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Immunosuppressive drugs are used for treating coronavirus disease 2019COVID-19pneumonia. This study examined the current status of screening and monitoring patients with COVID-19 pneumonia treated with immunosuppressive agents for hepatitis B virusHBVreactivation. Of 123 patients whose hepatitis B surface antigen level was measured, 2 were HBsAg-positive. Antihepatitis B core/surface antibodies were measured in all 121 HBsAg-negative patients. HBV DNA was measured in 31 of 32 patients who were positive for either or both antihepatitis B core/surface antibodies. Of 34 patients requiring regular monitoring, only 4 were monitored. The HBV monitoring rate at the initiation of COVID-19 treatment was high. How-ever, HBV monitoring after COVID-19 treatment was difficult because most patients were transferred to other hospitals or had their treatment terminated.Copyright © 2022 Takeshi Matsui et al.
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Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.Copyright © 2022 The Japan Society of Hepatology.
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Whipple disease is a rare multisystem inflammatory disease. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. We are reporting a case of a 46-year-old man who presented with fever, weight loss, and polyarthralgia for 2 months, and 1 month of diarrhea. The patient was thoroughly investigated for collagen diseases and COVID-19, with no definite diagnosis. A therapeutic trial by immunosuppressive drugs provided partial remission followed by a marked rebound of the symptoms. His occult blood in stool was positive and subsequent upper endoscopy with proximal small intestinal biopsies showed the pathological features of Whipple's disease. The patient showed a dramatic improvement following treatment with ceftriaxone and trimethoprim-sulfamethoxazole. Despite the rarity of Whipple's disease, its course mimics many rheumatological diseases, inflammatory bowel disease, and COVID-19 disease. It should always be a part of the differential diagnosis of obscure polyarthralgia and chronic diarrhea.Copyright © 2023 The Author(s).
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Introduction: During the Covid-19 pandemic, 540,895 people were identified as immunosuppressed and believed to be at increased risk of severe disease.1 As the pandemic evolved, biologic immunosuppression became a treatment of severe Covid-19.2 The true impact of immunosuppression on disease severity remains unclear. Objective(s): 1. Identify the incidence of immunosuppressed patients admitted to the ICU. 2. Analyse the mortality of those who are immunocompetent and immunosuppressed. 3. Examine the differences in mortality and level of care required between sub groups of patients on immunosuppression;those on biologics, non-biologics, and a combination of both. Method(s): A retrospective search of all Covid-19 positive admissions from March 2020 to November 2021 across two adult ICUs at Chelsea & Westminster NHS Trust was performed, using the EPR system. We identified those on immunosuppressive drugs, the level of care they required, and 28 day mortality. We categorised different types of immunosuppression, vaccination status, if applicable and co-morbidities. The exclusion criteria were primarily those with false positive swabs or incomplete data. Result(s): Baseline characteristics were median age (56 vs 56), and APCHE II score (20.08 in the immunosuppressed group vs 14.0 in immunocompetent). Thirteen immunosuppressed patients were identified. Reasons for drug immunosuppression in this group included solid organ transplant (6/13), and autoimmune conditions (7/13). Two patients were on biologic drugs alone, 8 were on non-biologics, and 3 were on a combination. Four of this group had received at least 2 doses of a Covid-19 vaccine. Mortality was 61.54% (8/13) in the immunosuppressed group vs 36.65% (199/543) in the immunocompetent group. Conclusion(s): Despite similar demographics, patients on immunosuppression had a significantly higher mortality than the immunocompetent group. Interestingly, those on targeted biological immunosuppression had the lowest incidence of requiring level 3 care, and no deaths. It is a possibility that biologics dampen the hyper-inflammation seen in severe Covid-19 pneumonitis, raising the question of a possible protective benefit from severe disease. This reflects the findings of the REMAP-CAP investigators,3 who showed that the IL-6 inhibiting biologics Tocilizumab and Sarilumab are efficacious against the most severe disease following admission to ICU with Covid-19 pneumonitis. The single centre and retrospective observational design, combined with small numbers on immunosuppression, despite a large inclusion criterion, mean it is not possible to make statistical conclusions. Confounding factors include the effects of vaccination, shielding and the change in SARS-CoV-2 variant prevalent during different times during the pandemic.
