM/CGM. According to the indications of the Italian Medicines Agency (AIFA), we excluded subjects with major cardiovascular risk factors and/or coagulation abnormalities;those who reported a previous allergic reaction to any anti-COVID19 vaccine were referred to an allergologist for an evaluation before TGM/CGM administration. Patients who agreed to be treated with TGM/CGM signed an informed consent. Clinical and demographic features were collected at baseline, and follow-up phone assessment was performed the day after and 1 month after TGM/CGM administration, to assess treatment tolerability and new COVID-19- related events. A descriptive analysis was performed.ResultsFrom 1 October 2022 to 31 December 2022, 90 subjects were screened for eligibility to TGM/CGM. Among them, 11 were excluded for contraindications due to comorbidities and 55 refused TGM/CGM administration. Among patients who agreed to receive PrEP of COVID-19, 21 received TGM/CGM before 31 December 2022 and 3 were scheduled for January2023. Patients treated with TGM/CGM had a mean age of 54 years (standard deviation: 17) and 19 (90.5%) were female;9 were affected by rheumatoid arthritis and 12 by other rheumatologic diseases (3 systemic lupus erythematosus, 2 systemic sclerosis, 1 Sjögren syndrome, 1 juvenile idiopathic arthritis, 3 anti-synthetase syndrome, 2 vasculitides). Most of them had completed the vaccination schedule against COVID-19 (19, 90.5%) and 9 (42.8%) reported an infectious event by SARS-CoV-2 in the previous year. One month after TGM/CGM administration, no patient reported adverse events related to TGM/CGM nor COVID-19 related symptoms.ConclusionPrEP of COVID-19 with TGM/CGM was well tolerated in our population of rheumatologic patients treated with RTX in the previous year and no COVID-19 related symptoms were observed in the month of follow-up after TGM/CGM administration. Future observations may provide further data on long-term efficacy of TGM/CGM in preventing COVID-19.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMaria Manara Speakers bureau: Novartis, Angelini, Consultant of: Lilly, MSD, Manuel Sette: None declared, Laura Giudice: None declared, Martina Biggioggero: None declared, Nicoletta Del Papa Speakers bureau: Janssen, Boehringer-Ingelheim, Actelion, Ennio Giulio Favalli Speakers bureau: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Maria Gerosa: None declared, Francesca Ingegnoli: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, UCB.

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

SeroNet Pooling Project of immunocompromised populations

Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.

Infectious mononucleosis combined with SARS-CoV-2 infection.

A clinical analysis of COVID-19 cases combined with acute respiratory diseases is presented. The aim of the study was to analyze clinical and laboratory data of patients with combined COVID-19 infection. In patient A. infected with SARS-CoV-2 without X-ray confirmation of lung damage, acute tonsillitis, polyadenopathy, hepatosplenomegaly, moderate leukocytosis, lymphomonocytosis and the presence of reactive lymphocytes were detected. Serological and molecular biological studies were carried out for the purpose of differential diagnosis. A positive test result for IgM antibodies to EBV was obtained. The method of polymerase chain reaction (PCR) revealed EBV DNA in blood plasma. The result of the determination of heterogeneous IgG antibodies to the EBV caspid antigen is negative. Clinical symptoms of the patient with coronavirus infection COVID-19, confirmed by radiological and serological screening, included: fever, sore throat, hyperemia and hypertrophy of the palatine tonsils, hepatomegaly, changes of the cellular composition of the blood. At the same time, the lymph nodes in the neck, chest and abdominal cavity were not enlarged;the presence of reactive lymphocytes and plasma cells was not detected. Serological markers of EBV were also not detected. A PCR test for Epstein-Barr virus DNA was negative.Copyright © 2022 Infectious Diseases: News, Opinions, Training.

Managing severe warm autoimmune haemolytic anaemia after the SARS-Cov- 2 vaccine with emergency splenectomy and eculizumab

Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.

