OBJECTIVES:

To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients.

METHODS:

In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort.

RESULTS:

Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040).

CONCLUSIONS:

MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.

INTRODUCTION:

The South-East Asian (SEA) region and India are highly susceptible to antibiotic resistance, which is caused due to lack of antimicrobial stewardship (AMS) knowledge, uncontrolled use of antibiotics, and poor infection control. Nonadherence to national/local guidelines, developed to combat antimicrobial resistance, is a major concern. A virtual advisory board was conducted to understand the current AMS standards and challenges in its implementation in these regions.

AREAS COVERED:

Procalcitonin (PCT)-guided antibiotic use was discussed in various clinical conditions across initiation, management, and discontinuation stages. Most experts strongly recommended using PCT-driven antibiotic therapy among patients with lower respiratory tract infections, sepsis, and COVID-19. However, additional research is required to understand the optimal use of PCT in patients with organ transplantation and cancer patients with febrile neutropenia. Implementation of the solutions discussed in this review can help improve PCT utilization in guiding AMS in these regions and reducing challenges.

EXPERT OPINION:

Experts strongly support the inclusion of PCT in AMS. They believe that PCT in combination with other clinical data to guide antibiotic therapy may result in more personalized and precise targeted antibiotic treatment. The future of PCT in antibiotic treatment is promising and may result in effective utilization of this biomarker.

BACKGROUND:

The sudden outbreak of severe acute hepatitis of unknown aetiology (SAHUA) in the first half of 2022 affected more than 1010 children in 35 countries worldwide. Dire clinical outcomes, such as acute liver failure necessitating transplantation, neurological symptoms, long-term sequelae, and death, highlight the need to determine the pathogenesis of this condition. Hypotheses on the aetiology include adenovirus and SARS-CoV-2 infections and an aberrant immune response to multiple pathogen exposure following lifting of lockdown measures but further investigation is required to reach an informed consensus.

METHODS:

A literature search was performed on MEDLINE and EMBASE in accordance with PRISMA guidelines for systematic reviews. Primary studies reporting data on severe acute hepatitis of unknown aetiology in children from the COVID-19 era were selected for inclusion in our review. Data on patient demographics, clinical presentation and outcomes, and diagnostic testing for coinfection were extracted. Meta-analysis used a random-effects model.

RESULTS:

The 33 included studies (30 case series and 3 case-control studies) described a total of 3636 cases of SAHUA (reported 1 January, 2019-31 December, 2022), with a median age of 3.5 years. Of these, 214 children (5.9%) received a liver transplant and 66 (1.8%) died. Whilst data on diagnostic testing was incomplete, the most frequently detected coinfections were with adenovirus and/or adeno-associated virus 2 (AAV2). Other common childhood respiratory and enteric pathogens, such as enterovirus, rhinovirus, and herpesviruses (EBV and HHV-6), were also identified.

CONCLUSION:

Coinfection with AAV2 and other common childhood pathogens may predispose children to develop this novel severe hepatitis. Altered susceptibility and response to such pathogens may be a consequence of immunological naivety following pandemic restrictions. Further investigations are needed to generate high-quality evidence on aetiology for different patient demographics and geographical areas.

BACKGROUND:

Despite widespread implementation of vaccination against coronavirus disease 2019 (COVID-19), solid organ transplant recipients (SOTRs) can remain particularly vulnerable to this disease. The present study was conducted to investigate the efficacy and safety of sotrovimab in the treatment of SOTRs with COVID-19.

METHODS:

A search was performed of PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar to gather relevant evidence through July 25, 2023. The quality of the included studies was assessed using the risk of bias tool. Comprehensive Meta-Analysis software (ver. 3.0, Biostat) was employed for data analysis.

RESULTS:

Ten studies, involving a total of 1,569 patients, were included. The meta-analysis revealed significant differences between the patients administered sotrovimab and those treated with the standard of care. These differences were observed in mortality rate (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.03-0.67), hospitalization rate (OR, 0.35; 95% CI, 0.21-0.57), intensive care unit (ICU) admission rate (OR, 0.16; 95% CI, 0.04-0.62), the need for supplemental oxygen therapy (OR, 0.22; 95% CI, 0.09-0.51), and the need for mechanical ventilation (OR, 0.09; 95% CI, 0.01-0.70). However, no significant difference was observed between sotrovimab and other treatments regarding the rates of hospitalization or ICU admission (P>0.05). Regarding safety, sotrovimab was associated with a lower rate of adverse events compared to the absence of sotrovimab (OR, 0.15; 95% CI, 0.02-0.86).

CONCLUSIONS:

These results suggest that sotrovimab may improve efficacy outcomes among SOTRs with COVID-19. Nevertheless, additional high-quality trials are necessary to confirm these findings.

Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse effects of additional different vaccinations in KTR patients in existing studies. Databases such as PubMed, Cochrane Library, Web of Science, Embase, ClinicalTrials.gov and others. Three high-quality RCT were included and showed no statistical difference in seroconversion rates between the two vaccines (RR = 0.93[0.76,1.13]). There was no statistical difference in seroconversion rates between the sexes, for men (RR = 0.93[0.69,1.25]) and women (RR = 0.91[0.62,1.33]). Among the adverse effects there was no statistically significant difference in fever (RR = 1.06[0.44,2.57]), while for injection site pain there was a statistically significant difference (RR = 1.14[1.18,1.84]). There was no significant difference in seroconversion rates in patients with KTR who received the two additional vaccines. Patients injected with the viral vector vaccine were less painful than those injected with the mRNA vaccine.

