According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and two weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with anti-thymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.

COVID‐19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Immunocompromised patients often present atypical presentations of viral diseases. Herein we report a case of a COVID‐19 infection in a solid organ transplant recipient, in which the first clinical symptoms were of gastrointestinal viral disease and fever, which further progressed to respiratory symptoms in 48h. In these high risk populations, protocols for screening for SARS‐Cov2 may be needed to be re‐evaluated.

Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID‐19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between Mar 4 and Apr 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data was analyzed. The mean age was 60 years. Forty‐seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; p=0.04). Significant age differences were not found among patients developing and not developing ARDS (61.3yr vs 57.8yr, p=0.16). Seventy‐six (73%) patients were discharged while 28 (27%) died. Death was more common among the elderly (55yr and 70.8yr, p<0.001) and those with preexisting pulmonary disease (OR 2.89 , p=0.009). At admission, higher baseline lactate dehydrogenase (257 IU/ml vs 358 IU/ml, p=0.001) or ARDS conferred higher risk of death (HR 2.09, p=0.044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin 6 (IL‐6) release. The IL‐6‐receptor blocker tocilizumab may control the aberrant host immune response in COVID‐19 patients. In this pandemic, kidney transplant (KT) recipients are a high‐risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID‐19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (HR 3.12 for those older than 60 years, p=0.039). IL‐6 and other inflammatory markers, including LDH, ferritin, and D‐dimer increased early after tocilizumab administration and their values were higher in non‐survivors. Instead, C‐reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in non‐survivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [CI 1.004‐1.024], p=0.003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration, and did not impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID‐19 but randomized trials are needed.

Background.: Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management. Methods.: Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples. dd-cfDNA was measured using the Prospera test (Natera, Inc.) and reported both as a fraction of the total cfDNA (fraction; %) and as concentration in the recipient’s plasma (quantity; copies/mL). Results.: In the absence of P-BPAR, dd-cfDNA was significantly higher in samples collected within the first 45 d after SPKTx compared with those measured afterward (median, 1.00% versus 0.30%; median, 128.2 versus 35.3 cp/mL, respectively with both; P = 0.001). In samples obtained beyond day 45, P-BPAR samples presented a significantly higher dd-cfDNA fraction (0.83 versus 0.30%; P = 0.006) and quantity (81.3 versus 35.3 cp/mL; P = 0.001) than stable samples. Incorporating dd-cfDNA quantity along with dd-cfDNA fraction outperformed dd-cfDNA fraction alone to detect active rejection. Notably, when using a quantity cutoff of 70 cp/mL, dd-cfDNA detected P-BPAR with a sensitivity of 85.7% and a specificity of 93.7%, which was more accurate than current biomarkers (area under curve of 0.89 for dd-cfDNA (cp/ml) compared with 0.74 of lipase and 0.46 for amylase). Conclusions.: dd-cfDNA measurement through a simple noninvasive blood test could be incorporated into clinical practice to help inform graft management in SPKTx patients.