ACCELERATED WANING OF HUMORAL IMMUNE RESPONSE TO A THIRD COVID-19 VACCINATION IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES

BackgroundA 3rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed.ObjectivesIt remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses.Methods50 patients under immunosuppression and 42 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period.ResultsAt week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781 – 10208] versus 9650 BAU/ml [6633 - 16050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological diseases modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported.ConclusionDue to a fast decline in anti-RBD antibodies in IMID patients an early 4th vaccination should be considered in this vulnerable group of patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsDaniel Mrak Consultant of: AstraZeneca, Felix Kartnig: None declared, Daniela Sieghart: None declared, Elisabeth Simader Speakers bureau: Lilly, Helga Radner Speakers bureau: Gilead, Merck Sharp and Pfizer, Peter Mandl: None declared, Lisa Göschl: None declared, Philipp Hofer: None declared, Thomas Deimel: None declared, Irina Gessl: None declared, Renate Kain Speakers bureau: Otsuka, Consultant of: AstraZeneca, Takeda Pharma, MEDahead and Janssen Cilag, Stefan Winkler: None declared, Josef S. Smolen Consultant of: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celltrion, Gilead-Galapagos, Janssen, Lilly, Pfizer, R-Pharma, Samsung, Sanofi, Chugai, Merck Sharp & Dohme, Novartis-Sandoz Roche, Samsung and UCB, Grant/research support from: Abbvie, AstraZeneca, Lilly, Novartis, and Roche, Thomas Perkmann: None declared, Helmuth Haslacher Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Consultant of: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Grant/research support from: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Leonhard Heinz: None declared, Michael Bonelli Consultant of: EliLilly.

COVID-19 and sepsis: clinical parallels of clinical course and treatment options

The article analyzes syndrome complex in sepsis and severe COVID-19, identifies the main pathophysiological priorities in the diagnosis and differences in treatment. Adap-tation of existing treatment regimens for diseases with similar pathogenesis may help to improve treatment outcomes and reduce SARS-CoV-2-related mortality. However, when discussing the parallels between COVID-19 and sepsis, focusing on their similarities in immunopathogenesis and pathophysiology, the proposed treatment options should be reviewed based on the patient's clinical assessment and laboratory parameters individually. © 2022, Zaslavsky Publishing House. All rights reserved.

LABORATORY PARAMETERS ASSOCIATED WITH CODIV-19 CYTOKINE STORM DEVELOPMENT

BackgroundSince the end of 2019, physicians became more and more familiar with SARS-CoV-2 infection and the variety of forms in which it may present and evolve. There have been a lot of studies trying to understand and predict why some patients develop a dysregulation of the immune response, with an exaggerated release of pro-inflammatory cytokines, called cytokine storm (1–4). There is scarce evidence in Romania regarding this aspect.ObjectivesThis study aims to verify the correlation between some laboratory parameters and the development of cytokine storm in SARS-CoV-2 infection in a cohort of over 200 patients admitted in a tertiary hospital from Romania, hoping that early identification of these risk factors of progression to a severe form of the disease can bring considerable benefit to patient care.MethodsThis is an analytical, observational, case-control study which includes 219 patients (all COVID-19 hospitalized patients on the Internal Medicine 3 department of Colentina Clinical Hospital, Bucharest, from 01 March 2020 to 1 April 2021). A series of data were collected, the laboratory parameters being the most important, including: albumin, lymphocyte (percentage), neutrophil (absolute value), aspartate aminotransferase, alanine aminotransferase, D-dimers, lactate dehydrogenase (LDH), anionic gap, chloremia, potassium and the BUN:creatinine ratio (BUN - blood urea nitrogen). The laboratory parameters used for the statistical analysis represent the average values of the first 7 days of hospitalization for those who did not develop cytokine storm, respectively until the day of its development, for the others. Patients were classified into these groups, those who developed cytokine storm, respectively those who did not have this complication taking into account the clinical and paraclinical criteria (impairment of respiratory function, elevations of certain markers 2-3 times above the upper limit of normal, those who died as a result of SARS-CoV-2 infection). Then Binary Univariate Logistic Regression was applied in order to verify the individual impact of every laboratory parameter on cytokine storm development. Furthermore, all laboratory parameters were subsequently included in the multivariate analysis, using the backward selection technique to achieve a model as predictive as possible.ResultsWe mention that the analysis of demographic data was previously performed, showing no statistically significant relationship between patient gender, age or comorbidities (history of neoplasm, lung diseases, cardiac pathology, obesity, type II diabetes and hypertension) and their evolution to cytokine storm. After performing binary univariate logistic regression we concluded that 8 of the 13 laboratory analyzes have had a significant change between groups (ferritin, PCR, albumin, Lymphocyte, Neutrophils, TGO, LDH, BUN:creatinine ratio). Only 150 patients were then included in the multivariate analysis. After the analysis, some of the variables lost their statistical significance, the final model including C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio. This model correctly predicts the development of cytokine storm in 88% of cases.ConclusionHigh C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio are risk factors for cytokine storm development and should be monitored in all COVID-19 patients in order to predict their evolution.References[1]Pedersen SF et all. SARS-CoV-2: A storm is raging[2]Mehta P et al. COVID-19: consider cytokine storm syndromes and immunosuppression[3]Hu B et al. The cytokine storm and COVID-19.[4]Caricchio R et al. Preliminary predictive criteria for COVID-19 cytokine stormAcknowledgements:NIL.Disclosure of InterestsNone Declared.