THE IMPACT OF IMMUNOMODULATING TREATMENT ON THE SEROLOGICAL IMMUNOGENICITY FOLLOWING THREE DOSES OF COVID-19 VACCINE AND PERSISTENCE OF IMMUNOGENICITY OF TWO VACCINE DOSES IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES - A SWEDISH STUDY (COVID19-REUMA)

BackgroundData on serological immunity after three doses and the long-term immunogenicity (persistence) of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with different immunomodulating drugs are still limited.ObjectivesTo elucidate if 1) a third dose COVID-19 vaccine improves antibody responses, compared to two doses, in patients with IRD treated with biologic or targeted synthetic DMARD (b/tsDMARDs) treatment given as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) compared to controls, and 2) the persistence of antibody response after two doses of COVID-19 vaccine in IRD patients.MethodsAntibody levels to two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previous COVID-19 infection) were measured in serum samples collected 2-12 and 21-40 weeks after the second vaccine dose and 2-12 weeks after the third dose using a multiplex bead-based serology assay. A sufficient antibody response (seropositivity) was defined as having antibodies over the cut-off level for both spike antigens (1). WT (wild type) anti-Spike IgG and omicron BA.1 and BA.2 variants were measured. Patients with IRD receiving immunomodulating treatment, regularly followed at a rheumatology department and a group of controls were recruited from five Swedish region.ResultsIn total, 323 of 414 patients with IRD and 36 controls who received three vaccine doses participated in this part of the study. Following treatment groups were included: rituximab (n=118;68% female;mean age 67 years), abatacept (n=18;72% female;mean age 64 years), IL6r inhibitors (n=60;73% female;mean age 64 years), JAK-inhibitors (n=44;80% female, mean age 52 years), TNF-inhibitors (n=59;70% female;mean age 47 years;), IL12/23/17 inhibitors (n=24;46% female;mean age 54 years) and controls (n=36;75% female, mean age 51 years). b/ts DMARD treatment was given as monotherapy or in combination with csDMARD, methotrexate (MTX) being the most frequently used csDMARD (32.5%). Compared to results after two vaccine doses, proportion (%) of seropositivity after three vaccine doses increased significantly in groups rituximab +/- DMARD (p=0.003 and p=0.004, respectively), IL6r inhibitors +DMARD (p=0.02), and abatacept+DMARD (p=0.01). However, the proportion of seropositivity after three vaccine doses was still significantly lower in rituximab treated patients (52%) compared to other treatment groups or controls (p<0.001) (Figure 1A/B). Antibody response to WT, omicron sBA.1 and sBA.2 showed similar pattern with the lowest levels among patients treated with rituximab.When antibody response was compared between 2-12 weeks and 21-40 weeks after second dose, the proportion of seropositive rituximab treated patients decreased from 34.9 % to 32.6%. All patients with JAK inhibitors and with JAK-inhibitors and IL6r-inhibitors seropositive 21-40 weeks after the second vaccine dose. Patients treated with other bDMARDs were not included in this analysis due to limited number participants.ConclusionIn this Swedish study including IRD patients receiving different b/t DMARDs, a sufficient immunogenicity of the third dose of COVID-19 vaccine was observed in all treatments with exception for rituximab. However, the increased proportion of seropositivity after the third COVID-19 vaccine doses in rituximab and other patients with insufficient response to two doses including response to the omicron variants, supports the current recommendations on additional booster doses. The immunogenicity of two vaccine doses was preserved to 40 weeks in majority of patients treated with different immunomodulating treatment with exception for rituximab.Figure 1.AcknowledgementsThe study has been supported by the independent research grants from Roche.Disclosure of InterestsMartina Frodlund: None declared, Per Nived: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Grant/research support from: Research grand from Galapagos, Anna ödergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Lars Klareskog: None declared, Meliha C Kapetanovic Grant/research support from: independent research grants från Pfizer and Roche.

Risk factors for worsening of somatic symptom burden in a prospective cohort during the COVID-19 pandemic

Aims: Little is known about risk factors for both Long COVID and somatic symptoms that develop in individuals without a history of COVID-19 in response to the pandemic. There is reason to assume an interplay between pathophysiological mechanisms and psychosocial factors in the etiology of symptom persistence. This study investigates specific risk factors for somatic symptom deterioration in a cohort of German adults with and without prior SARS-CoV-2 infection. Method(s): German healthcare professionals underwent SARS-CoV-2 IgG antibody testing and completed self-rating questionnaires at baseline and 21 months later between April 2020 and February 2022. Differences in variables between the time points were analyzed and a regression analysis was performed to predict somatic symptom deterioration at follow-up. Result(s): Seven hundred fifty-one adults completed both assessments. Until follow-up, n = 58 had contracted SARS-CoV-2 confirmed by serology. Between baseline and follow-up, signs of mental and physical strain increased significantly in the sample. Symptom expectations associated with COVID-19 and a self-reported history of COVID-19, but not serologically confirmed SARS-CoV-2 infection, significantly predicted somatic symptom deterioration at follow-up. A further predictor was baseline psychological symptom burden. Conclusion(s): This study supports a disease-overarching biopsychosocial model for the development of burdensome somatic symptoms during the COVID-19 pandemic and supports research findings that symptom burden may be more related to the psychosocial effects of the pandemic than to infection itself. Future studies on Long COVID should include SARS-CoV-2 negative control groups and consider symptom burden prior to infection in order to avoid an overestimation of prevalence rates.Copyright © 2023

