COVID-19–related Mortality During the First 60 Days After Kidney Transplantation

Abstract

Patient 2 commenced pembrolizumab 200 mg every 3 wk in November 2016; his PSA was 0.43 mg/l and scans revealed bilateral pelvic nodes, a large pelvic mass (53 mm), and a complex fistula between the rectum and bladder. He received 11 pembrolizumab courses with no immunological toxicity and experienced a partial response. However, pembrolizumab was stopped because of fistula worsening requiring intravenous antibiotics and surgical intervention. He made a full recovery and remains disease-free 40 mo after starting pembrolizumab (Fig. 1F,G). Tumour NGS had indicated an MSH6 mutation (Y214*), high MutLoad, and high MSINGS score, with MSH6 loss but incomplete MSH2 loss on IHC, as well as PD-L1 positivity (1%). IHC showed high TILs; most of these cells were CD4 + FOXP3 and Tregs (CD4 + FOXP3 + ; Fig. 1H). We previously showed that a small but important subset of mCRPC tumours have evidence of MMRd by IHC and this is associated with high MutLoad and MSI-NGS. However, only some MMRd cancers present with high T-cell infiltration, PD-L1 protein expression, and elevated T-cell-associated transcripts [2]. The rearrangement identified for patient 1 was associated with immune evasion and PD-L1 overexpression in mouse models using an N-terminal binding antibody [4]. This could explain his PD-L1 negativity (since the antibodies routinely used target the C-terminus) and extraordinary response to pembrolizumab in an otherwise immune "cold" tumour. Patient 2, besides MMRd, presented with a highly inflamed cancer, mainly represented by Tregs and CD4 + FOXP3 cells. Interestingly, in mCRPC models, ICIs reprogram CD4 + cells towards a Th1 rather than Th17 lineage in nodal disease, possibly explaining this responsiveness [5]. In conclusion, elucidation of the mCRPC subset benefiting from ICIs requires multiple orthogonal assays, including genomic analyses, IHC, and tumour microenvironment studies.

A Systematic Review of COVID-19 and Kidney Transplantation

“…Sánchez-Álavarez et al was a report from a national COVID-19 registry across Spain, 12 while Pascual et al and Pérez-Sáez et al reported on subgroups from this registry (those within 60 days of transplantation, and those treated with tocilizumab respectively). 13 , 14 Bell et al and Ravanan et al reported from national transplant registries in Scotland and England respectively, while Manganaro et al reported on from a regional registry in Italy. 11 , 15 , 16 Kates et al reported on data entered to a registry by over 50 transplant centres, almost all from the USA, 10 while Cravedi et al was a report of a consortium registry of 12 transplant centres across USA, Italy and Spain.…”

“…From left to right, quality items were starred black if they fulfilled pre-defined criteria: selection was starred on representativeness of patients with the exposure of interest (kidney transplant), selection of the non-exposed group, ascertainment of exposure, and demonstration that outcome of interest (death) was not present at start of the study; comparability was starred on the study controlling for the exposure of interest, and any additional factor; outcome was starred on how the outcome was assessed, whether follow-up was long enough for the outcome to occur, and whether loss to follow-up was adequate enough to be unlikely to introduce bias. Study design Selection Comparability Outcome Manganaro et al 16 Single-centre case series ☆☆★★ ☆☆ ☆☆☆ Boyarksy et al 18 Cross-sectional national survey ☆☆☆★ ☆☆ ☆☆☆ Pereira et al 21 Two-centre case series ★☆★★ ☆☆ ★☆☆ Sánchez-Álvarez et al 12 National registry cohort ★★☆★ ★☆ ☆★☆ Vistoli et al 19 Cross-sectional national survey ★☆☆★ ☆☆ ☆☆☆ Rodriguez-Cubillo et al 23 Single-centre case series ★☆★★ ☆☆ ★★★ Pascual et al 13 National registry case series ★☆★★ ☆☆ ★☆☆ Chen et al 27 Single-centre case series ★☆★★ ☆☆ ★★★ Mehta et al 28 Single-centre case series ★☆★★ ☆☆ ★★★ Bossini et al 25 Multi-centre case series ★☆★★ ☆☆ ★★★ Cravedi ...…”

“…We note that some studies had overlapping cohorts: patients from Mohamed et al would be included in Ravanan et al , 11 , 20 while patients in Pereira et al would have been included in Lubetzky et al 21 , 22 Some cases from Rodriguez-Cubillo et al are likely to have been included in the registry report by Sánchez-Álvarez et al , while Pascual et al and Pérez-Sáez et al were reports of subgroup analyses from this registry. 12 , 13 , 14 , 23 Cravedi et al excluded any patients from studies which had already been published but these were smaller studies not included in our summary. 17 Kates et al did not report which centres submitted data to its registry but there were over 50, of whom >98% were from the USA; 10 our review includes six other studies with data from USA which may have overlapped.…”

[Retracted] COVID‐19 and Living Donor Kidney Transplantation in Naples during the Pandemic

“…None of our patients has been infected by SARS-CoV-2 during hospitalization or follow-up, supporting the preliminary data that suggest a low risk of acquiring the viral infection by transplanted patients, with a clinical course not different from that of nontransplant individuals [ 4 , 12 – 14 ]. However, the affected patients seem to have a higher risk of becoming seriously ill and have an increased rate of mortality, especially in older patients [ 11 , 12 , 15 – 18 ].…”

“…Even our only preemptive patient decided to delay the transplantation till the end of the lockdown, accepting the probability of starting dialysis treatment. The temporary suspension of elective living donor transplantation is supported by the most recent recommendations worldwide [ 5 , 15 , 25 – 27 ].…”