CLINICAL CHARACTERISTICS & OUTCOMES AMONG PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES AND SARS-CoV-2 INFECTION: 2-YEAR DATA FROM A TERTIARY RHEUMATOLOGY CENTRE IN GREECE

BackgroundPatients with autoimmune rheumatic diseases (ARDs) under moderate/severe immunosuppression are considered a high-risk population to develop severe Covid-19 infection.ObjectivesThe aim of our study was to describe the clinical characteristics and the outcome of patients with ARD who contracted a Sars-Cov-2 infection.MethodsAmong patients with ARD being followed in our tertiary outpatient rheumatology clinic, we retrospectively identified those infected with SARS-CoV-2 between the beginning of the pandemic and August 2022. Patients' medical files were reviewed for demographics (age, gender and comorbidities) and disease-related characteristics, as well as coronavirus disease (COVID-19) characteristics, including vaccination status, treatment, and outcomes (covid-19 severity, hospitalization, death).ResultsA total of 209 cases of ARD patients with confirmed Covid-19 infection were recorded. Most of them were women (62.7%), with a mean age of 52.4± 13.8 years. The most prevalent ARDs were seronegative spondyloarthropathies (28.7%), systematic lupus erythematosus (21.5%), rheumatoid arthritis (16.5%), and systemic sclerosis (11.5%). More than half of the patients received corticosteroids (57.8%), while the most frequently used immunosuppressants were hydroxychloroquine (30.9%), TNF inhibitors (26.5%), mycophenolate mofetil (24.0%), methotrexate (19.1%) and rituximab (15.2%). One hundred and fifty-eight (76%) patients were either on remission or had mild disease activity. Most of the patients (131/209) had at least one comorbidity, more commonly arterial hypertension (48.5%) and pulmonary disease (45.2%). Most of the patients were vaccinated against Sars-Cov-2 (73.7%), either with two doses (38.0%), three doses (57.0%) or four doses (5.0%) of mRNA-based vaccines. The big majority of the patients (83.3%) were asymptomatic or had mild Covid-19 disease. About half of the patients (53.1%) reported to have received Covid-19 treatment. Thirty-two of them (15.3%) needed hospitalization, and five death cases were reported overall. Among the demographic characteristics, age (p<0.0001 for hospitalization) and comorbidities were associated with worse covid-19 outcomes. In particular, cardiovascular disease (OR 5.37, p=0.001 for covid-19 severity, OR 6.89, p=0.001 for hospitalization), pulmonary disease (OR 3.02, p=0.006 for hospitalization), and obesity (OR 3.46, p=0.044 for hospitalization) had the stronger associations. Non-vaccination status was also associated with a higher risk for hospitalization (OR 2.68, p=0.015). In relation to ARD-related factors, treatment with rituximab (OR 4.11, p=0.002 for hospitalization), systemic sclerosis diagnosis (OR 3.45, p=0.03 for Covid-19 severity) and myositis diagnosis (OR 4.91, p=0.033 for hospitalization) were associated with worse Covid-19 outcomes. On the other hand, spondyloarthropathies appear to be negatively associated with Covid-19 severity (OR=0.27, p=0.035).ConclusionAccording to our study, most ARD patients recovered uneventfully from Covid-19. However, there are several indications that we should be vigilant for patients who remain unvaccinated, are older, have a systemic sclerosis or myositis diagnosis, and/or receive intense immunosuppressive regiments such as rituximab.References[1]Papagoras C, Fragoulis GE, et al. Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases. Ann Rheum Dis. 2021 Nov 10.[2]Strangfeld A, Schäfer M, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2021 Jul;80(7):930-942.Table 1.N=209ARD Diagnosisn (%)Rheumatoid arthritis34 (16.3)Seronegative spondyloarthropathies60 (28.7)Systemic lupus erythematosus45 (21.5)Systemic sclerosis24 (11.5)Sjogren's syndrome15 (7.2)Vasculitis19 (9.1)Myositis9 (4.3)Other3 (1.4)Acknowledgements:NIL.Disclosure of InterestsNone Declared.

