key: cord-0990726-lsqnbdvu
authors: Toapanta, Néstor; Torres, Irina B; Sellarés, Joana; Chamoun, Betty; Serón, Daniel; Moreso, Francesc
title: Kidney transplantation and COVID-19 renal and patient prognosis
date: 2021-03-26
journal: Clin Kidney J
DOI: 10.1093/ckj/sfab030
sha: 10084293a3c7877473c41ac35f2d65c7f3f83cf5
doc_id: 990726
cord_uid: lsqnbdvu

Coronavirus disease 2019 (COVD-19) emerged as a pandemic in December 2019. Infection has spread quickly and renal transplant recipients receiving chronic immunosuppression have been considered a population at high risk of infection, complications and infection-related death. During this year a large amount of information from nationwide registries, multicentre and single-centre studies have been reported. The number of renal transplant patients diagnosed with COVID-19 was higher than in the general population, but the lower threshold for testing may have contributed to its better identification. Major complications such as acute kidney injury and acute respiratory distress syndrome were very frequent in renal transplant patients, with a high comorbidity burden, but further studies are needed to support that organ transplant recipients receiving chronic immunosuppression are more prone to develop these complications than the general population. Kidney transplant recipients experience a high mortality rate compared with the general population, especially during the very early post-transplant period. Despite the fact that some studies report more favourable outcomes in patients with a kidney transplant than in patients on the kidney waiting list, the higher mortality described in the very early post-transplant period would advise against performing a kidney transplant in areas where the spread of infection is high, especially in recipients >60 years of age. Management of transplant recipients has been challenging for clinicians and strategies such as less use of lymphocyte-depleting agents for new transplants or anti-metabolite withdrawal and calcineurin inhibitor reduction for transplant patients with COVID-19 are not based on high-quality evidence.

Coronavirus disease 2019 is caused by the singlestrand RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has become a worldwide threat. The first human case of COVID-19 was reported in Wuhan, China, in December 2019, and within a few weeks the infection spread around the world, becoming a pandemic [1] . A total of >62 million people have been diagnosed and 1.45 million died (https://coronavirus.jhu.edu/map.html; accessed 28 November 2020). There was an initial wave during March and April 2020 until a lockdown was ordered by many national governments. After progressive lifting of the lockdowns, a second wave is evolving, with the USA, India, Brazil, Russia, France and Spain having the highest rates of infection. Fever, fatigue and dry cough are the most common symptoms and patients may also experience shortness of breath, myalgia, sore throat and gastrointestinal (GI) symptoms [2] . Reverse transcription polymerase chain reaction (RT-PCR) is the gold standard for diagnosis. Treatment is based on oxygen supply and a combination of drugs that have evolved during the pandemic. Initially drugs with potential antiviral activity (e.g. lopinavir/ritonavir, hydroxychloroquine) were widely used, but later, randomized prospective trials demonstrated their lack of efficacy [3] and only remdesivir has been approved by regulatory agencies to treat COVID-19 [4] . Now the agents being studied to mitigate the clinical impact of this infection and decrease its severity are focused on immune mediators, stem cells and agents intended specifically to improve or support lung function (https://www.wcgclinical.com/covid-19/covid-19-trial-insights).

Renal transplant patients have been one of the populations most vulnerable to COVID-19 and many reports have been published. In this setting, immunomodulation has emerged as a promising option for patients with COVID-19-related cytokine storm, but the supporting evidence is scarce and of low quality [5] . Moreover, COVID-19 has had a big impact on wait-listed patients, highlighting the need to properly balance the risks and benefits of transplantation in the setting of an ongoing pandemic [6] .

The aim of this article is to review the available literature published until now regarding renal and patient prognosis in renal transplant patients with COVID-19.

