COVID‐19 in a high‐risk dual heart and kidney transplant recipient

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly infecting people worldwide, resulting in the infectious disease coronavirus disease 19 (COVID‐19) that has been declared a pandemic. Much remains unknown about COVID‐19, including its effects on solid organ transplant (SOT) recipients. Given their immunosuppressed state, SOT recipients are presumed to be at high risk of complications with viral infections such as SARS‐CoV‐2. Limited case reports in single SOT recipients, however, have not suggested a particularly severe course in this population. In this report, we present a dual‐organ (heart/kidney) transplant recipient who was found to have COVID‐19 and, despite the presence of a number of risk factors for poor outcomes, had a relatively mild clinical course.     

COVID‐19 in solid organ transplant recipients: Initial report from the US epicenter

Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.     

SARS‐CoV‐2 infection in two patients following recent lung transplantation

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) that causes coronavirus disease 2019 (COVID‐19) has become a global health problem with pandemic character. Lung transplant recipients may be particularly at risk due to the high degree of immunosuppression and the lung being the organ primarily affected by COVID‐19. We describe a 16‐year‐old male and a 64‐year‐old female recently lung transplanted patients with COVID‐19 during inpatient rehabilitation. Both patients were receiving triple immunosuppressive therapy and had no signs of allograft dysfunction. Both patients had close contact with a person who developed COVID‐19 and were tested positive for SARS‐CoV‐2. Subsequently, both patients underwent systematic screening and SARS‐CoV‐2 was ultimately detected. Although the 16‐year‐old boy was completely asymptomatic, the 64‐year‐old woman developed only mild COVID‐19. Immunosuppressive therapy was unchanged and no experimental treatment was initiated. No signs of graft involvement or dysfunction were noticed. In conclusion, our report of patients with asymptomatic SARS‐CoV‐2 infection and mild COVID‐19, respectively, may indicate that lung transplant recipients are not per se at risk for severe COVID‐19. Further observations and controlled trials are urgently needed to study SARS‐CoV‐2 infection in lung transplant recipients.     

Novel coronavirus (SARS‐CoV‐2) infection in a renal transplant recipient: Case report

An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS‐CoV‐2) started in Wuhan, China, with cases now confirmed in multiple countries. The clinical course of patients remains to be fully characterized, clinical presentation ranges from asymptomatic infection to acute respiratory distress syndrome and acute renal failure, and no pharmacological therapies of proven efficacy yet exist. We report a case of SARS‐CoV‐2 infection in a renal transplant recipient with excellent outcome. This case states the importance of close monitoring of the concentration of cyclosporine in patients treated with lopinavir/ritonavir; the routine treatment of corticosteroid can be continued. This is a rare report of SARS‐CoV‐2 infection in a renal transplant recipient. Further data are needed to achieve better understanding of the impact of immunosuppressive therapy on the clinical presentation, severity, and outcome of SARS‐CoV‐2 infections in solid organ transplant recipients.     

COVID‐19 in solid organ transplant recipients: A single‐center case series from Spain

The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID‐19 by March 23, 2020 at a tertiary‐care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon‐β (16.7%). As of April 4, the case‐fatality rate was 27.8% (5/18). After a median follow‐up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C‐reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS‐CoV‐2 infection has a severe course in SOT recipients.     

Strategies to halt 2019 novel coronavirus (SARS‐CoV‐2) spread for organ transplantation programs at the Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital,China

During the 2019 novel coronavirus (SARS‐CoV‐2) outbreak in China (from January 24 to March 11, 2020), our center performed 16 organ transplants (10 kidney, 4 liver, and 2 lung transplants) harvested from deceased donors. Regarding the strategies to prevent infections of SARS‐CoV‐2, we implemented specific measures for the donor and recipient management, as well as prevention of hospital‐acquired infections. All 16 organ recipients had a favorable outcome without SARS‐CoV‐2 infection. Our approaches aiming to interrupt the spread of SARS‐CoV‐2 within the transplantation wards were successful, and allowed us to maintain the transplantation program for deceased liver, kidney, and lung organ recipients.     