SAFETY AND IMMUNOGENICITY OF TWO HETEROLOGOUS VACCINE SCHEDULES AGAINST SARS-CoV-2 IN PATIENTS WITH RHEUMATOID ARTHRITIS: BRAZILIAN MULTICENTER STUDY

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with comorbidities associated. However, few studies in the literature assessed the safety and immunogenicity of the COVID-19 heterologous vaccine schedules in patients with RA.ObjectivesEvaluate the safety and immunogenicity of two heterologous vaccine schedules against SARS-CoV-2 in patients with RA.MethodsThese data are from the study "SAFER - Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases,” a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Immunogenicity and adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 plus additional dose of BNT162b2 or after two doses of inactivated SARS-CoV-2 vaccine CoronaVac plus additional dose of BNT162b2. The titers of neutralizing antibodies against the receptor-biding domain of protein spike (S) of SARS-CoV-2 (anti-RBD) were measured by chemiluminescence test after each dose of immunizers. Proportions between groups were compared using the chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test.ResultsA total of 107 patients with RA were include in the study, most of them female, with a mean age of 46 years. Biological disease modifying anti-rheumatic drugs (DMARDs) were used by 50 % of the patients and conventional synthetics DMARDs in 48 %. Two doses of CoronaVac plus additional dose of BNT162b2 was used in 66 patients and two doses of ChAdOx1 plus additional dose of BNT162b2 in 41. Only mild AEs were observed, mainly after the first dose. The most common AEs after all doses, regardless of the immunizer type, were pain at the injection, headache, arthralgia and myalgia. ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0,001) and arthralgia (68% vs 15%, p < 0,001) compared to CoronaVac. No patients had flare after the vaccination. The titers of anti-RBD after two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p < 0,001). However, after the additional dose of BNT162b2, the anti-RBD titers were similar in both groups (7.28 BAU/mL vs 7.06 BAU/mL, p = 0.56). Only two cases of COVID 19, with mild symptoms, were reported, one in each group.Figure 1.ConclusionChAdOx1, CoronaVac, and BNT162b2 vaccines are safe in RA patients. The frequency of local adverse effects, particularly pain at the injection site, is high. AEs are more frequent with ChAdOx1, especially after the first dose. The use of the immunizers does not change the degree of inflammatory activity of the disease. The immunogenicity of the two heterologous regimens analyzed was similar.References[1]Marques C, Kakehasi AM, Gomides APM, Paiva EDS, Dos Reis Neto ET, Pileggi GCS, et al. A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study. JMIR Res Protoc.[2]Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, Yuki EFN, Pedrosa T, Fusco SRG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med. 2021;27(10):1744-1751.[3]Machado PM, Lawson-Tovey S, Strangfeld A, Mateus EF, Hyrich KL, Gossec L, et al. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Ann Rheum Dis. 2022;81(5):695-709.[4]Tavares ACFMG, Melo AKG, Cruz VA, Souza VA, Carvalho JS, Machado KLLL, et al. Guidelines on COVID-19 vaccination in patients with immunemediated rheumatic diseases: a Brazilian Society of Rheumatology task force. Adv Rheumatol. 2022;62:3.Acknowledg ments:NIL.Disclosure of InterestsNone Declared.

