SARS-CoV-2 in Solid Organ Transplant Recipients: A Structured Review of 2020

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging health systems all over the world. Particularly high-risk groups show considerable mortality rates after infection. In 2020, a huge number of case reports, case series, and consecutively various systematic reviews have been published reporting on morbidity and mortality risk connected with SARS-CoV-2 in solid organ transplant (SOT) recipients. However, this vast array of publications resulted in an increasing complexity of the field, overwhelming even for the expert reader.MethodsWe performed a structured literature review comprising electronic databases, transplant journals, and literature from previous systematic reviews covering the entire year 2020. From 164 included articles, we identified 3451 cases of SARS-CoV-2–infected SOT recipients.ResultsInfections resulted in a hospitalization rate of 84% and 24% intensive care unit admissions in the included patients. Whereas 53.6% of patients were reported to have recovered, cross-sectional overall mortality reported after coronavirus disease 2019 (COVID-19) was at 21.1%. Synoptic data concerning immunosuppressive medication attested to the reduction or withdrawal of antimetabolites (81.9%) and calcineurin inhibitors (48.9%) as a frequent adjustment. In contrast, steroids were reported to be increased in 46.8% of SOT recipients.ConclusionsCOVID-19 in SOT recipients is associated with high morbidity and mortality worldwide. Conforming with current guidelines, modifications of immunosuppressive therapies mostly comprised a reduction or withdrawal of antimetabolites and calcineurin inhibitors, while frequently maintaining or even increasing steroids. Here, we provide an accessible overview to the topic and synoptic estimates of expectable outcomes regarding in-hospital mortality of SOT recipients with COVID-19.     

COVID-19 Infection in Heart Transplants in Pre- and Postvaccination Periods

BackgroundHeart transplant (HTx) recipients constitute a group vulnerable to COVID-19 infection. Vaccination has been a turning point in the evolution of the pandemic. The objective was to analyze a series of HTx recipients with COVID-19 prior to vaccination and post vaccination.MethodsInclusion: All HTx recipients diagnosed with COVID-19 (February 2020 to April 2022). Exclusion: HTx younger than 16 years. They were subdivided into prevaccination period (February 2020 to February 2021) and postvaccination period (March 2021 to April 2022).They were classified into 3 groups according to severity. Group 1: mild symptoms without admission. Group 2: admission for nonsevere pneumonia. Group 3: severe pneumonia according to American Thoracic Society/Infectious Diseases Society of America criteria. The general therapeutic attitude before and after vaccination was similar in both groups.ResultsA total of 65 HTx recipients have had COVID-19 to date (10.7% of the 374 HTx recipients alive).In the prevaccination period, 22 HTx recipients presented the disease (Fig 1A): 27% in group 1; 59% were admitted for nonsevere pneumonia (group 2), with favorable evolution and a mean stay of 16 days; and 14% in group 3 (criteria for severe pneumonia), with 2 HTx recipients dying in this group.In the postvaccination period, 43 HTx recipients have presented COVID-19 (Fig 1B), 49% in group 1, 42% in group 2, and 9% in group 3. The hospital stay is slightly reduced to 15 days and 3 of the 4 patients in group 3 have died (mortality rate 7%).ConclusionsA significant number of HTx recipients have been affected by COVID-19, associating high mortality in severe forms both in the pre- and postvaccination period. In our series of patients, vaccination has reduced the percentage of hospitalization for nonsevere pneumonia slightly below the average hospitalization and mortality.     

COVID-19 and solid organ transplantation: Finding the right balance

BackgroundThe COVID-19 pandemic has a great impact on solid organ transplant (SOT) recipients due to their comorbidities and their maintenance immunosuppression. So far, studies about the different aspects of the impact of the pandemic on SOT recipients are limited.ObjectivesThis systematic review summarizes the risk factors that make SOT patients more vulnerable for severe COVID-19 disease or mortality and the impact of immunosuppressive therapy. Furthermore, their clinical outcomes, mortality risk, immunosuppression, immunity and COVID-19 vaccination efficacy are discussed.MethodsA systematic search on PubMed was performed to select original articles on SOT recipients concerning the following four topics: (1) mortality and clinical course; (2) risk factors for mortality and composite outcomes; (3) maintenance immunosuppression; (4) immunity to COVID-19 infection and (5) vaccine immunogenicity. Relevant data were extracted, analyzed and summarized in tables.ResultsThis systematic review includes 77 articles. Mortality was associated with advanced age. Post-transplantation time or comorbidities were variably identified as independent risk factors for mortality or severe disease. However, generally, no comorbidity was reported as a major risk factor. SOT recipients have a higher risk of acute kidney injury, but no higher rate of mortality compared to non-transplanted patients was found. Immunosuppression was individually adjusted, without leading to high rates of graft dysfunction. Generally, no association between type of immunosuppression and mortality was found. SOT patients established humoral and cellular immune responses after COVID-19 disease comparable to immunocompetent people. At last, SOT patients experience a diminished immune response after two-dose vaccination with SARS-COV-2-mRNA-vaccines.ConclusionMore research is needed to address the direct effect of COVID-19 disease on the graft in lung transplant recipients, as well as the factors ameliorating the immune response in SOT recipients.     