Since the outbreak, a lot of information has been available from nationwide registries and multicentre and local studies. A European study conducted by the ERA-EDTA from the French and Spanish registry yielded an average infection rate of 14/ 1000 transplants at risk [7] . The Spanish registry [8] , with a longer period of observation, showed an incidence of 17.7/1000 transplants, while the French registry [9] , with a shorter observation period, showed an incidence of 9.5/1000 transplants. The kidney registry of the Dutch-speaking Belgian Society of Nephrology reports a similar incidence of 14.0/1000 transplants [10] . Similar incidences were reported from multicentre studies including patients from the USA, Italy and Spain [11, 12] . Importantly, the incidence during the observation periods was 2-5 times higher in renal transplants than in the general population. Even in small countries like Scotland with a lower COVID-19 incidence, with only 24 transplant patients diagnosed with COVID-19, the incidence was 3 times that of the general population [13] . However, single-centre analysis conducted in areas with a high rate of infection revealed higher incidences [14] [15] [16] . A summary of the larger studies conducted is shown in Table 1 . During the initial wave there were no studies providing information about asymptomatic patients since they were not generally screened. During the first wave, the hospitalization rate of symptomatic patients with COVID-19 was >80% in the nationwide registries and multicentre studies (Table 1) . Likewise, in a cohort of 44 patients with mild symptoms, 34 needed to be referred to the emergency department and managed as inpatients while only 9 patients with suspected COVID-19 (never tested due to limitations) were managed as outpatients, and the only patient with confirmed COVID-19 was never hospitalized [17] . Finally, in a cohort of 41 patients, the hospitalization rate was 55% for those patients with confirmed COVID-19 while it was 5% for suspected but never tested patients [18] .

Tests to detect antibodies against SARS-CoV-2 were incorporated into clinical practice later and they allow characterizing the proportion of asymptomatic or pauci-symptomatic patients not screened by RT-PCR. In a large study conducted in the Bronx borough of New York City, the combination of RT-PCR and antibodies characterized an incidence as high as 234/1000 transplant patients, with 41% diagnosed only by the presence of antibodies against SARS-CoV-2 [19] . For symptomatic patients (PCR positive), the hospitalization rate was high (84.1%), while for the overall cohort it was lower (48.5%).

Thus, although the number of renal transplant patients diagnosed with COVID-19 was higher than in the general population, the lower threshold for testing may have contributed to its better identification while many oligosymptomatic individuals in the general population were not tested and do not appear in the official statistics [10] .

The mean age of renal transplant patients with COVID-19 was 60 years and the proportion of males (two-thirds) and comorbidities (arterial hypertension >80%, diabetes >25%) correlates with the characteristics of transplanted patients. Clinical presentation is characterized by fever, cough and shortness of breath in >60% of patients, while GI symptoms were described in about one-third of patients [20] .

Acute kidney injury (AKI) is a common complication in patients with COVID-19 and is associated with increased intensive care unit (ICU) admission and mortality [21, 22] . AKI incidence is higher in patients admitted to the ICU due to COVID-19 than in patients admitted for other reasons [23] . In a large retrospective study (9657 patients), 39.9% developed AKI, of which 6.6% required renal replacement therapy (RRT) [24] . Approximately one-third of patients with AKI do not fully recover renal function [25] . The main risk factors associated with AKI are advanced age, male gender, severity of respiratory impairment, mechanical ventilation, pre-existing chronic renal failure, coinfection with other organisms and systemic inflammatory response [22] [23] [24] . Noticeably, AKI was increased in the subgroups with diabetes compared with subgroups without this condition [26] . A group to highlight is patients of African descent, in whom a greater risk of COVID-19 infection has been described [22, 27, 28] . In this population, the APOL1 genotype is closely related to the development of nephropathy and evidence suggests that the SARS-CoV-2 infection could act as a 'second blow' that leads to podocyte dysregulation [29] .

Considering that kidney transplant patients have a single functional kidney, receive a tacrolimus-based regimen that has nephrotoxic effects [30] , have a high prevalence of hypertension and diabetes [31] and that Black race increases the risk of AKI in kidney recipients [32, 33] , a higher incidence and severity of AKI in these settings would be expected. However, few studies have attempted to compare AKI in kidney transplant patients with the general population. Aziz et al. [34] reviewed 19 articles reporting AKI incidence in kidney transplant and nontransplanted patients. Despite the fact that AKI incidence was higher in kidney transplant patients (27.5% versus 13.3%), as well as RRT (15.4% versus 3.3%), the mortality rate was similar between groups. In a systemic review conducted by Marinaki et al. [35] including 420 patients, 44% of hospitalized kidney transplant patients developed AKI and 23% required RRT. In a multicentre study including 104 hospitalized kidney transplant patients, AKI was observed in 47% of patients and, interestingly, it was observed that tacrolimus trough levels were higher in patients with Stage 3 AKI. However, AKI or Stage 3 AKI were not associated with mortality [12] . Table 2 describes the incidence of AKI and the proportion of patients requiring RRT in kidney transplant and non-transplanted patients hospitalized due to COVID-19 infection.