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Background and Aim: Immunosuppressive agents (e.g., baricitinib [BAR], tricizumab [TCZ]) and steroids are used for treating coronavirus disease 2019 (COVID-19) pneumonia. These immunosuppressive agents are known to cause HBV reactivation. The current guidelines recommend HBV screening and HBV reactivation monitoring in Japan. However, the status of compliance among treated patients with COVID-19 pneumonia remains unclear. Herein, we report the status of compliance with the current guidelines on HBV reactivation. Method(s): We investigated the implementation of HBV screening and HBV reactivation monitoring for patients who received immunosuppressive agents in our hospital from April 2021 up to June 2021. Background factors related to the presence or absence of screening were analyzed. Result(s): There were 123 patients who received immunosuppressive agents in our hospital from April 2021 up to June 2021. The patients median age was 63 years old (31-95 years), and 90 patients were men. BAR/steroid therapy was given in 115 patients and TCZ/steroid therapy in 8 patients. Of the 123 patients in whom HBs antigen level was measured, 2 patients were positive for HBs antigen. Anti-HBc/ HBs antibodies were measured in all 121 HBsAg-negative patients according to the guidelines. Of 32 patients who were positive for either or both anti-HBc/HBs antibodies, HBV DNA was measured in 31 patients. Of 34 patients who required regular reactivation monitoring, 30 did not receive regular monitoring (6 died in the hospital, 11 were transferred to other hospitals, and 13 were terminated of their treatment early in the outpatient department of the hospital). Only 4 patients were monitored according to the guidelines. Of the 4 patients monitored, 1 was positive for HBs antigen and was given a nucleic acid analogue. In 1 patient, HBV DNA increased from signal-positive to 1.4 LIU/mL and then to 1.7 LIU/mL and nucleic acid analogue was started. The remaining 2 patients had undetectable HBV DNA or remained signal-positive. Conclusion(s): The HBV reactivation monitoring rate at the start of COVID-19 pneumonia treatment was high. However, HBV reactivation monitoring after the COVID-19 pneumonia treatment was difficult because most patients were transferred to other hospitals or had their treatment terminated.
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There is a description of two clinical cases of a new coronavirus infection COVID-19 in patients with a history of heart transplantation. Patients who receive immunosuppressants for life are at risk of developing infectious diseases. This requires the vigilance of doctors, especially in the face of a pandemic of a new coronavirus infection. Adequate and timely started therapy increases the effectiveness of treatment and reduces the risk of complications. The complex participation of different specialists is necessary to determine the tactics of treatment, correct pathogenetic and suppressive therapy.Copyright © 2021 Sovero Press Publishing House. All rights reserved.
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Objectives: Patients with systemic lupus erythematosus (SLE) present greater severity of SARS-CoV-2 infection compared to the general population, particularly those with glomerulonephritis and who are treated with glucocorticoids. Likewise, high disease activity and some immunosuppressants have been associated with worse outcomes. The aim of this study was to describe the characteristics of SARS-CoV-2 infection in patients with SLE in Argentina from the SAR-COVID registry and to establish factors associated with a worse outcome. Method(s): Observational study. Patients diagnosed with SLE with confirmed SARS-CoV-2 infection (RT-PCR and/or positive serology) from the SAR-COVID registry were included. Data were collected from August 2020 to March 2022. The outcome of the infection was measured using the World Health Organization-ordinal scale (WHO-OS). Severe COVID-19 was defined as an WHO-OS value >=5. Descriptive analysis, Student's t , Mann Whitney U, ANOVA, Chi2 and Fisher's tests. Multivariable logistic regression. Result(s): A total of 399 patients were included, 93%female, with a mean age of 40.9 years (SD 12.2), 39.6% had at least one comorbidity. At the time of infection, 54.9% were receiving glucocorticoids, 30.8% immunosuppressants, and 3.3% biological agents. SARS-CoV-2 infection was mild in most cases, while 4.6% had a severe course and/or died. The latter had comorbidities, used glucocorticoids, and had antiphospholipid syndrome (APS) more frequently and higher disease activity at the time of infection. In the multivariate analysis, high blood pressure (OR 5.1, 95% CI 1.8-15.0), the diagnosis of APS (4.7, 95% CI 1.2-15.8), and the use of glucocorticoids (10 mg/day or more: OR 5.5, 95% CI 1.6-20.5) were associated with severe hospitalization and/or death from COVID-19 (WHO-EO >= 5). Conclusion(s): In this cohort of SLE patients with confirmed SARS-CoV-2 infection, most had a symptomatic course, 22.1% were hospitalized, and 5% required mechanical ventilation. Mortality was close to 3%. The diagnosis of APS, having high blood pressure, and the use of glucocorticoids were significantly associated with severe COVID-19.
