The coronavirus pandemic has significantly impacted solid organ transplantation (SOT). Early in the outbreak period, transplant societies recommended suspending living kidney transplant programs in ...communities with widespread transmission to avoid exposing recipients to increased risk of immunosuppression, while recommendations were made to reserve deceased-donor kidney transplantation for likely life-saving indications. SOT recipients may be at high risk from COVID-19 disease due to chronic immunosuppressive treatment and other medical comorbidities. Mortality rates reported between 13 to over 30% in SOT recipients. In addition to high rates of complications and mortality attributable to COVID-19 infections, the pandemic has also led to additional complexities in transplantation including new questions regarding screening of donors and recipients, decision making to accept a patient for kidney transplant or wait after pandemic. The clinical implications of COVID-19 infection may also differ depending on the type of the transplanted organ and recipient comorbidities which further impacts decisions on continuing transplantation during the pandemic. Transplant activity during a pandemic should be tailored with careful selection of both donors and recipients. Furthermore, while tremendous strides have been made in treatment strategies and vaccinations, the impact of these in transplant recipients may be attenuated in the setting of their immunosuppression. In this review, we aim to summarize several aspects of COVID-19 in transplantation, including the immune response to SARS-CoV-2, SARS-CoV-2 diagnostics, clinical outcomes in SOT recipients, and end-stage kidney disease patients, transplant activity during the pandemic, and treatment options for COVID-19 disease.
Covid-19 and Kidney Transplantation Akalin, Enver; Azzi, Yorg; Bartash, Rachel ...
New England journal of medicine/The New England journal of medicine,
06/2020, Letnik:
382, Številka:
25
Journal Article
Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID‐19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized ...adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID‐19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID‐19 during the 9‐week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow‐up period of 52 days (IQR: 16‐66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin‐6 levels. In sum, hospitalized kidney transplant recipients with COVID‐19 have higher rates of acute kidney injury and mortality.
In this multinational cohort of 144 kidney transplanted patients from 11 transplant centers in the US and Europe who were hospitalized for COVID‐19, acute kidney injury occurred in 52% and respiratory failure requiring intubation occurred in 29%, with an overall mortality of 32%.
Among patients with COVID-19, kidney transplant recipients (KTRs) have poor outcomes compared with non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied ...immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.
We ascertained clinical data by chart review. A single sample of blood was collected for transcriptome analysis. Total RNA was poly-A selected and RNA was sequenced to evaluate transcriptome changes. We also measured cytokines and chemokines of serum samples collected during acute infection.
A total of 64 patients with COVID-19 in KTRs were enrolled, including 31 with acute COVID-19 (<4 weeks from diagnosis) and 33 with post-acute COVID-19 (>4 weeks postdiagnosis). In the blood transcriptome of acute cases, we identified genes in positive or negative association with COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways but downregulation of T cell and adaptive immune activation pathways. This finding was independent of lymphocyte count, despite reduced immunosuppressant use in most KTRs. Compared with acute cases, post-acute cases showed "normalization" of these enriched pathways after 4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of immunosuppression. Analysis of the non-KTR cohort with COVID-19 showed significant overlap with KTRs in these functions. Serum inflammatory cytokines followed an opposite trend (
, increased with disease severity), indicating that blood lymphocytes are not the primary source.
The blood transcriptome of KTRs affected by COVID-19 shows decreases in T cell and adaptive immune activation pathways during acute disease that, despite reduced immunosuppressant use, associate with severity. These pathways show recovery after acute illness.
To evaluate the chest radiographic severity score (CXR-SS) for coronavirus disease 2019 (COVID-19) patients who are kidney transplant recipients compared with patients on the waitlist.
This ...retrospective cohort includes 78 kidney transplant recipients (50 men, mean age 59.9±11.9 y) and 59 kidney transplant waitlist patients (33 men, mean age 58.8±10.8 y) diagnosed with COVID-19 between March 15 and May 30, 2020 with reverse transcriptase-polymerase chain reaction. Patient chest radiographs were divided into 6 zones and examined for consolidation. Primary outcome was mortality. Secondary outcomes included hospital admission, intensive care unit (ICU) admission, and intubation. Predictors of our primary and secondary outcomes were identified by bivariate analysis and multivariate regression analysis.
No significant difference was found in CXR-SS between 2 groups (P=0.087). Transplant recipients had significantly higher rates of hospitalization (odds ratio, 6.8; 95% confidence interval: 1.7, 39.3; P<0.001), ICU admission (odds ratio, 6.5; 95% confidence interval CI: 1.8-35.9; P=0.002), intubation (odds ratio, 11; 95% CI: 2.4-96.9; P=0.001), and mortality (odds ratio, 17; 95% CI: 3.9-153.1; P<0.001). A higher CXR-SS was not predictive of mortality, intubation, or ICU admission. CXR-SS was associated with hospital admission overall (odds ratio, 1.613; 95% CI: 1.04-2.49; P=0.0314).
The CXR-SS was not predictive of mortality, ICU admission or intubation in our population. Kidney transplant patients with COVID-19 had near universal hospital admission, more than one-third mortality and about a quarter were intubated and admitted to the ICU-all significantly worse outcomes than for patients on the transplant waitlist.
Kidney allocation system allows blood type B candidates accept kidneys from A2/A2B donors. There is no mandate by UNOS on which the anti-A2 level is acceptable. We aimed to investigate the safety of ...kidney transplant in blood group B patients with anti-A2 titers ≤16.
We performed 41 A2-incompatible kidney transplants in blood group B recipients between May 2015 and September 2019. Clinical outcomes were compared with a control group of 75 blood group B recipients who received blood group compatible kidney transplantation at the same period.
Of the 41 recipients, 85% were male, 48% African American, with a median age of 53 (20-73) y. Thirty-eight (93%) were deceased-donor and 3 (7%) were living-donor kidney transplant recipients. Pretransplant anti-A2 IgG titers were 2 in 16, 4 in 9, 8 in 6, and 16 in 5 and too weak to titer in 5 recipients. Eight patients had pretransplant donor-specific antibodies. During a median follow-up of 32.6 mo (6-57.3) patient and graft survival were 100% and 92% in the A2-incompatible kidney transplant group, and 91% and 92% in the blood group compatible group, respectively. Twelve A2-incompatible recipients underwent a 21 clinically indicated kidney biopsies at a median 28 d (6-390) after transplantation. None of the patients developed acute antibody-mediated rejection and 2 patients (5%) had acute T-cell-mediated rejection. Interestingly, peritubular capillary C4d positivity was seen in 7 biopsies which did not have any findings of acute rejection or microvascular inflammation but not in any of the rejection-free biopsies in the control group. C4d positivity was persistent in 5 of those patients who had follow-up biopsies.
A2-incompatible transplantation is safe in patients with anti-A2 titers ≤16 with excellent short-term kidney allograft outcomes. C4d positivity is frequent in allograft biopsies without acute rejection.
We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, ...132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8%) in the patients who required hospitalization. Twenty-three percent of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms; 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization.
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