If we consider the incidence of AKI in the general population and in kidney transplant patients, available data do not clearly support a higher incidence of AKI in transplanted patients. However, this statement should be taken with caution since more information is needed, especially, in kidney transplant patients.

Acute tubular necrosis is the main finding in patients with AKI [36, 37] . However, a high proportion of patients display proteinuria (44-66%) and microhaematuria (27-42%), suggesting that, in addition to classical factors leading to AKI, a direct cytopathic effect of the virus may contribute to renal damage [21, 38] . Angiotensin-converting enzyme 2 receptor is highly expressed in kidney podocytes and tubular cells, and viral particles have been observed in electron microscopy studies [36, 38, 39] . In the vast majority of patients, haematuria and proteinuria rapidly disappeared; however, in patients with severe proteinuria, collapsing glomerulopathy [40] [41] [42] [43] [44] [45] , minimal change disease, thrombotic microangiopathy [46, 47] and pauci-immune crescentic glomerulonephritis [48] have been described.

In kidney transplant patients there is scarce information on histological findings. In patients with AKI, apart from acute tubular injury, minimal change disease [49] , cortical necrosis [50] and collapsing glomerulopathy [51] [52] [53] have also been described. In addition, very few cases of T cell-or antibody-mediated rejection have been described, raising the question of whether COVID-19 infection may enhance the alloimmune response [46, 50] .

In the general population, the spectrum of COVID-19 varies widely, from asymptomatic to pneumonia and life-threatening complications, including ARDS, multisystem organ failure and ultimately death. ARDS occurs because of an acute systemic inflammatory response that can be caused by insults to the lung, either direct or indirect. The reported incidence of ARDS in the general population is 12-31%, being severe in 56-79% of cases [26, [54] [55] [56] [57] [58] [59] [60] . Age and the presence of comorbidities are the main risk factors for developing ARDS [61] . Kidney transplant recipients may be at high risk of developing severe COVID-19 disease due to chronic immunosuppression, comorbidities and frequent contact with the healthcare system. Indeed, they may be more likely to be diagnosed when they have symptoms due to closer follow-up at the transplant centre [8, [62] [63] [64] . However, there are few studies comparing ARDS in kidney transplant patients and the general population. In a study conducted at our centre [63] , 46 solid organ transplant (SOT) recipients (30 renal transplants) admitted due to COVID-19 were matched by age, sex and age-adjusted Charlson comorbidity index to 166 controls. As expected, hypertension and chronic kidney disease were more frequent in transplant recipients. A total of 27 (58.7%) transplant recipients and 71 (42.8%) controls suffered progressive respiratory failure. In a similar study conducted in Michigan, 41 SOT recipients (67% were Black; 16 single and 5 combined kidney transplants) were matched by age, race and admission status to 121 controls [32] . Severe disease-adjusted risk of death was similar in both groups and the severity of COVID-19 and number of intubations were also similar, but the incidence of AKI requiring RRT was higher in transplant patients (29.3% versus 5.8%).

Data from multicentre studies yielded similar results; Cravedi et al. [11] identified 144 hospitalized adult kidney transplant recipients and 29% required orotracheal intubation. A Spanish multicentre kidney transplant study with 104 hospitalized patients reported that 54.8% developed ARDS and that it was associated with obesity [odds ratio (OR) 2.63; P ¼ 0.04] [12] . No significant age difference was found between patients who developed or did not develop ARDS; however, the elderly may have a higher risk of death. Bossini et al. [15] [65] reported an initial series of 36 patients with COVID-19; 28 were admitted to the hospital and 27 (96%) had radiographic findings that were consistent with viral pneumonia. Eleven of 27 (39%) required mechanical ventilation and 7 of them (64%) died. Table 3 describes the incidence of ARDS and its severity in kidney transplant patients and in the general population hospitalized for COVID-19 infection.

Despite the high incidence of ARDS in the transplanted population and its deleterious consequences, more detailed studies are neeeded to support that organ transplant recipients receiving chronic immunosuppression are more prone to develop ARDS than the general population.

