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).

COVID-19 concerns, health services utilisation and social support among Western Australians with diabetes during the pandemic

People with diabetes face increased risk of serious COVID-19 complications, making self-care for optimal metabolic management crucial. However, the pandemic has reduced access to routine care among people with diabetes. The pandemic can also elicit distress, which can impact diabetes self-management and health. To understand the impact of COVID-19 on Western Australians with diabetes, we conducted an evaluation involving an online survey of consumers of diabetes health services and an analysis of routine program data (i.e. service utilisation/program attendance). Survey respondents were concerned about contracting COVID-19, many intended to change the way they utilised health services and many indicated they would continue to socially isolate. Utilisation of digital/telephone services peaked between April and June 2020. Despite the concerns indicated, a participation resurgence was observed upon resumption of face-to-face programs. Continued access to diabetes programs via multiple modes of delivery is critical to support optimal self-care and mitigate COVID-19 risks, distress and social isolation. This timely and pragmatic assessment of consumer beliefs synthesised with routinely collected evaluation data represents an agile approach to evaluation through an emerging public health crisis. The findings helped to ensure optimal service delivery to meet the needs of this priority population throughout the pandemic.