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Introduction: Preventive care guidelines for patients with Inflammatory Bowel Disease (IBD) emphasize the need for a patient-centered interdisciplinary approach, with assessment and management of the patient's physical and mental health as well as the IBD. There is no data about compliance with current IBD preventive care guidelines in Puerto Rico. This study aims to evaluate current IBD preventive care in the clinic, and knowledge among patients and gastroenterologists about the preventive care guidelines. The 3-phase study includes retrospective medical record review, an anonymous online survey of gastroenterologists, and an anonymous survey of patients. We report the results of the patient survey. Method(s): Adult patients with an established diagnosis of at least 6 months of ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis (IC), were recruited from the IBD Clinics and through IBDrelated social media. Questionnaires were filled in the clinic and online using Google forms. Statistical analysis was performed using descriptive statistics. Comparisons of proportions and means between groups was based on Fisher's exact and chi square tests. The study was approved by the MSC IRB. Result(s): 83 patients completed the survey, 42 from the clinics and 41 through social media. 60% had CD, 47.4% were diagnosed more than 10 years ago, 57.9% were younger than 38 years old and 68% were on immunosuppressants/biologics. 83.13% and 60.24% of patients knew that COVID and Influenza vaccines were indicated, respectively. However only 42.17%, 36.14%, 32.53% and 31.33% of patients knew about indications for HPV, pneumococcal, varicella and zoster vaccines, respectively. There was a significant difference about knowledge regarding screening for latent TB (p=0.019), anxiety and depression (p= 0.03) and smoking status (p=0.033) between CD and UC/IC patients, as shown in Table. Conclusion(s): Our study showed a significant lack of knowledge about IBD preventive care in patients. Strategies to improve patient education are needed. The results of the review of records from the clinic as well as the knowledge of gastroenterologists will point out other deficiencies in the healthcare system and help design methods to improve patient care. Another aspect that needs to be explored is access to preventive measures such as vaccines. (Table Presented).
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Patient suffering from autoimmune diseases (AID) typically have an increased risk of infection, which is attributed to the disease itself, but also to immunosuppressive drugs (IS) and comorbidities. During the current COVID-19 outbreak, the way to manage these diseases remains elusive. Limited data is currently available on AID and IS in the context of this new coronavirus infection. To date, there is no evidence to support an increase in complications of COVID-19 in these patients. In addition, certain drugs that are commonly used to treat AID could be part of the therapeutic arsenal used in COVID-19. The purpose of this article is to review the unique aspects of patients with AID during the COVID-19 outbreak.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.