During the first wave of the pandemic, the most widely used agents with presumed antiviral activity were hydroxychloroquine, antibiotics (azithromycin) and protease inhibitors, showing no benefit for prevention or treatment in both the general [54, [66] [67] [68] and SOT populations [8, 9, 11, 12, 14, 15] , and increasing the risk of interactions with other drugs [63, 69] . In the general population, remdesivir has been shown to decrease the in-hospital stay, but with no effect on the mortality rate. Importantly, its use is contraindicated in patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 and there are no studies on the use of remdesivir in the transplanted population [70] .

It has been shown that besides viral evasion to immune response, cytokine storm plays an important role in COVID-19 disease progression. Thus efforts have been made to mitigate the immune response with immunomodulators and large reviews exist on the potential role, efficacy and safety of these agents in the management of severe COVID-19 [71, 72] . Non-randomized studies have shown that treatment with tocilizumab in critically ill patients may offer some benefit in both the general [73] and kidney transplant population [74] . However, prospective randomized studies in hospitalized patients with COVID-19 pneumonia showed that although tocilizumab may reduce the likelihood of progression to mechanical ventilation, it did not improve survival [75, 76] . Importantly, the large RECOVERY trial showed that dexamethasone decreases 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone, but not among those receiving no respiratory support [77] . Thus research efforts should focus not only on the most relevant immunomodulatory strategies, but also the optimal timing of such immunomodulatory interventions to maximize the therapeutic effect [71] .

In kidney transplantation, the most widely used interventions were the modification of immunosuppression, reducing or suspending the antimetabolite or inhibitors of the mammalian target of rapamycin, while the calcineurin inhibitor was suspended in patients at risk for interaction with protease inhibitors [8, 11, 12, 66, 78] . Recently, the in vitro efficacy of cyclosporine A and FK506 to inhibit the replication of SARS-CoV-1 and other human coronaviruses has been reported [79] ; however, there is no clinical evidence for a protective effect to reduce the likelihood of severe COVID-19 or to treat the cytokine storm. Also, there is no evidence on what the management of immunosuppression should be. An approach like that of other serious viral infections (mycophenolate withdrawal and calcineurin inhibitor reduction) seems a safe option since this change in immunosuppression has been associated with very low incidences of acute rejection.

A British population-based study showed that SOT patients had one of the highest in-hospital risks of death (HR 4.23) due to COVID-19 [80] . In a large multicentre US study (423 SOT patients, including 318 kidney or kidney-pancreas recipients), the overall mortality rate by Day 28 was 20.5% among the hospitalized patients and 18.5% among the overall cohort [62] . Risk factors for mortality included age >65 years, chronic heart failure, chronic lung disease and obesity. Also, the presence of pneumonia and lymphopaenia at diagnosis were independently associated with mortality. Of interest, none of the multiple surrogates for immunosuppression that were explored showed any association with mortality. Focusing on renal transplants, a recent systematic review based on 20 studies from different countries revealed a patient mortality higher than in general population, ranging between 18% and 43% [81] . Risk factors associated with mortality (Table 4 ) included older age [13, 15, 74, [82] [83] [84] , plasma viral load [82] and the presence of higher inflammatory biomarkers such as C-reactive protein, interleukin-6 (IL-6), D-dimer or serum lactate dehydrogenase [8, 12, 74, 82] . Interestingly, in a Turkish cohort of 40 renal recipients, the use of previous antirejection treatment was an independent predictor for mortality and the use of cyclosporine as a maintenance immunosuppressant was associated with better survival [85] . Likewise, in a study that included 29 renal transplant patients, patients on cyclosporinebased immunosuppression experienced less mortality compared with immunosuppression minimization [86] .

The Spanish registry included 423 kidney transplants with a mortality rate of 28% [8] . Interestingly, the mortality rate declined to 15.8% after adjusting for age and gender, implying that baseline characteristics rather than the immunosuppressive state or the transplant itself has a remarkable effect on survival. Overall, the risk of death increased with age (>60 years) and mortality was higher among recipients who developed ARDS and in those with nosocomial COVID-19. No differences were found regarding baseline immunosuppression between survivors and non-survivors, but in patients with ARDS in whom the antimetabolite agent was discontinued, the mortality was lower [8] . A French registry-based study that included 279 renal transplant patients reported a mortality rate of 22.8% and independent risk factors for mortality included age >60 years, cardiovascular disease and dyspnoea [9] .