PRE-EXPOSURE PROPHYLAXIS WITH TIXAGEVIMAB/CILGAVIMAB: SINGLE CENTRE EXPERIENCE IN A COHORT OF RHEUMATIC PATIENTS

BackgroundVaccination against SARS-CoV2 had a critical role in the fight against COVID19 pandemic.A weaker humoral response to COVID19 vaccine has been found in rheumatic patients treated with Rituximab (RTX) or Mycophenolate Mofetil (MMF)[1]. Despite the evidence that anti-SARS-CoV-2 mRNA vaccines can elicit a T-cell response [2], some data show that even the cellular immunity could be impaired in rheumatic patients [3] but COVID19 serology is the only parameter that is feasible to measure in daily practice.Tixagevimab+cilgavimab are two human-derived monoclonal antibodies administered parenterally and authorized by regulatory agencies in February 2022 for pre-exposure prophylaxis (PrEP) against COVID19 from different virus variants in fragile patients.ObjectivesTo demonstrate safety and effectiveness of tixagevimab+cilgavimab.MethodsPatients with autoimmune rheumatic diseases undergoing immunosuppressive treatment with RTX or MMF during the vaccination campaign were enrolled between April and June 2022. All patients must have anti-spike antibody levels below the protective threshold (defined by anti-spike IgG titre <250 BAU/ml) after receiving at least 2 vaccine doses.Patients were monitored with a questionnaire every month about COVID19 symptoms (including respiratory and gastrointestinal symptoms, anosmia and ageusia, skin rash and potential contact with COVID19+ subjects) and were checked for anti-spike and anti-nucleocapside antibodies titres every 2 months for a total of a 6 month follow-up. MMF dose was reduced at 1 g/die at the time of vaccine administration.ResultsFifteen patients were enrolled: 9 participants had a connective tissue disease (CTD;1 dermatomyositis, 3 anti-syntethase syndrome, 4 systemic sclerosis, 1 systemic lupus erythematosus) and 6 had vasculitis (all granulomatosis with polyangiitis). 12 of them received RTX in the preceding 12 months and 3 were taking MMF.About safety, the therapy was very well tolerated and only 4 patients (26%) reported a non-severe adverse event in the 2 weeks following drug administration (2 myalgia, 1 headache, 1 fatigue), none of them requiring hospitalization nor pharmacologic treatment.Regarding effectiveness, 3/15 patients contracted SARS-Cov2 infection (20%) with mild symptoms and no need for hospitalization nor oxygen therapy. Only 1 of them received an antiviral drug (nirmatrelvir+ritonavir). All infected patients had a CTD diagnosis. No significant correlation was observed between the type of rheumatic disease and the risk of infection or response to tixagevimab+cilgavimab.ConclusionNone of our patients developed severe adverse events after tixagevimab+cilgavimab administration and, among the 3 SARS-CoV2 infected patients, none required hospitalization nor oxygen therapy.We conclude that in our experience tixagevimab+cilgavimab is a safe and useful complementary immunization strategy to vaccination for COVID19 prophylaxis.These data will be implemented in a larger study, comprehending various immunocompromised patients from several departments.References[1] Furer et al., Ann Rheum Dis, 2021[2] Mangalakumari et al., Nat Rev Immunol, 2020[3] Picchianti-Diamanti et al., Front Immunol, 2021Charateristic of the cohortIdentificativeAgeDiagnosisRTX/MMFSARS-CoV2 InfectionHospitalizationAntiviral drugs180SScMMF-//270ASSDRTX+nono370ASSDRTX+noyes452GPARTX-//551GPARTX-//649SSc+SSjRTX-//768SScMMF-//847LESRTX-//964ASSDRTX-//1068GPARTX-//1123GPARTX-//1258DMRTX+nono1361SScMMF-//1475GPARTX-//1569GPARTX-//Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