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Background/Aims Advances in rational drug design and recent clinical trials are leading to emergence of a range of novel therapies for SLE and therapeutic options in clinical practice are expected to broaden rapidly. The optimal real-world place of emerging and established agents will be guided by understanding their differential efficacy on specific SLE manifestations as well as efficacy for more resistant disease. Anifrolumab, a type-I interferon receptor blocking monoclonal antibody, showed efficacy in SLE in phase III trials with a notable effect on mucocutaneous disease although specific lesion subtypes and chroncicity were not explored. Severe refractory mucocutaneous SLE such as scarring discoid lesions are an important and common clinical challenge in current practice. We therefore prospectively evaluated the real-world efficacy and quality of life impact of anifolumab for active mucocutaneous SLE, recalcitrant to multiple biologic and immunosuppressant therapies. Methods Seven patients commenced anifrolumab (300mg by monthly iv infusion) following application to the manufacturer's early access programme (NCT 04750057). Prior biologic therapies were discontinued at least 5 half-lives in advance. Mucocutaneous disease activity was captured by Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score and medical photography. Patient reported health-related quality of life comprising the Dermatology Life Quality Index (DLQI);Lupus-QoL and EQ5D-5L were evaluated at baseline, three and six months. Results Seven female patients with active mucocutaneous SLE (Discoid LE n=5, chilblain LE n=1, subacute cutaneous LE n=1) and median disease duration of 17 years were evaluated. Median baseline CLASI activity score was 17 (range 10-26;higher scores indicating severe disease). Median number of previously failed therapies was 7 and included rituximab in 6/7, belimumab in 2/7 and thalidomide in 4/7. Rapid resolution of scale and erythema in DLE was established within 1 month of anifrolumab treatment. Improvements to chilblain lupus were evident by three months. CLASI activity score was improved >=75% in all patients at 3 months. Clinical responses were associated with significant improvements in DLQI (p<0.001) and EQ5D-VAS (p=0.002) by three months. Lupus-QoL trended toward improvement across all domains but most strongly for fatigue (p=0.01) and pain (p=0.002) by 6 months. One patient discontinued treatment after 4 months due to polydermatomal shingles complicated by sensorineural hearing loss. Infection coincided with background prednisolone dose >15mg daily, recent COVID-19 infection and new on-treatment hypogammaglobulinaemia (IgG <5g/L). Prolonged aciclovir treatment was required for lesion resolution. Conclusion We report rapid real-world efficacy and quality of life impact of anifrolumab on highly refractory mucocutaneous SLE, which exceeded that anticipated from existing clinical trial data. Findings suggest a unique role for emerging interferon targeting therapies in management of mucocutaneous SLE but emphasize need for enhanced VZV precautions among higher risk patients.
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Background/Aims The immune response to SARS-CoV-2 is known to be reduced in the immunocompromised. However, extent to which immunity is affected by immunosuppression in specific disease cohorts remains poorly characterised. Furthermore, implications of the ongoing vaccination booster programme require further study. Individuals with lupus nephritis (LN) require prolonged high-dose immunosuppression in order to maintain disease control, rendering them important to study in this context. We evaluated SARS-CoV-2 nucleocapsid and spike antibody response in this cohort during the Spring/Summer 2022 booster vaccine campaign. Nucleocapsid antibody indicates previous infection whilst spike antibody indicates previous infection and/or vaccination response. Titre of spike antibody to prevent infection is not known, but presence of antibodies is likely to protect against severe disease. Methods SARS-CoV-2 spike and nucleocapsid antibody were measured in adult patients with LN attending a tertiary centre rheumatology clinic. Data was collected retrospectively on disease, immunosuppression, vaccine status and history of natural exposure. Results 35 cases of LN were investigated, of which LN III, IV and V were predominant biopsy diagnoses. Regarding immunosuppressants, the Eurolupus Cyclophosphamide protocol had been used in the majority of patients to achieve initial control, with 3/35 patients still receiving pulsed courses at data collection. 18/35 were on Mycophenolate Mofetil;a further 13/35 had previously received this. 31/35 took at least 5mg Prednisolone daily;25/35 took Hydroxychloroquine;7/35 took Azathioprine;7/35 had previously been on Methotrexate, 3/35 took Tacrolimus;1/35 took Ciclosporin. Regarding B-cell depleting monoclonal antibody therapy, 13/35 had received Rituximab and 8/35 were receiving Belimumab. Antibody levels were measured between 4 weeks and 13 months after last dose of vaccination;mean duration was 6 months. 11/35 had confirmed COVID-19 infection;a further 8/35 reported a possible history. Of the 35, 32 (91%) had mounted detectable SARS-CoV-2 spike antibody above the bottom 10% of assay detection, indicating some immunity to vaccination or natural exposure. 20 (57%) had detectable nucleocapsid antibody, suggesting natural infection with antibody response. Only 2 (6%) had not mounted any antibody response. Of note, neither were fully vaccinated: one had 1 vaccination with blood test 8 months subsequent;one had 2 vaccinations with blood test 7 months subsequent. The latter was also notably on haemodialysis. All who received 3+ vaccinations had detectable spike antibody responses, as well as 75% of those who had received 2 vaccinations. Conclusion Our study is the first analysis, to our knowledge, of SARS-CoV-2 antibody response in a LN cohort. Whilst neutralising capacity and level of antibody providing protection remains under research, these findings provide at least some reassurance that individuals with LN on immunosuppression are capable of mounting an immune response against SARS-CoV-2. Further work is required to establish extent and duration of protection with serial vaccinations in this cohort.
