INTRODUCTION
Coronavirus infectious disease 2019 (COVID-19) has spread throughout the world affecting more 7.4 million persons with over 418 000 deaths since late December 2019.1 A variable proportion of them were detected in different countries depending on the testing policy. In Spain, most diagnoses have been achieved in persons with symptoms, with 242 707 persons testing positive until June 12.1
The severity of disease and outcomes of persons infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with age, comorbidities such as obesity, hypertension, diabetes, and immunosuppression among others.2,3 Both the Spanish Society of Nephrology and the Spanish Society of Transplantation worked on early protocols and recommendations to protect renal patients from infection considering that many of them accumulate several risk factors for a complicated clinical picture.4,5 We early insisted on general, as well as specific protection rules (informing patients, avoiding collective transportation, systematic interviews before dialysis sessions, live consultation at maximum) and put in place a registry to collect information regarding the impact of COVID-19 in renal patients on dialysis or with a functioning kidney transplant (KT).6
Some case reports and short series have described the clinical picture of COVID-19 in KT,7-21 with a higher fatality rate than the general population with similar variables associated with bad prognosis.13-21 The impact of specific transplant-related variables may be more adequately addressed evaluating a larger number of KT recipients. Here, we present the characteristics and outcomes of a large cohort of KT recipients with COVID-19.
MATERIALS AND METHODS
Registry of Kidney Transplant Recipients With COVID-19
A registry to collect information regarding debut and follow-up of dialysis or KT patients started to gather information on March 18, 2020. Members of the society could access it with credentials and register on the web page of the Spanish Society of Nephrology (www.senefro.com). The registry is voluntary and allows inclusion of all KT cases with COVID-19. Every participating transplant unit registered all positive cases they confirmed. During the study period, a period of lockdown and confinement, the Spanish general population (KT patients included) were screened (mainly at hospitals) only if they exhibited symptoms related to COVID-19 or needed admission for any clinical reason. Most transplant patients were tested even if admission was not clear or the clinical picture was not typical, as we clearly learned about the risk of a dismal outcome in this population. Sporadically, asymptomatic, tight contacts of a confirmed positive patient were also tested.
Confirmed diagnosis corresponds to a patient with positive reverse transcriptase-polymerase chain reaction (RT-PCR) assay of a specimen collected on a nasopharyngeal swab or bronchoalveolar lavage. Only laboratory-confirmed cases were included.
Variables Collected
The registry included demographics, baseline renal information, immunosuppressive and renin-angiotensin-system inhibitor treatments, and epidemiological and clinical data regarding COVID-19 disease: date of diagnosis, symptoms (including gastrointestinal symptoms), lymphopenia, drug treatment, need of mechanical ventilation or intensive care, and outcome.
Outcomes were assessed as COVID-19-related mortality or recovery until June 2, 2020. Time to events (death or recovery) was defined as the time measured in days from COVID-19 diagnosis or admission to events.
The study was conducted according to the guidelines as dictated by the Declaration of Helsinki. All data were recorded anonymously.
Statistical Analysis
Categorical variables were summarized as percentages, and continuous variables were expressed as the mean ± SD or median with interquartile range as appropriate. All categorical variables were compared using the Fisher exact test or chi-square test, and continuous variables were compared using the t test, the Mann-Whitney U test, the Anova test, or the Kruskal-Wallis test, as appropriate. Mood’s median test was performed to compare median scores.
Survival curves were plotted using the Kaplan-Meier method and compared between patients with and without risk factors for death by log-rank test. In the Kaplan-Meier analysis for age, values close to the median age were considered in accordance with those selected in previous studies.22 Kaplan-Meir survival analysis for posttransplant time, it was performed comparing patients in the first year after KT with the rest. Multivariate Cox proportional hazard regression analyses were used to determine the independent risk factors for the outcome of coronavirus-related death during follow-up. Several covariates were selected for analysis as potential confounding variables: age, sex, diabetes mellitus, use of renin-angiotensin-system inhibitor treatments, use of previous medications (hydroxychloroquine plus azithromycin), use of high-dose corticosteroids during hospitalization, lymphocyte count, fever, presence of gastrointestinal symptoms or pneumonia, and posttransplant follow-up time. A final parsimonious multivariate model selection was performed via backward step-down selection of variables with P > 0.05, using the likelihood-ratio test, to confirm that each removed factor did not contribute significantly to the multivariable model. Proportionality assumption in the model was assessed by visual inspection of the log-log survival plots. Covariates included in the model did not violate the proportionality assumption. In addition, interactions between the presence of COVID-19 and the other independent variables, including the presence of gastrointestinal symptoms, were investigated and no interactions were found.