PATIENTS WITH AXIAL SPONDYLOARTHRITIS HAVE BETTER SARS-CoV-2 OUTCOMES COMPARED WITH PATIENTS WITH RHEUMATOID ARTHRITIS: DATA FROM THE NATIONAL SAR-COVID REGISTRY

BackgroundPatients with rheumatic diseases may present more severe SARS-CoV-2 infection compared to the general population. However, in some studies, hospitalization and mortality due COVID-19 were lower in patients with axial spondyloarthritis (axSpA) compared to other rheumatic diseases.ObjectivesTo assess the severity of SARS-CoV-2 infection in patients with axSpA from the SAR-COVID registry, comparing them with patients with rheumatoid arthritis (RA), and to determine the factors associated with poor outcomes and death.MethodsPatients ≥18 years old from the SAR-COVID national registry with diagnosis of AxSpA (ASAS criteria 2009) and RA (ACR/EULAR criteria 2010) who had confirmed SARS-CoV-2 infection (RT-PCR or positive serology), recruited from August 2020 to June 2022 were included. Sociodemographic and clinical data, comorbidities, treatments and outcomes of the infection were collected. Infection severity was assessed using the WHO-ordinal scale (WHO-OS)[1]: ambulatory [1], mild hospitalizations (2.3 y 4), severe hospitalizations (5.6 y 7) and death [8].Statistical analysisDescriptive statistics. Chi[2] or Fischer test and Student T or Mann-Whitney as appropriate. Poisson generalized linear model.ResultsA total of 1226 patients were included, 59 (4.8%) with axSpA and 1167 (95.2%) with RA. RA patients were significantly older, more frequently female, and had a longer disease duration. More than a third of the patients were in remission. 43.9 % presented comorbidities, arterial hypertension being the most frequent. At the time of SARS-Cov-2 diagnosis, patients with RA used glucocorticoids and conventional DMARDs more frequently than those with axSpA, while 74.6% of the latter were under treatment with biological DMARDs being anti-TNF the most used (61%).94.9 % of the patients in both groups reported symptoms related to SARS-CoV-2 infection. Although the differences were not significant, patients with RA presented more frequently cough, dyspnea, and gastrointestinal symptoms, while those with axSpA reported more frequently odynophagia, anosmia, and dysgeusia. During the SARS-CoV-2 infection, 6.8% and 23.5% of the patients with axSpA and RA were hospitalized, respectively. All of the patients with axSpA were admitted to the general ward, while 26.6% of those with RA to intensive care units. No patient with axSpA had complications or severe COVID-19 (WHO-OS>=5) or died as a result of the infection while mortality in the RA group was 3.3% (Figure 1).In the multivariate analysis adjusted to poor prognosis factors, no association was found between the diagnosis of axSpA and severity of SARS-CoV-2 infection assessed with the WHO-OS (OR -0.18, IC 95%(-0.38, 0.01, p=0.074).ConclusionPatients with EspAax did not present complications from SARS-CoV-2 infections and none of them died due COVID-19.Reference[1]World Health Organization coronavirus disease (COVID-19) Therapeutic Trial Synopsis Draft 2020.Figure 1.Outcomes and severity of SARS-CoV-2 infection in patients with axSpA and RA.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsAndrea Bravo Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Tatiana Barbich Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Carolina Isnardi Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretati n, or writing the report. They do not have access to the information collected in the database., Gustavo Citera Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Emilce Edith Schneeberger Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Rosana Quintana Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Cecilia Pisoni Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Mariana Pera Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Edson Velozo Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Dora Aida Pereira Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Paula Alba Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Juan A Albiero Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Jaime Villafañe Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Hernan Maldonado Ficco Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Veronica Sa io Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Santiago Eduardo Aguero Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Romina Rojas Tessel Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Maria Isabel Quaglia Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., María Soledad Gálvez Elkin Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access tothe information collected in the database., Gisela Paola Pendon Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Carolina Aeschlimann Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Gustavo Fabian Rodriguez Gil Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Malena Viola Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Cecilia Romeo Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Carla Maldini Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Silvana Mariela Conti Grant/research support from: SAR-COVID is a multi-sponsor re istry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Rosana Gallo Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Leticia Ibañez Zurlo Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Maria Natalia Tamborenea Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Susana Isabel Pineda Vidal Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Debora Guaglianone Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Jonatan Marcos Mareco Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Cecilia Goizueta Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Elisa Novatti Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Fernanda Guzzanti Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Gimena Gómez Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Karen Roberts Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of t em participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database., Guillermo Pons-Estel Grant/research support from: SAR-COVID is a multi-sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or influenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database.

