Should cyclosporine be useful in renal transplant recipients affected by SARS-CoV-2?

Abstract

Minimization of immunosuppression and administration of antiretrovirals have been recommended for kidney transplant recipients (KTRs) with coronavirus disease 2019 (COVID‐19). However, outcomes remain poor. Given the likely benefit of cyclosporine because of its antiviral and immunomodulatory effect, we have been using it as a strategy in KTRs diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). We studied 29 kidney transplant recipients (KTRs) who were admitted to our institution with COVID‐19 between March 15and April, 24, 2020. Mycophenolate and/or mammalian target of rapamycin inhibitors (mTORi) were discontinued in all patients. Two therapeutic strategies were compared: Group 1, minimization of calcineurin inhibitors (N = 6); and Group 2, cyclosporine‐based therapy (N = 23), with 15 patients switched from tacrolimus. Hydroxychloroquine was considered in both strategies but antivirals in none. Six patients died after respiratory distress (20.6%). Five required mechanical ventilation (17.2%), and 3 could be weaned. Nineteen patients had an uneventful recovery (65.5%). In group 1, 3 of 6 patients died (50%) and 1 of 6 required invasive mechanical ventilation (16.7%). In group 2, 3 of 23 patients died (12.5%). Renal function did not deteriorate and signs of rejection were not observed in any patient on the second treatment regime. In conclusion, immunosuppressant treatment based on cyclosporine could be safe and effective for KTRs diagnosed with COVID‐19.

A Systematic Review of COVID-19 and Kidney Transplantation

“…11 , 12 In the largest multicentre series, Cravedi et al reported 32% mortality in 144 inpatients although it did not specify how many recovered to discharge, while Kates et al reported 28-day mortality as 18% from its dataset where 254/318 patients were hospitalised. 10 , 17 Of other studies from which inpatient mortality could be calculated, it was 7/39 patients (18%) in Lubetzky et al across New York, 22 6/29 patients (21%) in both Rodriguez-Cubillo et al in Madrid and Chen et al in New York City, 23 , 27 15/42 patients (36%) in Bossini et al in Brescia and 9/25 patients (36%) Mohamed et al in London. 20 , 25 …”

“…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.…”

“…Of the studies with available patient demographic data, average age ranged from 45 years in Demir et al to 66 years in Rodriguez-Cubillo et al 23 , 24 The percentage of male patients ranged from 46% in Pascual et al to 79% in Bossini et al 13 , 25 …”

Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review

“…Unfortunately, its use may be limited by its toxicity. However, a small case series of kidney transplant recipients changed to or maintained on cyclosporine A during treatment for COVID-19 did not show evidence of harm [73].…”