All analyses were performed with SPSS V 21.0 (SPSS Inc., Chicago, IL). A P < 0.05 was considered statistically significant.
RESULTS
Characteristics of the Kidney Transplant Patients With COVID-19
From March 18 to May 16, 509 KT recipients with COVID-19 were included in the Registry. Among them, 414 fully documented patients had a final outcome for the episode, recovery, and discharge or death (Table 1). They were most frequently men, with a median age of 62 years, transplanted from 1985 to 2020. Median time from KT to the COVID-19 episode was 6 years, and 13.1% had been transplanted recently (within the previous year). The most common immunosuppressive treatment (data available for 409 patients) was a combination of steroids, tacrolimus, and mycophenolate, followed by tacrolimus and mycophenolate. Fever, respiratory symptoms, and dyspnea were the most frequent COVID-19-related symptoms, and 81.4% of them had pneumonia. More than one-third of patients showed gastrointestinal symptoms at diagnosis, combinations of nausea, vomiting, and diarrhea. Only 20 patients (<5%) were asymptomatic, and their tests were performed for being tight contacts of positive patients. Most patients were hospitalized, 12.1% in intensive care unit (ICU), and 17.6% needed ventilator support (invasive or noninvasive).
TABLE 1. -
Characteristics of the KT patients with COVID-19 comparing those who died and those who recovered
| Variable |
All (n = 414) |
Dead (n = 109) |
Recovered (n = 305) |
P
|
| Males, n (%) |
265 (64) |
67 (61.5) |
198 (64.9) |
0.519 |
| Recipient age (y), median (IQR) |
62 (52–71) |
72 (63–76) |
59 (50–68) |
<0.001 |
| Age <55 y old, n (%) |
129 (31.2) |
6 (4.7) |
123 (95.3) |
<0.001 |
| Age 55–64 y old, n (%) |
107 (25.8) |
28 (26.2) |
79 (73.8) |
| Age ≥65 y old, n (%) |
178 (43) |
75 (42.1) |
103 (57.9) |
| Diabetes mellitus as primary nephropathy, n (%) |
59 (14.1) |
22 (20.2) |
37 (12.1) |
0.039 |
| Baseline immunosuppressive treatmenta, n (%) |
| Prednisone |
310 (75.8) |
87 (80.6) |
223 (74.1) |
0.178 |
| Tacrolimus |
338 (82.6) |
89 (82.4) |
249 (82.7) |
0.941 |
| Mycophenolate |
297 (72.6) |
80 (74.1) |
217 (72.1) |
0.692 |
| mTOR inhibitors |
94 (23) |
18 (16.7) |
76 (25.2) |
0.069 |
| ACEIs treatment, n (%) |
68 (16.4) |
21 (19.3) |
47 (15.4) |
0.351 |
| ARBs treatment, n (%) |
111 (26.8) |
24 (22) |
87 (28.5) |
0.188 |
| COVID-19 episode and associated features |
| Time from KT (mo), median (IQR) |
72 (31–145) |
68 (16–132) |
72.5 (33–154) |
0.143 |
| Time from KT ≤ 12 mo, n (%) |
54 (13.1) |
22 (20.2) |
32 (10.5) |
0.010 |
| Fever, n (%) |
340 (82.1) |
86 (78.9) |
254 (83.3) |
0.306 |
| Cough, expectoration and/or rhinorrhea, n (%) |
302 (72.9) |
85 (78) |
217 (71.1) |
0.168 |
| Dyspnea, n (%) |
181 (43.7) |
74 (67.9) |
107 (35.1) |
<0.001 |
| Gastrointestinal symptoms, n (%) |
152 (36.7) |
27 (24.8) |
125 (41) |
0.003 |
| Pneumonia, n (%) |
337 (81.4) |
101 (92.7) |
236 (77.4) |
<0.001 |
| Lymphopenia, n (%) |
337 (81.4) |
94 (86.2) |
243 (79.7) |
0.130 |
| COVID-19 management, n (%) |
| Hospitalization |
380 (91.8) |
107 (98.2) |
273 (89.5) |
0.005 |
| Ventilator support |
73 (17.6) |
60 (55.6) |
13 (4.3) |
<0.001 |
| ICU admission |
50 (12.1) |
33 (30.3) |
17 (5.6) |
<0.001 |
| Hydroxychloroquine |
369 (89.1) |
95 (87.2) |
274 (89.8) |
0.440 |
| Azithromycin |
206 (49.8) |
50 (45.9) |
156 (51.1) |
0.344 |
| Glucocorticoids |
203 (49) |
64 (58.7) |
139 (45.6) |
0.018 |
| Lopinavir/ritonavir |
140 (33.8) |
54 (49.5) |
86 (28.2) |
<0.001 |
| Tocilizumab |
77 (18.6) |
27 (24.8) |
50 (16.4) |
0.054 |
| Time (d) to death or recovery, median (IQR) |
14 (8–21) |
9 (4–17) |
15 (9–22) |
<0.001 |
aData of 409 patients: 301 survivors and 108 nonsurvivors.