TIME MANAGEMENT AND RISK FACTORS IN LIFE-THREATENING ANCA-VASCULITIS

BackgroundAccuracy of diagnosis and prompt therapeutic intervention are the mainstay in patients with ANCA-associated vasculitis(AAV) suffering from life-threatening complications [1].However, there is no definition of therapeutic window in vital AAV, nor its impact on patient outcome regarding length of hospital stay, intensive care unit(ICU) admission or survival.ObjectivesThe aim of the study is to analyze the process of care from the perspective of time management in vital organ involvement AAV patients and to identify potential risk factors for ICU admission.MethodsA retrospective multicenter study identified AAV patients with life-threatening organ involvement, defined as alveolar hemorrhage, rapidly progressive renal failure, myocarditis and cerebral granuloma. Demographic data was collected. Key time frames were recorded, namely the interval from acute symptom onset to hospital presentation, days until imaging(plain X-ray, cardiac ultrasound, CT-scan), time to therapeutic intervention with corticosteroids or biologic/non-biologic immunosuppression(cyclophosphamide or rituximab) and to renal replacement therapy(RRT) or plasmapheresis. Time to ICU admission, hospital length-of-stay, Birmingham Vasculitis Activity Score(BVAS) were also noted. Statistical analysis was performed using SPSS and Chi-square and Pearson correlation tests were applied.Results66 patients with AAV were enrolled, out of which 17 fulfilled inclusion criteria. Mean age in the study group was 58.6±11.1 years old,10 patients(58.8%) were females and 7 (41.2%) males.11(64.7%) patients were c-ANCA positive, while 6 (35.3%) had p-ANCA and all were diagnosed with AAV prior to life-threatening event. Two patients had COVID-19 triggered AAV.In the study group, the most frequent critical organ suffering was rapidly progressive renal failure(12), followed by alveolar hemorrhages(10), 2 cerebral granulomas and one acute myocarditis. Three patients(17.6%) had more than one vital manifestation. Ten patients(58.8%) had more than three additional non-organ-threatening manifestations. Mean interval from AAV diagnosis to emergency admission was 30.1± 61.1 days, median 3 and from severe episode onset to hospitalization 1.65±0.18 days, median 1. There was only one death in the study group. Three patients were admitted in the ICU in 0.59±1.5 days following hospital presentation and required either RRT or plasma exchange within 2.66 days. Imaging examination was performed unanimously the day upon hospital admission. All patients received corticosteroids in the first 5.95±14.3 days, while immunosuppression was given to 13(76.5%) patients within 11.5±15.5 days from hospitalization.12 patients(70.5%) suffered from associated infections. Mean BVAS(13.6±6.76) correlated to ICU admission(p 0.013, r 0.58).Patients in ICU revealed higher BVAS(22±9.53) versus non-ICU(11.8±4.76).Hospital length of stay was 14.7±10.7 days(median 14) and showed no relationship to the type of severe organ involvement. The need for ICU caring was dominant in males(p 0.05) and confirmed in patients with proteinuria(p 0.012) and at least two major organ damage.ConclusionThis study shows that severity risk factors for potential ICU admission for life-threatening AAV appear to be male gender, proteinuria and the number of affected organs.Moreover, BVAS should be considered a useful tool to predict patients' risk for intensive care management since a higher score indicates a more aggressive disease.However, time to investigational or therapeutic intervention did not correlate to patient outcome in AAV.References[1]Geetha, D., Seo, P. (2011). Life-Threatening Presentations of ANCA-Associated Vasculitis. In: Khamashta, M., Ramos-Casals, M. (eds) Autoimmune Diseases. Springer, London. https://doi.org/10.1007/978-0-85729-358-9_8Acknowledgements:NIL.Disclosure of InterestsNone Declared.

DO PATIENTS ON SUPPRESSIVE THERAPY HAVE A DECREASED HUMORAL RESPONSE TO SARS-CoV2 VACCINATION?