BACKGROUND AND AIMS:

As part of the COVID-19 control strategy, a growing number of vaccine portfolios evolved and got fast-tracked through regulatory agencies, with a limited examination of their efficacy and safety in vulnerable populations, such as patients with chronic conditions and immunocompromised states. Patients with chronic liver disease (CLD), and cohorts post liver transplant (LT) in particular, were underrepresented in the determinant trials of vaccine development, hence the paucity of data on their efficacy and safety in published literature. This systematic review aims to examine the available evidence and ascertain the effectiveness and safety of Covid-19 vaccination in patients with CLD and those with LT.

METHODS:

A systematic review of PubMed (Medline), Google Scholar, Cochrane Library, and ScienceDirect from inception until 1st March 2022 was conducted. We included observational studies and assessed vaccine efficacy regarding seroconversion or immunological rate, whereas serious or significant adverse effects have been considered safety outcomes when reported.

RESULTS:

Studies comprised 45275 patients, performed in 11 different countries. Seroconversion or immunological rate after Covid-19 vaccination was mostly the primary endpoint, whereas other endpoints like covid-19 related adverse effects were also reported. Twenty-four of the final analyzed studies are prospective cohort studies, while four are retrospective cohort studies. Twenty-one studies included patients who underwent LT and received the Covid vaccine; nine included patients who had CLD due to various etiologies. The median age range of all included patients varied from 43-69 years. All patients with LT who received at least two doses of Covid vaccine had a seroconversion rate of around 60%. Patients with CLD had a seroconversion rate of about 92% post two doses of Covid vaccination. The average seroconversion rate in post-transplant recipients was around 45% after two doses of the significant Covid vaccines: Pfizer, AstraZeneca, Moderna, and Jansen. Only two studies have reported a higher seroconversion rate of 75% and 73% after the third dose of Covid vaccine. No significant adverse effects were reported in all studies; the most commonly reported negative effect was local injection site pain.

CONCLUSION:

The present systematic review, comprising real-world observational data studies, concludes that Covid-19 vaccination was associated with 92% and 60% seroconversion rates in patients with CLD and LT, respectively. No significant side effects were reported in all studies. This finding helps to resolve the uncertainty associated with Covid-19 vaccination in this cohort of patients.

The systematic review and meta-analysis were conducted for COVID-19 infections in kidney transplant patients. Recent research on this topic was still scarce and limited meta-analysis research discussion, specific to some risks or treatment in kidney transplantation patients with COVID-19 infection. Therefore, this article demonstrated the fundamental steps to conducting systematic review and meta-analysis studies to derive a pooled estimate of predictor factors of worse outcomes in kidney transplant patients with positive for the SARS-CoV- 2 test•PICOT Framework to determine the research scope•PRISMA strategy for study selection•Forest Plot for meta-analysis study.

Purpose: Solid organ transplant recipients (SOTR) have a high risk for severe COVID-19 infection; hence it is necessary to find alternative treatment strategies to protect these patients from the complications caused by the severe progression of the disease. This study aimed to determine the effectiveness of sotrovimab among SOTR with COVID-19.Materials and methods: A systematic literature search was conducted with relevant keywords to find studies that reported clinical outcomes regarding sotrovimab administration in SOTR outpatients with confirmed COVID-19 infection, who had mild-to-moderate symptoms.Results: Of 796 records found by a systematic search, only 14 met the inclusion criteria for reporting in a systematic review and only 6 enrolled in a meta-analysis. This meta-analysis indicated that SOTR outpatients with mild to moderate COVID-19 who received sotrovimab had lower likelihood of all-cause hospitalization (OR: 0.29, CI: 0.16, 0.52, p < 0.001), ICU admission (OR: 0.17, CI: 0.05, 0.64, p = 0.009) and mortality (OR: 0.15, CI: 0.03, 0.64, p = 0.010) within 30 days of drug infusion compared to controls.Conclusions: Our findings confirm that monoclonal antibody therapy with sotrovimab in SOTR is associated with better outcomes and consequently a reduced risk of disease progression in this high-risk population.

BACKGROUND:

With new variants challenging the effectiveness of preventive measures, we are beginning to recognize the reality that COVID-19 will continue to pose an endemic threat. The manifestations of COVID-19 in lung transplant recipients during index admission are poorly understood with very few cases reported in recent lung transplant recipients. Optimal management of immunosuppression and antiviral therapy in recent transplant recipients is challenging.

METHODS:

We performed a retrospective analysis identifying lung transplant recipients at our institution who contracted COVID-19 in the immediate postoperative period (within index admission). In addition, we performed a systematic review from January 2020 to August 2023 identifying all publications on the PUBMED database regarding COVID-19 infection in lung transplant recipients during index admission.

RESULTS:

We report four cases of COVID-19 pneumonia in lung transplant recipients in the immediate postoperative period and we describe the clinical course, treatment options, and immunosuppression changes to manage this unique clinical problem. All patients made a full recovery and were eventually discharged home. Within our review of the literature, the most prevalent presenting symptoms were cough, dyspnea, and fatigue. Six (75%) patients decreased or held their antimetabolite. The two most common treatments were monoclonal antibodies (38%) and remdesivir (63%).

CONCLUSION:

Although previous literature demonstrates that COVID-19 can be deadly in recent lung transplant recipients, rapid treatment with anti-viral therapy/immunotherapy, deescalating immunosuppression, and treatment of respiratory decompensation with Decadron was effective in our patients.