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; COVID-19, coronavirus infectious disease 2019; ICU, intensive care unit; IQR, interquartile range; KT, kidney transplantation; mTOR, mammalian target of rapamycin.
Treatment for COVID-19 included frequently hydroxychloroquine (89.1%) with azithromycin (49.8%) and high-dose steroids (49%), lopinavir/ritonavir (33.8%), and tocilizumab (18.6%).
Mortality and Related Factors in Univariate Analyses
After a mean follow-up of 44 days, the fatality rate was 26.3% (109 cases), whereas recovery-rate was 73.7% (305 cases). We compared KT recipients who died with those who recovered within the same period (Table 1). KT patients who died were older, and mortality was significantly higher in patients aged over 65 years old (Figure 1). Diabetes mellitus was significantly associated with mortality. KT vintage was similar, but among the 54 patients transplanted within the last year who developed a COVID-19, 22 of them died (mortality was 40.7%). This higher mortality in patients with a recent KT was significant in Kaplan-Meier analysis (Figure 2). Immunosuppressive treatment and renin-angiotensin-blocker treatment were similar between survivors and nonsurvivors. Patients who died presented more frequently with dyspnea and pneumonia and less frequently with gastrointestinal symptoms. They needed intensive care and ventilator support more frequently than those who recovered. They were equally treated with hydroxychloroquine with or without azithromycin and more frequently treated with high-dose steroids, lopinavir-ritonavir, or IL-6 blockers.
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FIGURE 1.: Survival function for death according to patient age.
FIGURE 2.: Survival function for death according to time from kidney transplant to COVID-19. COVID-19, coronavirus infectious disease 2019; KT, kidney transplant.
Univariate Cox regression analysis for death after COVID-19 showed that age (continuous), age ≥65 years old, time after KT shorter than 12 months, diabetes mellitus (as cause of underlying nephropathy), the presence of dyspnea, pneumonia, the need of ventilator support or ICU admission, and treatments with lopinavir/ritonavir or high-dose steroids were significantly associated to mortality (Table 2).
TABLE 2. -
Univariate Cox regression analysis for death after COVID-19 in KT recipients
| Characteristic |
Exp (ß) |
95% CI |
P
|
| Male gender |
1.161 |
0.790-1.708 |
0.447 |
| Age (y) |
1.084 |
1.064-1.106 |
<0.001 |
| Age ≥ 65 y |
3.773 |
2.513-5.665 |
<0.001 |
| Diabetes mellitus as primary nephropathy |
1.672 |
1.047-2.671 |
0.031 |
| Baseline immunosuppressive treatment |
| Prednisone |
1.374 |
0.853-2.213 |
0.191 |
| Tacrolimus |
0.974 |
0.593-1.598 |
0.916 |
| Mycophenolate |
1.066 |
0.693-1.639 |
0.772 |
| mTOR inhibitors |
0.613 |
0.369-1.017 |
0.058 |
| ACEIs treatment |
1.232 |
0.765-1.983 |
0.391 |
| ARBs treatment |
0.720 |
0.458-1.133 |
0.156 |
| Time from KT (mo) |
0.998 |
0.996-1.001 |
0.186 |
| Time from KT ≤ 12 mo |
1.806 |
1.131-2.884 |
0.013 |
| Fever |
0.740 |
0.467-1.173 |
0.200 |
| Cough, expectoration, and/or rhinorrhea |
1.383 |
0.879-2.175 |
0.161 |
| Dyspnea |
3.248 |
2.171-4.859 |
<0.001 |
| Pneumonia |
3.142 |
1.530-6.455 |
0.002 |
| Gastrointestinal symptoms |
0.529 |
0.342-0.817 |
0.004 |
| Lymphopenia |
1.415 |
0.821-2.441 |
0.211 |
| Hospitalization |
5.139 |
1.269-20.818 |
0.022 |
| Ventilator support |
8.321 |
5.675-12.201 |
<0.001 |
| ICU admission |
3.417 |
2.269-5.146 |
<0.001 |
| COVID-19 treatment |
| Hydroxychloroquine |
0.698 |
0.398-1.223 |
0.208 |
| Azithromycin |
0.839 |
0.575-1.223 |
0.361 |
| Glucocorticoids |
1.521 |
1.039-2.228 |
0.031 |
| Lopinavir/ritonavir |
1.983 |
1.362-2.888 |
<0.001 |
| Tocilizumab |
1.397 |
0.904-2.159 |
0.132 |
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; COVID-19, coronavirus infectious disease 2019; ICU, intensive care unit; KT, kidney transplantation; mTOR, mammalian target of rapamycin.
We analyzed our patients dividing them between those with pneumonia alone (n = 204), gastrointestinal symptoms alone (n = 19), both features (n = 133), or absence of both (n = 58) (Table 3). Those patients developing only pneumonia were older, presented with dyspnea, and required ICU admission/ventilator more frequently than the other subgroups. Mortality was very high at 36.3% in this group. Interestingly, those developing pneumonia associated with gastrointestinal symptoms showed a more favorable evolution (mortality 19.5%). The lowest mortality was observed in patients developing only gastrointestinal symptoms, with only 1 death (5.3% mortality).
TABLE 3. -
Clinical characteristics of KT patients according to the presence of pneumonia and digestive or gastrointestinal symptoms
| Characteristic |
No pneumonia or digestive symptoms |
Only digestive symptoms |
Only pneumonia |
Pneumonia and digestive symptoms |
P
|
| Patients, n |
58 |
19 |
204 |
133 |
|
| Age (y), median (IQR) |
59 (26–86) |
56 (47–66) |
64 (54–73) |
60 (50–69) |
0.014 |
| Fever, n (%) |
41 (70.7) |
14 (73.7) |
166 (81.4) |
119 (89.5) |
0.011 |
| Dyspnea, n (%) |
8 (13.8) |
0 (0) |
121 (59.3) |
52 (39.1) |
<0.001 |
| Lymphopenia, n (%) |
32 (55.2) |
13 (68.4) |
174 (85.3) |
118 (88.7) |
<0.001 |
| Hospitalization, n (%) |
36 (62.1) |
14 (73.7) |
200 (98) |
130 (97.7) |
<0.001 |
| Ventilator support, n (%) |
0 (0) |
0 (0) |
48 (28.1) |
12 (13.5) |
<0.001 |
| ICU admission, n (%) |
1 (1.7) |
0 (0) |
27 (13.2) |
22 (16.5) |
0.011 |
| COVID-19 treatment, n (%) |
| Hydroxychloroquine |
41 (70.7) |
12 (63.2) |
188 (92.2) |
128 (96.2) |
<0.001 |
| Glucocorticoids |
9 (15.5) |
3 (15.8) |
113 (55.4) |
78 (58.6) |
<0.001 |
| Lopinavir/ritonavir |
15 (25.9) |
2 (10.5) |
78 (38.2) |
45 (33.8) |
0.046 |
| Tocilizumab |
3 (5.2) |
2 (10.5) |
34 (16.7) |
38 (28.6) |
0.001 |
| Mortality, n (%) |
7 (12.1) |
1 (5.3) |
74 (36.3) |
26 (19.5) |
<0.001 |
All variables of the study were compared between the 4 groups, showing only those with P < 0.05.
COVID-19, coronavirus infectious disease 2019; ICU, intensive care unit; IQR, interquartile range; KT, kidney transplantation.
Patients with pneumonia showed a worse prognosis (Figure 3A), whereas those showing gastrointestinal symptoms had a more favorable prognosis (Figure 3B). Interestingly, pneumonia alone was the worst prognostic indicator, followed by the combination of pneumonia plus gastrointestinal involvement. Isolated gastrointestinal symptoms constituted the most favorable phenotype (Figure 3C).
FIGURE 3.: Survival function for death according to the development of major clinical pictures. (A) pneumonia; (B) gastrointestinal symptoms; (C) association of pneumonia and digestive symptoms in 4 subgroups: only gastrointestinal symptoms, only pneumonia, both of them, none of them.