BackgroundSARS-Cov2 vaccination has been shown to be effective against severe forms of SARS-Cov2 infection. Several studies investigated the humoral and cellular response to SARS-Cov2 vaccines in patients followed for autoimmune and inflammatory diseases under immunosuppressive or immunomodulatory treatments. It has been shown that patients on immunosuppressive or immunomodulatory therapies have a poor humoral response to the vaccine[1]ObjectivesThe aim of our study was to investigate the humoral response in patients under conventional immunosuppressive and biotherapies compared to healthy controls.MethodsPatients followed for immuno-inflammatory diseases under immunosuppressive or immunomodulatory drugs who received at least one dose of anti- SARS-Cov2 vaccines were included. Quantitative Anti- SARS-Cov2 antibodies (IgM and IgG assay) VIDAS ® were assessed for all patients. Patients were then compared with healthy controls.ResultsWe enrolled 93 blood samples (63 patients with autoimmune and inflammatory disease and 30 healthy controls), the median age was 52 years [Q1 43, Q3 56]. The immuno-inflammatory diseases were: Crohn's disease (n=28), Rheumatoid arthritis (n=9), Hemorrhagic rectocolitis (n=5), Behçet's disease (n=5), Systemic lupus erythematosus (n=4), Sjogren's syndrome (n=3), Sarcoidosis (n=2), Takayasu disease (n=1). All patients continued their treatment during and after vaccination. Nineteen patients were on biotherapies: Infliximab (n=12), Adalimumab (n=3), etanercept (n=2), Ustekinumab (n=1), tocilizimab (n=1). Forty-three patients were on conventional immunosuppressive: azathioprine (n=18), methotrexate (n=16), corticosteroids > 10 mg/d (n=12). All patients had received at least one dose of vaccine: the median number of doses in both groups was 2[1-4] with no statistically significant difference between the 2 groups (p=0.2). The vaccines received in the group of patients were mRNA vaccine (n=35) and other type of vaccine (n=28). In the healthy control group, type of vaccine were mRNA (n=13) other type vaccine (n=17). The patient had a lower mean level of Ig G against SARS-Cov2 antibodies (24.64 IU +/- 16.65) comparing to healthy controls (33.05+/- 10) with statically significant difference (p= 0.014). No difference between the 2 groups was noted in Ig G levels according to the history of SARS-Cov2 infection. No difference was found between conventional immunosuppressive drugs and biotherapies regarding to the level of antibodies.ConclusionOur study highlights that patients with autoimmune disease and under immunosuppressive therapy displayed a decrease of humoral response comparing to healthy controls. This finding was reported in several studies, Geisen et al[2] reported that patients with chronic inflammatory condition and receiving TNF alfa blockers had a decreased protection and a low level Ig A against spike. Based on these data, patients with autoimmune and inflammatory diseases have decreased humoral immunity to SARS-Cov2 and should be encouraged to receive a booster dose of SARS-COv2 vaccine.References[1]Prendecki M, Clarke C, Edwards H, et al. Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression. Ann Rheum Dis 2021;80:1322–9. doi:10.1136/annrheumdis-2021-220626[2]Geisen UM, Sümbül M, Tran F, et al. Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies. RMD Open 2021;7:e002008. doi:10.1136/rmdopen-2021-002008AcknowledgementsMrs Hajer Mediouni.Disclosure of InterestsNone Declared.