COVID‐19 pneumonia in lung transplant recipients: Report of 2 cases

Coronavirus disease 2019 (COVID‐19) has been declared pandemic since March 2020. In Europe, Italy was the first nation affected by this infection. We report anamnestic data, clinical features, and therapeutic management of 2 lung transplant recipients with confirmed COVID‐19 pneumonia. Both patients were in good clinical condition before the infection and were receiving immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil, and corticosteroids. Whereas mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS‐CoV‐2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions, and had a fatal outcome. Further insight into SARS‐CoV‐2 infection is eagerly awaited to improve the outcome of transplant recipients affected by COVID‐19 pneumonia.     

Immunosuppressive therapy maintenance in a kidney transplant recipient with SARS‐CoV‐2 pneumonia: A case report

The role of systemic inflammation is proving crucial in determining unfavorable outcome in SARS‐CoV‐2–infected patients. Limited data are available regarding immunosuppression management in kidney transplant recipients (KTRs) with SARS‐CoV‐2 pneumonia. We report a case of a 32‐year‐old KTR who developed SARS‐CoV‐2 infection and fully recovered in 15 days while maintaining standard immunosuppressive therapy.     

Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City. Eligible patients were hospitalized and required to have positive nasopharyngeal polymerase chain reaction (PCR) diagnosis of SARS-CoV-2 infection, be at least 18 years old, and have either dyspnea, blood oxygen saturation ≤ 93% on ambient air, respiratory frequency ≥ 30 breaths/min, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, or lung infiltrates > 50%. Thirteen SOT recipients received convalescent plasma from April 9, 2020, to May 17, 2020. The median time from symptom onset to plasma infusion was 8 days. Eight of 13 patients (62%) had de-escalating oxygenation support by day 7 post-convalescent plasma. Nine (69%) patients were discharged, 1 (7%) patients remain hospitalized, and 3 (23%) patients died. This series supports the need for additional studies on convalescent plasma use in SOT recipients with COVID-19 to better determine efficacy and identify patients who are likely to benefit.     

A case of SARS‐CoV‐2 pneumonia with successful antiviral therapy in a 77‐year‐old man with a heart transplant

The SARS‐CoV‐2 infection can be seen as a single disease, but it also affects patients with relevant comorbidities who may have an increased risk of a severe course of infection. In this report, we present a 77‐year‐old patient with a heart transplant receiving relevant immunosuppressive therapy who tested positive for SARS‐CoV‐2 after several days of dyspnea, dry cough, and light general symptoms. Computed tomography confirmed interstitial pneumonia. The patient received antiviral therapy with hydroxychloroquine and showed no further deterioration of the clinical state. After 12 days of hospitalization, the patient was released; he was SARS‐CoV‐2 negative and completely asymptomatic.     

Real‐life food‐safety behavior and incidence of foodborne infections in solid organ transplant recipients

Food‐safety measures are recommended in solid organ transplant (SOT) recipients. However, the actual adherence of patients in a real‐life setting and the impact on the incidence of foodborne infections remain largely unexplored. We performed a survey among SOT recipients followed at our institution, aiming to evaluate their food‐safety behavior. We assessed the incidence of microbiologically proven foodborne infections by chart review. One hundred ninety‐seven SOT recipients (kidney = 117, lung = 35, liver = 29, and heart = 16) participated in the survey. Overall, 17.7% of the participants observed all food‐safety recommendations (22.0% avoided food at risk of contamination while 67.9% applied hygiene recommendations). Patients within the first year after transplantation (odds ratio [OR] 5.42; P = .001) and females (OR 4.67; P = .001) followed food‐safety recommendations more closely. Although the majority of SOT recipients felt concerned and actively sought information on food safety (68%‐70%), only 27% were able to recognize all risks of foodborne infection in hypothetical scenarios. Incidence of proven foodborne infections was 17.9% (95% confidence interval 9.9%‐30.9%) 5 years after transplantation. Importantly, foodborne infections occurred exclusively among patients not following food‐safety recommendations. In summary, most SOT recipients eat foods that make them at risk of foodborne infections. Our results indicate that there is room for improvement in patient education, particularly later after transplantation, and reinforce current food‐safety recommendations.     