Multivariate Analyses for the Relationship Between Risk Factors and Outcomes
Multivariate analysis showed that advanced age and pneumonia were independently associated with death, whereas gastrointestinal symptoms at presentation were associated with recovery (Table 4). Diabetes as a primary cause of renal disease and short time after KT was not finally related to a higher mortality when adjusted in multivariate analyses. None of the other variables associated with worse outcome and death remained significant when adjusted in multivariate models. These results were consistent when the models were repeated excluding gastrointestinal symptoms as a variable (Table 4), pneumonia as a variable (Table 4), or limiting the sample to the 337 patients with confirmed pneumonia (Table 4).
TABLE 4. -
Multivariate Cox regression analyses for death after COVID-19 in kidney transplant recipients
| Characteristic |
Exp (ß) |
95% CI |
P
|
| Model with all variables showing a P < 0.1 in the univariate analysis |
| Age |
1.081 |
1.060-1.103 |
<0.001 |
| Pneumonia |
3.043 |
1.476-6.273 |
0.003 |
| Gastrointestinal symptoms |
0.553 |
0.357-0.858 |
0.008 |
| Diabetes mellitus as renal disease |
1.184 |
0.739-1.897 |
0.483 |
| Model with all variables except for gastrointestinal symptoms |
| Age |
1.082 |
1.061-1.103 |
<0.001 |
| Pneumonia |
2.757 |
1.341-5.670 |
0.006 |
| Diabetes mellitus as renal disease |
1.265 |
0.792-2.023 |
0.325 |
| Model with all variables except for pneumonia |
| Age |
1.083 |
1.062-1.105 |
<0.001 |
| Gastrointestinal symptoms |
0.607 |
0.392-0.941 |
0.026 |
| Diabetes |
1.152 |
0.718-1.846 |
0.558 |
| Model only in KT recipients who developed pneumonia (n = 337) |
| Age |
1.078 |
1.056-1.100 |
<0.001 |
| Dyspnea |
2.357 |
1.528-3.635 |
<0.001 |
| Gastrointestinal symptoms |
0.603 |
0.385-0.945 |
0.027 |
| Diabetes mellitus as renal disease |
1.365 |
0.832-2.238 |
0.218 |
The results were similar when age was analyzed as a categorical variable and also when all the models were adjusted for sex and time from KT.
COVID-19, coronavirus infectious disease 2019; KT, kidney transplantation.
DISCUSSION
This is the largest report of KT cases with COVID-19 communicated until now. It collects information of 414 recipients with a positive SARS-CoV-2 RT-PCR and shows that symptomatic KT recipients infected with COVID-19 are at a great risk of developing a severe clinical picture and die. The fatality rate of 26.3% in this population is not very different than the reported 20.7% in the general population admitted to a large tertiary Spanish Hospital.23 Our study confirms that age and pneumonia independently associated with death in KT recipients as in the general population. Interestingly, a gastrointestinal COVID-19 phenotype was independently associated with survival. It also important to underline that the use of renin-angiotensin system blockers was not different between survivors and nonsurvivors, supporting that these drugs do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19, as previously reported in the general population.22
Respiratory pathology is the main driver of poor outcomes in COVID-19.24-26 Most common symptoms in our series included fever and dyspnea, both like the described in the general population,24-26 despite the spread perception that patients on immunosuppressive drugs may appear less symptomatic. Atypical pneumonia is the most common clinical presentation,25 as the lung epithelial cells are usually the primary target of the virus with its entry into the host cells mostly via the angiotensin-converting enzyme 2 receptor.27 In our series, 81.4% of the patients were diagnosed with pneumonia at presentation. Unfortunately, the registry does not include the radiological data that would have been useful to understand the different severity grades of the pneumonia. The negative impact of pneumonia in the prognosis of COVID-19 infected patients in the general population has been reported,28-30 and the results are even worse in series of recipients of solid organ transplants.18,20 In our analysis, pneumonia and associated dyspnea were also more frequent in nonsurvivors. Other factors like older age could have contributed to this worse evolution. Our report shows the crucial influence of pneumonia for in-hospital death in KT recipients with COVID-19. Therefore, it is of utmost importance to conduct a careful clinical and radiological vigilance of KT patients with COVID-19.
Age has been clearly linked with outcomes in the general population with COVID-19 in large studies.5,6 The recent literature includes some reports of KT recipients with COVID-19 including cases aged >65 years with high-mortality rates.11,17-19 In our experience, mortality is much higher in elderly patients and very low in patients younger than 55 years old.