THE CONTRIBUTION OF THE 3RD AND 4TH BOOSTER BNT162B2 MRNA VACCINES TO PREVENT SEVERE COVID-19 AMONG AUTOIMMUNE INFLAMMATORY RHEUMATOID DISEASES (AIRD) PATIENTS DURING THE OMICRON OUTBREAKS

BackgroundThe 3rd booster of mRNA vaccines against SARS COV2 was highly efficient against delta variant but data regarding the efficacy of the 3rd and 4th boosters against the omicron variants, among AIRD pts are scarce.ObjectivesWe aimed to assess the effect of the 3rd and 4th booster mRNA vaccines against SARS CoV2, in preventing severe COVID-19, in AIRD patients (pts) treated with immunomodulating drugs.Methods212 pts (mean age(SD) 57(13), disease duration 11.2(7.4), who received the 3rd booster (Pfizer) were included in the study. We performed serology tests 24 weeks after the second dose of vaccine and 4-8 weeks after the 3rd booster. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay. The test was considered positive above 50 AU/ml. Data regarding COVID-19 infection during the 5th outbreak (omicron) were collected from the medical files. The length of observation period was defined as the time from the 3rd booster to the last hospital visit or COVID 19 diagnosis, whichever occurred first.ResultsThe 3rd booster administration (Pfizer) significantly augmented the humoral response (from mean(SD) 1121(4723) AU/ml to 12153(13687)). 58 patients received the 4th booster and 18 the 5th booster. COVID-19 was diagnosed in 103 pts (49%) within mean(SD) 224.8(106.5) days after the 3rd booster vaccination. 109 pts remained free of disease during mean(SD) follow-up 230.6(133.9). Following the 4th booster, 26 (45%) out of 58pts contracted COVID-19 within mean(SD) 97.6(78.7) days after the vaccination. One 70 year old patient (vaccinated 3 times) died and 2 other pts (rituximab treated) had severe COVID-19. The IgG Ab titer after the 3rd booster was lower in pts who contracted COVID 19 compared to those uninfected (mean(SD), median 8777.9(11716.4),3475 AU/ml vs 15348.1(14649.1),10801, p=0.004).There were no statistically significant differences between the pts with COVID-19 and those without, regarding age, type of disease, treatment and humoral response 24 weeks after the 2nd vaccination.ConclusionDespite an enhanced humoral response obtained after the 3rd booster, 49% of AIRD pts vaccinated with 3 doses and 45% of pts vaccinated with 4 doses had COVID-19 during the omicron outbreaks. Higher humoral response to the 3rd booster was associated with a lower rate of COVID19. The booster vaccines conferred 99% protection against severe COVID-19.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Serological Detection for Toxoplasmosis among Patients with Covid-19 in Thi-Qar Province

Covid-19 is a viral disease that affects humans caused by a type of virus belonging to the family Coronaviridae called the SARS-CoV-2 virus. The parasitic infection associated with this disease affects the host's immune response regulation. The levels of IgG and IgM of Toxoplasma gondii in the serum of patients with COVID-19 were measured by immunoassay of the patient's sera by ELISA. Also, the level of interferon-gamma (IFN-gamma) in a covid-19 patient with or without Toxoplasmosis was evaluated. 120 samples were collected, 60 were positive for COVID-19, confirmed by clinically and radiographic examination, and 30 were in the control group. The results showed a significant difference between the infection with Covid-19 and T. gondii during the chronic phase of Toxoplasmosis compared to the negative relationship in the acute phase. The results of INF-gamma levels among Covid-19 patients were positive for all samples included in the test (30 Covid-19 patients and 30 patients COVID-19(+)/T. gondii IgG) compared to the control group. The chronic form of Toxoplasma disease, due to change in the production of this interferon, the COVID-19 infection has changed.Copyright © 2023 by Razi Vaccine & Serum Research Institute.