In the TANGO multicentre study (144 hospitalized kidney transplants), the mortality rate was 32% and older age, lower lymphocyte counts, higher lactate dehydrogenase, procalcitonin and IL-6 levels and lower eGFR were associated with mortality [11] . Moreover, the presence of dyspnoea at onset (61% versus 83%) was associated with mortality while the presence of diarrhoea was more frequent in survivors (45% versus 24%). Other factors such as the type of transplantation (living versus deceased donor), time post-transplantation (<1 versus >1 year), comorbidities or type of immunosuppression were not associated with mortality. None of the treatment strategies with [11] . In a multicentre study from Spain that included 104 kidney recipients, the mortality rate was 28% and older age, higher serum lactate dehydrogenase and having ARDS at admission were independently associated with a higher risk of death [12] .

A Belgium registry-based study that included 46 kidney transplant recipients with COVID-19 showed a mortality similar to that reported in the general population (14% versus 15.3%), but much lower than in patients on dialysis (14% versus 29%) [10] .

In another study that involved several European countries (ERACODA), 305 renal transplant patients were included, with a 28-day mortality rate of 21.3% as compared with 25% in patients on dialysis, and older age was the predominant risk factor for mortality in renal recipients [87] .

Most of the available data on survival involves long-term stable recipients, and there is scarce information regarding early transplant recipients. In studies in which the subgroup of early transplant recipients was analysed for <6 months [12] or <1 year [12, 88] , mortality was not different between groups, although in some of them there was a trend towards a higher mortality for the early group [12] . A recent report that included 24 recipients with COVID-19 diagnosed within 60 days after transplantation revealed a significant impact on patient survival with a mortality rate of 46% [89] . Recipients who died were older (61 versus 70 years), received high-dose steroids less frequently (25% versus 82%) and usually needed ventilation support (15% versus 78%). In another study that included 237 patients in the first-year post-transplant, of whom 16 had a COVID-19 diagnosis, the mortality rate was 37% [90] .

In this pandemic era, management of induction and maintenance immunosuppression has been challenging to clinicians treating kidney transplant patients. Regarding the use of induction therapy with lymphocyte-depleting agents (anti-thymocyte globulins, alemtuzumab and rituximab), a large study conducted in the USA showed that their use decreased during the first several weeks of the pandemic compared with the three previous years, while the use of basiliximab or no induction increased. Importantly, during the pandemic, lymphocytedepleting agents were associated with a lower risk of acute rejection, but without significant differences in mortality. These results question whether this shift in induction immunosuppression was a safe and effective approach to address the novel infectious risk [91] . Additionally, small studies conducted in single centres show that renal transplant patients treated with thymoglobulin who acquired the COVID-19 infection early after transplantation had a modest risk for severe disease [92] , especially using low doses [93] . However, it seems prudent to monitor absolute lymphocyte count following lymphocyte-depleting induction and consider temporary an antimetabolite dose reduction in patients with severe lymphopaenia [92] . Conversely, management of steroids was not modified in the USA during the pandemic and the practice of steroid avoidance/withdrawal has not been modified and its use did not modify the graft failure or mortality rates [91] .

Since the beginning of the pandemic, all transplant programmes have dramatically reduced their activity [94, 95] . In the early outbreak period, general recommendations from the different societies in areas in which the virus was widespread implied avoiding living-donor transplantation and reserving deceased-donor transplantation for life-threatening conditions or for hypersensitized patients with a suitable donor [96] [97] [98] . In this pandemic scenario, there are several studies that aimed to address whether it would be safer to undergo a renal transplantation or remain on the waiting list. In a single-centre study in which the outcomes of 56 patients included on the waiting list were compared with the outcomes of 80 kidney transplant recipients, wait-listed patients with COVID-19 were not only more likely to require more hospitalization (82% versus 65%), but also had an increased risk of death (25% versus 16%), with comparable baseline demographics and comorbidities between groups [6]. In this cohort, risk factors independently associated with mortality were wait list status, male sex, age and diabetes. On the same note, in a registry-based study from France in which renal transplant recipients and patients included on the waiting list were compared in different time periods, an increase in deaths was detected in both populations between March and June 2020 as compared with the same period in the two previous years [99] . This was explained by COVID-19, which caused the deaths of 44% of recipients and 42% of wait-listed patients. Interestingly, the increase in risk of death in both populations was similar in high-risk geographic areas, but in lowrisk areas the risk of death in wait-listed patients 4-fold higher, but there was no additional risk for renal transplant recipients, suggesting that transplant programmes should not be suspended in geographic areas with a low spread of infection. In a multicentre study in London, an area with a high prevalence of COVID-19 [100] , outcomes after SARS-CoV-2 infection in kidney transplant recipients (n ¼ 121) were compared with patients on the waiting list (n ¼ 51). Although no differences in mortality were found (30% versus 27%), the only risk factor independently associated with mortality was being >60 years of age in the kidney transplant group [OR 4.3 (95% CI 1.8-10.2)] [88] . Finally, in contrast with the previous data, there is a single-centre study performed in London in which the overall survival on a population level between wait-listed and kidney transplant patients was not different, but the mortality rate following SARS-CoV-2 infection was higher in the renal transplant group (37% versus 11%) [90] . Few studies exist in the paediatric population, but the available data support that since chronic immunosuppression is not associated with an increased risk of COVID-19 in young kidney transplant patients, transplant activity should be maintained even in areas with a high incidence of SARS-CoV-2 infection [101] .

