Beyond prevention: Unveiling the benefits of triple vaccination on COVID-19 severity and resource utilization in solid organ transplant recipients.

OBJECTIVE: Despite the widespread reduction in COVID-19-related morbidity and mortality attributed to vaccination in the general population, vaccine efficacy in solid organ transplant recipients (SOTR) remains under-characterized. This study aimed to investigate clinically relevant outcomes on double and triple-vaccinated versus unvaccinated SOTR with COVID-19. STUDY DESIGN AND SETTING: A retrospective propensity score-matched cohort study was performed utilizing data from the US Collaborative Network Database within TriNetX (n = 117,905,631). We recruited vaccinated and unvaccinated (matched controls) SOTR with COVID-19 over two time periods to control for vaccine availability: December 2020 to October 2022 (bi-dose, double-dose vaccine effectiveness) and December 2020 to April 2023 (tri-dose, triple-dose vaccine effectiveness). A total of 42 factors associated with COVID-19 disease severity were controlled for including age, obesity, diabetes, and hypertension. We monitored 30-day outcomes including acute respiratory failure, intubation, and death following a diagnosis of COVID-19. RESULTS: Subjects were categorized into two cohorts based on the two time periods: bi-dose cohort (vaccinated, n = 462; unvaccinated, n = 20,998); tri-dose cohort (vaccinated, n = 517; unvaccinated, n = 23,061).Compared to unvaccinated SOTR, 30-day mortality was significantly lower for vaccinated subjects in both cohorts: tri-dose (2.0% vs 7.5%, HR = 0.22 [95% CI: 0.11, 0.46]); bi-dose (3.7% vs 8.2%, HR = 0.43 [95% CI: 0.24, 0.76]). Hospital admission rates were similar between bi-dose vaccinated and unvaccinated subjects (33.1% vs 28.6%, HR = 1.2 [95% CI: 0.95, 1.52]). In contrast, tri-dose vaccinated subjects had a significantly lower likelihood of hospital admission (29.4% vs 36.6%, HR = 0.74 [95% CI: 0.6, 0.91]). Intubation rates were significantly lower for triple-vaccinated- (2.3% vs 5.2%, p < 0.05), but not double-vaccinated subjects (3.0% vs 5.2%, p > 0.05). CONCLUSION: In solid organ transplant recipients with COVID-19, triple vaccination, but not double vaccination, against SARS-CoV-2 was associated with significantly less hospital resource utilization, decreased disease severity, and fewer short-term complications. These real-world data from extensively matched controls support the protective effects of COVID-19 vaccination with boosters in this vulnerable population.

Monoclonal antibodies as COVID-19 prophylaxis therapy in immunocompromised patient populations.

OBJECTIVES: The objective of this review was to examine the latest literature regarding the effectiveness of monoclonal antibodies as COVID-19 prophylaxis therapy for immunocompromised patient populations. METHODS: Literature review of published real-world and randomized control trials (RCTs) from 2020 to May 2023. RESULTS: COVID-19 is highly transmissible with potentially serious health outcomes, underscoring the need for effective prevention and treatment strategies. Vaccines are highly effective at preventing COVID-19 for the general population; however, efficacy is often impaired in immunocompromised patients given insufficient response to initial exposure and/or memory for secondary exposures. Some individuals may also have contraindications to vaccination. As such, additional protective measures are needed to bolster the immune response in these populations. Monoclonal antibodies have been effective at bolstering immune system responses to COVID-19 among immunocompromised patients; however, they are proving ineffective against the most recent Omicron strains (BA.4 and BA.5). CONCLUSION: Several studies have investigated the efficacy of monoclonal antibodies as pre- and post-prophylaxis for COVID-19. Historical evidence is promising; however, new variants of concern are proving challenging for currently available regimens.

Chinese expert consensus on diagnosis and treatment strategies for SARS-CoV-2 infection in immunocompromised populations(2023 edition-2) / 中国感染控制杂志