About a third of our COVID-19 KT population presented with gastrointestinal symptoms. Interestingly, patients with this gastrointestinal COVID-19 phenotype recovered more frequently. In fact, the adjusted multivariate analysis showed that patients with gastrointestinal manifestations survived over 40% more than KT recipients without these symptoms. In addition, no significant interaction was observed in multivariate analysis. Initial reports of COVID-19 focused on the respiratory disease, but a progressive spreading in the availability of tests and in the indications for their performance allowed to evidence that a significant number of patients presented with nonrespiratory manifestations.16 COVID-19 infection may be associated with gastrointestinal symptoms because SARS-CoV-2 has a strong affinity to the angiotensin-converting enzyme 2 and to the transmembrane protease, serine 2, which is not only expressed in lung but also in the gastrointestinal tract.31 In the general population, the percentage of gastrointestinal symptoms, being the most frequent diarrhea, ranged from 2% in initial reports to 50%,31 whereas the percentage reported in solid organ and in only KT recipients ranges from 20% to 50%12-19 and up to 80% in hemodialysis patients.32 Although some studies reported a relationship between diarrhea and abdominal pain and a higher risk of death, need of mechanical ventilation and intensive care unit admission,33 this finding has not been confirmed.34 A metanalysis including 13 studies and 3027 patients with SARS-CoV-2 infection did not find a significant relationship between bad outcome and diarrhea or nausea and vomiting,35 which supports our results. Other studies specifically carried out in transplant recipients have not analyzed or not found any relationship between gastrointestinal symptoms and outcome but most of these studies were small case series.12-19 The appearance of COVID-19-related gastrointestinal symptoms only in some patients points out that not all patients suffer the same clinical picture potentially due to viral mutations and patient predisposing genetic and environmental conditions.36,37 The strong relationship between digestive symptoms and a better outcome reported in our study needs to be confirmed in further studies.
Of note, in our cohort, we found an accumulation of COVID-19 in patients transplanted within the last year. The maximum effect of immunosuppression is exerted in the first months after transplantation, and, similarly, recipients are at maximum risk of infection and severity by viral pathogens in this period.38 A short time since transplant was associated with a more severe disease in 2009 pandemic influenza A (H1N1).39 However, the stronger influence of the dysregulation of the inflammatory response driven by COVID-19 on the severity of the disease means that data from other viral infections cannot be extrapolated to COVID-19 without further studies.40 Immunosuppressive therapy in KT recipients increased the length and severity of the COVID-19 disease compared with a nonimmunosuppressed control group.40 In their study of 90 solid organ transplant recipients with COVID-19, Pereira et al did not find any relationship between time from transplant to infection and the severity of the disease defined as ICU admission, intubation, or death.19 The number of patients with the shortest follow-up from transplant was low, and, like in our own experience, there are risk factors more strongly related to death, such as age or respiratory disease.19 The relationship between timing after transplantation and COVID-19 severity and death risk deserves the joint effort of all registries in place to reach firm conclusions.
Based on the clinical knowledge, we ruled out from the multivariate analysis the significant differences between survivors and nonsurvivors in the pharmacological treatment used for COVID-19, as the latter group was more heavily treated for the severity of the disease and differences do not mirror the efficacy of treatment but are consequence of the clinical picture.
This study has limitations intrinsic to a voluntary registry. Thus, the true incidence of the disease should be taken with caution. The restricted number of variables collected made the registry an easy tool at a time of very high incidence of COVID-19 in the Spanish population but limited the analysis of some characteristics evaluated in other studies and associated with outcomes such as cardiovascular risk factors or renal function. Another potential limitation is that the Registry does not include the potential intensive care need and unavailability. At the peak of the pandemic in some centers, some patients that under nonpandemic conditions would have been admitted to an ICU might not have had access to ICU treatment because of lack of ICU beds. This might have had an influence on mortality.
Our registry has collected information of many KT cases diagnosed with COVID-19 within 9 weeks during the peak of the pandemic in Spain. It shows that the disease is of severity in aged KT recipients who present with pneumonia and produces death within 44 days of follow-up in 26% of them. Of interest, gastrointestinal symptoms are associated with better outcome in this big cohort. This finding needs further confirmation in larger cohorts of patients. These results should encourage transplant professionals to reinforce preventive measures even more efficiently in older transplant recipients and design treatment trials to modify substantially the outcome of those who present with pneumonia.
ACKNOWLEDGMENTS
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.
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