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.     

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1–2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6–7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.     

Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan,China

BackgroundPrevious studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations.ObjectiveTo evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients.Design, setting, and participantsA total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group.InterventionImmunosuppressant reduction and low-dose methylprednisolone therapy.Outcome measurements and statistical analysisThe clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis.Results and limitationsThe clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 ± 9.3 vs 12.2 ± 4.6 d in the control group) and a longer course of illness (35.3 ± 8.3 vs 18.8 ± 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure.ConclusionsKidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations.Patient summaryImmunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.     

Remdesivir in Solid Organ Recipients for COVID-19 Pneumonia

Solid organ transplant (SOT) recipients represent a vulnerable patient population and are of high risk for airborne viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Treatment of COVID-19 is still challenging, as no proven therapeutic regimen is available for immunocompromised patients. Our aim was to evaluate the efficacy and safety of remdesivir (RDV) therapy in infected hospitalized SOT patients. All transplanted recipients (N = 25; lung: 19; kidney: 3, liver: 2, heart: 1) who needed hospital care were reviewed in the time period between September 2020 and May 2021 out of the 945 patients treated at the Department. Case control matched patients receiving RDV (all in need of supplementary oxygen) and standard of care (SOC) were included as controls. Among the 25 SOT patients (female:male = 11:14; average age = 53.2 ± 12.7 years), 15 received RDV medication (RDV-TX), and in 10 cases SOC treatment was used (SOC-TX). Significantly worse clinical score was noted in RDV patients compared with RDV-TX; however, transfer to a higher intensity care unit as well as 60-day survival of RDV-TX patients were significantly worse. All SOT fatalities within 60 days of follow-up were lung transplant recipients (6 out of 19 lung transplant patients). No adverse events were noted related to RDV therapy. In SOT patients, especially lung transplant recipients, with severe COVID-19 needing supplementary oxygen, RDV treatment was safe; however, outcome was significantly worse as compared with nontransplanted individuals with initially worse clinical parameters.     

Impact of COVID-19 in solid organ transplant recipients

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exploded onto the world stage in early 2020. The impact on solid organ transplantation (SOT) has been profound affecting potential donors, candidates, and recipients. Importantly, decreased donations and the pressure of limited resources placed on health care by the pandemic also disrupted transplant systems. We address the impact of COVID-19 on organ transplantation globally and review current understanding of the epidemiology, outcomes, diagnosis, and treatment of COVID-19 in SOT recipients.     

Sex and organ-specific risk of major adverse renal or cardiac events in solid organ transplant recipients with COVID-19

While older males are at the highest risk for poor coronavirus disease 2019 (COVID-19) outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (January 1, 2020-June 21, 2021) from 56 sites across the United States identified using the National COVID Cohort Collaborative (N3C) Enclave, we used multivariable Cox proportional hazards models to assess time to MARCE after COVID-19 diagnosis in those with and without SOT. We examined the exposure of age-stratified recipient sex overall and separately in kidney, liver, lung, and heart transplant recipients. 3996 (36.4%) SOT and 91 646 (4.8%) non-SOT patients developed MARCE. Risk of post-COVID outcomes differed by transplant allograft type with heart and kidney recipients at highest risk. Males with SOT were at increased risk of MARCE, but to a lesser degree than the non-SOT cohort (HR 0.89, 95% CI 0.81–0.98 for SOT and HR 0.61, 95% CI 0.60–0.62 for non-SOT [females vs. males]). This represents the largest COVID-19 SOT cohort to date and the first-time sex-age–stratified and allograft-specific COVID-19 outcomes have been explored in those with SOT.     

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients.     

Coronavirus Disease 2019 in Kidney Transplant Recipients: Single-Center Experience and Case-Control Study

BackgroundKidney transplant recipients (KTR) are considered high-risk for morbidity and mortality from coronavirus disease 2019 (COVID-19). However, some studies did not show worse outcomes compared to non-transplant patients and there is little data about immunosuppressant drug levels and secondary infections in KTR with COVID-19. Herein, we describe our single-center experience with COVID-19 in KTR.MethodsWe captured KTR diagnosed with COVID-19 between March 1, 2020 and May 18, 2020. After exclusion of KTR on hemodialysis and off immunosuppression, we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by age and sex (controls).Results. Eleven KTR were hospitalized and matched with 44 controls. One KTR and 4 controls died (case fatality rate: 9.1%). There were no significant differences in length of stay or clinical outcomes between KTR and controls. Tacrolimus or sirolimus levels were >10 ng/mL in 6 out of 9 KTR (67%). Bacterial infections were more frequent in KTR (36.3%), compared with controls (6.8%, P = .02).ConclusionsIn our small case series, unlike earlier reports from the pandemic epicenters, the clinical outcomes of KTR with COVID-19 were comparable to those of non-transplant patients. Calcineurin or mammalian target of rapamycin inhibitor (mTOR) levels were high. Bacterial infections were more common in KTR, compared with controls.     

COVID-19 in transplant recipients: The Spanish experience

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).     

