Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose.

Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBDNEG; n = 42 anti-RBDLO), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8+%, and SARS-CoV-2-reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBDNEG remained seronegative; 5% KTRs developed BA.5 neutralization (vs 68% HCs, P < .001). Day 30 spike-specific CD8+% was negative in 91% KTRs (vs 20% HCs; P = .07), without correlation to anti-RBD (rs = 0.17). Day 30 SARS-CoV-2-reactive TCR repertoires were detected in 52% KTRs vs 74% HCs (P = .11). Spike-specific CD4+ TCR expansion was similar between KTRs and HCs, yet KTR CD8+ TCR depth was 7.6-fold lower (P = .001). Global negative response was seen in 7% KTRs, associated with high-dose MMF (P = .037); 44% showed global positive response. Of the KTRs, 16% experienced breakthrough infections, with 2 hospitalizations; prebreakthrough variant neutralization was poor. Absent neutralizing and CD8+ responses in KTRs indicate vulnerability to COVID-19 despite 3-dose mRNA vaccination. Lack of neutralization despite CD4+ expansion suggests B cell dysfunction and/or ineffective T cell help. Development of more effective KTR vaccine strategies is critical. (NCT04969263).

Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year.

BACKGROUND: Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction (CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not been investigated. METHODS: We performed a single center retrospective study including LTRs diagnosed with 5 different respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical outcomes in 1 year. The risk factors of IFIs were evaluated by logistic regression. The impact of IFIs on CLAD stage progression/death was examined by Cox regression. RESULTS: A total of 202 RVI episodes (50 influenza, 31 severe acute respiratory syndrome coronavirus-2, 30 metapneumovirus, 44 parainfluenza, and 47 respiratory syncytial virus) in 132 patients was included for analysis. Thirty-one episodes (15%) were associated with secondary IFIs, and 27 occurred in LTRs with lower respiratory tract infection (LRTI; 28% from 96 LRTI episodes). Aspergillosis was the most common IFI (80%). LTRs with IFIs had higher disease severity during RVI episodes. In multivariable analysis, RVI with LTRI was associated with IFI (adjusted odds ratio [95% confidence interval (CI)] of 7.85 (2.48-24.9). Secondary IFIs were associated with CLAD stage progression/death after accounting for LRTI, pre-existing CLAD, intensive care unit admission, secondary bacterial pneumonia and underlying lung diseases pre-transplant with adjusted hazard ratio (95%CI) of 2.45 (1.29-4.64). CONCLUSIONS: This cohort demonstrated 15% secondary IFI prevalence in LTRs with RVIs. Importantly, secondary IFIs were associated with CLAD stage progression/death, underscoring the importance of screening for fungal infections in this setting.

Smart Mushroom-Inspired Imprintable and Lightly Detachable (MILD) Microneedle Patterns for Effective COVID-19 Vaccination and Decentralized Information Storage.

The key to controlling the spread of the coronavirus disease 2019 (COVID-19) and reducing mortality is highly dependent on the safe and effective use of vaccines for the general population. Current COVID-19 vaccination practices (intramuscular injection of solution-based vaccines) are limited by heavy reliance on medical professionals, poor compliance, and laborious vaccination recording procedures, resulting in a waste of health resources and low vaccination coverage, etc. In this study, we developed a smart mushroom-inspired imprintable and lightly detachable (MILD) microneedle platform for the effective and convenient delivery of multidose COVID-19 vaccines and decentralized vaccine information storage. The mushroom-like structure allows the MILD system to be easily pressed into the skin and detached from the patch base, acting as a "tattoo" to record the vaccine counts in situ without any storage equipment, offering quick accessibility and effortless readout, saving a great deal of valuable time and energy for both patients and health professionals. After loading inactivated SARS-CoV-2 virus-based vaccines, MILD system induced a high level of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) in vivo without eliciting systemic toxicity and local damage. Collectively, this smart delivery platform serves as a promising carrier to improve COVID-19 vaccination efficacy through its dual capabilities of vaccine delivery and in situ data storage, thus exhibiting great potential for helping to contain the COVID-19 pandemic or a resurgence.

A third dose of SARS-CoV-2 vaccine increases neutralizing antibodies against variants of concern in solid organ transplant recipients.

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log10 (AU/ml) on the Euroimmun ELISA and >4 Log10 (AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

Incidence of workplace violence against nurses among Chinese hospitals: A meta-analysis.

AIMS: To explore the incidence of workplace violence against nurses in Chinese hospitals. BACKGROUND: Previous systematic reviews on the incidence of workplace violence against Chinese health care workers did not include many articles published in Chinese. Although several studies have investigated cases of violence against health care providers in China, no meta-analysis has been conducted to assess the incidence of violence against Chinese nurses. EVALUATION: In this study, relevant data were retrieved from studies published up to July 2020. A meta-analysis was conducted using R software (Version 4.0). KEY FINDINGS: The 12-month incidence of workplace violence among Chinese nurses was 71% (95% CI 67%-75%), and verbal violence was the most common sub-type of violence (63%, 95% CI 58%-67%). CONCLUSION: Chinese nurses are at a high risk of violence at workplace. Hospital managers should explore ways to reduce violence against their employees, especially the younger nurses who work in secondary hospitals. IMPLICATIONS FOR NURSING MANAGEMENT: The findings of this study highlight the need to enhance the legal system in terms of laws meant to effectively mitigate violence against nurses in Chinese hospitals. Measures should be particularly taken to protect younger nurses who work in secondary hospitals.