SARS‐CoV‐2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID‐19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID‐19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti‐COVID‐19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post‐KT should be considered when selecting recipients for transplantation in the COVID‐19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

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.

Introduction Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury (AKI) have been reported. There is little available data on the use and safety of remdesivir in kidney transplant (KT) recipients. Methods We present a multicenter cohort study of 51 KT recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. Results Mean age at diagnosis was 60 years, with a median time since KT of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 non-invasive). Mortality was 18.9%, markedly higher if ≥65 years-old (45% vs. 3.2% in younger patients). AKI was present in 27.7% of patients, but in 50% of cases it was diagnosed before treatment. Remdesivir did not require discontinuation because of adverse events in any case. We did not find significant hepatoxicity or systemic symptoms resultant from the drug. Conclusions In our cohort of KT recipients, remdesivir was well tolerated and safe in terms of renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

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