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Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).
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Background/Aims Immunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination, and are at a high risk of SARSPOSTERS CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a combination of two monoclonal antibodies which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. Tixagevimab/Cilgavimab has been approved as COVID-19 prophylaxis for immunocompromised individuals, and is being used in over 32 different countries. The phase III PROVENT clinical trial found that high-risk participants prophylactically administered Tixagevimab/Cilgavimab had a significantly reduced risk of COVID- 19 infection after three and six months compared to controls. However, the PROVENT trial was conducted prior to the SARS-CoV- 2 Omicron wave, and did not include participants who had been previously vaccinated or infected. This systematic review provides an updated summary of the real-world clinical evidence of the efficacy of Tixagevimab/Cilgavimab for immunocompromised patients. The review reports breakthrough COVID-19 infections as its primary outcome. COVID-19-related hospitalisations, ITU admissions and mortality were included as secondary outcomes. Methods Two independent reviewers conducted electronic searches of PubMed and Medxriv, on 03/08/22 and 01/10/22. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. Odds ratios and 95% confidence intervals (CI) between intervention and control groups were also calculated. The GRADE tool was used to assess the level of certainty for the primary outcome. Results 17 clinical studies were included in the review, with a total of 24,773 immunocompromised participants from across the world, of whom 10,775 received Tixagevimab/Cilgavimab. One randomised controlled trial, ten retrospective cohort studies (two of which were preprints) and six prospective cohort studies (one preprint) were included. The majority of studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Reasons for participant immunocompromise included rheumatology patients treated with immunosuppressant drugs, transplant recipients and those with malignancies. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID- 19 breakthrough infection was 40.47% (CI 29.82-49.67;p<0.0001), COVID-19 hospitalisation- 69.23% (CI: 50.78-81.64;p<0.00001), ITU admission- 87.89% (CI: 47.12-98.66;p=0.0008), all-cause mortality- 81.29% (66.93-90.28;p<0.0001 and COVID-19-specifc mortality- 86.36% (CI:-6.21-99.70;p=0.0351). Conclusion There is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised groups, notably demonstrating effectiveness during the Omicron wave. This systematic review demonstrates the significant clinical effectiveness of prophylactic Tixagevimb/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is critically important that largerscale and better-controlled studies are performed to highlight the significant clinical benefit of prophylactic antibody treatment in immunocompromised groups.
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Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine's immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naive patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and diseasematched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p=0.04) and cellular immune responses (59% vs 100%, p=0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine's immunogenicity.
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Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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Introduction: In this study, we share the results of immunosuppressed patients who suffered from acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonia managed in our ICU. Method(s): We tracked all patients admitted to ICU of a Tertiary Hospital diagnosed with severe SARS-COV2 pneumonia from March 1, 2020 to January 31, 2022. The definition of Immunocompromised patient is based on history of transplantation, active neoplasia, autoimmune diseases or HIV. Collected data includes: sex, age, type of immunosuppression, vaccination, mechanical ventilation, ECMO VV, incidence of superinfections and mortality. Result(s): From a cohort of 425 patients, 55 met the inclusion criteria. 33% were women and 67% male. The average age was 58 years for women and 62 years for men. Out of these patients, 27% had solid organ transplants. 40% suffered from neoplasic disease. 27% had autoimmune diseases and were under treatment with immunosuppressants. 3 had HIV. Only the 29% had received at least 1 dose of COVID 19 vaccine. 80% required orotracheal intubation. 3.64% (2) required Veno-Venous ECMO. 61% presented bacterial superinfection, with the most frequent germs being Pseudomonas aeruginosa and Enterococcus. 36% had viral superinfection, being cytomegalovirus the most frequent one. 32% had fungal superinfection, mainly by Aspergillus fumigatus. 27% did not suffer any superinfection. 40% of the total sample died. After logistic regression, in our model (AUC 83,4% (Se 57.1%, Sp 87.9%), we identified need of intubation as independent variable of mortality (OR 27,06 IC95% 1.76-415.55, p = 0.018). Conclusion(s): Immunocompromised patients with ARDS secondary to COVID-19 pneumonia present high mortality, with statistically significant difference when mechanical ventilation is needed. The most frequently isolated germs causing superinfection in this group of patients are bacterias. We believe that this group of patients require special care in our ICU units and an in-depth analysis and study to optimize their prognosis.