Since the end of 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has swept the world,bringing great harm to human society and significantly increasing the health burden.Due to stron-ger infectivity,faster transmission,and higher reinfection rate of the Omicron variant,it has now replaced the Delta variant as the main epidemic strain for both imported and local outbreaks in China.Chinese Diagnosis and treatment protocol for SARS-CoV-2 infection(10th trial version)emphasizes"strengthening the protection of key popula-tions,"which includes the increasing number of immunocompromised population.These people have a high inci-dence of severe diseases and a high fatality rate after infected with SARS-CoV-2,and belong to the high-risk popula-tions of severe or critical diseases.Moreover,due to underlying diseases,these people take immunosuppressants and other related drugs chronically.The interactions between anti-SARS-CoV-2 infection treatment drugs and origi-nal drugs are complicated,thus bring significant challenges to the treatment after the SARS-CoV-2 infection.Cur-rently,there is a lack of guidelines or consensus on the diagnosis and treatment of SARS-CoV-2 infection among im-munocompromised population.Therefore,the Guangzhou Institute of Respiratory Health and National Center for Respiratory Medicine organized experts from multiple disciplines(respiratory and critical care medicine,organ transplantation,rheumatology and immunology,hematology,infection,critical care medicine,etc.)in China.Af-ter multiple rounds of discussions,13 items of recommendations are made as the reference for peers based on evi-dence-based medical evidence,so as to provide a theoretical and practical reference for the diagnosis and treatment strategies of this population.

Diagnostic Value of Interferon-Gamma Release Assays for Tuberculosis in the Immunocompromised Population.

Interferon-gamma release assays (IGRAs) are widely used in the diagnosis of Mycobacterium tuberculosis (M. tuberculosis) infection by detecting interferon-γ released by previously sensitized T-cells in-vitro. Currently, there are two assays based on either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot (ELISPOT) technology, with several generations of products available. The diagnostic value of IGRAs in the immunocompromised population is significantly different from that in the immunocompetent population because their results are strongly affected by the host immune function. Both physiological and pathological factors can lead to an immunocompromised situation. We summarized the diagnostic value and clinical recommendations of IGRAs for different immunocompromised populations, including peoplewith physiological factors (pregnant and puerperal women, children, and older people), as well as people with pathological factors (solid organ transplantation recipients, combination with human immunodeficiency virus infection, diabetes mellitus, end-stage renal disease, end-stage liver disease, and chronic immune-mediated inflammatory diseases). Though the performance of IGRAs is not perfect and often requires a combination with other diagnostic strategies, it still has some value in the immunocompromised population. Hopefully, the newly developed IGRAs could better target this population.

Bacterial bloodstream infections and patterns of resistance in patients with haematological malignancies at a tertiary centre in Lebanon over 10 years.

OBJECTIVES: Bacterial bloodstream infections (BSIs) with resistant pathogens in patients with haematological malignancies are rising due to increased use of novel chemotherapeutic agents and prophylactic antibiotics. Our goal was to understand the epidemiology and resistance patterns of bacterial pathogens in patients with haematological malignancies to help tailor empirical antibiotics and to limit resistance. METHODS: This was a retrospective chart review looking at bacterial BSI episodes between 2007-2017 in patients previously diagnosed with haematological malignancy at a tertiary-care centre in Lebanon. RESULTS: Among 165 hospitalised patients with haematological malignancy and bacterial BSI over 10 years, Gram-negative bacteria (GNB) caused 65.0% of all episodes, with the most common pathogens being Escherichia coli (45.6%), 79.6% of which were ESBL-producers, Pseudomonas aeruginosa (7.5%) and Acinetobacter baumannii (4.0%). The majority of the organisms (61.0%) were multidrug-resistant (MDR), with ANC < 100 neutrophils/µL (OR = 0.12, 95% CI 0.03-0.54) identified as an independent marker for increased multidrug resistance. The risk factors associated with increased mortality included recent use of amikacin (p<0.001) and infections with organisms resistant to amikacin (p<0.001) or ciprofloxacin (p=0.04). Our results reflect a persistent pattern of Gram-negative predominance with E. coli remaining the most common isolated pathogen in bacterial BSIs in patients with haematological malignancies. The relative frequency of GNB to Gram-positive bacteria remains similar to our data from 2007. CONCLUSION: The persistent divergence between worldwide data and the results observed in our centre and the increasing rates of MDR pathogens emphasise the importance of tailoring empirical antimicrobial therapy according to the centre's epidemiology.

The COVID-19 Vaccination Hesitancy Among the People With Inflammatory Bowel Disease in China: A Questionnaire Study.

Objective: To explore the attitudes and views of patients with inflammatory bowel disease (IBD) on COVID-19 vaccination. Methods: An online interview questionnaire concerning the acceptance or hesitancy toward vaccination for COVID-19 was designed and 543 patients with IBD in China were invited to complete the structured self-administered anonymous questionnaire. Results: Of all the participants, 50.7% were indecisive about the vaccination and only 16.0% opted for it. Vaccination hesitancy was significantly associated with women and those without medical or biomedical backgrounds. The acceptance of COVID-19 vaccination was higher in participants with no history of immune-modifying therapies, especially in those without immunosuppressants. Participants who considered vaccination critically important to self-health or the health of others were more likely to choose immediately or later vaccination. Safety and potential adverse reactions, personal hypoimmunity, efficacy, and reliability of COVID-19 vaccines were the top three concerns of the participants that were independent of their willingness for vaccination. Conclusions: This study discloses the presence of hesitancy for COVID-19 vaccination in patients with IBD. Further studies are warranted to evaluate the efficacy and safety of COVID-19 vaccines in IBD individuals, with a specific focus on the impact of immune-modifying therapies. Health education and recommendation from authoritative sources may facilitate COVID-19 vaccination efforts.