FLARES AFTER COVID-19 INFECTION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES: RESULTS FROM THE COVAD STUDY

BackgroundViral infections are known triggers of disease flares in idiopathic inflammatory myopathies (IIMs). Reports of post-COVID-19 flares of IIMs have raised suspicion of a possible role of SARS-COV-2 in their onset [1,2]. However, despite rising flare rates in this vulnerable patient group during the pandemic, the risk factors for post-COVID-19 IIMs flares remain unknown [3,4].ObjectivesDisease flares among patients with idiopathic inflammatory myopathies (IIMs) can lead to significant disability, though are poorly explored in the post-COVID-19 period. We analysed risk factors for post-COVID-19 flares in a global sample of IIM patients in a subset analysis as part of the ongoing COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.MethodsA cross-sectional patient self-reporting survey was circulated by the international COVAD study group (157 collaborators, 106 countries) to patients with autoimmune diseases and healthy controls from February-June 2022. Data was collected on demographics, autoimmune disease details, treatment history, comorbidities, COVID-19 history and course and COVID-19 vaccination details. Patients with IIMs who flared post COVID-19 were compared to those who did not using the χ2 test, factors found significant in univariate analysis and deemed clinically important, underwent multivariable analysis (binary logistic regression using the Enter method) with adjustment for age, gender, ethnicity, vaccine type, immunosuppression, autoimmune and non-autoimmune comorbidities, COVID-19 antibody status, and clinical symptoms of COVID-19. Statistical analyses were performed using IBM SPSS version 28.0, with statistical significance considered at p<0.05.Results15,165 respondents completed the survey of whom 1,169 contracted COVID-19. Of these, 207 had IIMs [median (IQR) age 57.0 (47.0-67.0), 71% female, 74.4% Caucasian]. We noted with concern that nearly a third of patients with IIMs (63/207, 30.4%) reported experiencing a flare. A past medical history significant for Asthma, (34.9% vs 6.9%, multivariable OR: 7.1;95%CI: 3.1-16.4, p<0.001) and specific clinical symptoms during COVID-19 including joint pains (multivariable OR: 6.05;95%CI: 1.60-22.9, p=0.008), and difficulty in breathing (multivariable OR: 3.43;95%CI: 1.09-10.8, p=0.036) were found to confer conferred a higher risk of flares (Table 1).Table 1Patient Reported Flares following COVID-19 infection among IIM patientsTotal IIMs (n=207)IIMs with flare after COVID-19 (n=63)IIMs without flare after COVID-19 (n=144)OR (95%CI)PAge (median, IQR) years57.0 (47.0-67.0)53.0 (47.0-62.0)59.0 (47.0-69.0)-0.024GenderMale Female60 (29.0) 147 (71.0)7 (11.1) 56 (88.9)53 (36.8) 91 (63.2)0.2 (0.09-0.5)< 0.001ComorbiditiesAsthma ILD32 (15.5) 31 (15.0)22 (34.9) 11 (17.5)10 (6.9) 20 (13.9)7.1 (3.1-16.4) 1.3 (0.5-2.9)<0.001 00.508Clinical features in previous COVID-19 infectionFatigue Myalgia Arthralgia Difficulty in breathing134 (64.7) 94 (45.4) 56 (27.1) 41 (19.8)52 (82.5) 44 (69.8) 36 (57.1) 27 (42.9)82 (56.9) 50 (34.7) 20 (13.9) 14 (9.7)3.5 (1.7-7.4) 4.3 (2.3-8.2) 8.2 (4.1-16.4) 6.9 (3.3-14.6)<0.001 <0.001 <0.001 <0.001ConclusionWe observed a high frequency of patients with IIM experiencing post-COVID-19 disease flares. A past history of Asthma and those with certain acute COVID-19 symptoms were at higher risk.References[1]Saud A, Naveen R, Aggarwal R, Gupta L. COVID-19 and Myositis: What We Know So Far. Curr Rheumatol Rep 2021;23:63.[2]Gokhale Y, Patankar A, Holla U, Shilke M, Kalekar L, Karnik ND, et al. Dermatomyositis during COVID-19 Pandemic (A Case Series): Is there a Cause Effect Relationship? J Assoc Physicians India 2020;68:20–4.[3]Gupta L, Lilleker JB, Agarwal V, Chinoy H, Aggarwal R. COVID-19 and myositis - unique challenges for patients. Rheumatology (Oxford) 2021;60:907–10.[4]Naveen R, Sundaram TG, Agarwal V, Gupta L. Teleconsultation experience with the idiopathic inflammatory myopathies: a prospective observational cohort study during the COVID-19 pandemic. Rheumatol Int 2021;41:67–76.Acknowledgements:NIL.Disclosure of InterestsSa dia Sasha Ali: None declared, Naveen Ravichandran: None declared, Parikshit Sen: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Mrudula Joshi: None declared, Sreoshy Saha: None declared, Rohit Aggarwal Consultant of: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Grant/research support from: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Vikas Agarwal: None declared, Hector Chinoy Speakers bureau: Speaker for UCB, and Biogen. HC was supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme., Grant/research support from: Has received grant support from Eli Lilly and UCB, consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Oliver Distler Speakers bureau: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Carlo Vinicio Caballero: None declared, Carlos Enrique Toro Gutierrez: None declared, Dey Dzifa: None declared, Ashima Makol: None declared, Ai Lyn Tan Speakers bureau: Has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Consultant of: has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Samuel Katsuyuki Shinjo: None declared, Vishwesh Agarwal: None declared, Latika Gupta: None declared.

No Associations Between Physical Activity and Immunogenicity in SARS-CoV-2 Seropositive Patients With Autoimmune Rheumatic Diseases Prior to and After Vaccination.

AIM: To investigate the association between physical activity and immunogenicity among SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and following a 2-dose schedule of CoronaVac (Sinovac inactivated vaccine). METHODS: This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial conducted in Sao Paulo, Brazil. In this substudy, only SARS-CoV-2 seropositive patients were included. Immunogenicity was assessed by seroconversion rates of total anti-SARS-CoV-2 S1/S2 immunoglobulin G (IgG), geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity before and after vaccination. Physical activity was assessed through a questionnaire. Model-based analyses were performed controlling for age (<60 or ≥60 y), sex, body mass index (<25, 25-30, and >30 kg/m2), and use of prednisone, immunosuppressants, and biologics. RESULTS: A total of 180 seropositive autoimmune rheumatic disease patients were included. There was no association between physical activity and immunogenicity before and after vaccination. CONCLUSIONS: This study suggests that the positive association between physical activity and greater antibody responses seen in immunocompromised individuals following vaccination is overridden by previous SARS-CoV-2 infection, and does not extend to natural immunity.

Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients.

OBJECTIVES: Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines. METHODS: We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers. RESULTS: Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients. CONCLUSIONS: Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity.

Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

PURPOSE: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. METHODS: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. RESULTS: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. CONCLUSIONS: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.

A case of nocardiosis in a patient with ulcerative colitis on chronic corticosteroids, infliximab, and upadacitinib.

Key Clinical Message: Immunosuppression, malnutrition, and underlying infection can unmask obscure infections which can be challenging to identify. Early diagnosis and treatment of infections in immunosuppressed patients are essential due to high morbidity and mortality. Abstract: The immunosuppressive effects of treatment for ulcerative colitis (UC), including chronic corticosteroids, anti-TNF agents, and JAK inhibitors, can impact the spread of latent or obscure infections. Clinicians should have a low threshold for pursuing aggressive diagnostic and therapeutic intervention in patients who show signs of clinical deterioration while on immunosuppressing medications. Our unique case highlights an immunosuppressed patient with UC who developed Nocardiosis after initiation of upadacitinib while hospitalized for concurrent UC flare and Clostridium difficile infection.

Xenotransplantation literature update March 2021-March 2023.

After a significant hiatus imposed by the COVID-19 pandemic, we hereby restart Xenotransplantation literature updates. With the recently performed clinical xenotransplantation cases and the much-heightened interest in the field, we have determined that this is an optimal time to reinstate this section. There has been an invigorated focus on unique challenges posed by pig-to-human xenotransplantation, and specific attention will be given to this aspect. In this issue, we aimed to cover the gap and compiled the most relevant publications from March 2021 to March 2023.

Orthotopic Liver Transplantation of a SARS-CoV-2 Negative Recipient from a Positive Donor: The Border between Uncertainty and Necessity in a Pandemic Era- Case Report and Overview of the Literature.

(1) Introduction: Liver transplantation represents the gold-standard therapy in eligible patients with acute liver failure or end-stage liver disease. The COVID-19 pandemic dramatically affected the transplantation landscape by reducing patients' addressability to specialized healthcare facilities. Since evidence-based acceptance guidelines for non-lung solid organ transplantation from SARS-CoV-2 positive donors are lacking, and the risk of bloodstream-related transmission of the disease is debatable, liver transplantation from SARS-CoV-2 positive donors could be lifesaving, even if long-term interactions are unpredictable. The aim of this case report is to highlight the relevance of performing liver transplantation from SARS-CoV-2 positive donors to negative recipients by emphasizing the perioperative care and short-term outcome. (2) Case presentation: A 20-year-old female patient underwent orthotropic liver transplantation for Child-Pugh C liver cirrhosis secondary to overlap syndrome, from a SARS-CoV-2 positive brain death donor. The patient was not infected nor vaccinated against SARS-CoV-2, and the titer of neutralizing antibodies against the spike protein was negative. The liver transplantation was performed with no significant complications. As immunosuppression therapy, the patient received 20 mg basiliximab (Novartis Farmacéutica S.A., Barcelona, Spain) and 500 mg methylprednisolone (Pfizer Manufacturing Belgium N.V, Puurs, Belgium) intraoperatively. Considering the risk of non-aerogene-related SARS-CoV-2 reactivation syndrome, the patient received remdesivir 200 mg (Gilead Sciences Ireland UC, Carrigtohill County Cork, Ireland) in the neo-hepatic stage, which was continued with 100 mg/day for 5 days. The postoperative immunosuppression therapy consisted of tacrolimus (Astellas Ireland Co., Ltd., Killorglin, County Kerry, Ireland) and mycophenolate mofetil (Roche România S.R.L, Bucharest, Romania) according to the local protocol. Despite the persistent negative PCR results for SARS-CoV-2 in the upper airway tract, the blood titer of neutralizing antibodies turned out positive on postoperative day 7. The patient had a favorable outcome, and she was discharged from the ICU facility seven days later. (3) Conclusions: We illustrated a case of liver transplantation of a SARS-CoV-2 negative recipient, whose donor was SARS-CoV-2 positive, performed in a tertiary, university-affiliated national center of liver surgery, with a good outcome, in order to raise the medical community awareness on the acceptance limits in the case of COVID-19 incompatibility for non-lung solid organs transplantation procedures.