The COVID-19 pandemic has been challenging for kidney transplantation programmes around the world, with a big impact on transplant policies and in the management of infected and uninfected patients. The rate of infected transplants was high in geographic areas with widespread infection and patient outcomes were compromised due to high rates of complications and COVID-19-related deaths. In managing infected patients during the pandemic, only the use of steroids and remdesivir has been demonstrated to be useful after performing randomized controlled clinical trials. Since chronic immunosuppression may influence a patient's outcome, different changes based on art and theory were applied. Thus, in the absence of trial-based evidence, we should include transplant patients in prospective studies and registries to help guide optimal care [102] . 

A novel coronavirus from patients with pneumonia in China

Symptom profiles of a convenience sample of patients with COVID-19 -United States

Drug treatments for covid-19: living systematic review and network metaanalysis

drugs/drug-safety-and-availability/fdas-approvalveklury-remdesivir-treatment-covid-19-science-safetyand-effectiveness

Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe

COVID-19 in transplant recipients: the Spanish experience

An initial report from the French SOT COVID registry suggests high mortality due to Covid-19 in recipients of kidney transplants

Incidence, characteristics, and outcome of COVID-19 in adults on kidney replacement therapy: a regionwide registry study

COVID-19 and kidney transplantation: results from the TANGO international transplant consortium

Clinical characteristics and risk factors for severe COVID-19 in hospitalized kidney transplant recipients: a multicentric cohort study

COVID-19 in patients undergoing chronic kidney replacement therapy and kidney transplant recipients in Scotland: findings and experience from the Scottish renal registry

COVID-19 infection in kidney transplant recipients: disease incidence and clinical outcomes

Kidney transplant patients with SARS-CoV-2 infection: the Brescia Renal COVID task force experience

COVID-19 in elderly kidney transplant recipients

Outpatient management of kidney transplant recipients with suspected COVID-19-single-center experience during the New York City surge

Early outcomes of outpatient management of kidney transplant recipients with coronavirus disease 2019

COVID-19 infection in kidney transplant recipients at the epicenter of pandemics

Respiratory and gastrointestinal COVID-19 phenotypes in kidney transplant recipients

Renal involvement and early prognosis in patients with COVID-19 pneumonia

Acute kidney injury in patients hospitalized with COVID-19

AKI in hospitalized patients with and without COVID-19: a comparison study

Outcomes among patients hospitalized with COVID-19 and acute kidney injury

AKI in hospitalized patients with COVID-19

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area

Hospitalization and mortality among black patients and white patients with Covid-19

Asian and minority ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data

COVID-19-associated collapsing glomerulopathy: an emerging entity

Clinical and histological analysis of acute tacrolimus (TAC) nephrotoxicity in renal allografts

Hypertension in chronic kidney disease: the influence of renal transplantation

COVID-19 outcomes among solid organ transplant recipients: a case-control study

Acute kidney injury in a predominantly African American cohort of kidney Kidney transplantation and COVID-19 | i27 transplant recipients with COVID-19 infection

Early report on published outcomes in kidney transplant recipients compared to nontransplant patients infected with coronavirus disease 2019

A systematic review of COVID-19 infection in kidney transplant recipients: a universal effort to preserve patients' lives and allografts

Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China

Clinicopathological features and outcomes of acute kidney injury in critically Ill COVID-19 with prolonged disease course: a retrospective cohort

Ultrastructural evidence for direct renal infection with SARS-CoV-2

Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Collapsing glomerulopathy in a patient of Indian descent in the setting of COVID-19