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Introduction: Anemia of inflammation is considered to be a main cause of anemia on the ICU. Inflammatory cytokines, most importantly IL-6, play a role in this pathogenesis. Given that both anemia and red blood cell (RBC) transfusions are associated with adverse outcomes, and iron is ineffective, novel treatments of anemia are wanted. The aim of this study is to investigate the effect of immunosuppressive agents on anemia development and RBC transfusions in critically ill COVID patients. Method(s): This retrospective cohort study included all ICU patients of two hospitals in the Netherlands between February 2020 and April 2022 with a PCR-positive COVID-19 ARDS. Actively bleeding patients were excluded. Evolving insights in the treatment protocol resulted in three treatment groups: no treatment, steroids or combination of steroids with tocilizumab. Daily lab results and number of RBC transfusion were retrieved and the decline in Hb level between ICU admission day 1 and 7 was calculated. A multiple linear regression analysis was used to compare outcomes. Result(s): In total, 719 patients were included, of which 168 in the no-treatment group, 337 in the steroid group and 212 in the steroids and tocilizumab group. Hb levels declined in all groups. The median decline in Hb level in the combination group was lowest, with -0.3 mmol/l [-0.9 to 0.2], -0.8 mmol/l [-1.3 to -0.1] in the group receiving steroids in the steroid group and [-1.6 to -0.5] in the no treatment group. The number of RBC transfusions was 1 [1-3] in the group receiving combination therapy, 3[1-6] in the group receiving steroids and 3[2-8] in the group receiving no treatment (p < 0.002). In a multivariate analysis, the receipt of combination therapy remained associated with inhibition of decline in Hb as well as with lowering the number of RBC transfusions. Conclusion(s): Treatment with either steroids or a combination of steroids and tocilizumab was associated with a slower decline in Hb levels during ICU stay and less RBC transfusions when compared to no treatment.
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Background: Nirmatrelvir/ritonavir (NMV/r), a preferred antiviral for high-risk outpatients with COVID-19, is associated with major drug-drug interactions (DDIs). Given the lack of DDI data with short course ritonavir (RTV), initial NMV/r product information was extrapolated from chronic, full dose RTV use. In Jan 2022, DDI experts from the University of Liverpool (UoL), NIH COVID-19 Guidelines Panel, and Ontario Science Table (OST) contributors established a global collaboration to address DDI challenges limiting NMV/r use in real-life settings. We report how safe, pragmatic, and consistent resources were developed to support NMV/r prescribing, and the utilization of these resources globally. Method(s): The 3 teams met monthly to discuss DDIs, review NMV/r DDI literature, and achieve consensus on recommendations. Additional experts were invited as needed. Metrics from the UoL DDI checker guided review of most searched DDIs overall and by severity. 2022 usage metrics for each DDI guide were collected. Differences in recommendations between initial DDI guides and product information were compared. Result(s): In 2022, 12 meetings were convened. Each team's DDI guide was revised and expanded (Table 1). To factor in the lower RTV dose and shorter treatment duration, some recommendations differed from product information. Drug categories that required the most discussion and revision included: anticoagulants (ACs), immunosuppressants, calcium channel blockers. NMV/r accounted for 85% of queries on the UoL site. NMV/r DDI guidance was the most viewed page of the NIH guidelines and among the OST ID/clinical care Science Briefs. Top searched drugs on the UoL site with serious DDIs were certain ACs and statins. Utilization of DDI guides was not limited to in-country resources: 51% and 7% of UoL queries came from the USA and Canada, respectively. NIH users followed links to the UoL and OST sites 161,478 and 37,619 times, respectively. Conclusion(s): Significant efforts have been made by the 3 teams to provide upto-date, complementary DDI guidance. Usage metrics confirm the demand for DDI guidance during the pandemic. Cross-utilization of the DDI guides confirms the need for consistency. DDI recommendations were more permissive than initial product information, expanding clinicians' ability to prescribe NMV/r. DDI guidance for ACs and immunosuppressants was particularly challenging. During drug development, complex interactions likely to be encountered in target populations should be addressed.