Multiplex Real-Time Polymerase Chain Reaction on Sputum for the Diagnosis of Pneumocystis jirovecii Pneumonia in Children: A Retrospective Study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in immunocompromised children. Real-time polymerase chain reaction (PCR) is widely used for the diagnosis of PCP due to its good accuracy. However, the diagnostic performance of multiplex real-time PCR on sputum in children with PCP has never been explored. METHODS: Medical records of 63 consecutive pediatric patients were analyzed retrospectively, including 13 cases with PCP and 50 with non-PCP pneumonia. Pneumocystis jirovecii (P. jirovecii) and other co-pathogens detected by multiplex real-time PCR in sputum samples were summarized. Using clinical composite diagnosis as the reference standard, we further compared the diagnostic performance of multiplex real-time PCR to combined serological markers (1,3)-ß-D-glucan plus lactate dehydrogenase. Additionally, modifications of antimicrobial treatment for pediatric PCP patients after the report of multiplex real-time PCR results were reviewed. RESULTS: In children with PCP, nonproductive cough and shortness of breath were more common, lymphocyte count in peripheral blood was markedly lower, and serum levels of (1,3)-ß-D-glucan and lactate dehydrogenase were much higher than non-PCP group. Multiplex real-time PCR reached a sensitivity of 100% in diagnosing PCP, which was better than serum (1,3)-ß-D-glucan plus lactate dehydrogenase (76.9%). Its specificity (98.0%) significantly surpassed serum (1,3)-ß-D-glucan plus lactate dehydrogenase (84.4%). Furthermore, multiplex real-time PCR showed a good performance in identifying co-pathogens in sputum of pediatric PCP patients. Cytomegalovirus, Epstein-Barr virus and Streptococcus pneumoniae were the most common co-pathogens in these patients. Initial antimicrobial treatment was modified in 76.9% of children with PCP after the report of PCR results. CONCLUSION: Multiplex real-time PCR on sputum is a diagnostic tool with good performance for the identification of P. jirovecii as well as co-pathogens in children with PCP. Sputum may be an alternative to bronchoalveolar lavage fluid for PCR assay in children when bronchoscopic examination is not feasible.

Trends in Hospitalizations Related to Invasive Aspergillosis and Mucormycosis in the United States, 2000-2013.

BACKGROUND: Invasive aspergillosis (IA) and mucormycosis contribute to substantial mortality, especially among immunocompromised persons, including those with hematopoietic stem cell transplant (HSCT), hematologic malignancy (HM), and solid organ transplant (SOT). METHODS: Using International Classification of Diseases, Ninth Revision codes available in the National Inpatient Sample, a hospital discharge database, we estimated IA-related hospitalizations (IA-RH), mucormycosis-RH (M-RH), HSCT-RH, HM-RH, and SOT-RH during 2000-2013. United States census data were used to calculate overall M-RH and IA-RH rates and present trends; estimated annual numbers of HSCT-RH, HM-RH, and SOT-RH served as denominators to calculate M-RH and IA-RH rates occurring with these conditions. Weighted least-squares technique was used to test for linear trends and calculate average annual percentage change (APC). RESULTS: There were an estimated 169 110 IA-RH and 9966 M-RH during 2000-2013. Overall, IA-RH and M-RH rates per million persons rose from 32.8 to 46.0 (APC = +2.9; P < .001) and 1.7 to 3.4 (APC = +5.2%; P < .001), respectively, from 2000 to 2013. Among HSCT-RH, there was no significant change in M-RH rate, but a significant decline occurred in IA-RH rate (APC = -4.6%; P = .004). Among HM-RH, the rate of M-RH increased (APC = +7.0%; P < .001), but the IA-RH rate did not change significantly (APC = +1.2%; P = .073). Among SOT-RH, M-RH (APC = +6.3%; P = .038) and IA-RH rates (APC = +4.1%; P < .001) both increased. CONCLUSIONS: Overall IA-RH and M-RH rates increased during 2000-2013, with a doubling of M-RH. Mucormycosis-related hospitalization occurring in conjunction with certain comorbidities increased, whereas IA-RH rates among patients with the comorbidities, decreased, remained stable, or increased to a lesser extent than M-RH.