COVID‐19 in kidney transplant recipients

There is minimal information on coronavirus disease 2019 (COVID‐19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47‐67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID‐19 testing was 2822 days (IQR 1272‐4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X‐ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID‐19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.     

Earliest cases of coronavirus disease 2019 (COVID‐19) identified in solid organ transplant recipients in the United States

With the rapidly expanding pandemic of SARS‐CoV‐2, there is concern that solid organ transplant recipients will be particularly vulnerable to infection and may experience a more severe clinical course. We report four cases of COVID‐19 in solid organ transplant recipients including recipients of kidney, liver, lung, and heart transplants. We describe each patient's medical history including transplantation history, their clinical presentation and workup, and their course from diagnosis to either hospital discharge or to improvement in symptoms. These reports demonstrate a range of symptoms, clinical severity, and disease course in solid organ transplant recipients with COVID‐19, including two hospitalized patients and two patients managed entirely in the outpatient setting.     

COVID‐19 in elderly kidney transplant recipients

The SARS‐Cov‐2 infection disease (COVID‐19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID‐19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti‐retroviral and tocilizumab. Short‐term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D‐dimer, C‐reactive protein, and IL‐6 at their first tests. COVID‐19 is frequent among the elderly KT population and associates a very early and high mortality rate.     

Clinical features of patients undergoing hemodialysis with COVID‐19

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID‐19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality‐related risk factors for those who undergoing hemodialysis with COVID‐19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID‐19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36‐89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty‐eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground‐glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID‐19, and similar manifestations could be found in patients without SARS‐CoV‐2 infection. In conclusion, for hemodialysis patients with COVID‐19, lymphocytopenia and ground‐glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS‐CoV‐2 infection.     

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case‐control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty‐eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38‐0.58), with the highest rate in lung (1.48, 95% CI 0.93‐2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29‐6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03‐10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15‐4.37; P = .02). These findings may help to improve the management of SOT recipients.     

SARS Cov‐2 infection in a renal‐transplanted patient: A case report

The clinical manifestation of COVID‐19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV‐2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can “be protective” as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.     

COVID‐19 pneumonia in a kidney transplant recipient successfully treated with tocilizumab and hydroxychloroquine

Coronavirus disease 2019 (COVID‐19) pneumonia has been poorly reported in solid organ transplanted patients; prognosis is uncertain and best management unclear. We describe the case of a 61‐year‐old kidney transplant recipient with several comorbidities who was hospitalized and later received a diagnosis of COVID‐19 pneumonia; the infection was successfully managed with the use of hydroxychloroquine and a single administration of tocilizumab, after immunosuppression reduction; the patient did not require mechanical ventilation. During the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, transplant clinicians should be readily informed about new cases of COVID‐19 pneumonia in solid organ transplant recipients, with focus on therapeutic strategies employed and their outcome.     

Higher rates of rejection in HIV‐infected kidney transplant recipients on ritonavir‐boosted protease inhibitors: 3‐year follow‐up study

Rejection rates in HIV‐infected kidney transplant (KTx) recipients are higher than HIV‐negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug‐drug interactions, likely influencing outcomes. This is an IRB‐approved, single‐center, retrospective study of adult HIV‐infected KTx patients between 5/2009 and 12/2014 with 3‐year follow‐up, excluding antibody‐depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre‐transplant dialysis. All patients received IL‐2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir‐boosted PI‐based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1‐, 2‐, and 3‐year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy‐proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV‐infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.     

Burden,epidemiology, and outcomes of microbiologically confirmed respiratory viral infections in solid organ transplant recipients: a nationwide,multi-season prospective cohort study

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61–5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7–20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62–3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15–5.52), and influenza (aHR 3.57; 95% CI 1.75–7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies.