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

The COVID-19 pandemic prompted the decision to suspend most organ transplantation programs in affected countries, especially in Europe [1]. A recent large population-based report revealed that the cohort at highest risk of in-hospital death due to COVID-19 was the organ transplant population, with a hazard ratio of 4.27 [2]. Published experiences have been restricted to long-term stable kidney transplant (KT) recipients. Despite initial low mortality reported from China [3], further case series have shown mortality rates of up to 75% [4]. The decision to suspend KT programs has been arbitrary, as no reports of COVID-19 in the most vulnerable population, that is, patients with a very recent KT and profound immunosuppression, are available.

A registry to collect information regarding dialysis or KT patients with COVID-19 in Spain started to gather information on March 18, 2020 (www.senefro.com). A confirmed COVID-19 diagnosis was defined as a patient with positive reverse transcriptase-polymerase chain reaction (RT-PCR) assay of a specimen collected via nasopharyngeal swab or bronchoalveolar lavage. Comparisons between groups were made using a two-sided χ2 test with a significance level of 0.05, using SPSS v22. The study was approved by the ethics committee of Hospital del Mar.

Among the 502 KT patients with COVID-19 included until May 9, 2020, 24 had received a KT less than 60 d before being diagnosed as having COVID-19. Cases were diagnosed in 12 Spanish transplant centers between March 17 and April 18, 2020 and had at least 1 mo of follow-up. During the period and 60 d before the first case, 275 KT surgeries were performed in those 12 centers. Therefore, the cumulative incidence of COVID-19 was 9%.

The median age of the 24 patients was 66.5 yr (range 40–75) and immunosuppression regimens were conventional (Table 1 ). Fever, cough, and pneumonia were the usual COVID-19 signs and symptoms and all of the patients were hospitalized. Respiratory failure led to ventilatory support in eight patients and intensive care unit (ICU) admission in four. ICU admission was initially indicated but finally denied in nine patients. Specific COVID-19 management was attempted with immunosuppression reduction (mycophenolate withdrawal in 96% and tacrolimus withdrawal in 62.5%) and different combinations of hydroxychloroquine, antiviral agents, and steroids. Interestingly, eight patients were treated with the anti-IL6 antibody tocilizumab and five of them recovered. No relevant surgical or urological complications were recorded.

Table 1

Characteristics of 24 patients who suffered from COVID-19 during the first 60 d after kidney transplantation.

Variable	Alive (n = 13)	Dead (n = 11)	p value
Male, n (%)	6 (46.2)	5 (45.5)	0.97
Median age, yr (range)	61.1 (40–74)	69.6 (60–75)	0.006
Age ≥65 yr, n (%)	4 (30.8)	8 (72.7)	0.04
Hypertension, n (%)	12 (92.3)	10 (90.9)	1
Diabetes, n (%)	8 (66,7)	4 (36.4)	0.15
Deceased donor, n (%)	13 (100)	10 (91)	0,46
Delayed graft function n (%)	5 (38.5)	7 (63.6)	0.41
Acute rejection, n (%)	2 (15.4)	0 (0)	0.48
Median time from KT to COVID-19 Dx, d (range)	39 (15–59)	28.8 (8–56)	0.07
Baseline immunosuppressive treatment, n (%)
Prednisone	13 (100)	11 (100)	1
Tacrolimus	13 (100)	11 (100)	1
Mycophenolate	12 (92,3)	9 (81.8)	0.58
mTOR inhibitors	0 (0)	2 (18.2)	0.2
Fever, n (%)	9 (69.2)	6 (54.5)	0.67
Cough, expectoration, and/or rhinorrhea, n (%)	6 (46.2)	8 (72.7)	0.24
Dyspnea, n (%)	6 (46.2)	8 (72.7)	0.24
Pneumonia, n (%)	12 (92.3)	10 (90.9)	1
Digestive symptoms, n (%)	1 (7.7)	2 (18.2)	0.58
Lymphopenia, n (%)	13 (100)	11 (100)	1
Hospitalization, n (%)	13 (100)	11 (100)	1
Renal failure, n (%)	6 (46.2)	7 (63.6)	0.26
Ventilator support, n (%)	2 (15.4)	7 (77.8)	0.007
Intensive care unit admission, n (%)	2 (15.4)	2 (18.2)	1
COVID-19 treatment, n (%)
Hydroxychloroquine	12 (92.3)	10 (90.9)	1
Glucocorticoids	3 (25)	9 (81.8)	0.006
Lopinavir/ritonavir	4 (30.8)	4 (36.4)	1
Tocilizumab	5 (38.5)	3 (27.3)	0.68
Median time from admission to death or recovery, d (range)	23 (4–48)	13.7 (6–36)	0.08

KT = kidney transplantation; Dx = diagnosis.

The fatality rate was 45.8%, which is markedly higher than the usual very low 2-mo mortality observed outside the COVID-19 pandemic. Compared with survivors, patients who died were older, were infected closer to transplantation, more frequently needed ventilator support, and were treated less often with high-dose steroids.

The maximum effect of immunosuppression is exerted in the first months after transplantation and recipients are at maximum risk of viral infection and severity in this period. A short time since transplantation was associated with more severe disease in the 2009 pandemic of influenza A (H1N1) [5]. In cities and areas with very high incidence of COVID-19, KT is not a safe option for renal patients, especially those aged >60 yr. When COVID-19 significantly decreases, and as part of the measures to open up after lockdown, KT programs may be resumed under strict preventive measures.

The authors have nothing to disclose.

We are indebted to the many physicians and nurses who take care of these patients and are facing the COVID-19 pandemic in our country. The registry for COVID-19 renal patients is supported by the Spanish Society of Nephrology.

CRediT authorship contribution statement

Julio Pascual: Conceptualization, Formal analysis, Methodology, Supervision, Visualization, Writing - original draft. Edoardo Melilli: Investigation, Writing - review & editing. Carlos Jiménez-Martín: Investigation, Writing - review & editing. Esther González-Monte: Investigation, Writing - review & editing. Sofía Zárraga: Investigation, Writing - review & editing. Alex Gutiérrez-Dalmau: Investigation, Writing - review & editing. Veronica López-Jiménez: Investigation, Writing - review & editing. Javier Juega: Investigation, Writing - review & editing. Miguel Muñoz-Cepeda: Investigation, Writing - review & editing. Inmaculada Lorenzo: Investigation, Writing - review & editing. Carme Facundo: Investigation, Writing - review & editing. María del Carmen Ruiz-Fuentes: Investigation, Writing - review & editing. Auxiliadora Mazuecos: Investigation, Writing - review & editing. Emilio Sánchez-Álvarez: Investigation, Writing - review & editing. Marta Crespo: Conceptualization, Formal analysis, Methodology, Supervision, Visualization, Writing - original draft.