Functions of double-negative B cells in autoimmune diseases, infections, and cancers.

Most mature B cells can be divided into four subtypes based on the expression of the surface markers IgD and CD27: IgD+ CD27- naïve B cells, IgD+ CD27+ unswitched memory B cells, IgD- CD27+ switched memory B cells, and IgD- CD27- double-negative (DN) B cells. Despite their small population size in normal peripheral blood, DN B cells play integral roles in various diseases. For example, they generate autoimmunity in autoimmune conditions, while these cells may generate both autoimmune and antipathogenic responses in COVID-19, or act in a purely antipathogenic capacity in malaria. Recently, DN B cells have been identified in nasopharyngeal carcinoma and non-small-cell lung cancers, where they may play an immunosuppressive role. The distinct functions that DN B cells play in different diseases suggest that they are a heterogeneous B-cell population. Therefore, further study of the mechanisms underlying the involvement of DN B cells in these diseases is essential for understanding their pathogenesis and the development of therapeutic strategies. Further research is thus warranted to characterize the DN B-cell population in detail.

Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study.

Background: Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs. Methods: We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4-10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway. Findings: The study included 3607 KTRs (59 [48-70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3-4] vaccines (range 2-6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31-57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference. Interpretation: Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic. Funding: CEPI and internal funds.

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines.

Background: Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs' compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. Results: The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3-3]) and seven months (2.4 [1.7-2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3-3]) and seven months (2.4 [1.9-2.6]) after vaccination (p<0.01). Conclusion: KTRs' humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India.

Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

Development and validation of multivariable prediction models of serological response to SARS-CoV-2 vaccination in kidney transplant recipients.

Repeated vaccination against SARS-CoV-2 increases serological response in kidney transplant recipients (KTR) with high interindividual variability. No decision support tool exists to predict SARS-CoV-2 vaccination response to third or fourth vaccination in KTR. We developed, internally and externally validated five different multivariable prediction models of serological response after the third and fourth vaccine dose against SARS-CoV-2 in previously seronegative, COVID-19-naïve KTR. Using 20 candidate predictor variables, we applied statistical and machine learning approaches including logistic regression (LR), least absolute shrinkage and selection operator (LASSO)-regularized LR, random forest, and gradient boosted regression trees. For development and internal validation, data from 590 vaccinations were used. External validation was performed in four independent, international validation cohorts comprising 191, 184, 254, and 323 vaccinations, respectively. LASSO-regularized LR performed on the whole development dataset yielded a 20- and 10-variable model, respectively. External validation showed AUC-ROC of 0.840, 0.741, 0.816, and 0.783 for the sparser 10-variable model, yielding an overall performance 0.812. A 10-variable LASSO-regularized LR model predicts vaccination response in KTR with good overall accuracy. Implemented as an online tool, it can guide decisions whether to modulate immunosuppressive therapy before additional active vaccination, or to perform passive immunization to improve protection against COVID-19 in previously seronegative, COVID-19-naïve KTR.

Outcome of lung transplant recipients infected with SARS-CoV-2/Omicron/B.1.1.529: a Nationwide German study.

PURPOSE: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is currently the major threat for immunocompromised individuals. The course of COVID-19 in lung transplant recipients in the Omicron era remains unknown. The aim of the study was to assess outcome and associated factors in lung transplant recipients in a German-wide multicenter approach. METHODS: All affected individuals from January 1st to March 20th, 2022 from 8 German centers during the Omicron wave were collected. Baseline characteristics and antiviral measures were associated with outcome. RESULTS: Of 218 patients with PCR-proven SARS-CoV-2 infection 166 patients (76%) received any early (< 7 days) antiviral therapy median 2 (interquartile range 1-4) days after symptom onset. Most patients received sotrovimab (57%), followed by remdesivir (21%) and molnupiravir (21%). An early combination therapy was applied in 45 patients (21%). Thirty-four patients (16%) developed a severe or critical disease severity according to the WHO scale. In total, 14 patients (6.4%) died subsequently associated with COVID-19. Neither vaccination and antibody status, nor applied treatments were associated with outcome. Only age and glomerular filtration rate < 30 ml/min/1.73m2 were independent risk factors for a severe or critical COVID-19. CONCLUSION: COVID-19 due to Omicron remains an important threat for lung transplant recipients. In particular, elderly patients and patients with impaired kidney function are at risk for worse outcome. Prophylaxis and therapy in highly immunocompromised individuals need further improvement.