Spectrum of podocytopathies in new-onset nephrotic syndrome following COVID-19 disease: a report of 2 cases

Collapsing glomerulopathy in a COVID-19 patient

Collapsing focal segmental glomerulosclerosis and acute oxalate nephropathy in a patient with COVID-19: a double whammy

First case of COVID-19-associated collapsing glomerulopathy in sub-Saharan Africa

COVID-19-associated collapsing focal segmental glomerulosclerosis: a report of 2 cases

Multicenter clinicopathologic correlation of kidney biopsies performed in COVID-19 patients presenting with acute kidney injury or proteinuria

Thrombotic microangiopathy in a patient with COVID-19

COVID-19-associated kidney injury: a case series of kidney biopsy findings

Minimal change disease with nephrotic syndrome associated with coronavirus disease 2019 after apolipoprotein L1 risk variant kidney transplant: a case report

Kidney biopsy findings in patients with COVID-19

Lessons for the clinical nephrologist: recurrence of nephrotic syndrome induced by SARS-CoV-2

Collapsing glomerulopathy affecting native and transplant kidneys in individuals with COVID-19

COVID-19-related collapsing glomerulopathy in a kidney transplant recipient

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirusinfected pneumonia in Wuhan, China

Clinical characteristics of coronavirus disease 2019 in China

Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study

Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain

Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China

COVID-19 in solid organ transplant: a multi-center cohort study

COVID-19 in solid organ transplantation: a matched retrospective cohort study and evaluation of immunosuppression management

A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia

Covid-19 and kidney transplantation

Hydroxychloroquine with or without azithromycin in mildto-moderate Covid-19

A clusterrandomized trial of hydroxychloroquine for prevention of Covid-19

Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Pharmacologic treatment of transplant recipients infected with SARS-CoV-2: considerations regarding therapeutic drug monitoring and drug-drug interactions

Remdesivir for severe covid-19: a clinical practice guideline

Pharmaco-Immunomodulatory therapy in COVID-19

Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: a systematic review and network meta-analysis

Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: a single-center cohort study

Use of tocilizumab in kidney transplant recipients with COVID-19

Efficacy of tocilizumab in patients hospitalized with covid-19

Tocilizumab in patients hospitalized with Covid-19 pneumonia

Dexamethasone in hospitalized patients with Covid-19 -preliminary report

Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: a case-control study

Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506

OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients

COVID-19 and kidney transplantation: a systematic review

In-depth virological assessment of kidney transplant recipients with COVID-19

SARS-CoV-2 infection and early mortality of wait-listed and solid organ transplant recipients in England: a national cohort study

Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN)

COVID-19 in kidney transplant recipients: a multicenter experience in Istanbul

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

COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration

Mortality rates in transplant recipients and transplantation candidates in a high prevalence COVID-19 environment

COVID-19-related mortality during the first 60 days after kidney transplantation

Informing the risk of kidney transplantation versus remaining on the wait list in the COVID-19 era

Early changes in kidney transplant immunosuppression regimens during the COVID-19 pandemic

Kidney transplantation using lymphocyte depleting induction and standard maintenance immunosuppression at the height of the SARS-CoV-2 pandemic in New York City: a single-center experience

COVID-19 in recent kidney transplant recipients

Early impact of COVID-19 on transplant center practices and policies in the United States

Organ procurement and transplantation during the COVID-19 pandemic

Global transplantation COVID report

Position statement of transplant activity in the Middle East in era of COVID-19 pandemic

The COVID-19 pandemic: a community approach

IMPact of the COVID-19 epidemic on the moRTAlity of kidney transplant recipients and candidates in a French Nationwide registry sTudy (IMPORTANT)

Office of National Statistics. Deaths registered weekly in England and Wales, provisional: week ending 13

Risk of COVID-19 in young kidney transplant recipients. Results from a singlecenter observational study

Practicing with uncertainty: kidney transplantation during the COVID-19 pandemic

Kidney transplantation and COVID-19 | i29

The authors received grants from Red de Investigació n Renal (REDinREN RD16/0009/0030) and Fondo de Investigació n Sanitaria del Instituto de Salud Carlos III (PI 18/01704, PI 18/01382). B.C. is supported by a Vall d'Hebron Institute of Research grant. This article is part of a supplement supported by Fresenius Medical Care without any influence on its content.

The authors declare no conflicts interest.