ABSTRACT
In rheumatology, the problem of infectious pathology is quite acute. This is primarily due to the participation of various infectious agents in the development of immuno-inflammatory rheumatic diseases (IIRD), in which microorganisms play a trigger role, triggering the immunopathological mechanisms of inflammation. Vivid examples of such diseases are acute rheumatic fever and reactive arthritis. The infectious etiology of Lyme disease has been proven. An equally difficult task is the fight against comorbid infection (CI), which often complicates the course of many IIRD due to a violation of the immune status caused by both the background disease and the use of immunosuppressive drugs. The predominance of respiratory tract lesions in the structure of CI in patients with IIRD makes it necessary to use influenza and pneumococcal vaccines in them, since the risk of deaths from these infections among these patients is quite high. During the development of the COVID-19 pandemic, which has become a challenge to all mankind, a large number of new fundamental and medical problems have been revealed concerning the relationship between viral infection and many widespread chronic non-communicable diseases, among which IIRDs occupy an important position. As one of the methods of combating the current COVID-19 pandemic, great hopes are pinned on the widespread use of vaccination. The possibility of using monoclonal antibodies for pre-exposure prophylaxis of COVID-19, including in patients with IIRD, is discussed.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
ABSTRACT
Background. Rituximab (RTX) is a chimeric monoclonal antibody that binds the CD20 molecule on the surface of B cells and leads to B cell depletion. RTX is recommended by the European League Against Rheumatism (EULAR) as off-label in patients affected by idiopathic inflammatory myopathies (IIM). The real-world experience has shown that hypogammaglobulinemia occurring early after anti-CD20 treatment can be multifactorial (active disease, effect of other drugs) and usually transient, with a minimal increase in the risk of infections. The present study aimed to analyse the differences in the rate of RTX-associated hypogammaglobulinemia in a cohort of IIM patients in clinical practice, as well as the onset of major infections and its correlation with hypogammaglobulinemia. Methods. Patients followed at Rheumatology Unit of Siena University Hospital from January 2020 to September 2021 were retrospectively enrolled. Inclusion criteria were as follows: fulfilment of disease-specific classification criteria 2017 EULAR criteria and /or Peter and Bohan criteria for dermatomyositis (DM) and polymyositis (PM), positivity of anti-synthetase antibody and typical clinical features for anti-synthetase syndrome (ASS) and the measurement of serum Ig levels at the time of RTX administration (maximum 2 weeks before) (T0) and 6 (T1) to 12 (T2) months later, consistently with previous studies. Ig serum levels, measured by standard nephelometry (normal ranges: IgG 700-1600 mg/dL, IgM 40-240 mg/dL, IgA 70-400 mg/dL) were assessed as part of routine clinical care. Hypogammaglobulinemia was defined as moderate (serum IgG <600 mg/dL) and severe (IgG <400 mg/dL), as previously reported. Results. Seven patients (mean+/-SD, 57.3+/-19.7 years;7 female) were enrolled. Three of them had diagnosis of DM, three ASS and one PM. Two patients showed MDA5-positivity, two JO1-positivity, one TIF1-gamma-positivity, one PL7-positivity and the other one PM/Scl-positivity. All patients had at least two organs involved, and 4 out of 7 (57%) suffered from interstitial lung disease. Before starting RTX treatment, three and four patients underwent at least one and two synthetic immunosuppressants. All patients underwent low dosage of corticosteroids, and four patients underwent concomitant synthetic immunosuppressants (2 hydroxychloroquine and 2 MTX). IgG concentrations were statically lower at T2 compared to those at baseline (p=0.0391). None of them showed severe hypogammaglobulinemia. Similarly, IgM concentration significantly decreased at T2 compared to those at baseline (p=0.0078). Two patients showed major infections and two patients had paucisymptomatic COVID-19 (one of them had twice). Corticosteroids dosages were inversely correlated with IgG T2 concentrations (p=0.040, r=-0.919). Conclusion. Hypogammaglobulinemia following RTX is uncommon in IIM and is more likely in patients with high glucocorticoids, immunosuppressants and CYC exposure. IgG monitoring at least 6 months after RTX treatment may be useful in stratifying patients to identify those who require closer monitoring. These results shine a spotlight for increased awareness of the role of immunoglobulin measurement before maintenance doses of RTX.