Risk of Severe Coronavirus Disease 2019 Infection in Kidney Transplant Recipients

BackgroundDespite all efforts, the incidence of severe coronavirus disease 2019 (COVID-19) infection has been high in renal transplant recipients, as in other groups (eg, older adults, patients with comorbidities or immunosuppression). The detection of any possible predictor of gravity could improve the early approach in these patients.Patients and methodsWe registered data from renal transplant recipients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection in our area for a year (March 2020 to March 2021). We collected demographics, comorbidity, body mass index, lymphocyte count, and vitamin D levels before the diagnosis. We performed statistical analysis using SPSS Statistics version 20 (IBM Corp, Armonk, NY, United States).ResultsOf 63 patients, 57.1% required hospital admission and 14.3% required intensive care. The incidence of acute renal failure was 28.6%; 34.9% developed hyperinflammatory syndrome; 67% had lymphopenia, which was severe in 13.1%; and 11 patients died. There was significant correlation between lymphocyte count before and during the infection. For hospitalization, we found differences in age, pulmonary disease, and renal function. Related factors for admission to an intensive care unit were obesity, severe lymphopenia, altered renal function, and low level of vitamin D. Predictors for mortality were age, renal function, and minimum lymphocyte count.ConclusionIn kidney transplant recipients with COVID-19 infection, renal function determines hospitalization, and body mass index determines admission to an intensive care unit. Previous vitamin D levels are also significantly lower in patients requiring intensive care. The analysis of lymphocyte count previous to infection is correlated with the minimum level during the disease, which is a predictor of mortality, and could be a prognosis factor.     

Is Early COVID-19 in Kidney Transplant Recipients Concerning Enough to Halt Transplantation? A Multicenter Comparative Analysis from India

BackgroundLimited data exist on the incidence and outcome of early coronavirus disease 2019 (COVID-19) in kidney transplantation recipients (KTR).MethodsA retrospective multicenter research study was conducted across 12 centers in India. We explored the symptomatology, demographic, laboratory findings, and outcome of COVID-19 within 30 days of transplantation. The outcome was compared with the overall KTR and waitlisted patients acquiring COVID-19.ResultsThe incidence of early COVID-19 was 2.6% (n = 22) for the cumulative 838 renal transplants performed since nationwide lockdown in March 2020 until May 2021. Overall, 1049 KTR were diagnosed with COVID-19 and 2% of those had early COVID-19. The median age of the early COVID-19 cohort was 43 (31-46) years. COVID-19 severity ranged from asymptomatic (18.2%), mild (59.1%), moderate (9.1%), and severe (13.6%). Among clinical symptoms, dyspnea and anosmia were frequent, and in laboratory parameters, neutrophil lymphocyte ratio, high-sensitivity C-reactive protein, and D-dimer were higher in patients requiring oxygen. The mortality in early COVID-19 was not higher than overall KTR (4.5% vs 8.5%; P = 1). COVID-19 severity (23.9% vs 15.7%; P = .0001) and mortality (15.5% vs 8.5%; P = .001) among waitlisted patients (n = 1703) were higher compared with overall KTR.ConclusionsWe report higher burden of COVID-19 in waitlisted patients compared with KTR and a favorable outcome in early COVID-19 in KTR. Our report will help the transplant physicians in dealing with the ongoing dilemma of halting or resuming transplantation in the COVID-19 era.     

Kinetics of Anti–SARS-CoV-2 IgG Antibodies in Hemodialysis Patients Six Months after Infection

BackgroundThe humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the hemodialysis population, including its dynamics over time, remains poorly understood.MethodsTo analyze initial and long-term humoral responses against SARS-CoV-2 in a hemodialysis population, we retrospectively evaluated findings from SARS-CoV-2 IgG serologic assays targeting the nucleocapsid antigen or spike antigen up to 6 months of follow-up in patients on hemodialysis in the Paris, France, region who had recovered from coronavirus disease 2019 (COVID-19).ResultsOur analysis included 83 patients (median age 65 years); 59 (71%) were male and 28 (34%) had presented with severe COVID-19. We observed positive initial SARS-CoV-2 IgG antinucleocapsid serology in 74 patients (89%) at a median of 67 days postdiagnosis. By multivariable analysis, immunocompromised status was the only factor significantly associated with lack of an IgG antinucleocapsid antibody response. Follow-up data were available at 6 months postdiagnosis for 60 of 74 patients (81%) with positive initial antinucleocapsid serology, and 15 (25%) of them had negative antinucleocapsid serology at month 6. In total, 14 of 15 sera were tested for antispike antibodies, 3 of 14 (21%) of which were also negative. Overall, 97% of antinucleocapsid-antibody–positive specimens were also antispike-antibody positive. Female sex, age >70 years, and nonsevere clinical presentation were independently associated with faster IgG antinucleocapsid titer decay in multivariable analysis. After adjustment for sex and age >70 years, nonsevere clinical presentation was the only factor associated with faster decay of IgG antispike antibodies.ConclusionsThis study characterizes evolution of the SARS-CoV-2 antibody response in patients on hemodialysis and identifies factors that are associated with lack of seroconversion and with IgG titer decay.